1α,25-(OH)_2D_3介导成骨细胞影响破骨细胞形成及活化的研究
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摘要
骨代谢是维持骨组织不断更新,保持生命活力的基本过程,这一过程是依靠骨再建(bone remodeling)完成的。大量研究表明,动物骨营养不良的发生主要是破骨细胞(osteoclasts,OC)引起的骨吸收大于成骨细胞(osteoblasts,OB)引起的骨再建。许多研究认为,骨代谢调控因子主要通过调节OB表达核因子κB受体活化因子配体(receptor activator of NF-κB ligand,RANKL)及骨保护素(osteoprotegerin,OPG),从而间接调控OC的形成及骨吸收功能。维生素D及其活性代谢物是动物钙、磷代谢的重要调节因素之一。然而,钙、磷及维生素D制剂的疗效却参差不齐。因此进一步理解维生素D在骨骼生理和病理学中的确切机制有助于更好地防止代谢性骨病。本文研究了不同浓度1α,25-(OH)_2D_3对体外培养OB增殖、分化及RANKL、OPG蛋白和mRNA表达的影响,并观察了RANKL对体外培养OC形成及骨吸收活性的影响,旨在阐明维生素D调节骨代谢的部分机制。
1. 1α,25-(OH)_2D_3对体外培养成骨细胞增殖、分化及周期的影响
2.5 g/L胰酶和1 g/LⅡ型胶原酶两步消化法分离3-4日龄SD大鼠乳鼠颅盖骨细胞。采用倒置显微镜、扫描电镜观察细胞形态,碱性磷酸酶(ALP)特异染色鉴定OB。在此基础上,向培养体系中添加不同浓度的1α,25-(OH)_2D_3(0 [无水乙醇溶剂对照]、10~(-9)、10~(-8)、10~(-7) mol/L)。作用24、48、72 h,MTT法测定OB增殖率、PNPP法测定ALP活性,流式细胞仪测定OB周期。结果显示,10~(-9) mol/L 1α,25-(OH)_2D_3作用24、48、72 h均促进OB增殖(P<0.05或P<0.01),抑制ALP活性(P<0.01);10~(-8)、10~(-7) mol/L作用24、48 h,OB增殖率与对照组差异不显著(P>0.05),但24 h时ALP活性均明显升高(P<0.05或P<0.01),48 h则抑制了ALP活性并使OB滞留在G2/M期(P<0.05或P<0.01);72 h时10~(-7) mol/L组OB增殖率极显著低于其余各组(P<0.01),并又使ALP活性升高(P<0.01)。说明,低浓度1α,25-(OH)_2D_3(10~(-9) mol/L)促进OB增殖,抑制其分化;中高浓度1α,25-(OH)_2D_3(10~(-8)、10~(-7) mol/L)抑制OB增殖,促进其分化,并使细胞滞留在G2/M期。
2. 1α,25-(OH)_2D_3对体外培养成骨细胞骨架、GJIC及[Ca~(2+)]_i的影响
在OB培养的基础上,不同浓度的1α,25-(OH)_2D_3(0 [无水乙醇溶剂对照]、10~(-9)、10~(-8)、10~(-7) mol/L)作用20 min、24 h,流式细胞仪测定[Ca~(2+)]_i;24、48 h,荧光显微镜观察F-actin及细胞间隙连接通讯(GJIC)。结果显示,20 min时,不同浓度1α,25-(OH)_2D_3组[Ca~(2+)]_i均显著高于对照组(P<0.05);24 h时10~(-9) mol/L组[Ca~(2+)]_i则显著低于对照组(P<0.05),其余各组间差异不显著(P>0.05),此时10~(-8)、10~(-7) mol/L组大部分细胞变得扁平,F-actin排列较对照组有序,形成应力纤维;48 h时,对照组及10~(-9) mol/L组F-actin表达减少,10~(-9) mol/L组GJIC极显著弱于对照组(P<0.01),而10~(-8)、10~(-7) mol/L组大部分细胞F-actin表达完好,GJIC均极显著强于其余两组(P<0.01)。说明,1α,25-(OH)_2D_3能够影响钙离子通道,同时低浓度1α,25-(OH)_2D_3(10~(-9) mol/L)抑制F-actin表达及细胞间隙连接通讯,中高浓度1α,25-(OH)_2D_3(10~(-8)、10~(-7) mol/L)则能维持OB形态,增强细胞间隙连接通讯。
3. 1α,25-(OH)_2D_3对体外培养成骨细胞超微形态结构的影响
在OB体外培养的基础上,不同浓度1α,25-(OH)_2D_3(0 [无水乙醇溶剂对照]、10~(-9)、10~(-8)、10~(-7) mol/L)处理48 h,扫描电镜、透射电镜观察OB超微形态结构。结果,与对照组比较,10~(-9) mol/L 1α,25-(OH)_2D_3组细胞铺展较好,表面针状突起、胞内线粒体增多;10~(-8) mol/L 1α,25-(OH)_2D_3组细胞趋于扁平,表面突起减少,变得细长,内质网增多;10~(-7) mol/L 1α,25-(OH)_2D_3组细胞外基质中大量丝状纤维连接成网状,细胞内线粒体较少,出现大量空泡及钙颗粒沉积。说明,低浓度1α,25-(OH)_2D_3(10~(-9) mol/L)能促进OB增殖,而中高浓度1α,25-(OH)_2D_3(10~(-8)、10~(-7) mol/L)抑制OB增殖,促进细胞外胶原形成及基质矿化。
4. 1α,25-(OH)_2D_3对体外培养成骨细胞RANKL及OPG表达的影响
在OB体外培养的基础上,不同浓度1α,25-(OH)_2D_3(0 [无水乙醇溶剂对照]、10~(-9)、10~(-8)、10~(-7) mol/L)作用24、48、72 h,分别采用ELISA及FQ-PCR法测定RANKL、OPG蛋白及mRNA含量。结果,10~(-8)、10~(-7) mol/L 1α,25-(OH)_2D_3较对照组、10~(-9) mol/L组显著或极显著促进RANKL蛋白及mRNA的表达(P<0.05或P<0.01);10~(-9)、10~(-8) mol/L 1α,25-(OH)_2D_3在不同时间,较对照组显著或极显著促进OPG蛋白及mRNA的表达(P<0.05或P<0.01),而10~(-7) mol/L则极显著抑制OPG mRNA表达(P<0.01);最终,10~(-9) mol/L组48 h时RANKL/OPG比值增高(P<0.05),10~(-8)、10~(-7) mol/L 1α,25-(OH)_2D_3组RANKL mRNA/OPG mRNA及RANKL/OPG比值则始终高于对照组和10~(-9) mol/L组(P<0.01)。说明,1α,25-(OH)_2D_3可剂量依赖性地上调RANKL mRNA/OPG mRNA及RANKL/OPG比值,促进OC的生成及骨吸收功能,增强骨更新。
5. RANKL对体外培养破骨细胞形成和活化的影响
分离5-6周龄ICR小鼠长骨骨髓细胞,分两阶段培养。第一阶段分三组(A、对照组[不添加任何因子];B、50 ng/mL RANKL;C、25 ng/mL M-CSF)培养3 d,进入第二阶段(Ⅰ、对照组[不添加任何因子];Ⅱ、25 ng/mL M-CSF;Ⅲ、25 ng/mL M-CSF + 50 ng/mL sRANKL)继续培养。倒置显微镜观察细胞形态,酸性磷酸酶(ACP)染色、抗酒石酸酸性磷酸酶(TRAP)染色及扫描电镜观察骨吸收陷窝,鉴定OC的生成及骨吸收活性,同时荧光显微镜观察F-actin。结果,第一阶段培养3 d,对照组和50 ng/mL RANKL组细胞均无贴壁及增殖能力,而25 ng/mL M-CSF明显促进细胞贴壁与增殖。第二阶段培养2 d,25 ng/mL M-CSF + 50 ng/mL RANKL组较25 ng/mL M-CSF组出现更多单核巨细胞,随着时间的延长单核巨细胞增多,出现2个核以上的巨细胞,且M-CSF存在的各组细胞均可表达ACP活性;培养9 d,25 ng/mL M-CSF + 50 ng/mL sRANKL组出现3个核的TRAP阳性OC(10.17±1.55个/孔),OC数极显著高于对照组(0个/孔)和25 ng/mL M-CSF组(0.67±0.69个/孔)(P<0.01)。同时,sRANKL可诱导F-actin的表达,促进骨吸收陷窝的生成。说明,RANKL在M-CSF存在时可诱导OC的生成及骨吸收活性,但OC数量仍不多。
Bone metabolism is the basic process of life to maintain bone tissue updating continuously and to keep vitality of life, and this process depends on the bone remodeling. In various skeletal disease associated with bone loss, such as bone malnutrition, increased osteoclastic bone resorption exceeds formation resulting in low bone mass, skeletal fragility and increased risk of fracture. Recent researchs have showed that many regulating factors for bone metabolism can regulate osteocalsts’formation and activation indirectly by effecting osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) expressed in osteoblasts. Vitamin D and its active metabolite is one of the important regulators for calcium and phosphorus metabolism. However, the therapeutic effect of calcium, phosphorus and vitamin D praeparatum are variable. Therefore, further understanding of the exact mechanisms of vitamin D in bone physiology and pathology is important to prevent metabolic bone disease. To elucidate the mechanism of bone metabolism accommodated by vitamin D, we investigated the effects on osteoblasts’proliferation, differentiation and the expression of RANKL, OPG in osteoblasts treated by different concentrations of 1α,25-(OH)_2D_3, meanwhile the influences of RANKL on osteoclasts’formation and activation detected by histochemistry staining for Tartrate-resistant acid phosphatase (TRAP) and so on.
1. The effects of 1α,25-(OH)_2D_3 on proliferation, differentiation and cell cycle of osteoblasts in vitro
To study the influence of 1α,25-(OH)_2D_3 on proliferation, differentiation and Cell Cycle of Osteoblasts (OB) in vitro. OB were isolated from calvaria bone, then dealt with various concentration of 1α,25-(OH)_2D_3 (0, 10~(-9), 10~(-8), 10~(-7) mol/L). After 24, 48, 72 h cultivation, the proliferation and the activity of alkali phosphatase (ALP) of OB was observed. 48 h incubation later, the changes of cell phase were analyzed using flow cytometer. Compared with the control group, 10~(-9) mol/L 1α,25-(OH)_2D_3 promoted proliferation of OB in vitro significantly, and inhibited the ALP activity very significantly. The group with 10~(-8), 10~(-7) mol/L 1α,25-(OH)_2D_3 had lower proliferation rate of OB than group with 10~(-9) mol/L 1α,25-(OH)_2D_3 significantly or very significantly, but stimulated the ALP activity significantly or very significantly within 48 h. At 72 h, 10~(-7) mol/L 1α,25-(OH)_2D_3 had the lowest proliferation rate of OB, and the highest ALP activity. 10~(-8), 10~(-7) mol/L 1α,25-(OH)_2D_3 caused G2/M arrest significantly or very significantly. These results showed that low dosage of 1α,25-(OH)_2D_3 can promote proliferation and inhibit differentiation, while higher dosage of 1α,25-(OH)_2D_3 can inhibit proliferation, promote differentiation and cause G2/M arrest.
2. The effects of 1α,25-(OH)_2D_3 on cytoskeleton, GJIC and [Ca~(2+)]_i of osteoblasts in vitro
To study the influence of 1α,25-(OH)_2D_3 on cytoskeleton, gap junction intercellular communication (GJIC) and intracellular Ca2+ ([Ca~(2+)]_i) in Osteoblasts in vitro. OB were isolated from calvaria bone. After 20 min and 24 h treated by 1α,25-(OH)_2D_3 (0, 10~(-9), 10~(-8), 10~(-7) mol/L), [Ca~(2+)]_i was evaluated. 24 and 48 h incubation later, F-actin and GJIC were observed. Compared with the control group, [Ca~(2+)]_i in group with 1α,25-(OH)_2D_3 all increased significantly (P<0.05) at time 20 min. 24 h incubation later, [Ca~(2+)]_i in the group with 10~(-9) mol/L 1α,25-(OH)_2D_3 was the lowest (P<0.05). OB in the group with 10~(-8) and 10~(-7) mol/L 1α,25-(OH)_2D_3 were applanation, stress fibers formed. 48 h later, the expression of F-actin in the control group and group with 10~(-9) mol/L 1α,25-(OH)_2D_3 reduced. Compared with the control group, GJIC was weakened after treated with 10~(-9) mol/L 1α,25-(OH)_2D_3 very significantly (P<0.01), while GJIC enhanced in the group with 10~(-8) and 10~(-7) mol/L 1α,25-(OH)_2D_3 very significantly (P<0.01). These results demonstrated that [Ca~(2+)]_i can be mediated by 1α,25-(OH)_2D_3, higher dosage of 1α,25-(OH)_2D_3 can maintain the morphous of OB and stimulate the communication among OB, while lower dosage of 1α,25-(OH)_2D_3 can inhibit the expression of F-actin and reduce the communication among OB.
3. The effects of 1α,25-(OH)_2D_3 on the morphous and ultrastructure of osteoblasts in vitro
To investigate the effects on the development and ultrastructure of osteoblasts (OB) under different dosages of 1α,25-(OH)_2D_3 in vitro. The morphous and ultrastructure were observed using scanning electron microscope (SEM) and transmission electron microscope (TEM) independently after cultured for 48 h. Compared with the control group, more microvillus and mitochondria were observed in the group with 10~(-9) mol/L 1α,25-(OH)_2D_3. In the group with 10~(-8) mol/L 1α,25-(OH)_2D_3, osteoblasts became flatter, and contained abundant slender cytoplasmic processes and endoplasmic reticula. Lots of filiform fibers forming network in the Extracellular Matrix of OB, more vacuole and calcium granule, less organelles were observed in the group with 10~(-7) mol/L 1α,25-(OH)_2D_3. In conclusion, the present study verified further morphologically that higher concentration of 1α,25-(OH)_2D_3 had obviously facilitative effects on differentiation and functional expression of osteoblasts cultured in vitro, while lower dosage of 1α,25-(OH)_2D_3 stimulate proliferation.
4. The expression of RANKL and OPG in osteoblasts treated by 1α,25-(OH)_2D_3 in vitro
To investigate the expression of RANKL, OPG and RANKL mRNA, OPG mRNA, osteobalsts obtained from Sprague Dawley rats were treated with different concentrations of 1α,25-(OH)_2D_3. The expression of RANKL and OPG was detected by the method of Immunohistochemistry and ELISA. RANKL mRNA and OPG mRNA were determined through FQ-PCR. Compared with the control group and the group with 10~(-9) mol/L 1α,25-(OH)_2D_3, 10~(-8) and 10~(-7) mol/L 1α,25-(OH)_2D_3 can significantly or very significantly induce the expression of RANKL and RANKL mRNA. 10~(-9), 10~(-8) mol/L 1α,25-(OH)_2D_3 can stimulate the expression of OPG and OPG mRNA significantly or very significantly, while 10~(-7) mol/L 1α,25-(OH)_2D_3 can inhibit the expression of OPG mRNA significantly. The ratio of RANKL/OPG in group with 10~(-9) mol/L 1α,25-(OH)_2D_3 was higher than control group at the 48th hour. However the expression of RANKL/OPG and RANKL mRNA/OPG mRNA in the group with 10~(-8), 10~(-7) mol/L were higher than the control group and the group with 10~(-9) mol/L 1α,25-(OH)_2D_3 all the time. These results showed that 1α,25-(OH)_2D_3 can enhance bone turnover through facilitating the formation and activity of osteoclasts via enhance RANKL mRNA/OPG mRNA and RANKL/OPG dose dependently.
5. The effects of RANKL on osteoclasts’formation and activation in vitro
To investigate the effects of RANKL on osteoclasts’formation and activation in vitro, bone marrow cells were isolated from 5 to 6 weeks old ICR mice. The first step of culture with different cytokines (A: the control group without any cytokines; B: 50 ng/mL RANKL; C: 25 ng/mL M-CSF) was followed by the second step (Ⅰ: the control group without any cytokines;Ⅱ: 25 ng/mL M-CSF;Ⅲ: 25 ng/mL M-CSF + 50 ng/mL RANKL). The morphology was observed by phase-contrast microscope. Osteoclasts’shap and activation were identified by acid phosphatase (ACP) staing, tartrate resistant acid phosphatase (TRAP) staining and observating of F-actin, detection of resorption lacunae through scanning electron microscopy. The cells at the control group and the group with 50 ng/mL RANKL had no ability of adherence and proliferation, while 25 ng/mL M-CSF could promote cells’adherence and proliferation at the 3rd day of the first step. After 2 days incubation at the second step, there were more mononuclear giant cells treated by 25 ng/mL M-CSF + 50 ng/mL RANKL than that treated by M-CSF alone. However, all the cells formed under 25 ng/mL M-CSF had ACP activity. 9 days incubation later, the number of osteoclasts with three nucleus in the group with 25 ng/mL M-CSF + 50 ng/mL RANKL (10.17±1.55/well) was more than those in the control group (0/well) and the group with 25 ng/mL M-CSF (0.67±0.69/well) very significantly. RANKL could induce the expression of F-actin, and facilitate the formation of bone resorption lacunar. These results demonstrated that RANKL could induce osteoclats’formation and activation at presence of M-CSF, but the number of osteoclasts was still parum.
1. 1α,25-(OH)_2D_3对体外培养成骨细胞增殖、分化及周期的影响
2.5 g/L胰酶和1 g/LⅡ型胶原酶两步消化法分离3-4日龄SD大鼠乳鼠颅盖骨细胞。采用倒置显微镜、扫描电镜观察细胞形态,碱性磷酸酶(ALP)特异染色鉴定OB。在此基础上,向培养体系中添加不同浓度的1α,25-(OH)_2D_3(0 [无水乙醇溶剂对照]、10~(-9)、10~(-8)、10~(-7) mol/L)。作用24、48、72 h,MTT法测定OB增殖率、PNPP法测定ALP活性,流式细胞仪测定OB周期。结果显示,10~(-9) mol/L 1α,25-(OH)_2D_3作用24、48、72 h均促进OB增殖(P<0.05或P<0.01),抑制ALP活性(P<0.01);10~(-8)、10~(-7) mol/L作用24、48 h,OB增殖率与对照组差异不显著(P>0.05),但24 h时ALP活性均明显升高(P<0.05或P<0.01),48 h则抑制了ALP活性并使OB滞留在G2/M期(P<0.05或P<0.01);72 h时10~(-7) mol/L组OB增殖率极显著低于其余各组(P<0.01),并又使ALP活性升高(P<0.01)。说明,低浓度1α,25-(OH)_2D_3(10~(-9) mol/L)促进OB增殖,抑制其分化;中高浓度1α,25-(OH)_2D_3(10~(-8)、10~(-7) mol/L)抑制OB增殖,促进其分化,并使细胞滞留在G2/M期。
2. 1α,25-(OH)_2D_3对体外培养成骨细胞骨架、GJIC及[Ca~(2+)]_i的影响
在OB培养的基础上,不同浓度的1α,25-(OH)_2D_3(0 [无水乙醇溶剂对照]、10~(-9)、10~(-8)、10~(-7) mol/L)作用20 min、24 h,流式细胞仪测定[Ca~(2+)]_i;24、48 h,荧光显微镜观察F-actin及细胞间隙连接通讯(GJIC)。结果显示,20 min时,不同浓度1α,25-(OH)_2D_3组[Ca~(2+)]_i均显著高于对照组(P<0.05);24 h时10~(-9) mol/L组[Ca~(2+)]_i则显著低于对照组(P<0.05),其余各组间差异不显著(P>0.05),此时10~(-8)、10~(-7) mol/L组大部分细胞变得扁平,F-actin排列较对照组有序,形成应力纤维;48 h时,对照组及10~(-9) mol/L组F-actin表达减少,10~(-9) mol/L组GJIC极显著弱于对照组(P<0.01),而10~(-8)、10~(-7) mol/L组大部分细胞F-actin表达完好,GJIC均极显著强于其余两组(P<0.01)。说明,1α,25-(OH)_2D_3能够影响钙离子通道,同时低浓度1α,25-(OH)_2D_3(10~(-9) mol/L)抑制F-actin表达及细胞间隙连接通讯,中高浓度1α,25-(OH)_2D_3(10~(-8)、10~(-7) mol/L)则能维持OB形态,增强细胞间隙连接通讯。
3. 1α,25-(OH)_2D_3对体外培养成骨细胞超微形态结构的影响
在OB体外培养的基础上,不同浓度1α,25-(OH)_2D_3(0 [无水乙醇溶剂对照]、10~(-9)、10~(-8)、10~(-7) mol/L)处理48 h,扫描电镜、透射电镜观察OB超微形态结构。结果,与对照组比较,10~(-9) mol/L 1α,25-(OH)_2D_3组细胞铺展较好,表面针状突起、胞内线粒体增多;10~(-8) mol/L 1α,25-(OH)_2D_3组细胞趋于扁平,表面突起减少,变得细长,内质网增多;10~(-7) mol/L 1α,25-(OH)_2D_3组细胞外基质中大量丝状纤维连接成网状,细胞内线粒体较少,出现大量空泡及钙颗粒沉积。说明,低浓度1α,25-(OH)_2D_3(10~(-9) mol/L)能促进OB增殖,而中高浓度1α,25-(OH)_2D_3(10~(-8)、10~(-7) mol/L)抑制OB增殖,促进细胞外胶原形成及基质矿化。
4. 1α,25-(OH)_2D_3对体外培养成骨细胞RANKL及OPG表达的影响
在OB体外培养的基础上,不同浓度1α,25-(OH)_2D_3(0 [无水乙醇溶剂对照]、10~(-9)、10~(-8)、10~(-7) mol/L)作用24、48、72 h,分别采用ELISA及FQ-PCR法测定RANKL、OPG蛋白及mRNA含量。结果,10~(-8)、10~(-7) mol/L 1α,25-(OH)_2D_3较对照组、10~(-9) mol/L组显著或极显著促进RANKL蛋白及mRNA的表达(P<0.05或P<0.01);10~(-9)、10~(-8) mol/L 1α,25-(OH)_2D_3在不同时间,较对照组显著或极显著促进OPG蛋白及mRNA的表达(P<0.05或P<0.01),而10~(-7) mol/L则极显著抑制OPG mRNA表达(P<0.01);最终,10~(-9) mol/L组48 h时RANKL/OPG比值增高(P<0.05),10~(-8)、10~(-7) mol/L 1α,25-(OH)_2D_3组RANKL mRNA/OPG mRNA及RANKL/OPG比值则始终高于对照组和10~(-9) mol/L组(P<0.01)。说明,1α,25-(OH)_2D_3可剂量依赖性地上调RANKL mRNA/OPG mRNA及RANKL/OPG比值,促进OC的生成及骨吸收功能,增强骨更新。
5. RANKL对体外培养破骨细胞形成和活化的影响
分离5-6周龄ICR小鼠长骨骨髓细胞,分两阶段培养。第一阶段分三组(A、对照组[不添加任何因子];B、50 ng/mL RANKL;C、25 ng/mL M-CSF)培养3 d,进入第二阶段(Ⅰ、对照组[不添加任何因子];Ⅱ、25 ng/mL M-CSF;Ⅲ、25 ng/mL M-CSF + 50 ng/mL sRANKL)继续培养。倒置显微镜观察细胞形态,酸性磷酸酶(ACP)染色、抗酒石酸酸性磷酸酶(TRAP)染色及扫描电镜观察骨吸收陷窝,鉴定OC的生成及骨吸收活性,同时荧光显微镜观察F-actin。结果,第一阶段培养3 d,对照组和50 ng/mL RANKL组细胞均无贴壁及增殖能力,而25 ng/mL M-CSF明显促进细胞贴壁与增殖。第二阶段培养2 d,25 ng/mL M-CSF + 50 ng/mL RANKL组较25 ng/mL M-CSF组出现更多单核巨细胞,随着时间的延长单核巨细胞增多,出现2个核以上的巨细胞,且M-CSF存在的各组细胞均可表达ACP活性;培养9 d,25 ng/mL M-CSF + 50 ng/mL sRANKL组出现3个核的TRAP阳性OC(10.17±1.55个/孔),OC数极显著高于对照组(0个/孔)和25 ng/mL M-CSF组(0.67±0.69个/孔)(P<0.01)。同时,sRANKL可诱导F-actin的表达,促进骨吸收陷窝的生成。说明,RANKL在M-CSF存在时可诱导OC的生成及骨吸收活性,但OC数量仍不多。
Bone metabolism is the basic process of life to maintain bone tissue updating continuously and to keep vitality of life, and this process depends on the bone remodeling. In various skeletal disease associated with bone loss, such as bone malnutrition, increased osteoclastic bone resorption exceeds formation resulting in low bone mass, skeletal fragility and increased risk of fracture. Recent researchs have showed that many regulating factors for bone metabolism can regulate osteocalsts’formation and activation indirectly by effecting osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) expressed in osteoblasts. Vitamin D and its active metabolite is one of the important regulators for calcium and phosphorus metabolism. However, the therapeutic effect of calcium, phosphorus and vitamin D praeparatum are variable. Therefore, further understanding of the exact mechanisms of vitamin D in bone physiology and pathology is important to prevent metabolic bone disease. To elucidate the mechanism of bone metabolism accommodated by vitamin D, we investigated the effects on osteoblasts’proliferation, differentiation and the expression of RANKL, OPG in osteoblasts treated by different concentrations of 1α,25-(OH)_2D_3, meanwhile the influences of RANKL on osteoclasts’formation and activation detected by histochemistry staining for Tartrate-resistant acid phosphatase (TRAP) and so on.
1. The effects of 1α,25-(OH)_2D_3 on proliferation, differentiation and cell cycle of osteoblasts in vitro
To study the influence of 1α,25-(OH)_2D_3 on proliferation, differentiation and Cell Cycle of Osteoblasts (OB) in vitro. OB were isolated from calvaria bone, then dealt with various concentration of 1α,25-(OH)_2D_3 (0, 10~(-9), 10~(-8), 10~(-7) mol/L). After 24, 48, 72 h cultivation, the proliferation and the activity of alkali phosphatase (ALP) of OB was observed. 48 h incubation later, the changes of cell phase were analyzed using flow cytometer. Compared with the control group, 10~(-9) mol/L 1α,25-(OH)_2D_3 promoted proliferation of OB in vitro significantly, and inhibited the ALP activity very significantly. The group with 10~(-8), 10~(-7) mol/L 1α,25-(OH)_2D_3 had lower proliferation rate of OB than group with 10~(-9) mol/L 1α,25-(OH)_2D_3 significantly or very significantly, but stimulated the ALP activity significantly or very significantly within 48 h. At 72 h, 10~(-7) mol/L 1α,25-(OH)_2D_3 had the lowest proliferation rate of OB, and the highest ALP activity. 10~(-8), 10~(-7) mol/L 1α,25-(OH)_2D_3 caused G2/M arrest significantly or very significantly. These results showed that low dosage of 1α,25-(OH)_2D_3 can promote proliferation and inhibit differentiation, while higher dosage of 1α,25-(OH)_2D_3 can inhibit proliferation, promote differentiation and cause G2/M arrest.
2. The effects of 1α,25-(OH)_2D_3 on cytoskeleton, GJIC and [Ca~(2+)]_i of osteoblasts in vitro
To study the influence of 1α,25-(OH)_2D_3 on cytoskeleton, gap junction intercellular communication (GJIC) and intracellular Ca2+ ([Ca~(2+)]_i) in Osteoblasts in vitro. OB were isolated from calvaria bone. After 20 min and 24 h treated by 1α,25-(OH)_2D_3 (0, 10~(-9), 10~(-8), 10~(-7) mol/L), [Ca~(2+)]_i was evaluated. 24 and 48 h incubation later, F-actin and GJIC were observed. Compared with the control group, [Ca~(2+)]_i in group with 1α,25-(OH)_2D_3 all increased significantly (P<0.05) at time 20 min. 24 h incubation later, [Ca~(2+)]_i in the group with 10~(-9) mol/L 1α,25-(OH)_2D_3 was the lowest (P<0.05). OB in the group with 10~(-8) and 10~(-7) mol/L 1α,25-(OH)_2D_3 were applanation, stress fibers formed. 48 h later, the expression of F-actin in the control group and group with 10~(-9) mol/L 1α,25-(OH)_2D_3 reduced. Compared with the control group, GJIC was weakened after treated with 10~(-9) mol/L 1α,25-(OH)_2D_3 very significantly (P<0.01), while GJIC enhanced in the group with 10~(-8) and 10~(-7) mol/L 1α,25-(OH)_2D_3 very significantly (P<0.01). These results demonstrated that [Ca~(2+)]_i can be mediated by 1α,25-(OH)_2D_3, higher dosage of 1α,25-(OH)_2D_3 can maintain the morphous of OB and stimulate the communication among OB, while lower dosage of 1α,25-(OH)_2D_3 can inhibit the expression of F-actin and reduce the communication among OB.
3. The effects of 1α,25-(OH)_2D_3 on the morphous and ultrastructure of osteoblasts in vitro
To investigate the effects on the development and ultrastructure of osteoblasts (OB) under different dosages of 1α,25-(OH)_2D_3 in vitro. The morphous and ultrastructure were observed using scanning electron microscope (SEM) and transmission electron microscope (TEM) independently after cultured for 48 h. Compared with the control group, more microvillus and mitochondria were observed in the group with 10~(-9) mol/L 1α,25-(OH)_2D_3. In the group with 10~(-8) mol/L 1α,25-(OH)_2D_3, osteoblasts became flatter, and contained abundant slender cytoplasmic processes and endoplasmic reticula. Lots of filiform fibers forming network in the Extracellular Matrix of OB, more vacuole and calcium granule, less organelles were observed in the group with 10~(-7) mol/L 1α,25-(OH)_2D_3. In conclusion, the present study verified further morphologically that higher concentration of 1α,25-(OH)_2D_3 had obviously facilitative effects on differentiation and functional expression of osteoblasts cultured in vitro, while lower dosage of 1α,25-(OH)_2D_3 stimulate proliferation.
4. The expression of RANKL and OPG in osteoblasts treated by 1α,25-(OH)_2D_3 in vitro
To investigate the expression of RANKL, OPG and RANKL mRNA, OPG mRNA, osteobalsts obtained from Sprague Dawley rats were treated with different concentrations of 1α,25-(OH)_2D_3. The expression of RANKL and OPG was detected by the method of Immunohistochemistry and ELISA. RANKL mRNA and OPG mRNA were determined through FQ-PCR. Compared with the control group and the group with 10~(-9) mol/L 1α,25-(OH)_2D_3, 10~(-8) and 10~(-7) mol/L 1α,25-(OH)_2D_3 can significantly or very significantly induce the expression of RANKL and RANKL mRNA. 10~(-9), 10~(-8) mol/L 1α,25-(OH)_2D_3 can stimulate the expression of OPG and OPG mRNA significantly or very significantly, while 10~(-7) mol/L 1α,25-(OH)_2D_3 can inhibit the expression of OPG mRNA significantly. The ratio of RANKL/OPG in group with 10~(-9) mol/L 1α,25-(OH)_2D_3 was higher than control group at the 48th hour. However the expression of RANKL/OPG and RANKL mRNA/OPG mRNA in the group with 10~(-8), 10~(-7) mol/L were higher than the control group and the group with 10~(-9) mol/L 1α,25-(OH)_2D_3 all the time. These results showed that 1α,25-(OH)_2D_3 can enhance bone turnover through facilitating the formation and activity of osteoclasts via enhance RANKL mRNA/OPG mRNA and RANKL/OPG dose dependently.
5. The effects of RANKL on osteoclasts’formation and activation in vitro
To investigate the effects of RANKL on osteoclasts’formation and activation in vitro, bone marrow cells were isolated from 5 to 6 weeks old ICR mice. The first step of culture with different cytokines (A: the control group without any cytokines; B: 50 ng/mL RANKL; C: 25 ng/mL M-CSF) was followed by the second step (Ⅰ: the control group without any cytokines;Ⅱ: 25 ng/mL M-CSF;Ⅲ: 25 ng/mL M-CSF + 50 ng/mL RANKL). The morphology was observed by phase-contrast microscope. Osteoclasts’shap and activation were identified by acid phosphatase (ACP) staing, tartrate resistant acid phosphatase (TRAP) staining and observating of F-actin, detection of resorption lacunae through scanning electron microscopy. The cells at the control group and the group with 50 ng/mL RANKL had no ability of adherence and proliferation, while 25 ng/mL M-CSF could promote cells’adherence and proliferation at the 3rd day of the first step. After 2 days incubation at the second step, there were more mononuclear giant cells treated by 25 ng/mL M-CSF + 50 ng/mL RANKL than that treated by M-CSF alone. However, all the cells formed under 25 ng/mL M-CSF had ACP activity. 9 days incubation later, the number of osteoclasts with three nucleus in the group with 25 ng/mL M-CSF + 50 ng/mL RANKL (10.17±1.55/well) was more than those in the control group (0/well) and the group with 25 ng/mL M-CSF (0.67±0.69/well) very significantly. RANKL could induce the expression of F-actin, and facilitate the formation of bone resorption lacunar. These results demonstrated that RANKL could induce osteoclats’formation and activation at presence of M-CSF, but the number of osteoclasts was still parum.
引文
[1] Spangler J G. Bone biology and physiology: lmplications for novel osteoblastic osteosarcoma treatments?[J]. Medical Hypotheses, 2008, 70: 281-286
[2]陈棣,闫莹,陈默,沈汇,邓红文.骨生物学研究的最新进展.邓红文,刘耀中主编.骨生物学前沿[M].北京:高等教育出版社, 2006. 15, 19-21
[3]徐家科, Phan T C A,郑铭豪.在骨疾病中成骨细胞和破骨细胞之间的通讯.邓红文,刘耀中主编.骨生物学前沿[M].北京:高等教育出版社, 2006. 57-67
[4]邵水金主编.实用躯体解剖学[M].上海:上海科学技术文献出版社, 2006. 1, 4-5
[5]黎小坚,朱绍舜.骨组织解剖生理学.邓红文,刘耀中主编.骨生物学前沿[M].北京:高等教育出版社, 2006. 5-24
[6]赵定麟主编.现代骨病学[M].北京:科学出版社, 2004. 21-23
[7] Marks S C, Odgren P R. Structure and development of the skeleton. In Bilezikian J P, Raisz L G, Rodan G A. (Eds.), Principles of bone biology [M]. San Diego: Academic Press, 2002 (1). 3-15
[8] Mackie E J. Osteoblasts: novel roles in orchestration of skeletal architecture[J]. The International Journal of Biochemistry & Cell Biology, 2003, 35: 1301-1305
[9] Jilka R L, Weinstein R S, Bellido T, Roberson P, Parfitt A M, Manolagas S C. Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone[J]. The Journal of Clinical Investigation, 1999, 104: 439–446
[10]Boyden L M, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick M A, Wu D, Insogna K, Lifton R P. High bone density due to a mutation in LDL-receptor-related protein 5[J]. The New England Journal of Medicine, 2002, 346: 1513–1521
[11]Gong Y, Slee R B, Fukai N, Rawadi G, Roman-Roman S, Reginato A M, Wang H, Cundy T, Glorieux F H, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development[J]. Cell, 2001, 107: 513–523
[12]Kato M, Patel M S, Levasseur R, Lobov I, Chang B H, Glass 2nd D A, Hartmann C, Li L, Hwang T H, Brayton C F, Lang R A, Karsenty G, Chan L. Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in LRP5, a Wnt coreceptor[J]. The Journal of Cell Biology, 2002, 157: 303–314
[13]熊志立,孟繁浩,李遇伯,李发美.成骨细胞的骨形成调控机制[J].生命的化学, 2004, 24 (1): 44-46
[14]Mackie E J, Ramsey S. Modulation of osteoblast behaviour by tenascin[J]. Journal of Cell Science, 1996, 109: 1597–1604
[15]Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesisinhibitory factor and is identical to TRANCE/RANKL[J]. The Proceedings of the National Academy of Sciences of USA, 1998, 95: 3597–3602
[16]Udagawa N, Takahashi N, Jimi E, Matsuzaki K, Tsurukai T, Itoh K, Nakagawa N, Yasuda H, Goto M, Tsuda E, Higashio K, Gillespie M T, Martin T J, Suda T. Osteoblasts/stromal cells stimulate osteoclast activation through expression of osteoclast differentiation factor/RANKL but not macrophage colony-stimulating factor: Receptor activator of NF-kappa B ligand[J]. Bone, 1999, 25: 517–523
[17]Rossouw J E, Anderson G L, Prentice R L, LaCroix A Z, Kooperberg C, Stefanick M L, Jackson R D, Beresford S A, Howard B V, Johnson K C, Kotchen J M, Ockene J. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial[J]. The Journal of the American Medicical Association, 2002, 288: 321–333
[18]Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker K L, Armstrong D, Ducy P, Karsenty G. Leptin regulates bone formation via the sympathetic nervous system[J]. Cell, 2002, 111: 305–317
[19]Tonna E A, Gronkite E P. Naturwissenschaften, 1961, 190: 459
[20]Walker D G. Osteopetrosis cured by temporary parabiosis[J]. Science, 1973, 180: 275
[21]Walker D G. Bone resorption restored in osteopetrotic mice by transplants of normal bone marrow and spleen cells[J]. Science, 1975, 190: 784-785
[22]Matsuzaki K, Udagawa N, Takahashi N, Yamaguchi K, Yasuda H, Shima N, Morinaga T, Toyama Y, Yabe Y, Higashio K, Suda T. Osteoclast differentiation factor (ODF) induces osteoclast-like cell formation in human peripheral blood mononuclear cell cultures[J]. Biochemical & Biophysical Research Communications, 1998, 246: 199-204
[23]冯旭,周虹.破骨细胞生物学.邓红文,刘耀中主编.骨生物学前沿[M].北京:高等教育出版社, 2006. 42-50
[24]Vaananen H K, Laitala-Leinonen T. Osteoclast lineage and function[J]. Archives of Biochemistry and Biophysics, 2008, 473: 132-138
[25]Husheem M, Nyman J K E, V??r?nemi J, Vaananen H K, Hentunen, T A. Characterization of Circulating Human Osteoclast Progenitors: Development of In Vitro Resorption Assay[J]. Calcified Tissue International, 2005, 76: 222-230
[26]Anthony J, Janckila, Ruth M. Alternative immunoassay for tartrate-resistant acid phosphatase isoform 5b using the fluorogenic substrate naphthol ASBI-phosphate and heparin [J]. Clinica Chimica Acta ,347, 2004: 157-167
[27]Lakkakorpi P T, V??n?nen H K. Kinetics of the osteoclast cytoskeleton during the resorption cycle in vitro[J]. Journal of Bone Mineral Research, 1991, 6: 817–826
[28]Bossard M J, Tomaszek T A, Thompson S K, Amegadzie B Y, Hanning C R, Jones C, Kurdyla J T, McNulty D E, Drake F H, Gowen M, Levy M A. Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification[J]. Journal of Biological Chemistry, 1996, 271: 12517-12524
[29]Drake F H, Dodds R A, James I E, Connor J R, Debouck C, Richardson S, Lee-Rykaczewski E, Coleman L, Rieman D, Barthlow R, Hastings G, Gowen M. Cathepsin K, but not Cathepsins B, L, or S, is abundantly expressed in human osteoclasts[J]. Journal of Biological Chemistry, 1996, 271: 12511-12516
[30]Gleb B D, Shi G P, Chapman H A, Desnick R J. Pyenodystosis, a lysosomal disease caused by cathepsin K deficiency[J]. Science, 1996, 273: 1236-1238
[31]Green D M. Stimulus selection in adaptive psychophysical procedures[J]. Journal of the Acoustical Society of America, 1990, 87: 2662-2674
[32]Salo J, Lehenkari P, Mulari M, Metsikk? K, V??n?nen H K. Removal of osteoclast bone resorption products by transcytosis[J]. Science, 1997, 276: 270-273
[33]Jimi E, Nakamura I, Amano H, Taguchi Y, Tsurukai T, Tamura M, Takahashi N, Suda T. Osteoclast function is activated by osteoblastic cells through a mechanism involving cell-to-cell contact[J]. Endocrinology, 1996, 137 (8): 2187–2190
[34]Matsuo K, Irie N. Osteoclast-osteoblast communication[J]. Archives of Biochemistry and Biophysics, 2008, 473: 201-209
[35]Domon T, Suzuki R, Takata K, Yamazaki Y, Takahashi S, Yamamoto T, Wakita M. The natureand function of mononuclear cells on the resorbed surfaces of bone in the reversal phase during remodeling[J]. Annals of Anatomischer Anzeiger. 2001, 183(2): 103–110
[36]Li X, Qin L, Bergenstock M, Bevelock L M, Novack D V, Partridge N C. Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts[J]. Journal of Biological Chemistry, 2007, 282: 33098–33106
[37]Kim M S, Day C J, Morrison N A. MCP-1 is induced by receptor activator of nuclear factor-{kappa}B ligand, promotes human osteoclast fusion, and rescues granulocyte macrophage colony-stimulating factor suppression of osteoclast formation[J]. Journal of Biological chemistry, 2005, 280 (16): 16163–16169
[38]Yu X, Huang Y, Collin-Osdoby P, Osdoby P. Stromal cell-derived factor-1 (SDF-1) recruits osteoclast precursors by inducing chemotaxis, matrix metalloproteinase-9 (MMP-9) activity, and collagen transmigration[J]. Journal of Bone and Mineral Research, 2003, 18 (8): 1404–1418
[39]Wright L M, Maloney W, Yu X, Kindle L, Collin-Osdoby P, Osdoby P. Stromal cell-derived factor-1 binding to its chemokine receptor CXCR4 on precursor cells promotes the chemotactic recruitment, development and survival of human osteoclasts[J]. Bone, 2005, 36 (5): 840–853
[40]Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, Saiura A, Isobe M, Yokochi T, Inoue J, Wagner E F, Mak T W, Kodama T, Taniguchi T. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts[J]. Developemntal Cell, 2002, 6(3): 889–901
[41]Koga T, Matsui Y, Asagiri M, Kodama T, Crombrugghe B D, Nakashima K, Takayanagi H. NFAT and Osterix cooperatively regulate bone formation[J]. Natural Medicine, 2005, 11: 880–885
[42]Winslow M M, Pan M, Starbuck M, Gallo E M, Deng L, Karsenty G, Crabtree G R. Calcineurin/NFAT signaling in osteoblasts regulates bone mass[J]. Development of Cell, 2006, 10 (6): 771–782
[43]Verborgt O, Gibson G J, Schaffler M B. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo[J]. Journal of Bone and Mineral Research, 2000, 15(1): 60–67
[44]Hedgecock N L, Hadi T, Chen A A, Curtiss S B, Martin R B, Hazelwood S J. Quantitativeregional associations between remodeling, modeling, and osteocyte apoptosis and density in rabbit tibial midshafts[J]. Bone, 2007, 40(3): 627–637
[45]Simonet W S, Lacey D L, Dunstan C R, Kelley M, Chang M S, Lüthy R, Nguyen H Q, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan H L, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes T M, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Boyle W J. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density[J]. Cell, 1997, 89 (2): 309–319
[46]Koga T, Inui M, Inoue K, Kim S, Suematsu A, Kobayashi E, Iwata T, Ohnishi H, Matozaki T, Kodama T, Taniguchi T, Takayanagi H, Takai T. Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis[J]. Nature, 2004, 428: 758–763
[47]Kim N, Takami M, Rho J, Josien R, Choi Y. A Novel Member of the Leukocyte Receptor Complex Regulates Osteoclast Differentiation[J]. The Journal of Experimental Medicine, 2002, 195(2): 201–209
[48]Takai T. A Novel Recognition System for MHC Class I Molecules Constituted by PIR[J]. Advances in Immunol, 2005, 88: 161–192
[49]Delorme G, Saltel F, Bonnelye E, Jurdic P, Machuca-Gayet I. Expression and function of semaphorin 7A in bone cells[J]. Biology Cell, 2005, 97(7): 589–597
[50]Gomez C, Burt-Pichat B, Mallein-Gerin F, Merle B, Delmas P D, Skerry T M, Vico L, Malaval L, Chenu C. Expression of Semaphorin-3A and its receptors in endochondral ossification: potential role in skeletal development and innervation[J]. Developemental Dynamics, 2005, 234 (2): 393–403
[51]Matsuo K, Galson D L, Zhao C, Peng L, Laplace C, Wang K Z, Bachler M A, Amano H, Aburatani H, Ishikawa H, Wagner E F. Nuclear Factor of Activated T-cells (NFAT) Rescues Osteoclastogenesis in Precursors Lacking c-Fos[J]. Journal of Biological Chemistry, 2004, 279(25): 26475–26480
[52]Karsdal M A, Martin T J, Bollerslev J, Christiansen C, Henriksen K. Are nonresorbing osteoclasts sources of bone anabolic activity?[J]. Journal of Bone and Mineral Research, 2007, 22(4): 487–494
[53]Kornak U, Schulz A, Friedrich W, Uhlhaas S, Kremens B, Voit T, Hasan C, Bode U, Jentsch T J, Kubisch C. Mutations in the a3 subunit of the vacuolar H+-ATPase cause infantile malignant osteopetrosis[J]. Human Molecular Genetics, 2000, 9(13): 2059–2063
[53]Kornak U, Kasper D, Bosl M R, Kaiser E, Schweizer M, Schulz A, Friedrich W, Delling G, Jentsch T J. Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man[J]. Cell, 2001, 104(2): 205–215
[54]Li Y P, Chen W, Liang Y, Li E, Stashenko P. Atp6i-deficient mice exhibit severe osteopetrosis due to loss of osteoclast-mediated extracellular acidification[J]. Nature Genetics, 1999, 23: 447–451
[55]Del Fattore A., B. Peruzzi, N. Rucci, I. Recchia, A. Cappariello, M. Longo, D. Fortunati, P. Ballanti, M. Iacobini, M. Luciani, R. Devito, R. Pinto, M. Caniglia, E. Lanino, C. Messina, S. Cesaro, C. Letizia, G. Bianchini, H. Fryssira, P. Grabowski, N. Shaw, N. Bishop, D. Hughes, R.P. Kapur, H.K. Datta, A. Taranta, R. Fornari, S. Migliaccio, A. Teti, Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment[J]. Journal of Medical Genetics, 2006, 43(4): 315–325
[56]Karsdal M A, Henriksen K, Sorensen M G, Gram J, Schaller S, Dziegiel M H, Heegaard A M, Christophersen P, Martin T J, Christiansen C, Bollerslev J. Acidification of the Osteoclastic Resorption Compartment Provides Insight into the Coupling of Bone Formation to Bone Resorption[J]. The American Journal Pathology, 2005,166(2): 467–476
[57]Hayman A R, Jones S J, Boyde A, Foster D, Colledge W H, Carlton M B, Evans M J, Cox T M. Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disrupted endochondral ossification and mild osteopetrosis[J]. Development, 1996, 122(10): 3151–3162
[58]Roberts H C, Knott L, Avery N C, Cox T M, Evans M J, Hayman A R. Altered Collagen in Tartrate-Resistant Acid Phosphatase (TRAP)-Deficient Mice: A Role for TRAP in Bone Collagen Metabolism[J]. Calcified Tissue International, 2007, 80: 400–410
[59]Angel N Z, Walsh N, Forwood M R, Ostrowski M C, Cassady A I, Hume D A. Transgenic mice overexpressing tartrate-resistant acid phosphatase exhibit an increased rate of bone turnover [J]. Journal of Bone Mineral Research, 2000, 15(1): 103–110
[60]Ryu J, Kim H J, Chang E J, Huang H, Banno Y, Kim H H. Sphingosine 1-phosphate as a regulator of osteoclast differentiation and osteoclast–osteoblast coupling[J]. The EMBO Journal, 2006, 25: 5840–5851
[61]Kubota K, Sakikawa C, Katsumata M, Nakamura T, Wakabayashi K. Platelet-derived growth factor BB secreted from osteoclasts acts as an osteoblastogenesis inhibitory factor[J]. Journal of Bone Mineral Research, 2002, 17(2): 257–265
[62]O’Sullivan S, Naot D, Callon K, Porteous F, Horne A, Wattie D, Watson M, Cornish J, Browett P, Grey A. Imatinib promotes osteoblast differentiation by inhibiting PDGFR signaling and inhibits osteoclastogenesis by both direct and stromal cell-dependent mechanisms[J]. Journal of Bone Mineral Research, 2007, 22(11): 1679–1689
[63]Grano M, Galimi F, Zambonin G, Colucci S, Cottone E, Zallone A Z, Comoglio P M. Hepatocyte growth factor is a coupling factor for osteoclasts and osteoblasts in vitro[J]. Proceeding of the National Academy of Sciences of the United States of America, 1996, 93(15): 7644–7648
[64]Pasquale E B. Eph receptor signalling casts a wide net on cell behaviour[J]. Nature Reviews Molecular Cell Biology, 2005, 6(7): 462–475
[65]Zhao C, Irie N, Takada Y, Shimoda K, Miyamoto T, Nishiwaki T, Suda T, Matsuo K. Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis[J]. Cell Metabolism, 2006, 4 (2): 111–121
[66]Harmey D, Stenbeck G, Nobes C D, Lax A J, Grigoriadis A E. Regulation of osteoblast differentiation by Pasteurella multocida toxin (PMT): A role for Rho GTPase in bone formation[J]. Journal of bone and mineral research, 2004, 19: 661–670
[67]McBeath R, Pirone D M, Nelson C M, Bhadriraju K, Chen C S. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment[J]. Development Cell 2004, 6(4): 483–495
[68]Mundy G R, Elefteriou F. Boning up on ephrin signaling[J]. Cell, 2006, 126(3): 441–443
[69]Van Bezooijen R L, Roelen B A, Visser A, Wee-Pals Van D L, Wilt E D, Karperien M, Hamersma H, Papapoulos S E, Dijke P Ten, L?wik C W G M. J. Sclerostin Is an Osteocyte-expressed Negative Regulator of Bone Formation, But Not a Classical BMP Antagonist[J]. The Journal of Experimental Medicine, 2004, 199(6): 805–814
[70]Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, Lacza C, Wuyts W, Van Den Ende J, Willems P, Paes-Alves A F, Hill S, Bueno M, Ramos F J, Tacconi P, Dikkers F G, Stratakis C, Lindpaintner K, Vickery B, Foernzler D, Hul W V. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST)[J]. Human Molecular Genetics, 2001, 10(5): 537–543
[71]Brunkow M E, Gardner J C, Van Ness J, Paeper B W, Kovacevich B R, Proll S, Skonier J E, Zhao L, Sabo P J, Fu Y, Alisch R S, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H,Beighton P, Mulligan J. Bone Dysplasia Sclerosteosis Results from Loss of the SOST Gene Product, a Novel Cystine Knot–Containing Protein[J]. The American Journal of Human Genetics, 2001, 68(3): 577–589
[72]Glass D A 2nd, Bialek P, Ahn J D, Starbuck M, Patel M S, Clevers H, Taketo M M, Long F, McMahon A P, Lang R A, Karsenty G. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation[J]. Development Cell, 2005, 8(5): 751–764
[73]Kieslinger M, Folberth S, Dobreva G, Dorn T, Croci L, Erben R, Consalez G G, Grosschedl R. EBF2 regulates osteoblast-dependent differentiation of osteoblasts[J]. Development Cell, 2005, 9(6): 757–767
[74]Bai S, Kopan R, Zou W, Hilton M J, Ong C T, Long F, Ross F P, Teitelbaum S L. Notch1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells[J]. Journal of Biological Chemisty, 2008, 283(10): 6509–6518
[76]Seeman E. Bone quality: the material and structural basis of bone strength[J]. Journal of Bone Mineral Metabolism, 2008, 26(1): 1–8
[77]Mashiba T, Turner C H, Hirano T, Forwood M R, Jacob D S, Johnston C C, Burr D B. Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures[J]. Bone, 2001, 29(3): 271–278
[78]朱宪彝主编.代谢性骨病学[J].天津:天津科学技术出版社, 1989: 202-219
[79]付强,刘源.钙、磷与维生素D对动物骨代谢的影响研究进展[J].中国比较医学杂志, 2006, 16 (8): 502-505
[80]唐文山.骨营养不良乳牛血清钙及血清游离羟脯氨酸含量测定[J].中国兽医科技, 2002, 32(11): 26-28
[81]刘宗平,马卓,杨得兵,池斌.双峰驼骨质疏松症的流行特点及其与生物地球化学因子之间的关系[J].应用与环境生物学报, 1997, 3 (4): 345-348
[82]邹纪平,钟琼莎,王耀光.对维生素D和钙的再认识:比较争鸣[J].中国临床康复, 2004, 8 (29): 6478-6479
[83]熊学华,余克强,刘庆思.维生素D与骨质疏松[J]. 2002, 14 (6): 54-55
[84]St-Arnaud R. The direct role of the vitamin D on bone homeostasis[J]. Archives of Biochemistry and Biophysics, 2008, 473(2): 225-230
[85]冯志华,刘观忠,张仪明.维生素D在动物营养中的应用研究[J].中国畜牧兽医, 2004, 31(8): 16-18
[86]Fraser D R. The influence factor of metabolism of vitamin D[J]. Nature, 1970, 228: 764-766
[87]Horward G A, Turner R T, Sherrard D J, Baylink D J. Human bone cells in culture metabolize 25-hydroxyvitamin D3 to 1, 25-dihydroxyvitamin D3 and 24, 25-dihydroxyvitamin D3[J]. The Journal of Biological chemistry, 1981, 256(15): 7738-7740
[88]Atkins G J, Anderson P H, Findlay D M, Welldon K J, Vincent C, Zannettino A C, O’Loughlin P D, Morris H A. Metabolism of vitamin D(3) in human osteoblasts: evidence for autocrine and paracrine activities of 1alpha,25-dihydroxyvitamin D(3)[J]. Bone, 2007, 40(6): 1517–1528
[89]王淑萍,宋新德.维生素D与骨质疏松概述[J].中国骨质疏松杂志, 2000, 6 (1): 10-13
[90]Norman A W , Song X , Zanello L , Bula C, Okamura W H. Rapid and genomic biological responses are mediated by different shapes of the agonist steroid hormone, 1α,25(OH)2vitamin D3 [J]. Steroid, 1999, 64(1-2): 120-128
[91]李丽华,周玉坤,王丽丽.维生素D与骨的生长和矿化[J].国外医学妇幼保健分册, 2004, 15 (5): 257-259
[92]Ames S K, Ellis K J, Gunn S K, Copeland K C, Abrams S A. Vitamin D receptor gene Fok1 polymorphism Predicts Calcium aborption and bone mineral Density in children[J]. Journal of Bone and Mineral Research,1999, 14: 740-746
[93]Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K, Tonai T, Nishisho T, Mori S, Takeda E. A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women[J]. Journal of Bone Mineral Research, 1997, 12 (6): 915-921
[94]郗永义,郑秀芬,叶健,霍赛虎,张健,陈帅锋.维生素D受体研究进展[J].大连医科大学学报, 2004, 26(3): 227-230
[95]Nemere I, Mcmanus W, Ray R. Immunochemical studies on the putative plasmalemmal receptor for 1,25(OH)2D3.Ⅰ. Chick intestine [J]. American Journal of Physiology Endocrinology and Metabolism, 2000, 278: E1104-E1114
[96]Boyan B D, Sylvia V L, Dean D D, Pedrozo H, Del T F, Nemere I, Posner G H, Schwartz Z. 1,25(OH)2D3 modulates growth plate chondrocytes via membrane receptor-mediated protein kinase C by a mechanism the action of arachidonic acid and PGE2[J]. Steroids,1999, 64: 129-165
[97]Kveiborg M, Rattan S, Clark B F , Eriksen E F, Kassem M. Treatment with 1, 25-dihydroxyvitamin D3 reduces impairment of human osteoblast functions during cellular aging in culture[J]. Journal of Cellular Physiology, 2001, 186(2): 298–306
[98]Lee D B N, Walling M W, Brautbar N. Intestinal phosphate absorption: Influence of vitamin D and non-vitamin D factors[J] . American Journal of Physiology, 1986, 250: G369-373
[99]Owen T A, Aronow M S, Barone L M, Bettencourt B, Stein G S, Lian J B. Pleiotropic effects of vitamin D on osteoblast gene expression are related to the proliferative and differentiated state of the bone cell phenotype: dependency upon basal levels of gene expression, duration of exposure, and bone matrix competency in normal rat osteoblast cultures[J]. Endocrinology, 1991, 128: 1496–1504
[100]Sooy K, Sabbagh Y, Demay M B. Osteoblasts lacking the vitamin D receptor display enhanced osteogenic potential in vitro[J]. Journal of Cell Biochemistry, 2005, 94(1): 81–87
[101]Yamamoto Y, Yoshizawa T, Fukuda T, Kawano H, Nakamura T, Yamada T, Karsenty G, Kato S. A genetic evidence of direct VDR function in osteoblasts-generation and analysis of osteoblast-specific VDRKO[J]. Jounal of Bone and Mineral Research, 2004, 19 (Suppl.1): S26
[102]Baldock P A, Thomas G P, Hodge J M, Baker S U, Dressel U, O’Loughlin P D, Nicholson G C, Briffa K H, Eisman J A, Gardiner E M. Vitamin D action and regulation of bone remodeling: Suppression of osteoclastogenesis by the mature osteoblast[J]. Jounal of Bone and Mineral Research, 2006, 21 (10): 1618–1626
[103]Gardiner E M, Baldock P A, Thomas G P, Sims N A, Henderson N K, Hollis B, White C P, Sunn K L, Morrison N A, Walsh W R, Eisman J A. Increased formation and decreased resorption of bone in mice with elevated vitamin D receptor in mature cells of the osteoblastic lineage[J]. The FASEB Journal, 14 2000, 14: 1908–1916
[104] Misof B M, Roschger P, Tesch W, Baldock P A, Valenta A, Messmer P, Eisman J A, Boskey A L, Gardiner E M, Fratzl P, Klaushofer K. Targeted Overexpression of Vitamin D Receptor in Osteoblasts Increases Calcium Concentration Without Affecting Structural Properties of Bone Mineral Crystals[J]. Calcified Tissue International, 2003, 73: 251–257
[105]Schwartz Z, Dean D, Walton J, Brooks B, Boyan B. Treatment of resting zone chondrocytes with 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3) induces differentiation into a 1,25-(OH)2D3-responsive phenotype characteristic of growth zone chondrocytes[J]. Endocrinology,1995, 136(2): 402–411
[106]Swain L D, Schwartz Z, Caulfield K, Brooks B P, Boyan B D. Nongenomic regulation of chondrocyte membrane fluidity by 1,25-(OH)2D3 and 24,25-(OH)2D3 is dependent on cell maturation[J]. Bone, 1993, 14(4): 609–617
[107]Schwartz Z, Boyan B. The effects of vitamin D metabolites on phospholipase A2 activity of growth zone and resting zone cartilage cells in vitro[J]. Endocrinology, 1988, 122(5): 2191–2198
[108]Schwartz Z, Swain L D, Ramirez V, Boyan B D. Regulation of arachidonic acid turnover by 1,25-(OH)2D3 and 24,25-(OH)2D3 in growth zone and resting zone chondrocyte cultures[J]. Biochimica et Biophysica Acta, 1990, 1027(3): 278–286
[109]Sylvia V L, Schwartz Z, Schuman L, Morgan R T, Mackey S, Gomez R, Boyan B D. Maturation-dependent regulation of protein kinase C activity by vitamin D3 metabolites in chondrocyte cultures[J]. Journal of Cellular Physiology, 1993, 157(2): 271–278
[110]Nemere I, Farach-Carson M C, Rohe B, Sterling T M, Norman A W, Boyan B D, Safford S E. Ribozyme knockdown functionally links a 1,25(OH)2D3 membrane binding protein (1,25D3-MARRS) and phosphate uptake in intestinal cells[J]. Proceedings of National Academy of Sciences of the United States of America,2004, 101(19): 7392–7397
[111]Schwartz Z, Graham E J, Wang L, Lossdorfer S, Gay I, Johnson-Pais T L, Carnes D L, Sylvia V L, Boyan B D. Phospholipase A2 activating protein (PLAA) is required for 1alpha,25(OH)2D3 signaling in growth plate chondrocytes[J]. Journal of Cell Physiology, 2005, 203(1): 54–70
[112]Schwartz Z, Shaked D, Hardin R R, Gruwell S, Dean D D, Sylvia V L, Boyan B D. 1α, 25(OH)2D3 causes a rapid increase in phosphatidylinositol-specific PLC-βactivity via phospholipase A2-dependent production of lysophospholipid[J]. Steroids 2003, 68: 423–437
[113]Deurs B V, Roepstorff K, Hommelgaard A M, Sandvig K. Caveolae: anchored, multifunctional platforms in the lipid ocean[J]. Trends Cell Biology, 2003, 13(2): 92–100
[114]Boyan B D, Wong K L, Wang L, Yao H, Guldberg R E, Drab M, Jo H, Schwartz Z. Regulation of growth plate chondrocytes by 1,25-dihydroxyvitamin D3 requires[J]. Journal of Bone and Mineral Research, 2006, 21(10): 1637–1647
[115]Boyan B D, Sylvia V L, McKinney N, Schwartz Z. Membrane actions of vitamin D metabolites 1alpha,25(OH)2D3 and 24R,25(OH)2D3 are retained in growth plate cartilage cells from vitamin D receptor knockout mice[J]. Journal of Cellular Biochemistry, 2003, 90(6): 1207–1223
[116]Masuyama R, Stockmans I, Torrekens S, Van Looveren R, Maes C, Carmeliet P, Bouillon R, Carmeliet G. Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulatesFGF23 production in osteoblasts[J]. The Journal of Clinical Investigation, 2006, 116(12): 3150–3159
[117]Lin R, Amizuka N, Sasaki T, Aarts M M, Ozawa H, Goltzman D, Henderson J E, White J H. 1Alpha,25-dihydroxyvitamin D3 promotes vascularization of the chondro-osseous junction by stimulating expression of vascular endothelial growth factor and matrix metalloproteinase 9[J]. Journal of Bone and Mineral Research, 2002, 17(9): 1604–1612
[118]Liu S, Gupta A, Quarles L D. Emerging role of fibroblast growth factor 23 in a bone-kidney axis regulating systemic phosphate homeostasis and extracellular matrix mineralization[J]. Current Opinion in Nephrology and Hypertension, 2007, 16(4): 329–335
[119]Saito H, Kusano K, Kinosaki M, Ito H, Hirata M, Segawa H, Miyamoto K, Fukushima N. Human Fibroblast Growth Factor-23 Mutants Suppress Na+-dependent Phosphate Co-transport Activity and 1α,25-Dihydroxyvitamin D3 Production [J]. The Journal of Biological Chemistry, 2003, 278(4): 2206–2211
[120]Takeda S, Yoshizawa T, Nagai Y, Yamato H, Fukumoto S, Sekine K, Kato S, Matsumoto T, Fujita T. Stimulation of osteoclast formation by 1,25-dihydroxyvitamin D requires its binding to vitamin D receptor (VDR) in osteoblastic cells: studies using VDR knockout mice[J]. Endocrinology, 1999, 140(2): 1005–1008
[121]Mimura H, Cao X, Ross F P, Chiba M, Teitelbaum S L. 1,25-Dihydroxyvitamin D3 transcriptionally activates the beta 3-integrin subunit gene in avian osteoclast precursors[J]. Endocrinology, 1994, 134(3): 1061–1066
[122]Medhora M M, Teitelbaum S, Chappel J, Alvarez J, Mimura H, Ross F P, Hruska K. 1alpha,25-Dihydroxyvitamin D3 up-regulates expression of the osteoclast integrin alpha v beta 3[J]. Journal of Biological Chemistry, 1993, 268(2): 1456–1461
[123]Andersson G, Johansson E K. Adhesion of human myelomonocytic (HL-60) cells induced by 1,25-dihydroxyvitamin D3 and phorbol myristate acetate is dependent on osteopontin synthesis and the alpha v beta 3 integrin[J]. Connective Tissue Research, 1996, 35(1–4): 163–171
[124]Kido S, Inoue D, Hiura K, Javier W, Ito Y, Matsumoto T. Expression of RANK is dependent upon differentiation into the macrophage/osteoclast lineage: induction by 1alpha,25-dihydroxyvitamin D3 and TPA in a human myelomonocytic cell line, HL60[J]. Bone,2003, 32(6): 621–629
[125]Vincent C, Kogawa M., Findlay D M, Atkins G J. The generation of osteoclasts from RAW264.7 precursors in defined, serum free conditions[J]. Journal of Bone Mineral Metablism, 2009, 27(1):114-119
[126]Kveiborg M, Rattan S I, Clark B F, Eriksen E F, Kassem M. Treatment with 1,25-dihydroxyvitamin D3 reduces impairment of human osteoblast functions during cellular aging in culture[J]. Journal of Cellular Physiology, 2001, 186(2): 298 - 306
[127]Gardiner E M, Baldock P A, Thomas G P, Sims N A, Henderson N K, Hollis B, White C P, Sunn K L, Morrison N A, Walsh W R, Eisman J A. Increased formation and decreased resorption of bone in mice with elevated vitamin D receptor in mature cells of the osteoblastic lineage[J]. The FASEB Journal, 2000, 14(13): 1908-1916
[128]Adams J S, Chen H, Chun R, Gacad M A, Encinas C, Ren S, Nguyen L, Wu S, Hewison M, Barsony J. Response element binding proteins and intracellular vitamin D binding proteins: novel regulators of vitamin D trafficking, action and metabolism[J]. Journal of Steroid Biochemistry and molecular biology, 2004, 89–90: 461–465
[129]Theoleyre S, Wittrant Y, Tat S K, Fortun Y, Redini F, Heymann D. The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling [J]. Cytokine & Growth Factor Review, 2004, 15(6): 457-475
[130]刘继中,纪宗玲,陈苏民. OPG/RANKL/RANK系统与骨破坏性疾病[J].生物工程学报, 2003, 19(6): 655-660
[131]田庆显,黄公怡. OPG/RANK/RANKL系统和骨质疏松[J].中华骨科杂志, 2004, 24(11): 683-686
[132]于丽云. RANKL和破骨细胞[J].国外医学内分泌学分册, 2003, 23(2): 123-126
[133]Suda T, Tadahashi N, Martin T. Modulation of osteoclast differentiation[J]. Endocrine Reviews, 1992, 13: 66-80
[134]Lacey D, Timms E, Tan H L, Kelley M J, Dunstan C R, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian Y X, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle W J. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation[J]. Cell, 1998, 93: 165-176
[135]Wong B, Rho J J, Arronet J, Robinson E, Orlinick J, Chao M, Kalachikov S, Cayani E, Bartlett F S 3rd, Frankle W N, Lee S Y, Choi Y. TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates C-Jun N-termind kinase in T cell[J]. Journal ofBiological and Chemical, 1997, 272: 25190-25194
[136]王晋东. RANKL与骨免疫学[J].国际免疫学杂志, 2006, 29(3): 165-167
[137]Yasuda H , Shima N , Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S I, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCEP/RANKL[J]. Proceedings of the National Academy of Sciences of United States of America, 1998, 95: 3597-3602
[138]Kearns A E, Khosla S, Kostenuik P. RANKL and OPG Regulation of Bone Remodeling in Health and Disease[J]. Endocrine Reviews, 2008, 29: 155-192
[139]Lum L, Wong B R, Josien R, Becherer J D, Erdjument-Bromage H, Schl?ndorff J, Tempst P, Choi Y, Blobel C P. Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival[J]. The Journal of Biological Chemistry, 1999, 274: 13613-13618
[140]Suzuki J, Ikeda T, Kuroyama H, Sesai M, Utsuyama M, Tatsumi M, Uematsu H, Hirokawa K. Regulation of osteoclastogenesis by three human RANKL isoforms expressed in NIH3T3 cells[J]. Biochemical and Biophysical Research Communications, 2004, 314(4): 1021-1027
[141]Ikeda T, Kasai M, Suzuki J, Kuroyama H, Seki S, Utsuyama M, Hirokawa K. Multimerization of the receptor activator of nuclear factor-kappa B ligand (RANKL) isoforms and regulation of osteoclastogenesis[J]. Journal of Biological Chemistry, 2003, 278(47): 47217-47222
[142]Ikeda T, Kasai M, Utsuyama M, Hirokawa K. Determination of three isoforms of the receptor activator of nuclear factor-kappa B ligand and their differential expression in bone and thymus[J]. Endocrinology, 2001, 142(4): 1419-1426
[143]Tat S W, Pelletier J-P, Lajeunesse D, Fahmi H, Duval N, Pelletier J M. Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: Influence of osteotropic factor[J]. Bone, 2008, 43(2): 284-291
[144]Kong Y Y, Yoshida H, Sarosi I. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis [J]. Nature, 1999, 397 (6717): 315-323
[145]Tsurukai T, Udagawa N, Matsuzaki K, Takahashi N, Suda T. Roles of macrophage-colony stimulating factor and osteocalast differentiation factor in osteoclastogenesis[J]. Journal ofBone and Mineral Metabolism, 2000, 18(4): 177-184
[146]Burgess T L, Qian Y X , Kaufman S, Ring B D, Van G, Capparelli C, Kelley M, Hsu H, Boyle W J, Dunstan C R, Hu S, Lacey D L. The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts[J]. Journal of Biological Chemistry,1999, 145(3): 527-538
[147]Wittrant Y, Theoleyre S, Couillaud S, Dunstan C, Heymann D, Rédini F. Relevance of an in vitro osteoclastogenesis system to study receptor activator of NF-κB ligand and osteoprotegerin biological activities[J]. Experimental Cell Research, 2004, 293(2): 292-301
[148]Allison P A, Tometsk M E, Glaccum M, Cosman D, Dougall W C. A RANK/TRAF6-dependent signal transduction pathway is essential for osteoclast cytoskeletal organization and resorptive function[J]. Journal of Biological Chemistry, 2002, 277(46): 44347-44356
[149]Xing L, Venegas A M, Chen A, Garrett-Beal L, Boyce B F, Schwartzberg P L. Genetic evidence for a role for Src family in TNF family receptor signaling and cell survival[J]. Genes and Development, 2001, 15(2): 241-253
[150]Srivastava S, Yorablo G, Weitzman M N, Cenci S, Ross F P, Pacifici R. Estrogen decrease osteoclast formation by down-reglation receptor of NF-κB ligand (RANKL)-induced JNK activation[J]. Journal of Biological Chemistry, 2001, 276(12): 8836-8840
[151]Mizukami J, Takaesu G, Akatsuka H, Sakurai H, Ninomiya-Tsuji J, Matsumoto K, Sakurai N. Receptor activator of NF-κB ligand (RANKL) activates TAK1 mitogen-activated protein kinase kinase kinase through a signaling complex containg RANK, TAB2, and TRAF6[J]. Molecular and Cellular Biology, 2002, 22(4): 992-1000
[152]Matsuo K, Galson D L, Zhao C, Peng L, Laplace C, Wang K Z, Bachler M A, Amano H, Aburatani H, Ishikawa H, Wanger E F. Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos[J]. Journal of Biological Chemistry, 2004, 279(25): 26475–26480
[153]Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, Saiura A, Isobe M, Yokochi T, Inoue J, Wagner E F, Mak T W, Kodama T Taniquchi T. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts[J]. Developmental Cell, 2002, 3(6): 889–901
[154]Yamashita T, Yao Z, Li F, Zhang Q, Badell I R, Schwarz E M, Takeshita S, Wagner E F, Noda M, Matsuo K, Xing L, Boyce B E. NF-kappaB p50 and p52 regulate receptor activator ofNF-kappaB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1[J]. Journal of Biological Chemistry, 2007, 282(25): 18245–18253
[155]Boyce B F, Xing L P. Functions of RANKL/RANK/OPG in bone modeling and remodeling[J]. Archives of Biochemistry and Biophysics, 2008, 473: 139-146
[156]Wei S, Teitelbaum S L, Wang M W H, Ross F P. Receptor activator of nuclear factor-kappa b ligand activates nuclear factor-kappa b in osteoclast precursor[J]. Endocrinology, 2001, 142(3): 1290-1295
[157]姚静,侯加法. OPG/RANKL/RANK系统的研究进展[J].动物医学进展, 2006, 27(2): 5-9
[158]Hsu H, Lacey D L, Dunstan C R, Solovyev I, Colombero A, Timms E, Tan H L, Elliott G, Kelley M J, Sarosi I, Wang L, Xia X Z, Elliott R, Chiu L, Black T, Scully S, Capparelli C, Morony S, Shimamoto G, Bass M B, Boyle W J. Tumor necrosis factor receptor family member RANK mediated osteoclast differentiation and activation induced by osteoprotegerin ligand[J]. Proceedings of National Academy Sciences of the United States of America, 1999, 96(7): 3540-3545
[159]Fata J E, Kong Y Y, Li J, Sasaki T, Irie-Sasaki J, Moorehead R A, Elliott R, Scully S, Voura E B, Lacey D L, Boyle W J, Khokha R, Penninger J M. The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development[J]. Cell 2000, 103(1): 41–50
[160]Kim N S, Kim H J, Koo B K, Kwon M C, Kim Y W, Cho Y, Yokota Y, Penninger J M, Kong Y Y. Receptor activator of NF-kappaB ligand regulates the proliferation of mammary epithelial cells via Id2[J]. Molecular and Cellular Biology, 2006, 26(3): 1002–1013
[161]Chen G, Sircar K, Aprikian A, Potti A, Goltzman D, Rabbani S A. Expression of RANKL/RANK/OPG in primary and metastatic human prostate cancer as markers of disease stage and functional regulation[J]. Cancer 2006, 107(2): 289–298
[162]Li J, Sarisu I, McCabe S M, Tan H L, Capparelli C, Morony S, Elliot R, Van G, Kaufman S. Absolute requirement for the TNFR-related protein RANK during osteoclastogenesis and in regulation of bone mass and calcium metabolism[J]. Journal of Bone Mineral Research, 1999, 14 (suppl.1): S149
[163]Hughes A E, Ralston S H, Marken J, Bell C, MacPherson H, Wallace R G, Hul W V, Whyte M P, Nakatsuka K, Hovy L, Anderson D M. Mutations in TNFRSF11A, affecting the signalpeptide of RANK, cause familial expansile osteolysis[J]. Nature Genetics, 2000, 24(1): 45–48
[164]Tsuda E, Goto M, Monochizuki S I, Yano K, Kobayashi F, Morinaga T, Higashio K. Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis[J]. Biochemical and Biophysical Research Communication, 1997, 234(1): 137-142
[165]Suda T, Takahashi N , Udagawa N, Jimi E, Gillespie M T, Martin T J. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families[J]. Endocrine Reviews, 1999, 20(3): 345-357
[166]Hofbauer L C, Khosla S, Dunstan C R, Lacey D L, Boyle W J, Riggs B L. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption[J]. Journal of Bone and Mineral Research, 2000, 15(1): 2–12
[167]Blair J M, Zheng Y, Dunstan C R. RANK Ligand[J]. The International Journal of Biochemistry & Cell Biology, 2007, 39(6): 1077–81
[168]Yasuda H, Shima N, Nakagawa N, Mochizuki S I, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T, Murakami A, Tsuda E, Morinaga T, Higashio K. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG inhibits osteoclastogenesis in vitro[J]. Endocrinology, 1998, 139(3): 1329–37
[169]Mizuno A, Amizuka N, Irie K, Murakami A, Fujise N, Kanno T, Sato Y, Nakagawa N, Yasuda H, Mochizuki S, Gomibuchi T, Yano K, Shima N, Washida N, Tsuda E, Morinaga T, Higashio K, Ozawa H. Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin[J]. Biochemical and Biophysical Research Communication, 1998, 247: 610-615.
[170]Kong Y Y, Feige U, Sabino I, Bolon B, Tafuri A, Morony S, Capparelli C, Li J, Elliott R, McCabe S, Wong T, Campagnuolo G, Moran E, Bogoch E R, Van G, Nquyen L T, Ohashi P S, Lacey D L, Fish E, Boyle W J, Penninger J M. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand [J]. Nature, 1999a, 402 (6759): 304-309
[171]Hofbauer L C. Osteoprotegerin ligand and osteoprotegerin: novel implication for osteoclast biology and bone metabolism[J]. European Journal of Endocrinol, 1999, 141: 195-210
[172]Kostenuik P J. Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength[J]. Current Opinion in Pharmacology, 2005, 5(6): 618–25
[173]Hakeda Y, Kobayashi Y, Yamaguchi K, Yasuda H, Tsuda E, Higashio K, Miyata T, Kumegawa M. Osteoclastogenesis inhibitory factor (OCIF) directly inhibits bone-resorbing activity of isolated mature osteoclasts[J]. Biochemical and Biophysical Research Communications, 1998, 251: 796-801
[174]杨旭,杨庆铭,邓廉夫.重组人骨保护素对体外培养兔破骨细胞的影响[J].中华骨科杂志, 2003, 23 (6): 365-368
[175]Tsukii K, Shima N, Mochizuld S, Yamaguchi K, Kinosaki M, Yano K, Shibata O, Udagawa N, Yasuda H, Suda T, Higashio K. Osteoclast differentiation factor mediates an essential signal for bone resorption induced by 1α, 25-dihydroxyvitamin D3, prostaglandin E2, or parathyroid hormone in the microenvironment of bone[J]. Biochemical and Biophysical Research Communication, 1998, 246 (2): 337-41
[176]Takai H, Kanematsu M,Yano K, Tsuda E, Higashio K, Ikeda K, Watanabe K, Yamada Y. Transforming growth factor-βstimulates the production of osteoprotegerin/osteoclastogenesis inhibitory factor by bone marrow stromal cells[J]. Journal of Biological Chemistry, 1998, 273(42): 27091-27096
[177]Hofbauer L C, Khosla S, Dunstan C R, Lacey D L, Spelsberg T C, Riggs B L. Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells[J]. Endocrinology, 1999a, 140(9): 4367- 4370
[178]Hofbauer L C, Gori F, Riggs B L, Lacey D L, Dunstan C R, Spelsberg T C, Khosla S. Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoidinduced osteoporosis[J]. Endocrinology, 1999b, 140: 4382-4389
[179]Lee S K, Lorenzo J A. Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures:correlation with osteoclast-like cell formation[J]. Endocrinology, 1999, 140: 3552-3561
[180]Giner M, Rios M J, Montoya M J, Vázquez M A, Naji L, Pérez-Cano. RANKL/OPG in primary cultures of osteoblasts from post-menopausal women. Differences between osteoporotic hip fractures and osteoarthritis[J]. Journal of Steroid Biochemistry & Molecular Biology, 2009, 113(1-2): 46-51
[181]吴小涛,王海军,宋萍. 1,25(OH)2D3对体外培养大鼠成骨细胞RANKL/OPG mRNA表达的影响[J].东南大学学报(医学版), 2007, 26(1): 32-35
[182]Manolagas S C. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis[J]. Endocrine Reviews, 2000, 21(2): 115–37
[183]Zhang Y H, Heulsmann A, Tondravi M M, Mukherjee A, Abu-Amer Y. Tumor necrosis factor-alpha (TNF) stimulates RANKL-induced osteoclastogenesis via coupling of TNF type 1 receptor and RANK signaling pathways[J]. Journal of Biological Chemistry, 2001, 276(1): 563–8
[184]Azuma Y, Kaji K, Katogi R, Takeshita S, Kudo A. Tumor necrosis factor-alpha induces differentiation of and bone resorption by osteoclasts[J]. Journal of Biological Chemistry, 2000, 275(7): 4858–64.
[185]Gori F, Hofbauer L C, Dunstan C R, Spelsberg T C, Khosla S, Riggs B L. The expression of osteoprotegerin and RANK ligand and the support of osteoclast formation by stromalosteoblastlineage cells is developmentally regulated[J]. Endocrinology 2000, 141(12):4768–76
[186]Schett G, Hayer S, Zwerina J, Redlich K, Smolen J S. Mechanisms of Disease: the link between RANKL and arthritic bone disease[J]. Nature Clinical Practice Rheumatology, 2005, 1: 47–54
[187]Humphrey E L, Williams J H, Davie M W, Marshall M J. Effects of dissociated glucocorticoids on OPG and RANKL in osteoblastic cells[J]. Bone, 2006, 38: 652–661 188]Blair J M, Zhou H, Seibel M J, Dunstan C R. Mechanisms of disease: roles of OPG, RANKL and RANK in the pathophysiology of skeletal metastasis[J]. Nature Clinical Practice Oncology, 2006, 3: 41–49
[189]Dougall W C, Chaisson M. The RANK/RANKL/OPG triad in cancer-induced bone diseases[J]. Cancer Metastasis Reviews, 2006, 25(4): 541–549
[190]Bekker P J, Holloway D, Nakanishi A, Arrighi M, Leese P T, Dunstan C R. The effect of a single dose of osteoprotegerin in postmenopausal women[J]. Journal of Bone and Mineral Research, 2001, 16(2): 348–360
[191]Body J J, Greipp P, Coleman R E, Facon T, Geurs F, Fermand J P, Harousseau J L, Lipton A, Mariette X, Williams C D, Nakanishi A, Holloway D, Martin S W, Dunstan C R, Bekker P J. A phase I study of AMGN-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases[J]. Cancer, 2003, 97: 887–892
[192]Bekker P J, Holloway D L, Rasmussen A S, Murphy R, Martin S W, Leese P T, Holmes G B,Dunstan C R, DePaoli A M. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women[J]. Journal of Bone and Mineral Research, 2004, 19(7): 1059–1066
[1]刘宗平.现代动物营养代谢病学[M].北京:化学工业出版社, 2003. 83
[2] Sutton A L M, Zhang X X, Ellison T I, Macdonald P N. The 1,25 (OH)2 D3-regulated transcription factor MN1 stimulates Vitamin D receptor-mediated transcription and inhibits osteoblastic cell proliferation[J]. Molecular Endocrinology, 2005, 19(9): 2234-2244
[3] Atkins G J, Anderson P H, Findlay D M, Welldon K J, Vincent C, Zannettino A C, O’Loughlin P D, Morris H A. Metabolism of vitamin D3 in human osteoblasts: Evidence for autocrine and paracrine activities of 1α,25-dihydroxyvitamin D3[J]. Bone, 2007, 40(6): 1517-1528
[4]魏义勇,石印玉.维生素D调控成骨细胞的作用机制[J].国外医学·骨科学分册, 2003, 24 (3): 165-167
[5] Langub M C, Reinhardt T A, Horst R L, Malluche H H, Koszewski N J. Characterization of vitamin D receptor immunoreactivity in human bone cells[J]. Bone, 2000, 27(3): 383-387
[6]吴培福,韩博,黄有德.氟对动物成骨细胞的影响[J].中国兽医杂志, 2005, 41(10): 40-42
[7] Martin T J, Udagawa N. Hormal regulation of osteoclast function[J]. Trends Endocrinol Metab, 1998, 9(1): 6-12
[8]傅德皓,杨述华,马德彰,李鲲,郜勇.鼠胚成骨细胞的原代培养与鉴定[J].创伤外科杂志, 2006, 8 (12): 157-160
[9]王洪复主编.骨细胞图谱与骨细胞体外培养技术[M].上海:上海科学技术出版社, 2001. 55-69
[10]胡静,郑洪新.改良成骨细胞体外培养和鉴定方法[J].中国老年学杂志, 2006, 1(26): 76-78
[11]Sammons R, Marquis P. Application of the low vacuum scanning electron microscope to the study of biomaterials and mammalian cells[J]. Biomaterials, 1997, 18(1): 81-86
[12]钟代彬,吴培福,曲伟杰,王梅,苏敬良,金久善,韩博.山羊成骨细胞的体外培养和鉴定[J].中国兽医科技, 2005, 35(5): 399-403
[13]余克强.补肾中药血清对体外培养成骨细胞合成碱性磷酸酶及骨钙素的调控[J].中国临床康复, 2005, 9(34): 124-126
[14]裴育,周学瀛,孟迅吾,夏维波,刑小平,刘怀成,胡莹莹. 1,25双羟维生素D3及转化生长因子β1对人胚成骨细胞增殖和分化的影响[J].中华医学杂志, 2003, 83(12): 1084-1088
[15]Maehata Y, Takamizawa S, Ozawa S, Kato Y, Sato S, Kubota E, Hata R. Both direct and collagen-mediated signals are required for active vitamin D3-elicited differentiation of humanosteoblastic cells: Role of osterix, an osteoblast-related transcription factor[J]. Matrix Biology, 2006, 25: 47-58
[16]Verlinden L, Eelen G, Van H R, Engelen K, Beullens I, Van C M, Marchal K, Mathieu C, Bouillon R, Verstuyf A. 1α, 25-dihydroxybitamin D3-induced down-regulation of the checkpoint proteins, Chk1 and Claspin, is mediated by the pocket proteins p107 and p130[J]. Journal of Steroid Biochemistry & Molecular Biology, 2007, 103: 411-415
[17]Shiels M J, Mastro A M, Gay C V. The effect of donor age on the sensitivity of osteoblasts to the proliferative effects of TGFβand 1,25(OH)2 vitamin D3[J]. Life Sciences, 2002, 70: 2967-2975
[18]Chatterjee M. Vitamin D and genomic stability[J]. Mutation Research, 2001, 475: 69-88
[19]孙兰,胡静,郑虎,刘景生.在人的类成骨细胞TE85中雌激素对活性维生素D作用的影响[J].药学学报, 2000, 35(6): 413-416
[20]唐林,林珠,李永明,王华.不同大小机械牵张力对成骨细胞增殖及碱性磷酸酶的影响[J].解放军医学杂志, 2006, 31(6): 580-581
[21]Wang L P, Zhao G, Olivares-Navarrete R, Bell B F, Wieland M, Cochran D L, Schwartz Z, Boyan B D. Integrinβ1 silencing in osteoblasts alters substrate-dependent responses to 1,25-dihydroxy vitamin D3[J]. Biomaterials, 2006, 27(20): 3716-3725
[22]Rapuri P, Gallagher J C, Nawaz Z. Caffeine decrease vitamin D receptor protein expression and 1,25(OH)2D3 stimulated alkaline phosphatase activity in human osteoblast cells[J]. Journal of Steroid Biochemistry & Molecular Biology, 2007, 103 (3-5): 368-371
[23]Kong Y Y, Penninger J M. Molecular control of bone remodeling and osteoporosis[J]. Experimental Gerontology, 2000, 35(8): 947-956
[24]Majeska R J, Rodan? G A. The effect of 1,25(OH)2D3 on Alkaline Phosphatase in osteoblastic osteosarcoma cells[J]. The Journal of Biological Chemistry, 1982, 257(7): 3362-3365
[25]Shi Y C, Worton L, Esteban L, Baldock P, Fonq C, Eisman J A, Gardiner E M. Effects of continuous activation of vitamin D and Wnt response pathways on osteblastic proliferation and differentiation[J]. Bone, 2007, 41(1): 87-96
[26]国家自然科学基金委员会主编.细胞生物学[M].北京:科学出版社, 1997. 97
[27]陈旭,杨志明,解慧琪,李胜富. WO-1对成骨细胞的生物学效应研究[J].中国修复重建外科杂志, 2005, 19(10): 822-825
[28]王凌,王玉东,李大金,王文君,朱影.补肾宁心方药物血清对鼠成骨细胞的增殖与凋亡的影响[J].中华中医药杂志, 2006, 21(1): 30-34
[29]田庆显,黄公怡. 1,25-二羟基维生素D3对小鼠成骨细胞增殖的影响[J].中华老年医学杂志, 2006, 25(12): 922-924
[30]Jiang F, Li P F, Fornace Jr A J, Nicosia S V, Bai W L. G2/M Arrest by 1,25-dihydroxyvitamin D3 in ovarian cancer cells mediated through the induction of GADD45 via an exonic enhancer[J]. The Journal of Biological Chemistry, 2003, 278 (48): 48030-48040
[31]刘景生主编.细胞信息与调控[M].第二版.北京:中国协和医科大学出版社, 2004. 315-316, 586
[32]孙大业,郭艳林,马力耕,崔素娟主编.细胞信号转导[M].第三版.北京:科学出版社, 2001. 93
[33]王金发主编.细胞生物学[M].北京:科学出版社, 2003. 163-165
[34]吕海宏,李茂欣.连接蛋白43与骨质疏松[J].中国康复理论与实践, 2005, 11(4): 265-266
[35]Lips P. Vitamin D physiology[J]. Progress in Biophysics and Molecular Biology, 2006, 92(1): 4-8
[36]St-Arnaud R. The direct role of vitamin D on bone homeostasis[J]. Archives of Biochemistry and Biophysics. 2008, 473(2): 225-230
[37]付强,刘源.钙、磷与维生素D对动物骨代谢的影响研究进展[J].中国比较医学杂志, 2006, 16(8): 502-505
[38]Zhang X Y, Payal B, Melissa O, Zanello L P. 1α,25 (OH)2-vitamin D3 membrane-initiated calcium signaling modulates exocytosis and cell survival[J]. Journal of Sterold Biochemistry & Molecular Biology, 2007, 103(3-5): 457-461
[39]Zanello L P, Norman A W. Electrical responses to 1α,25(OH)2-Vitamin D3 and their physiological significance in osteoblasts[J]. Steroids, 2004, 69(8-9): 561-565
[40]Lajdova I, Chorvat D, Chorvatova A. Rapid effects of 1α,25(OH)2D3 in resting human peripheral blood mononuclear cells[J]. European Journal of Pharmacology, 2008, 586(1-3): 14-23
[41]Balint E, Marshall C F, Sprague S M. Effect of vitamin D analogues paricalcitol and calcitriol on bone mineral in vitro[J]. American Journal of Kidney Disease, 2000, 36(4): 789-796
[42]Farach-Carson M C. Bioactive analogs that simulate subsets of biological activities of 1α,25(OH)2D3 in osteoblasts[J]. Steroids, 2001, 66(3-5): 357-361
[43]Farach-Carson M C, Ridall A L. Dual 1,25-dihydroxyvitamin D3 signal response pathways inosteoblasts: cross-talk between genomic and membrane-initiated pathways[J]. American Journal of Kidney Diseases, 1998, 31(4): 729-742
[44]邓耀祖,屈伸主编.医学分子细胞生物学[M].北京:科学出版社, 2002. 128-129
[45]马慧军,朱文元,王大光,岳学状,李诚让.内皮素-1对毛囊外根鞘无色素黑素细胞黏附和移行及其细胞骨架形态的影响[J].临床皮肤科杂志, 2005, 34(10): 643-646
[46]王稚英,王英,肖军军,董晓敏.牵引成骨体外模型的建立及成骨细胞骨架的观察[J].中华口腔医学杂志, 2006, 41(2): 111-113
[47]Luegmayr E, Varga F, Frank T, Roschger P, Klaushofer K. Effects of Triiodothyronine on morphology, growth behavior, and the actin cytoskeleton in mouse osteoblastic cells (MC3T3-E1)[J]. Bone, 1996, 18(6): 591-599
[48]Gao T J, T.Aro H, Yl?nen H, Vuorio E. Silica-based bioactive glasses modulate expression of bone morphogenetic protein-2 mRNA in Saos-2 oseoblasts in vitro[J]. Biomaterials, 2001, 22(12): 1475-1483
[49]Scotchford C A, Ball M, Winkelmann M, V?r?s J, Csucs C, Brunette D M, Danuser G, Textor M. Chemically patterned, metal-oxide-based surfaces produced by photolithographic techniques for studying protein-and cell-interactions.Ⅱ: Protein adsorption and early cell interactions[J]. Biomaterials, 2003, 24(7): 1147-1158
[50]Gough J E, Christian P, Scotchford C A, Jones I A. Craniofacial osteoblast responses to polycaprolactone produced using a novel boron polymerization technique and postassium fluoride post-treatment[J]. Biomaterials, 2003, 24(27): 4905-4912
[51]Wu T J, Huang H H. Lan C W, Lin C H, Hsu F Y, Wang Y J. Studies on the microspheres comprised of reconstituted collagen and hydroxyapatite[J]. Biomaterials, 2004, 25(4): 651-658
[52]Wang C M, Gong Y H, Lin Y M, Shen J B, Wang D A. A novel gellan gel-based microcarrier for anchorage-dependent cell delivery[J]. Acta Biomaterialia, 2008, 4(5): 1226-1234
[53]薛延,袁润英,相东,王红霞,李希斌,刘正梅,吴克斌,范慕贞. 1,25双羟维生素D3对成骨样细胞骨架和基因表达的影响[J].解剖学报, 1998, 29(1): 67-68
[54]Alexopoulos H, B?ttger A, Flscher S, Levin A, Wolf A, Fujisawa T, Hayakawa S, Gojobori T, Davles J A, David C N, Bacon J P. Evolution of gap junctions: the missing link?[J]. Current Biology, 2004, 14(20): R879-880
[55]Bukauskas F F, Verselis V K. Gap junction channel gating[J]. Biochimica et Biophysica Acta, 2004, 1662(1-2): 42-60
[56]Stains J P, Civitelli R. Cell-to-cell interactions in bone[J]. Biochemical and Biophysical Research Communications, 2005, 328(3): 721-727
[57]Stains J P, Civitelli R. Gap junction in skeletal development and function[J]. Biochimia et Biophysica Acta, 2005, 1719(1-2): 69-81
[58]Civitelli R. Cell-cell communication in the osteobalst/osteocyte lineage[J]. Archives of Biochemistry and Biophysics, 2008, 473: 188-192
[59]崔爎,陈槐卿.骨细胞间隙连接与物理—生物信号传导研究进展[J].国外医学生物医学工程分册, 2003, 26 (3): 108-112
[60]田庆显,黄公怡. 1,25二羟基维生素D3对小鼠成骨细胞OPG和RANKL基因表达的影响[J].中国医学科学院学报, 2004, 26(4): 418-422
[61]Friedenstein. Precursor cells of mechanocytes[J]. Inernational Review of Cytology, 1976, 47(3): 327-240
[62]卢卫忠,唐康来,杨柳,吴梅英. TGF-β对成骨细胞的作用[J].第三军医大学学报, 2000, 22: 94-96
[63]李丽华,周玉坤,王丽丽.维生素D与骨的生长和矿化[J].国外医学妇幼保健, 2004, 15(5): 257-258
[64]史炜镔.骨质疏松症的药物治疗[J].国外医学老年医学分册, 1996, 17: 177-181
[65]吴培福,钟代彬,曲伟杰,王梅,黄有德,韩博.小鼠成骨细胞改良酶的消化分离培养[J].甘肃农业大学学报, 2004, 39(5): 512-515
[66]孟繁浩,熊志立,陶胜宇,李发美.成骨细胞的生物学特征及其调控活性物质[J].化学与生物工程, 2005,11: 8-10
[67]周彬,程祥荣,杨惠,蒋淘,夏大弘,王贻宁.牙周韧带细胞及成骨样细胞在纯钛表面附着的形态学比较[J].中国口腔种植学杂志, 2002, 7(4): 158-161
[68]Takanori Domon, Yoshinori Yamazaki, Ami Fukui et al. Ultrastructural study of cell-cell interaction between osteoclasts and osteoblasts/stroma cells in vitro[J]. Annals of Anatomy, 2002, 184(3): 221-227
[69]Feng Chei, Nicolas Mathis. Osteoblast interaction with DLC-coated Si substrates[J]. Acta Biomaterialia, 2008(4): 1369-1381
[70]张金超,李晓新,许善锦,王夔,于世凤,林琴.稀土离子对体外培养的成骨细胞增殖、分化和功能表达的影响[J].自然科学进展, 2004, 14(4): 404-409
[71]杨玉生,孙俊英,朱国兴.生物活性玻璃对鼠成骨细胞体外增殖的形态学研究[J].生物医学工程研究, 2007, 26(2): 146-150
[72]任高宏,裴国献,王钢,金丹,魏宽海,陈莉光,陈滨.成人骨髓成骨细胞体外培养[J].骨与关节损伤杂志, 2003, 18(2): 118-121
[73]陈建庭,李菊根,金大地.血小板衍生生长因子促进成骨细胞DNA合成的实验研究[J].中华外科杂志, 1997, 37(7): 409-411
[74]朱进才,任战平,李旭奎,安文生,王黎.电刺激活化牙槽骨成骨细胞增殖功能的实验研究[J].西安交通大学学报, 2003, 24(4): 300-302
[75]Beresford J N, Gallagher J A, Russell R G G. 1, 25-dihydroxyvitamin D3 and human bone-derived cells in vitro: effects on alkaline phosphatase, type I collagen and proliferation[J]. Endocrinology, 1986, 119: 1176-1785
[76]Ikeda T, Kohno H, Yamamuro T, Kasai R, Ohta S, Okumura H, Konishi J, Kikuchi H, Shigeno C. The effect of active vitamin D3 analogs and dexamethasone on the expression of osteocalcin gene in rat tibiae in vivo[J]. Biochemical and Biophysical Research Communications, 1992, 189 : 1231-1235
[77]Hideaki Nagaoka, Yoshiyuki Mochida, Phimon Atsawasuwan, Masaru K, Kondon T, Yamauchi M. 1,25(OH)2D3 regulates collagen quality in an osteoblastic cell culture system[J]. Biochemical and Biophysical Research Communications, 2008, 377(2): 674-678
[78]童安莉,陈璐璐,丁桂芝.成骨细胞骨形成机制研究进展[J].中国骨质疏松杂志, 1999, 5 (3): 60-64
[79]唐文山.骨营养不良乳牛血清钙及血清游离羟脯氨酸含量测定[J].中国兽医科技, 2002, 32(11): 26-28
[80]刘宗平,马卓,杨得兵,池斌.双峰驼骨质疏松症的流行特点及其与生物地球化学因子之间的关系[J].应用与环境生物学报, 1997, 3(4): 345-348
[81]Mohr S B. A Brief History of Vitamin D and Cancer Prevention[J]. Annals of Epidemiology, 2009, 19(2): 79-83
[82]Hofstetter W, Felix R. 1,25(OH)2D3 and PTH act mainly on cells of the osteoblasts but not of the osteoclast lineage[J]. Bone, 1995, 17(6): 557-596
[83]Simonet W S, Lacey D L, Dunstan C R, Kelley M, Chang M S, Lüthy R, Nguyen H Q, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan H L, Trail G, Sullivan J, Davy E, Bucay N, Gegg L R, Hughes T M, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee P, Program A E, Boyle W J. Osteoprotegerin: A Novel SecretedProtein Involved in the Regulation of Bone Density[J]. Cell, 1997, 89: 309-319
[84] Yasuda H, Shima N, Nakagawa N, Yamaquchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis- inhibitory factor and is identical to TRANCE/RANK[J]. Proceeding of the National Academy of Sciences in USA, 1998, 95(7): 3597-3602
[85]Mizuno A, Amizuka N, Irie K, Murakami A, Fujise N, Kanno T, Sato Y, Nakagawa N, Yasuda H, Mochizuki S, Gomibuchi T, Yano K, Shima N, Washida N, Tsuda E, Morinaga T, Higashio K, Ozawa H. Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin[J]. Biochemical and Biophysical Research Communication, 1998, 247(3): 610-615
[86]刘俊栋,顾建红,翟必华,刘学忠,卞建春,刘宗平.骨保护素对体外培养大鼠破骨细胞的影响[J].中国农业科学, 2008, 41(2): 581-586
[87]顾建红,刘俊栋,卓丽玲,王林,赵瑞英,刘宗平.钙磷对RANKL诱导番鸭破骨细胞生成及活性的影响[J].江苏农业科学, 2007, 6: 175-178
[88]Suda T, Ueno Y, Fujii K, Shinki T. Vitamin D and bone[J]. Journal of Cellular Biochemistry, 2003, 88(2): 259-266
[89]Lum L, Wong B R, Josien R, Becherer J D, Erdjument-Bromage H, Schl?ndorff J, Tempst P, Choi Y, Blobel C P. Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival[J]. The Journal of Biological Chemistry, 1999, 274: 13613-13618
[90]Zhang Y Y, Chen D C, Lu C Y. Influence of vitamin D on proliferation, differentiation and secretion of OPG and RANKL of cultured marrow mesenchymal cells of rhesus monkey[J]. Abstrants/Bone, 2008, 43: S38-S75
[91]吴小涛,王海军,宋萍. 1,25(OH)2D3对体外培养大鼠成骨细胞RANKL/OPG mRNA表达的影响[J].东南大学学报(医学版), 2007, 26(1): 32-35
[92]王科,王晓雄,石炳毅.实时荧光定量PCR在细胞因子mRNA检测研究中的应用[J].北京生物医学工程, 2006, 25(2): 217-221
[93]陈兆鹏,黄瞻云,张文芳,徐红菊,陈文雨,万海英.荧光定量PCR和ELISA测定乙肝病毒标志物2005例结果分析[J].同济大学学报(医学版), 2003, 24(2): 138-143
[94]Hofbauer L C, Dunstan C R, Spelsberg T C, Riggs B L, Khosla S. Osteoprotegerin production by human osteoblast lineage cells is stimulated by vitamin D, bone morphogenetic protein-2, and cytokines[J]. Biochem Biophys Res Commun, 1998, 250(3): 776–781
[95]Giner M, Rios M J, Montoya M J, Vázquez M A, Naji L, Pérez-Cano. RANKL/OPG in primary cultures of osteoblasts from post-menopausal women. Differences between osteoporotic hip fractures and osteoarthritis[J]. Journal of Steroid Biochemistry & Molecular Biology, 2009, 113(1-2): 46-51
[96]Theoleyre S, Wittrant Y, Tat S K, Fortun Y, Redini F, Heymann D. The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling[J]. Cytokine & Growth Factor Reviews, 2004, 15(6): 457-475
[97]Seriwatanachai D, Thongchote K, Charoenphandhu N, Pandaranandaka J, Tudpor K, Teerapornpuntakit J, Suthiphongchai T, Krishnamra N. Prolactin directly enhances bone turnover by raising osteoblast-expressed receptor activator of nuclear factorκB ligand/osteoprotegerin ratio[J]. Bone, 2008, 42(3): 535-546
[98]Thomas G P, Baker S U K, Eisman J A, Gardiner E M. Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts[J]. Journal of Endocrinology, 2001, 170: 451-460
[99]Wiberg K, Ljunghall S, Binderup L, Ljunggren?. Studies on two new vitamin D Analogs, EB 1089 and KH 1060: Effects on bone resorption and osteoclast recruitment in vitro[J]. Bone, 1995, 17(4): 391-395
[100]李新锋,周振雷,张建鹏,侯加法.肉鸡胫骨软骨发育不良研究进展[J].畜牧与兽医, 2008, 40(3): 103-106
[101]Chamber T J, Magnus C J. Calcitonin alters behavior of isolated osteoclasts[J]. The Journal of Pathology, 1982, 137(1): 27
[102]邓力.体外破骨细胞培养及研究进展[J].华西要学杂志, 2000, 15(3): 195-196
[103]Tsuda E, Goto M, Monochizuki S I. Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis[J]. Biochemical and Biophysical Research Communications, 1997, 234(1): 137-142
[104]Lacey D, Timms E, Tan H L, Kelley M J, Dunstan C R, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian Y X, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle W J. Osteoprotegerinligand is a cytokine that regulates osteoclast differentiation and activation[J]. Cell, 1998, 93: 165-176
[105]Kong Y Y, Yoshida H, Sarosi I, Tan H L, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos A J, Van G, Itie A, Khoo W, Wakeham A, Dunstan C R, Lacey D L, Mak T W, Boyle W J, Penninger J M. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis[J]. Nature, 1999, 397(28): 315–323
[106]Quinn J M W, Fujikawa Y, Mcgee J O’D, Athanasou N A. Rodent osteoblast-like cells support osteoclastic differentiation of human cord blood monocytes in the presence of M-CSF and 1,25 dihydroxyvitamin D3[J]. The International Journal of Biochemistry & Cell Biology, 1997, 29(1):173-179
[107]Okahashi N, Koide M, Jimi E, Suda T, Nishihara T. Caspases (interleukin-1β-converting enzyme family proteases) are involved in the regulation of the survival of osteoclasts[J]. Bone, 1998, 23(1): 33-41
[108]Kim J H, Kim K, Jin H M, Youn B U, Song I, Choi H S, Kim N. Upstream stimulatory factors regulate OSCAR gene expression in RANKL-mediated osteoclast differentiation[J]. Journal of Molecular Biology, 2008, 383(3): 502-511
[109]Battaglino R A, Pham L, Morse L R, Vokes M, Sharma A, Odgren P R, Yang M, Sasaki H, Stashenko P. NHA-oc/NHA2: A mitochondrial cation-proton antiporter selectively expressed in osteoclast[J]. Bone, 2008, 42: 180-192
[110]顾建红,刘俊栋,刘海霞,谢献胜,郑中朝,张力,刘宗平.番鸭破骨细胞的培养及鉴定[J].中国兽医学报, 2008, 28(1): 75-78
[111]高建军,顾淑珠,金慰芳,邓华云,王洪复.高纯度破骨细胞分离培养与功能表达[J].中国骨质疏松杂志, 2001, 7(1): 15-17
[112]Anthony J, Janckila, Ruth M. Alternative immunoassay for tartrate-resistant acid phosphatase isoform 5b using the fluorogenic substrate naphthol ASBI-phosphate and heparin[J]. Clinica Chimica Acta , 347, 2004: 157-167
[113]Theoleyre S, Wittrant Y, Couillaud S, Vusio P, Berreur M, Dunstan C, Blanchard F, Rédini F, Heymann D. Cellular activity and signaling induced by ostoprotegerin in osteoclasts: involvement of receptor activator of nuclear factorκB ligand and MAPK[J]. Biochimica et Biophysica Acta, 2004, 1644(1): 1-7
[114]Chung H, Kang Y S, Hwang C S, Moon I K, Yim C H, Choi K H, Han K O, Jang H C, YoonH K, Han I K. Deflazacort Increases Osteoclast Formation in Mouse Bone Marrow Culture and the Ratio of RANKL/OPG mRNA Expression in Marrow Stromal Cells[J]. Journal of Korean Medical Science, 2001, 16(6): 769-773
[115]Horowitz MC, Xi Y, Wimberly Y, Kacena M A. Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands[J]. Cytokine and Growth Factor Reviews, 2001,12(1): 9-18
[116]Kitazawa R, Kitazawa S. Vitamin D3 Augments Osteoclastogenesis via Vitamin D-Responsive Element of Mouse RANKL Gene Promoter[J]. Biochemical and Biophysical Research Communications, 2002, 290: 650-655
[117]Kong Y Y, William J B, Josef M P. Osteoprotegerin ligand: a regulator of immune responses and bone physiology[J]. Immunology Today, 2000, 21(10): 495-502
[118]Tsurukai T, Udagawa N, Matsuzaki K, Takahashi N, Suda T. Roles of macrophage-colony stimulating factor and osteocalast differentiation factor in osteoclastogenesis[J]. Journal of Bone and Mineral Metabolism, 2000, 18(4): 177-184
[119]钱红波,赵建宁,妖静,曾晓峰,陆维举,胡云峰.小鼠破骨细胞骨髓诱导培养体系的建立[J].医学研究生学报, 2006, 19 (8): 692-695
[120]黄红铭,姜华,张慧,侯健.外周血单个核细胞诱导培养破骨细胞[J].国际病理科学与临床杂志, 2008, 28 (1): 10-13
[121]Sato M, Nakamichi Y, Nakamura M, Sato N, Ninomiya T, Muto A, Nakamura H, Ozawa H, Iwasaki Y, Kobayashi E, Shimizu M, Deluca H F, Takahashi N, Udagawa N. New 19-nor-(20S)-1α,25-dihydroxyvitamin D3 analogs strongly stimulate osteoclast formation both in vivo and in vitro[J]. Bone, 2007, 40: 293-304
[122]Hayashi H, Nakaham K I, Sato T, Tuchiya T, Asakawa Y, Maemura T, Tanaka M, Morita M, Morita I. The role of Mac-1 (CD11b/CD118) in osteoclast differentiation induced by receptor activator of nuclear factor-κB[J]. FEBS Letters, 2008, 582: 3234-3248
[123]Lakkakorpi P T, V??n?nen H K. Kinetics of the osteoclast cytoskeleton during the resorption cycle in vitro[J]. Journal of Bone Mineral Research, 1991, 6: 817–826
[124]Burgess T L, Qian Y X, Kaufman S, Ring B D, Van G, Capparelli C, Kelley M, Hsu H, Boyle W J, Dunstan C R, Hu S, Lacey D L. The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts[J]. Journal of Biological Chemistry, 1999, 145(3): 527-538
[125]Fuller K, Owens J M, Tagger C J, Wilson A, Moss R, Chambers T J. Macrophagecolony-stimulating factor stimulates survival and chemotactic behavior in isolated osteoclasts [J]. The Journal of Experimental Medicine, 1993, 178(5): 1733-1744
[126]Fujikawa Y, Sabokbar A, Neale S D, Itonaga I, Torisu T, Athanasou N A. The effect of macrophage-colony stimulating factor and other humoral factors (interleukin-1, -3, -6, and -11, tumor necrosis factor-alpha, and granulocyte macrophage-colony stimulating factor) on human osteoclast formation from circulating cells[J]. Bone, 2001, 28(3): 261-267
[127]Troen B R. Molecular mechanisms underlying osteoclast formation and activation[J]. Experimental Gerontology, 2003, 38(6): 605-614
[2]陈棣,闫莹,陈默,沈汇,邓红文.骨生物学研究的最新进展.邓红文,刘耀中主编.骨生物学前沿[M].北京:高等教育出版社, 2006. 15, 19-21
[3]徐家科, Phan T C A,郑铭豪.在骨疾病中成骨细胞和破骨细胞之间的通讯.邓红文,刘耀中主编.骨生物学前沿[M].北京:高等教育出版社, 2006. 57-67
[4]邵水金主编.实用躯体解剖学[M].上海:上海科学技术文献出版社, 2006. 1, 4-5
[5]黎小坚,朱绍舜.骨组织解剖生理学.邓红文,刘耀中主编.骨生物学前沿[M].北京:高等教育出版社, 2006. 5-24
[6]赵定麟主编.现代骨病学[M].北京:科学出版社, 2004. 21-23
[7] Marks S C, Odgren P R. Structure and development of the skeleton. In Bilezikian J P, Raisz L G, Rodan G A. (Eds.), Principles of bone biology [M]. San Diego: Academic Press, 2002 (1). 3-15
[8] Mackie E J. Osteoblasts: novel roles in orchestration of skeletal architecture[J]. The International Journal of Biochemistry & Cell Biology, 2003, 35: 1301-1305
[9] Jilka R L, Weinstein R S, Bellido T, Roberson P, Parfitt A M, Manolagas S C. Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone[J]. The Journal of Clinical Investigation, 1999, 104: 439–446
[10]Boyden L M, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick M A, Wu D, Insogna K, Lifton R P. High bone density due to a mutation in LDL-receptor-related protein 5[J]. The New England Journal of Medicine, 2002, 346: 1513–1521
[11]Gong Y, Slee R B, Fukai N, Rawadi G, Roman-Roman S, Reginato A M, Wang H, Cundy T, Glorieux F H, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development[J]. Cell, 2001, 107: 513–523
[12]Kato M, Patel M S, Levasseur R, Lobov I, Chang B H, Glass 2nd D A, Hartmann C, Li L, Hwang T H, Brayton C F, Lang R A, Karsenty G, Chan L. Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in LRP5, a Wnt coreceptor[J]. The Journal of Cell Biology, 2002, 157: 303–314
[13]熊志立,孟繁浩,李遇伯,李发美.成骨细胞的骨形成调控机制[J].生命的化学, 2004, 24 (1): 44-46
[14]Mackie E J, Ramsey S. Modulation of osteoblast behaviour by tenascin[J]. Journal of Cell Science, 1996, 109: 1597–1604
[15]Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesisinhibitory factor and is identical to TRANCE/RANKL[J]. The Proceedings of the National Academy of Sciences of USA, 1998, 95: 3597–3602
[16]Udagawa N, Takahashi N, Jimi E, Matsuzaki K, Tsurukai T, Itoh K, Nakagawa N, Yasuda H, Goto M, Tsuda E, Higashio K, Gillespie M T, Martin T J, Suda T. Osteoblasts/stromal cells stimulate osteoclast activation through expression of osteoclast differentiation factor/RANKL but not macrophage colony-stimulating factor: Receptor activator of NF-kappa B ligand[J]. Bone, 1999, 25: 517–523
[17]Rossouw J E, Anderson G L, Prentice R L, LaCroix A Z, Kooperberg C, Stefanick M L, Jackson R D, Beresford S A, Howard B V, Johnson K C, Kotchen J M, Ockene J. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial[J]. The Journal of the American Medicical Association, 2002, 288: 321–333
[18]Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker K L, Armstrong D, Ducy P, Karsenty G. Leptin regulates bone formation via the sympathetic nervous system[J]. Cell, 2002, 111: 305–317
[19]Tonna E A, Gronkite E P. Naturwissenschaften, 1961, 190: 459
[20]Walker D G. Osteopetrosis cured by temporary parabiosis[J]. Science, 1973, 180: 275
[21]Walker D G. Bone resorption restored in osteopetrotic mice by transplants of normal bone marrow and spleen cells[J]. Science, 1975, 190: 784-785
[22]Matsuzaki K, Udagawa N, Takahashi N, Yamaguchi K, Yasuda H, Shima N, Morinaga T, Toyama Y, Yabe Y, Higashio K, Suda T. Osteoclast differentiation factor (ODF) induces osteoclast-like cell formation in human peripheral blood mononuclear cell cultures[J]. Biochemical & Biophysical Research Communications, 1998, 246: 199-204
[23]冯旭,周虹.破骨细胞生物学.邓红文,刘耀中主编.骨生物学前沿[M].北京:高等教育出版社, 2006. 42-50
[24]Vaananen H K, Laitala-Leinonen T. Osteoclast lineage and function[J]. Archives of Biochemistry and Biophysics, 2008, 473: 132-138
[25]Husheem M, Nyman J K E, V??r?nemi J, Vaananen H K, Hentunen, T A. Characterization of Circulating Human Osteoclast Progenitors: Development of In Vitro Resorption Assay[J]. Calcified Tissue International, 2005, 76: 222-230
[26]Anthony J, Janckila, Ruth M. Alternative immunoassay for tartrate-resistant acid phosphatase isoform 5b using the fluorogenic substrate naphthol ASBI-phosphate and heparin [J]. Clinica Chimica Acta ,347, 2004: 157-167
[27]Lakkakorpi P T, V??n?nen H K. Kinetics of the osteoclast cytoskeleton during the resorption cycle in vitro[J]. Journal of Bone Mineral Research, 1991, 6: 817–826
[28]Bossard M J, Tomaszek T A, Thompson S K, Amegadzie B Y, Hanning C R, Jones C, Kurdyla J T, McNulty D E, Drake F H, Gowen M, Levy M A. Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification[J]. Journal of Biological Chemistry, 1996, 271: 12517-12524
[29]Drake F H, Dodds R A, James I E, Connor J R, Debouck C, Richardson S, Lee-Rykaczewski E, Coleman L, Rieman D, Barthlow R, Hastings G, Gowen M. Cathepsin K, but not Cathepsins B, L, or S, is abundantly expressed in human osteoclasts[J]. Journal of Biological Chemistry, 1996, 271: 12511-12516
[30]Gleb B D, Shi G P, Chapman H A, Desnick R J. Pyenodystosis, a lysosomal disease caused by cathepsin K deficiency[J]. Science, 1996, 273: 1236-1238
[31]Green D M. Stimulus selection in adaptive psychophysical procedures[J]. Journal of the Acoustical Society of America, 1990, 87: 2662-2674
[32]Salo J, Lehenkari P, Mulari M, Metsikk? K, V??n?nen H K. Removal of osteoclast bone resorption products by transcytosis[J]. Science, 1997, 276: 270-273
[33]Jimi E, Nakamura I, Amano H, Taguchi Y, Tsurukai T, Tamura M, Takahashi N, Suda T. Osteoclast function is activated by osteoblastic cells through a mechanism involving cell-to-cell contact[J]. Endocrinology, 1996, 137 (8): 2187–2190
[34]Matsuo K, Irie N. Osteoclast-osteoblast communication[J]. Archives of Biochemistry and Biophysics, 2008, 473: 201-209
[35]Domon T, Suzuki R, Takata K, Yamazaki Y, Takahashi S, Yamamoto T, Wakita M. The natureand function of mononuclear cells on the resorbed surfaces of bone in the reversal phase during remodeling[J]. Annals of Anatomischer Anzeiger. 2001, 183(2): 103–110
[36]Li X, Qin L, Bergenstock M, Bevelock L M, Novack D V, Partridge N C. Parathyroid hormone stimulates osteoblastic expression of MCP-1 to recruit and increase the fusion of pre/osteoclasts[J]. Journal of Biological Chemistry, 2007, 282: 33098–33106
[37]Kim M S, Day C J, Morrison N A. MCP-1 is induced by receptor activator of nuclear factor-{kappa}B ligand, promotes human osteoclast fusion, and rescues granulocyte macrophage colony-stimulating factor suppression of osteoclast formation[J]. Journal of Biological chemistry, 2005, 280 (16): 16163–16169
[38]Yu X, Huang Y, Collin-Osdoby P, Osdoby P. Stromal cell-derived factor-1 (SDF-1) recruits osteoclast precursors by inducing chemotaxis, matrix metalloproteinase-9 (MMP-9) activity, and collagen transmigration[J]. Journal of Bone and Mineral Research, 2003, 18 (8): 1404–1418
[39]Wright L M, Maloney W, Yu X, Kindle L, Collin-Osdoby P, Osdoby P. Stromal cell-derived factor-1 binding to its chemokine receptor CXCR4 on precursor cells promotes the chemotactic recruitment, development and survival of human osteoclasts[J]. Bone, 2005, 36 (5): 840–853
[40]Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, Saiura A, Isobe M, Yokochi T, Inoue J, Wagner E F, Mak T W, Kodama T, Taniguchi T. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts[J]. Developemntal Cell, 2002, 6(3): 889–901
[41]Koga T, Matsui Y, Asagiri M, Kodama T, Crombrugghe B D, Nakashima K, Takayanagi H. NFAT and Osterix cooperatively regulate bone formation[J]. Natural Medicine, 2005, 11: 880–885
[42]Winslow M M, Pan M, Starbuck M, Gallo E M, Deng L, Karsenty G, Crabtree G R. Calcineurin/NFAT signaling in osteoblasts regulates bone mass[J]. Development of Cell, 2006, 10 (6): 771–782
[43]Verborgt O, Gibson G J, Schaffler M B. Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo[J]. Journal of Bone and Mineral Research, 2000, 15(1): 60–67
[44]Hedgecock N L, Hadi T, Chen A A, Curtiss S B, Martin R B, Hazelwood S J. Quantitativeregional associations between remodeling, modeling, and osteocyte apoptosis and density in rabbit tibial midshafts[J]. Bone, 2007, 40(3): 627–637
[45]Simonet W S, Lacey D L, Dunstan C R, Kelley M, Chang M S, Lüthy R, Nguyen H Q, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan H L, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes T M, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Boyle W J. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density[J]. Cell, 1997, 89 (2): 309–319
[46]Koga T, Inui M, Inoue K, Kim S, Suematsu A, Kobayashi E, Iwata T, Ohnishi H, Matozaki T, Kodama T, Taniguchi T, Takayanagi H, Takai T. Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis[J]. Nature, 2004, 428: 758–763
[47]Kim N, Takami M, Rho J, Josien R, Choi Y. A Novel Member of the Leukocyte Receptor Complex Regulates Osteoclast Differentiation[J]. The Journal of Experimental Medicine, 2002, 195(2): 201–209
[48]Takai T. A Novel Recognition System for MHC Class I Molecules Constituted by PIR[J]. Advances in Immunol, 2005, 88: 161–192
[49]Delorme G, Saltel F, Bonnelye E, Jurdic P, Machuca-Gayet I. Expression and function of semaphorin 7A in bone cells[J]. Biology Cell, 2005, 97(7): 589–597
[50]Gomez C, Burt-Pichat B, Mallein-Gerin F, Merle B, Delmas P D, Skerry T M, Vico L, Malaval L, Chenu C. Expression of Semaphorin-3A and its receptors in endochondral ossification: potential role in skeletal development and innervation[J]. Developemental Dynamics, 2005, 234 (2): 393–403
[51]Matsuo K, Galson D L, Zhao C, Peng L, Laplace C, Wang K Z, Bachler M A, Amano H, Aburatani H, Ishikawa H, Wagner E F. Nuclear Factor of Activated T-cells (NFAT) Rescues Osteoclastogenesis in Precursors Lacking c-Fos[J]. Journal of Biological Chemistry, 2004, 279(25): 26475–26480
[52]Karsdal M A, Martin T J, Bollerslev J, Christiansen C, Henriksen K. Are nonresorbing osteoclasts sources of bone anabolic activity?[J]. Journal of Bone and Mineral Research, 2007, 22(4): 487–494
[53]Kornak U, Schulz A, Friedrich W, Uhlhaas S, Kremens B, Voit T, Hasan C, Bode U, Jentsch T J, Kubisch C. Mutations in the a3 subunit of the vacuolar H+-ATPase cause infantile malignant osteopetrosis[J]. Human Molecular Genetics, 2000, 9(13): 2059–2063
[53]Kornak U, Kasper D, Bosl M R, Kaiser E, Schweizer M, Schulz A, Friedrich W, Delling G, Jentsch T J. Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man[J]. Cell, 2001, 104(2): 205–215
[54]Li Y P, Chen W, Liang Y, Li E, Stashenko P. Atp6i-deficient mice exhibit severe osteopetrosis due to loss of osteoclast-mediated extracellular acidification[J]. Nature Genetics, 1999, 23: 447–451
[55]Del Fattore A., B. Peruzzi, N. Rucci, I. Recchia, A. Cappariello, M. Longo, D. Fortunati, P. Ballanti, M. Iacobini, M. Luciani, R. Devito, R. Pinto, M. Caniglia, E. Lanino, C. Messina, S. Cesaro, C. Letizia, G. Bianchini, H. Fryssira, P. Grabowski, N. Shaw, N. Bishop, D. Hughes, R.P. Kapur, H.K. Datta, A. Taranta, R. Fornari, S. Migliaccio, A. Teti, Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment[J]. Journal of Medical Genetics, 2006, 43(4): 315–325
[56]Karsdal M A, Henriksen K, Sorensen M G, Gram J, Schaller S, Dziegiel M H, Heegaard A M, Christophersen P, Martin T J, Christiansen C, Bollerslev J. Acidification of the Osteoclastic Resorption Compartment Provides Insight into the Coupling of Bone Formation to Bone Resorption[J]. The American Journal Pathology, 2005,166(2): 467–476
[57]Hayman A R, Jones S J, Boyde A, Foster D, Colledge W H, Carlton M B, Evans M J, Cox T M. Mice lacking tartrate-resistant acid phosphatase (Acp 5) have disrupted endochondral ossification and mild osteopetrosis[J]. Development, 1996, 122(10): 3151–3162
[58]Roberts H C, Knott L, Avery N C, Cox T M, Evans M J, Hayman A R. Altered Collagen in Tartrate-Resistant Acid Phosphatase (TRAP)-Deficient Mice: A Role for TRAP in Bone Collagen Metabolism[J]. Calcified Tissue International, 2007, 80: 400–410
[59]Angel N Z, Walsh N, Forwood M R, Ostrowski M C, Cassady A I, Hume D A. Transgenic mice overexpressing tartrate-resistant acid phosphatase exhibit an increased rate of bone turnover [J]. Journal of Bone Mineral Research, 2000, 15(1): 103–110
[60]Ryu J, Kim H J, Chang E J, Huang H, Banno Y, Kim H H. Sphingosine 1-phosphate as a regulator of osteoclast differentiation and osteoclast–osteoblast coupling[J]. The EMBO Journal, 2006, 25: 5840–5851
[61]Kubota K, Sakikawa C, Katsumata M, Nakamura T, Wakabayashi K. Platelet-derived growth factor BB secreted from osteoclasts acts as an osteoblastogenesis inhibitory factor[J]. Journal of Bone Mineral Research, 2002, 17(2): 257–265
[62]O’Sullivan S, Naot D, Callon K, Porteous F, Horne A, Wattie D, Watson M, Cornish J, Browett P, Grey A. Imatinib promotes osteoblast differentiation by inhibiting PDGFR signaling and inhibits osteoclastogenesis by both direct and stromal cell-dependent mechanisms[J]. Journal of Bone Mineral Research, 2007, 22(11): 1679–1689
[63]Grano M, Galimi F, Zambonin G, Colucci S, Cottone E, Zallone A Z, Comoglio P M. Hepatocyte growth factor is a coupling factor for osteoclasts and osteoblasts in vitro[J]. Proceeding of the National Academy of Sciences of the United States of America, 1996, 93(15): 7644–7648
[64]Pasquale E B. Eph receptor signalling casts a wide net on cell behaviour[J]. Nature Reviews Molecular Cell Biology, 2005, 6(7): 462–475
[65]Zhao C, Irie N, Takada Y, Shimoda K, Miyamoto T, Nishiwaki T, Suda T, Matsuo K. Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis[J]. Cell Metabolism, 2006, 4 (2): 111–121
[66]Harmey D, Stenbeck G, Nobes C D, Lax A J, Grigoriadis A E. Regulation of osteoblast differentiation by Pasteurella multocida toxin (PMT): A role for Rho GTPase in bone formation[J]. Journal of bone and mineral research, 2004, 19: 661–670
[67]McBeath R, Pirone D M, Nelson C M, Bhadriraju K, Chen C S. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment[J]. Development Cell 2004, 6(4): 483–495
[68]Mundy G R, Elefteriou F. Boning up on ephrin signaling[J]. Cell, 2006, 126(3): 441–443
[69]Van Bezooijen R L, Roelen B A, Visser A, Wee-Pals Van D L, Wilt E D, Karperien M, Hamersma H, Papapoulos S E, Dijke P Ten, L?wik C W G M. J. Sclerostin Is an Osteocyte-expressed Negative Regulator of Bone Formation, But Not a Classical BMP Antagonist[J]. The Journal of Experimental Medicine, 2004, 199(6): 805–814
[70]Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, Lacza C, Wuyts W, Van Den Ende J, Willems P, Paes-Alves A F, Hill S, Bueno M, Ramos F J, Tacconi P, Dikkers F G, Stratakis C, Lindpaintner K, Vickery B, Foernzler D, Hul W V. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST)[J]. Human Molecular Genetics, 2001, 10(5): 537–543
[71]Brunkow M E, Gardner J C, Van Ness J, Paeper B W, Kovacevich B R, Proll S, Skonier J E, Zhao L, Sabo P J, Fu Y, Alisch R S, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H,Beighton P, Mulligan J. Bone Dysplasia Sclerosteosis Results from Loss of the SOST Gene Product, a Novel Cystine Knot–Containing Protein[J]. The American Journal of Human Genetics, 2001, 68(3): 577–589
[72]Glass D A 2nd, Bialek P, Ahn J D, Starbuck M, Patel M S, Clevers H, Taketo M M, Long F, McMahon A P, Lang R A, Karsenty G. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation[J]. Development Cell, 2005, 8(5): 751–764
[73]Kieslinger M, Folberth S, Dobreva G, Dorn T, Croci L, Erben R, Consalez G G, Grosschedl R. EBF2 regulates osteoblast-dependent differentiation of osteoblasts[J]. Development Cell, 2005, 9(6): 757–767
[74]Bai S, Kopan R, Zou W, Hilton M J, Ong C T, Long F, Ross F P, Teitelbaum S L. Notch1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells[J]. Journal of Biological Chemisty, 2008, 283(10): 6509–6518
[76]Seeman E. Bone quality: the material and structural basis of bone strength[J]. Journal of Bone Mineral Metabolism, 2008, 26(1): 1–8
[77]Mashiba T, Turner C H, Hirano T, Forwood M R, Jacob D S, Johnston C C, Burr D B. Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures[J]. Bone, 2001, 29(3): 271–278
[78]朱宪彝主编.代谢性骨病学[J].天津:天津科学技术出版社, 1989: 202-219
[79]付强,刘源.钙、磷与维生素D对动物骨代谢的影响研究进展[J].中国比较医学杂志, 2006, 16 (8): 502-505
[80]唐文山.骨营养不良乳牛血清钙及血清游离羟脯氨酸含量测定[J].中国兽医科技, 2002, 32(11): 26-28
[81]刘宗平,马卓,杨得兵,池斌.双峰驼骨质疏松症的流行特点及其与生物地球化学因子之间的关系[J].应用与环境生物学报, 1997, 3 (4): 345-348
[82]邹纪平,钟琼莎,王耀光.对维生素D和钙的再认识:比较争鸣[J].中国临床康复, 2004, 8 (29): 6478-6479
[83]熊学华,余克强,刘庆思.维生素D与骨质疏松[J]. 2002, 14 (6): 54-55
[84]St-Arnaud R. The direct role of the vitamin D on bone homeostasis[J]. Archives of Biochemistry and Biophysics, 2008, 473(2): 225-230
[85]冯志华,刘观忠,张仪明.维生素D在动物营养中的应用研究[J].中国畜牧兽医, 2004, 31(8): 16-18
[86]Fraser D R. The influence factor of metabolism of vitamin D[J]. Nature, 1970, 228: 764-766
[87]Horward G A, Turner R T, Sherrard D J, Baylink D J. Human bone cells in culture metabolize 25-hydroxyvitamin D3 to 1, 25-dihydroxyvitamin D3 and 24, 25-dihydroxyvitamin D3[J]. The Journal of Biological chemistry, 1981, 256(15): 7738-7740
[88]Atkins G J, Anderson P H, Findlay D M, Welldon K J, Vincent C, Zannettino A C, O’Loughlin P D, Morris H A. Metabolism of vitamin D(3) in human osteoblasts: evidence for autocrine and paracrine activities of 1alpha,25-dihydroxyvitamin D(3)[J]. Bone, 2007, 40(6): 1517–1528
[89]王淑萍,宋新德.维生素D与骨质疏松概述[J].中国骨质疏松杂志, 2000, 6 (1): 10-13
[90]Norman A W , Song X , Zanello L , Bula C, Okamura W H. Rapid and genomic biological responses are mediated by different shapes of the agonist steroid hormone, 1α,25(OH)2vitamin D3 [J]. Steroid, 1999, 64(1-2): 120-128
[91]李丽华,周玉坤,王丽丽.维生素D与骨的生长和矿化[J].国外医学妇幼保健分册, 2004, 15 (5): 257-259
[92]Ames S K, Ellis K J, Gunn S K, Copeland K C, Abrams S A. Vitamin D receptor gene Fok1 polymorphism Predicts Calcium aborption and bone mineral Density in children[J]. Journal of Bone and Mineral Research,1999, 14: 740-746
[93]Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K, Tonai T, Nishisho T, Mori S, Takeda E. A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women[J]. Journal of Bone Mineral Research, 1997, 12 (6): 915-921
[94]郗永义,郑秀芬,叶健,霍赛虎,张健,陈帅锋.维生素D受体研究进展[J].大连医科大学学报, 2004, 26(3): 227-230
[95]Nemere I, Mcmanus W, Ray R. Immunochemical studies on the putative plasmalemmal receptor for 1,25(OH)2D3.Ⅰ. Chick intestine [J]. American Journal of Physiology Endocrinology and Metabolism, 2000, 278: E1104-E1114
[96]Boyan B D, Sylvia V L, Dean D D, Pedrozo H, Del T F, Nemere I, Posner G H, Schwartz Z. 1,25(OH)2D3 modulates growth plate chondrocytes via membrane receptor-mediated protein kinase C by a mechanism the action of arachidonic acid and PGE2[J]. Steroids,1999, 64: 129-165
[97]Kveiborg M, Rattan S, Clark B F , Eriksen E F, Kassem M. Treatment with 1, 25-dihydroxyvitamin D3 reduces impairment of human osteoblast functions during cellular aging in culture[J]. Journal of Cellular Physiology, 2001, 186(2): 298–306
[98]Lee D B N, Walling M W, Brautbar N. Intestinal phosphate absorption: Influence of vitamin D and non-vitamin D factors[J] . American Journal of Physiology, 1986, 250: G369-373
[99]Owen T A, Aronow M S, Barone L M, Bettencourt B, Stein G S, Lian J B. Pleiotropic effects of vitamin D on osteoblast gene expression are related to the proliferative and differentiated state of the bone cell phenotype: dependency upon basal levels of gene expression, duration of exposure, and bone matrix competency in normal rat osteoblast cultures[J]. Endocrinology, 1991, 128: 1496–1504
[100]Sooy K, Sabbagh Y, Demay M B. Osteoblasts lacking the vitamin D receptor display enhanced osteogenic potential in vitro[J]. Journal of Cell Biochemistry, 2005, 94(1): 81–87
[101]Yamamoto Y, Yoshizawa T, Fukuda T, Kawano H, Nakamura T, Yamada T, Karsenty G, Kato S. A genetic evidence of direct VDR function in osteoblasts-generation and analysis of osteoblast-specific VDRKO[J]. Jounal of Bone and Mineral Research, 2004, 19 (Suppl.1): S26
[102]Baldock P A, Thomas G P, Hodge J M, Baker S U, Dressel U, O’Loughlin P D, Nicholson G C, Briffa K H, Eisman J A, Gardiner E M. Vitamin D action and regulation of bone remodeling: Suppression of osteoclastogenesis by the mature osteoblast[J]. Jounal of Bone and Mineral Research, 2006, 21 (10): 1618–1626
[103]Gardiner E M, Baldock P A, Thomas G P, Sims N A, Henderson N K, Hollis B, White C P, Sunn K L, Morrison N A, Walsh W R, Eisman J A. Increased formation and decreased resorption of bone in mice with elevated vitamin D receptor in mature cells of the osteoblastic lineage[J]. The FASEB Journal, 14 2000, 14: 1908–1916
[104] Misof B M, Roschger P, Tesch W, Baldock P A, Valenta A, Messmer P, Eisman J A, Boskey A L, Gardiner E M, Fratzl P, Klaushofer K. Targeted Overexpression of Vitamin D Receptor in Osteoblasts Increases Calcium Concentration Without Affecting Structural Properties of Bone Mineral Crystals[J]. Calcified Tissue International, 2003, 73: 251–257
[105]Schwartz Z, Dean D, Walton J, Brooks B, Boyan B. Treatment of resting zone chondrocytes with 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3) induces differentiation into a 1,25-(OH)2D3-responsive phenotype characteristic of growth zone chondrocytes[J]. Endocrinology,1995, 136(2): 402–411
[106]Swain L D, Schwartz Z, Caulfield K, Brooks B P, Boyan B D. Nongenomic regulation of chondrocyte membrane fluidity by 1,25-(OH)2D3 and 24,25-(OH)2D3 is dependent on cell maturation[J]. Bone, 1993, 14(4): 609–617
[107]Schwartz Z, Boyan B. The effects of vitamin D metabolites on phospholipase A2 activity of growth zone and resting zone cartilage cells in vitro[J]. Endocrinology, 1988, 122(5): 2191–2198
[108]Schwartz Z, Swain L D, Ramirez V, Boyan B D. Regulation of arachidonic acid turnover by 1,25-(OH)2D3 and 24,25-(OH)2D3 in growth zone and resting zone chondrocyte cultures[J]. Biochimica et Biophysica Acta, 1990, 1027(3): 278–286
[109]Sylvia V L, Schwartz Z, Schuman L, Morgan R T, Mackey S, Gomez R, Boyan B D. Maturation-dependent regulation of protein kinase C activity by vitamin D3 metabolites in chondrocyte cultures[J]. Journal of Cellular Physiology, 1993, 157(2): 271–278
[110]Nemere I, Farach-Carson M C, Rohe B, Sterling T M, Norman A W, Boyan B D, Safford S E. Ribozyme knockdown functionally links a 1,25(OH)2D3 membrane binding protein (1,25D3-MARRS) and phosphate uptake in intestinal cells[J]. Proceedings of National Academy of Sciences of the United States of America,2004, 101(19): 7392–7397
[111]Schwartz Z, Graham E J, Wang L, Lossdorfer S, Gay I, Johnson-Pais T L, Carnes D L, Sylvia V L, Boyan B D. Phospholipase A2 activating protein (PLAA) is required for 1alpha,25(OH)2D3 signaling in growth plate chondrocytes[J]. Journal of Cell Physiology, 2005, 203(1): 54–70
[112]Schwartz Z, Shaked D, Hardin R R, Gruwell S, Dean D D, Sylvia V L, Boyan B D. 1α, 25(OH)2D3 causes a rapid increase in phosphatidylinositol-specific PLC-βactivity via phospholipase A2-dependent production of lysophospholipid[J]. Steroids 2003, 68: 423–437
[113]Deurs B V, Roepstorff K, Hommelgaard A M, Sandvig K. Caveolae: anchored, multifunctional platforms in the lipid ocean[J]. Trends Cell Biology, 2003, 13(2): 92–100
[114]Boyan B D, Wong K L, Wang L, Yao H, Guldberg R E, Drab M, Jo H, Schwartz Z. Regulation of growth plate chondrocytes by 1,25-dihydroxyvitamin D3 requires[J]. Journal of Bone and Mineral Research, 2006, 21(10): 1637–1647
[115]Boyan B D, Sylvia V L, McKinney N, Schwartz Z. Membrane actions of vitamin D metabolites 1alpha,25(OH)2D3 and 24R,25(OH)2D3 are retained in growth plate cartilage cells from vitamin D receptor knockout mice[J]. Journal of Cellular Biochemistry, 2003, 90(6): 1207–1223
[116]Masuyama R, Stockmans I, Torrekens S, Van Looveren R, Maes C, Carmeliet P, Bouillon R, Carmeliet G. Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulatesFGF23 production in osteoblasts[J]. The Journal of Clinical Investigation, 2006, 116(12): 3150–3159
[117]Lin R, Amizuka N, Sasaki T, Aarts M M, Ozawa H, Goltzman D, Henderson J E, White J H. 1Alpha,25-dihydroxyvitamin D3 promotes vascularization of the chondro-osseous junction by stimulating expression of vascular endothelial growth factor and matrix metalloproteinase 9[J]. Journal of Bone and Mineral Research, 2002, 17(9): 1604–1612
[118]Liu S, Gupta A, Quarles L D. Emerging role of fibroblast growth factor 23 in a bone-kidney axis regulating systemic phosphate homeostasis and extracellular matrix mineralization[J]. Current Opinion in Nephrology and Hypertension, 2007, 16(4): 329–335
[119]Saito H, Kusano K, Kinosaki M, Ito H, Hirata M, Segawa H, Miyamoto K, Fukushima N. Human Fibroblast Growth Factor-23 Mutants Suppress Na+-dependent Phosphate Co-transport Activity and 1α,25-Dihydroxyvitamin D3 Production [J]. The Journal of Biological Chemistry, 2003, 278(4): 2206–2211
[120]Takeda S, Yoshizawa T, Nagai Y, Yamato H, Fukumoto S, Sekine K, Kato S, Matsumoto T, Fujita T. Stimulation of osteoclast formation by 1,25-dihydroxyvitamin D requires its binding to vitamin D receptor (VDR) in osteoblastic cells: studies using VDR knockout mice[J]. Endocrinology, 1999, 140(2): 1005–1008
[121]Mimura H, Cao X, Ross F P, Chiba M, Teitelbaum S L. 1,25-Dihydroxyvitamin D3 transcriptionally activates the beta 3-integrin subunit gene in avian osteoclast precursors[J]. Endocrinology, 1994, 134(3): 1061–1066
[122]Medhora M M, Teitelbaum S, Chappel J, Alvarez J, Mimura H, Ross F P, Hruska K. 1alpha,25-Dihydroxyvitamin D3 up-regulates expression of the osteoclast integrin alpha v beta 3[J]. Journal of Biological Chemistry, 1993, 268(2): 1456–1461
[123]Andersson G, Johansson E K. Adhesion of human myelomonocytic (HL-60) cells induced by 1,25-dihydroxyvitamin D3 and phorbol myristate acetate is dependent on osteopontin synthesis and the alpha v beta 3 integrin[J]. Connective Tissue Research, 1996, 35(1–4): 163–171
[124]Kido S, Inoue D, Hiura K, Javier W, Ito Y, Matsumoto T. Expression of RANK is dependent upon differentiation into the macrophage/osteoclast lineage: induction by 1alpha,25-dihydroxyvitamin D3 and TPA in a human myelomonocytic cell line, HL60[J]. Bone,2003, 32(6): 621–629
[125]Vincent C, Kogawa M., Findlay D M, Atkins G J. The generation of osteoclasts from RAW264.7 precursors in defined, serum free conditions[J]. Journal of Bone Mineral Metablism, 2009, 27(1):114-119
[126]Kveiborg M, Rattan S I, Clark B F, Eriksen E F, Kassem M. Treatment with 1,25-dihydroxyvitamin D3 reduces impairment of human osteoblast functions during cellular aging in culture[J]. Journal of Cellular Physiology, 2001, 186(2): 298 - 306
[127]Gardiner E M, Baldock P A, Thomas G P, Sims N A, Henderson N K, Hollis B, White C P, Sunn K L, Morrison N A, Walsh W R, Eisman J A. Increased formation and decreased resorption of bone in mice with elevated vitamin D receptor in mature cells of the osteoblastic lineage[J]. The FASEB Journal, 2000, 14(13): 1908-1916
[128]Adams J S, Chen H, Chun R, Gacad M A, Encinas C, Ren S, Nguyen L, Wu S, Hewison M, Barsony J. Response element binding proteins and intracellular vitamin D binding proteins: novel regulators of vitamin D trafficking, action and metabolism[J]. Journal of Steroid Biochemistry and molecular biology, 2004, 89–90: 461–465
[129]Theoleyre S, Wittrant Y, Tat S K, Fortun Y, Redini F, Heymann D. The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling [J]. Cytokine & Growth Factor Review, 2004, 15(6): 457-475
[130]刘继中,纪宗玲,陈苏民. OPG/RANKL/RANK系统与骨破坏性疾病[J].生物工程学报, 2003, 19(6): 655-660
[131]田庆显,黄公怡. OPG/RANK/RANKL系统和骨质疏松[J].中华骨科杂志, 2004, 24(11): 683-686
[132]于丽云. RANKL和破骨细胞[J].国外医学内分泌学分册, 2003, 23(2): 123-126
[133]Suda T, Tadahashi N, Martin T. Modulation of osteoclast differentiation[J]. Endocrine Reviews, 1992, 13: 66-80
[134]Lacey D, Timms E, Tan H L, Kelley M J, Dunstan C R, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian Y X, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle W J. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation[J]. Cell, 1998, 93: 165-176
[135]Wong B, Rho J J, Arronet J, Robinson E, Orlinick J, Chao M, Kalachikov S, Cayani E, Bartlett F S 3rd, Frankle W N, Lee S Y, Choi Y. TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates C-Jun N-termind kinase in T cell[J]. Journal ofBiological and Chemical, 1997, 272: 25190-25194
[136]王晋东. RANKL与骨免疫学[J].国际免疫学杂志, 2006, 29(3): 165-167
[137]Yasuda H , Shima N , Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S I, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCEP/RANKL[J]. Proceedings of the National Academy of Sciences of United States of America, 1998, 95: 3597-3602
[138]Kearns A E, Khosla S, Kostenuik P. RANKL and OPG Regulation of Bone Remodeling in Health and Disease[J]. Endocrine Reviews, 2008, 29: 155-192
[139]Lum L, Wong B R, Josien R, Becherer J D, Erdjument-Bromage H, Schl?ndorff J, Tempst P, Choi Y, Blobel C P. Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival[J]. The Journal of Biological Chemistry, 1999, 274: 13613-13618
[140]Suzuki J, Ikeda T, Kuroyama H, Sesai M, Utsuyama M, Tatsumi M, Uematsu H, Hirokawa K. Regulation of osteoclastogenesis by three human RANKL isoforms expressed in NIH3T3 cells[J]. Biochemical and Biophysical Research Communications, 2004, 314(4): 1021-1027
[141]Ikeda T, Kasai M, Suzuki J, Kuroyama H, Seki S, Utsuyama M, Hirokawa K. Multimerization of the receptor activator of nuclear factor-kappa B ligand (RANKL) isoforms and regulation of osteoclastogenesis[J]. Journal of Biological Chemistry, 2003, 278(47): 47217-47222
[142]Ikeda T, Kasai M, Utsuyama M, Hirokawa K. Determination of three isoforms of the receptor activator of nuclear factor-kappa B ligand and their differential expression in bone and thymus[J]. Endocrinology, 2001, 142(4): 1419-1426
[143]Tat S W, Pelletier J-P, Lajeunesse D, Fahmi H, Duval N, Pelletier J M. Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: Influence of osteotropic factor[J]. Bone, 2008, 43(2): 284-291
[144]Kong Y Y, Yoshida H, Sarosi I. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis [J]. Nature, 1999, 397 (6717): 315-323
[145]Tsurukai T, Udagawa N, Matsuzaki K, Takahashi N, Suda T. Roles of macrophage-colony stimulating factor and osteocalast differentiation factor in osteoclastogenesis[J]. Journal ofBone and Mineral Metabolism, 2000, 18(4): 177-184
[146]Burgess T L, Qian Y X , Kaufman S, Ring B D, Van G, Capparelli C, Kelley M, Hsu H, Boyle W J, Dunstan C R, Hu S, Lacey D L. The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts[J]. Journal of Biological Chemistry,1999, 145(3): 527-538
[147]Wittrant Y, Theoleyre S, Couillaud S, Dunstan C, Heymann D, Rédini F. Relevance of an in vitro osteoclastogenesis system to study receptor activator of NF-κB ligand and osteoprotegerin biological activities[J]. Experimental Cell Research, 2004, 293(2): 292-301
[148]Allison P A, Tometsk M E, Glaccum M, Cosman D, Dougall W C. A RANK/TRAF6-dependent signal transduction pathway is essential for osteoclast cytoskeletal organization and resorptive function[J]. Journal of Biological Chemistry, 2002, 277(46): 44347-44356
[149]Xing L, Venegas A M, Chen A, Garrett-Beal L, Boyce B F, Schwartzberg P L. Genetic evidence for a role for Src family in TNF family receptor signaling and cell survival[J]. Genes and Development, 2001, 15(2): 241-253
[150]Srivastava S, Yorablo G, Weitzman M N, Cenci S, Ross F P, Pacifici R. Estrogen decrease osteoclast formation by down-reglation receptor of NF-κB ligand (RANKL)-induced JNK activation[J]. Journal of Biological Chemistry, 2001, 276(12): 8836-8840
[151]Mizukami J, Takaesu G, Akatsuka H, Sakurai H, Ninomiya-Tsuji J, Matsumoto K, Sakurai N. Receptor activator of NF-κB ligand (RANKL) activates TAK1 mitogen-activated protein kinase kinase kinase through a signaling complex containg RANK, TAB2, and TRAF6[J]. Molecular and Cellular Biology, 2002, 22(4): 992-1000
[152]Matsuo K, Galson D L, Zhao C, Peng L, Laplace C, Wang K Z, Bachler M A, Amano H, Aburatani H, Ishikawa H, Wanger E F. Nuclear factor of activated T-cells (NFAT) rescues osteoclastogenesis in precursors lacking c-Fos[J]. Journal of Biological Chemistry, 2004, 279(25): 26475–26480
[153]Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, Saiura A, Isobe M, Yokochi T, Inoue J, Wagner E F, Mak T W, Kodama T Taniquchi T. Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts[J]. Developmental Cell, 2002, 3(6): 889–901
[154]Yamashita T, Yao Z, Li F, Zhang Q, Badell I R, Schwarz E M, Takeshita S, Wagner E F, Noda M, Matsuo K, Xing L, Boyce B E. NF-kappaB p50 and p52 regulate receptor activator ofNF-kappaB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1[J]. Journal of Biological Chemistry, 2007, 282(25): 18245–18253
[155]Boyce B F, Xing L P. Functions of RANKL/RANK/OPG in bone modeling and remodeling[J]. Archives of Biochemistry and Biophysics, 2008, 473: 139-146
[156]Wei S, Teitelbaum S L, Wang M W H, Ross F P. Receptor activator of nuclear factor-kappa b ligand activates nuclear factor-kappa b in osteoclast precursor[J]. Endocrinology, 2001, 142(3): 1290-1295
[157]姚静,侯加法. OPG/RANKL/RANK系统的研究进展[J].动物医学进展, 2006, 27(2): 5-9
[158]Hsu H, Lacey D L, Dunstan C R, Solovyev I, Colombero A, Timms E, Tan H L, Elliott G, Kelley M J, Sarosi I, Wang L, Xia X Z, Elliott R, Chiu L, Black T, Scully S, Capparelli C, Morony S, Shimamoto G, Bass M B, Boyle W J. Tumor necrosis factor receptor family member RANK mediated osteoclast differentiation and activation induced by osteoprotegerin ligand[J]. Proceedings of National Academy Sciences of the United States of America, 1999, 96(7): 3540-3545
[159]Fata J E, Kong Y Y, Li J, Sasaki T, Irie-Sasaki J, Moorehead R A, Elliott R, Scully S, Voura E B, Lacey D L, Boyle W J, Khokha R, Penninger J M. The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development[J]. Cell 2000, 103(1): 41–50
[160]Kim N S, Kim H J, Koo B K, Kwon M C, Kim Y W, Cho Y, Yokota Y, Penninger J M, Kong Y Y. Receptor activator of NF-kappaB ligand regulates the proliferation of mammary epithelial cells via Id2[J]. Molecular and Cellular Biology, 2006, 26(3): 1002–1013
[161]Chen G, Sircar K, Aprikian A, Potti A, Goltzman D, Rabbani S A. Expression of RANKL/RANK/OPG in primary and metastatic human prostate cancer as markers of disease stage and functional regulation[J]. Cancer 2006, 107(2): 289–298
[162]Li J, Sarisu I, McCabe S M, Tan H L, Capparelli C, Morony S, Elliot R, Van G, Kaufman S. Absolute requirement for the TNFR-related protein RANK during osteoclastogenesis and in regulation of bone mass and calcium metabolism[J]. Journal of Bone Mineral Research, 1999, 14 (suppl.1): S149
[163]Hughes A E, Ralston S H, Marken J, Bell C, MacPherson H, Wallace R G, Hul W V, Whyte M P, Nakatsuka K, Hovy L, Anderson D M. Mutations in TNFRSF11A, affecting the signalpeptide of RANK, cause familial expansile osteolysis[J]. Nature Genetics, 2000, 24(1): 45–48
[164]Tsuda E, Goto M, Monochizuki S I, Yano K, Kobayashi F, Morinaga T, Higashio K. Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis[J]. Biochemical and Biophysical Research Communication, 1997, 234(1): 137-142
[165]Suda T, Takahashi N , Udagawa N, Jimi E, Gillespie M T, Martin T J. Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families[J]. Endocrine Reviews, 1999, 20(3): 345-357
[166]Hofbauer L C, Khosla S, Dunstan C R, Lacey D L, Boyle W J, Riggs B L. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption[J]. Journal of Bone and Mineral Research, 2000, 15(1): 2–12
[167]Blair J M, Zheng Y, Dunstan C R. RANK Ligand[J]. The International Journal of Biochemistry & Cell Biology, 2007, 39(6): 1077–81
[168]Yasuda H, Shima N, Nakagawa N, Mochizuki S I, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T, Murakami A, Tsuda E, Morinaga T, Higashio K. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG inhibits osteoclastogenesis in vitro[J]. Endocrinology, 1998, 139(3): 1329–37
[169]Mizuno A, Amizuka N, Irie K, Murakami A, Fujise N, Kanno T, Sato Y, Nakagawa N, Yasuda H, Mochizuki S, Gomibuchi T, Yano K, Shima N, Washida N, Tsuda E, Morinaga T, Higashio K, Ozawa H. Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin[J]. Biochemical and Biophysical Research Communication, 1998, 247: 610-615.
[170]Kong Y Y, Feige U, Sabino I, Bolon B, Tafuri A, Morony S, Capparelli C, Li J, Elliott R, McCabe S, Wong T, Campagnuolo G, Moran E, Bogoch E R, Van G, Nquyen L T, Ohashi P S, Lacey D L, Fish E, Boyle W J, Penninger J M. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand [J]. Nature, 1999a, 402 (6759): 304-309
[171]Hofbauer L C. Osteoprotegerin ligand and osteoprotegerin: novel implication for osteoclast biology and bone metabolism[J]. European Journal of Endocrinol, 1999, 141: 195-210
[172]Kostenuik P J. Osteoprotegerin and RANKL regulate bone resorption, density, geometry and strength[J]. Current Opinion in Pharmacology, 2005, 5(6): 618–25
[173]Hakeda Y, Kobayashi Y, Yamaguchi K, Yasuda H, Tsuda E, Higashio K, Miyata T, Kumegawa M. Osteoclastogenesis inhibitory factor (OCIF) directly inhibits bone-resorbing activity of isolated mature osteoclasts[J]. Biochemical and Biophysical Research Communications, 1998, 251: 796-801
[174]杨旭,杨庆铭,邓廉夫.重组人骨保护素对体外培养兔破骨细胞的影响[J].中华骨科杂志, 2003, 23 (6): 365-368
[175]Tsukii K, Shima N, Mochizuld S, Yamaguchi K, Kinosaki M, Yano K, Shibata O, Udagawa N, Yasuda H, Suda T, Higashio K. Osteoclast differentiation factor mediates an essential signal for bone resorption induced by 1α, 25-dihydroxyvitamin D3, prostaglandin E2, or parathyroid hormone in the microenvironment of bone[J]. Biochemical and Biophysical Research Communication, 1998, 246 (2): 337-41
[176]Takai H, Kanematsu M,Yano K, Tsuda E, Higashio K, Ikeda K, Watanabe K, Yamada Y. Transforming growth factor-βstimulates the production of osteoprotegerin/osteoclastogenesis inhibitory factor by bone marrow stromal cells[J]. Journal of Biological Chemistry, 1998, 273(42): 27091-27096
[177]Hofbauer L C, Khosla S, Dunstan C R, Lacey D L, Spelsberg T C, Riggs B L. Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells[J]. Endocrinology, 1999a, 140(9): 4367- 4370
[178]Hofbauer L C, Gori F, Riggs B L, Lacey D L, Dunstan C R, Spelsberg T C, Khosla S. Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoidinduced osteoporosis[J]. Endocrinology, 1999b, 140: 4382-4389
[179]Lee S K, Lorenzo J A. Parathyroid hormone stimulates TRANCE and inhibits osteoprotegerin messenger ribonucleic acid expression in murine bone marrow cultures:correlation with osteoclast-like cell formation[J]. Endocrinology, 1999, 140: 3552-3561
[180]Giner M, Rios M J, Montoya M J, Vázquez M A, Naji L, Pérez-Cano. RANKL/OPG in primary cultures of osteoblasts from post-menopausal women. Differences between osteoporotic hip fractures and osteoarthritis[J]. Journal of Steroid Biochemistry & Molecular Biology, 2009, 113(1-2): 46-51
[181]吴小涛,王海军,宋萍. 1,25(OH)2D3对体外培养大鼠成骨细胞RANKL/OPG mRNA表达的影响[J].东南大学学报(医学版), 2007, 26(1): 32-35
[182]Manolagas S C. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis[J]. Endocrine Reviews, 2000, 21(2): 115–37
[183]Zhang Y H, Heulsmann A, Tondravi M M, Mukherjee A, Abu-Amer Y. Tumor necrosis factor-alpha (TNF) stimulates RANKL-induced osteoclastogenesis via coupling of TNF type 1 receptor and RANK signaling pathways[J]. Journal of Biological Chemistry, 2001, 276(1): 563–8
[184]Azuma Y, Kaji K, Katogi R, Takeshita S, Kudo A. Tumor necrosis factor-alpha induces differentiation of and bone resorption by osteoclasts[J]. Journal of Biological Chemistry, 2000, 275(7): 4858–64.
[185]Gori F, Hofbauer L C, Dunstan C R, Spelsberg T C, Khosla S, Riggs B L. The expression of osteoprotegerin and RANK ligand and the support of osteoclast formation by stromalosteoblastlineage cells is developmentally regulated[J]. Endocrinology 2000, 141(12):4768–76
[186]Schett G, Hayer S, Zwerina J, Redlich K, Smolen J S. Mechanisms of Disease: the link between RANKL and arthritic bone disease[J]. Nature Clinical Practice Rheumatology, 2005, 1: 47–54
[187]Humphrey E L, Williams J H, Davie M W, Marshall M J. Effects of dissociated glucocorticoids on OPG and RANKL in osteoblastic cells[J]. Bone, 2006, 38: 652–661 188]Blair J M, Zhou H, Seibel M J, Dunstan C R. Mechanisms of disease: roles of OPG, RANKL and RANK in the pathophysiology of skeletal metastasis[J]. Nature Clinical Practice Oncology, 2006, 3: 41–49
[189]Dougall W C, Chaisson M. The RANK/RANKL/OPG triad in cancer-induced bone diseases[J]. Cancer Metastasis Reviews, 2006, 25(4): 541–549
[190]Bekker P J, Holloway D, Nakanishi A, Arrighi M, Leese P T, Dunstan C R. The effect of a single dose of osteoprotegerin in postmenopausal women[J]. Journal of Bone and Mineral Research, 2001, 16(2): 348–360
[191]Body J J, Greipp P, Coleman R E, Facon T, Geurs F, Fermand J P, Harousseau J L, Lipton A, Mariette X, Williams C D, Nakanishi A, Holloway D, Martin S W, Dunstan C R, Bekker P J. A phase I study of AMGN-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases[J]. Cancer, 2003, 97: 887–892
[192]Bekker P J, Holloway D L, Rasmussen A S, Murphy R, Martin S W, Leese P T, Holmes G B,Dunstan C R, DePaoli A M. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women[J]. Journal of Bone and Mineral Research, 2004, 19(7): 1059–1066
[1]刘宗平.现代动物营养代谢病学[M].北京:化学工业出版社, 2003. 83
[2] Sutton A L M, Zhang X X, Ellison T I, Macdonald P N. The 1,25 (OH)2 D3-regulated transcription factor MN1 stimulates Vitamin D receptor-mediated transcription and inhibits osteoblastic cell proliferation[J]. Molecular Endocrinology, 2005, 19(9): 2234-2244
[3] Atkins G J, Anderson P H, Findlay D M, Welldon K J, Vincent C, Zannettino A C, O’Loughlin P D, Morris H A. Metabolism of vitamin D3 in human osteoblasts: Evidence for autocrine and paracrine activities of 1α,25-dihydroxyvitamin D3[J]. Bone, 2007, 40(6): 1517-1528
[4]魏义勇,石印玉.维生素D调控成骨细胞的作用机制[J].国外医学·骨科学分册, 2003, 24 (3): 165-167
[5] Langub M C, Reinhardt T A, Horst R L, Malluche H H, Koszewski N J. Characterization of vitamin D receptor immunoreactivity in human bone cells[J]. Bone, 2000, 27(3): 383-387
[6]吴培福,韩博,黄有德.氟对动物成骨细胞的影响[J].中国兽医杂志, 2005, 41(10): 40-42
[7] Martin T J, Udagawa N. Hormal regulation of osteoclast function[J]. Trends Endocrinol Metab, 1998, 9(1): 6-12
[8]傅德皓,杨述华,马德彰,李鲲,郜勇.鼠胚成骨细胞的原代培养与鉴定[J].创伤外科杂志, 2006, 8 (12): 157-160
[9]王洪复主编.骨细胞图谱与骨细胞体外培养技术[M].上海:上海科学技术出版社, 2001. 55-69
[10]胡静,郑洪新.改良成骨细胞体外培养和鉴定方法[J].中国老年学杂志, 2006, 1(26): 76-78
[11]Sammons R, Marquis P. Application of the low vacuum scanning electron microscope to the study of biomaterials and mammalian cells[J]. Biomaterials, 1997, 18(1): 81-86
[12]钟代彬,吴培福,曲伟杰,王梅,苏敬良,金久善,韩博.山羊成骨细胞的体外培养和鉴定[J].中国兽医科技, 2005, 35(5): 399-403
[13]余克强.补肾中药血清对体外培养成骨细胞合成碱性磷酸酶及骨钙素的调控[J].中国临床康复, 2005, 9(34): 124-126
[14]裴育,周学瀛,孟迅吾,夏维波,刑小平,刘怀成,胡莹莹. 1,25双羟维生素D3及转化生长因子β1对人胚成骨细胞增殖和分化的影响[J].中华医学杂志, 2003, 83(12): 1084-1088
[15]Maehata Y, Takamizawa S, Ozawa S, Kato Y, Sato S, Kubota E, Hata R. Both direct and collagen-mediated signals are required for active vitamin D3-elicited differentiation of humanosteoblastic cells: Role of osterix, an osteoblast-related transcription factor[J]. Matrix Biology, 2006, 25: 47-58
[16]Verlinden L, Eelen G, Van H R, Engelen K, Beullens I, Van C M, Marchal K, Mathieu C, Bouillon R, Verstuyf A. 1α, 25-dihydroxybitamin D3-induced down-regulation of the checkpoint proteins, Chk1 and Claspin, is mediated by the pocket proteins p107 and p130[J]. Journal of Steroid Biochemistry & Molecular Biology, 2007, 103: 411-415
[17]Shiels M J, Mastro A M, Gay C V. The effect of donor age on the sensitivity of osteoblasts to the proliferative effects of TGFβand 1,25(OH)2 vitamin D3[J]. Life Sciences, 2002, 70: 2967-2975
[18]Chatterjee M. Vitamin D and genomic stability[J]. Mutation Research, 2001, 475: 69-88
[19]孙兰,胡静,郑虎,刘景生.在人的类成骨细胞TE85中雌激素对活性维生素D作用的影响[J].药学学报, 2000, 35(6): 413-416
[20]唐林,林珠,李永明,王华.不同大小机械牵张力对成骨细胞增殖及碱性磷酸酶的影响[J].解放军医学杂志, 2006, 31(6): 580-581
[21]Wang L P, Zhao G, Olivares-Navarrete R, Bell B F, Wieland M, Cochran D L, Schwartz Z, Boyan B D. Integrinβ1 silencing in osteoblasts alters substrate-dependent responses to 1,25-dihydroxy vitamin D3[J]. Biomaterials, 2006, 27(20): 3716-3725
[22]Rapuri P, Gallagher J C, Nawaz Z. Caffeine decrease vitamin D receptor protein expression and 1,25(OH)2D3 stimulated alkaline phosphatase activity in human osteoblast cells[J]. Journal of Steroid Biochemistry & Molecular Biology, 2007, 103 (3-5): 368-371
[23]Kong Y Y, Penninger J M. Molecular control of bone remodeling and osteoporosis[J]. Experimental Gerontology, 2000, 35(8): 947-956
[24]Majeska R J, Rodan? G A. The effect of 1,25(OH)2D3 on Alkaline Phosphatase in osteoblastic osteosarcoma cells[J]. The Journal of Biological Chemistry, 1982, 257(7): 3362-3365
[25]Shi Y C, Worton L, Esteban L, Baldock P, Fonq C, Eisman J A, Gardiner E M. Effects of continuous activation of vitamin D and Wnt response pathways on osteblastic proliferation and differentiation[J]. Bone, 2007, 41(1): 87-96
[26]国家自然科学基金委员会主编.细胞生物学[M].北京:科学出版社, 1997. 97
[27]陈旭,杨志明,解慧琪,李胜富. WO-1对成骨细胞的生物学效应研究[J].中国修复重建外科杂志, 2005, 19(10): 822-825
[28]王凌,王玉东,李大金,王文君,朱影.补肾宁心方药物血清对鼠成骨细胞的增殖与凋亡的影响[J].中华中医药杂志, 2006, 21(1): 30-34
[29]田庆显,黄公怡. 1,25-二羟基维生素D3对小鼠成骨细胞增殖的影响[J].中华老年医学杂志, 2006, 25(12): 922-924
[30]Jiang F, Li P F, Fornace Jr A J, Nicosia S V, Bai W L. G2/M Arrest by 1,25-dihydroxyvitamin D3 in ovarian cancer cells mediated through the induction of GADD45 via an exonic enhancer[J]. The Journal of Biological Chemistry, 2003, 278 (48): 48030-48040
[31]刘景生主编.细胞信息与调控[M].第二版.北京:中国协和医科大学出版社, 2004. 315-316, 586
[32]孙大业,郭艳林,马力耕,崔素娟主编.细胞信号转导[M].第三版.北京:科学出版社, 2001. 93
[33]王金发主编.细胞生物学[M].北京:科学出版社, 2003. 163-165
[34]吕海宏,李茂欣.连接蛋白43与骨质疏松[J].中国康复理论与实践, 2005, 11(4): 265-266
[35]Lips P. Vitamin D physiology[J]. Progress in Biophysics and Molecular Biology, 2006, 92(1): 4-8
[36]St-Arnaud R. The direct role of vitamin D on bone homeostasis[J]. Archives of Biochemistry and Biophysics. 2008, 473(2): 225-230
[37]付强,刘源.钙、磷与维生素D对动物骨代谢的影响研究进展[J].中国比较医学杂志, 2006, 16(8): 502-505
[38]Zhang X Y, Payal B, Melissa O, Zanello L P. 1α,25 (OH)2-vitamin D3 membrane-initiated calcium signaling modulates exocytosis and cell survival[J]. Journal of Sterold Biochemistry & Molecular Biology, 2007, 103(3-5): 457-461
[39]Zanello L P, Norman A W. Electrical responses to 1α,25(OH)2-Vitamin D3 and their physiological significance in osteoblasts[J]. Steroids, 2004, 69(8-9): 561-565
[40]Lajdova I, Chorvat D, Chorvatova A. Rapid effects of 1α,25(OH)2D3 in resting human peripheral blood mononuclear cells[J]. European Journal of Pharmacology, 2008, 586(1-3): 14-23
[41]Balint E, Marshall C F, Sprague S M. Effect of vitamin D analogues paricalcitol and calcitriol on bone mineral in vitro[J]. American Journal of Kidney Disease, 2000, 36(4): 789-796
[42]Farach-Carson M C. Bioactive analogs that simulate subsets of biological activities of 1α,25(OH)2D3 in osteoblasts[J]. Steroids, 2001, 66(3-5): 357-361
[43]Farach-Carson M C, Ridall A L. Dual 1,25-dihydroxyvitamin D3 signal response pathways inosteoblasts: cross-talk between genomic and membrane-initiated pathways[J]. American Journal of Kidney Diseases, 1998, 31(4): 729-742
[44]邓耀祖,屈伸主编.医学分子细胞生物学[M].北京:科学出版社, 2002. 128-129
[45]马慧军,朱文元,王大光,岳学状,李诚让.内皮素-1对毛囊外根鞘无色素黑素细胞黏附和移行及其细胞骨架形态的影响[J].临床皮肤科杂志, 2005, 34(10): 643-646
[46]王稚英,王英,肖军军,董晓敏.牵引成骨体外模型的建立及成骨细胞骨架的观察[J].中华口腔医学杂志, 2006, 41(2): 111-113
[47]Luegmayr E, Varga F, Frank T, Roschger P, Klaushofer K. Effects of Triiodothyronine on morphology, growth behavior, and the actin cytoskeleton in mouse osteoblastic cells (MC3T3-E1)[J]. Bone, 1996, 18(6): 591-599
[48]Gao T J, T.Aro H, Yl?nen H, Vuorio E. Silica-based bioactive glasses modulate expression of bone morphogenetic protein-2 mRNA in Saos-2 oseoblasts in vitro[J]. Biomaterials, 2001, 22(12): 1475-1483
[49]Scotchford C A, Ball M, Winkelmann M, V?r?s J, Csucs C, Brunette D M, Danuser G, Textor M. Chemically patterned, metal-oxide-based surfaces produced by photolithographic techniques for studying protein-and cell-interactions.Ⅱ: Protein adsorption and early cell interactions[J]. Biomaterials, 2003, 24(7): 1147-1158
[50]Gough J E, Christian P, Scotchford C A, Jones I A. Craniofacial osteoblast responses to polycaprolactone produced using a novel boron polymerization technique and postassium fluoride post-treatment[J]. Biomaterials, 2003, 24(27): 4905-4912
[51]Wu T J, Huang H H. Lan C W, Lin C H, Hsu F Y, Wang Y J. Studies on the microspheres comprised of reconstituted collagen and hydroxyapatite[J]. Biomaterials, 2004, 25(4): 651-658
[52]Wang C M, Gong Y H, Lin Y M, Shen J B, Wang D A. A novel gellan gel-based microcarrier for anchorage-dependent cell delivery[J]. Acta Biomaterialia, 2008, 4(5): 1226-1234
[53]薛延,袁润英,相东,王红霞,李希斌,刘正梅,吴克斌,范慕贞. 1,25双羟维生素D3对成骨样细胞骨架和基因表达的影响[J].解剖学报, 1998, 29(1): 67-68
[54]Alexopoulos H, B?ttger A, Flscher S, Levin A, Wolf A, Fujisawa T, Hayakawa S, Gojobori T, Davles J A, David C N, Bacon J P. Evolution of gap junctions: the missing link?[J]. Current Biology, 2004, 14(20): R879-880
[55]Bukauskas F F, Verselis V K. Gap junction channel gating[J]. Biochimica et Biophysica Acta, 2004, 1662(1-2): 42-60
[56]Stains J P, Civitelli R. Cell-to-cell interactions in bone[J]. Biochemical and Biophysical Research Communications, 2005, 328(3): 721-727
[57]Stains J P, Civitelli R. Gap junction in skeletal development and function[J]. Biochimia et Biophysica Acta, 2005, 1719(1-2): 69-81
[58]Civitelli R. Cell-cell communication in the osteobalst/osteocyte lineage[J]. Archives of Biochemistry and Biophysics, 2008, 473: 188-192
[59]崔爎,陈槐卿.骨细胞间隙连接与物理—生物信号传导研究进展[J].国外医学生物医学工程分册, 2003, 26 (3): 108-112
[60]田庆显,黄公怡. 1,25二羟基维生素D3对小鼠成骨细胞OPG和RANKL基因表达的影响[J].中国医学科学院学报, 2004, 26(4): 418-422
[61]Friedenstein. Precursor cells of mechanocytes[J]. Inernational Review of Cytology, 1976, 47(3): 327-240
[62]卢卫忠,唐康来,杨柳,吴梅英. TGF-β对成骨细胞的作用[J].第三军医大学学报, 2000, 22: 94-96
[63]李丽华,周玉坤,王丽丽.维生素D与骨的生长和矿化[J].国外医学妇幼保健, 2004, 15(5): 257-258
[64]史炜镔.骨质疏松症的药物治疗[J].国外医学老年医学分册, 1996, 17: 177-181
[65]吴培福,钟代彬,曲伟杰,王梅,黄有德,韩博.小鼠成骨细胞改良酶的消化分离培养[J].甘肃农业大学学报, 2004, 39(5): 512-515
[66]孟繁浩,熊志立,陶胜宇,李发美.成骨细胞的生物学特征及其调控活性物质[J].化学与生物工程, 2005,11: 8-10
[67]周彬,程祥荣,杨惠,蒋淘,夏大弘,王贻宁.牙周韧带细胞及成骨样细胞在纯钛表面附着的形态学比较[J].中国口腔种植学杂志, 2002, 7(4): 158-161
[68]Takanori Domon, Yoshinori Yamazaki, Ami Fukui et al. Ultrastructural study of cell-cell interaction between osteoclasts and osteoblasts/stroma cells in vitro[J]. Annals of Anatomy, 2002, 184(3): 221-227
[69]Feng Chei, Nicolas Mathis. Osteoblast interaction with DLC-coated Si substrates[J]. Acta Biomaterialia, 2008(4): 1369-1381
[70]张金超,李晓新,许善锦,王夔,于世凤,林琴.稀土离子对体外培养的成骨细胞增殖、分化和功能表达的影响[J].自然科学进展, 2004, 14(4): 404-409
[71]杨玉生,孙俊英,朱国兴.生物活性玻璃对鼠成骨细胞体外增殖的形态学研究[J].生物医学工程研究, 2007, 26(2): 146-150
[72]任高宏,裴国献,王钢,金丹,魏宽海,陈莉光,陈滨.成人骨髓成骨细胞体外培养[J].骨与关节损伤杂志, 2003, 18(2): 118-121
[73]陈建庭,李菊根,金大地.血小板衍生生长因子促进成骨细胞DNA合成的实验研究[J].中华外科杂志, 1997, 37(7): 409-411
[74]朱进才,任战平,李旭奎,安文生,王黎.电刺激活化牙槽骨成骨细胞增殖功能的实验研究[J].西安交通大学学报, 2003, 24(4): 300-302
[75]Beresford J N, Gallagher J A, Russell R G G. 1, 25-dihydroxyvitamin D3 and human bone-derived cells in vitro: effects on alkaline phosphatase, type I collagen and proliferation[J]. Endocrinology, 1986, 119: 1176-1785
[76]Ikeda T, Kohno H, Yamamuro T, Kasai R, Ohta S, Okumura H, Konishi J, Kikuchi H, Shigeno C. The effect of active vitamin D3 analogs and dexamethasone on the expression of osteocalcin gene in rat tibiae in vivo[J]. Biochemical and Biophysical Research Communications, 1992, 189 : 1231-1235
[77]Hideaki Nagaoka, Yoshiyuki Mochida, Phimon Atsawasuwan, Masaru K, Kondon T, Yamauchi M. 1,25(OH)2D3 regulates collagen quality in an osteoblastic cell culture system[J]. Biochemical and Biophysical Research Communications, 2008, 377(2): 674-678
[78]童安莉,陈璐璐,丁桂芝.成骨细胞骨形成机制研究进展[J].中国骨质疏松杂志, 1999, 5 (3): 60-64
[79]唐文山.骨营养不良乳牛血清钙及血清游离羟脯氨酸含量测定[J].中国兽医科技, 2002, 32(11): 26-28
[80]刘宗平,马卓,杨得兵,池斌.双峰驼骨质疏松症的流行特点及其与生物地球化学因子之间的关系[J].应用与环境生物学报, 1997, 3(4): 345-348
[81]Mohr S B. A Brief History of Vitamin D and Cancer Prevention[J]. Annals of Epidemiology, 2009, 19(2): 79-83
[82]Hofstetter W, Felix R. 1,25(OH)2D3 and PTH act mainly on cells of the osteoblasts but not of the osteoclast lineage[J]. Bone, 1995, 17(6): 557-596
[83]Simonet W S, Lacey D L, Dunstan C R, Kelley M, Chang M S, Lüthy R, Nguyen H Q, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan H L, Trail G, Sullivan J, Davy E, Bucay N, Gegg L R, Hughes T M, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee P, Program A E, Boyle W J. Osteoprotegerin: A Novel SecretedProtein Involved in the Regulation of Bone Density[J]. Cell, 1997, 89: 309-319
[84] Yasuda H, Shima N, Nakagawa N, Yamaquchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis- inhibitory factor and is identical to TRANCE/RANK[J]. Proceeding of the National Academy of Sciences in USA, 1998, 95(7): 3597-3602
[85]Mizuno A, Amizuka N, Irie K, Murakami A, Fujise N, Kanno T, Sato Y, Nakagawa N, Yasuda H, Mochizuki S, Gomibuchi T, Yano K, Shima N, Washida N, Tsuda E, Morinaga T, Higashio K, Ozawa H. Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin[J]. Biochemical and Biophysical Research Communication, 1998, 247(3): 610-615
[86]刘俊栋,顾建红,翟必华,刘学忠,卞建春,刘宗平.骨保护素对体外培养大鼠破骨细胞的影响[J].中国农业科学, 2008, 41(2): 581-586
[87]顾建红,刘俊栋,卓丽玲,王林,赵瑞英,刘宗平.钙磷对RANKL诱导番鸭破骨细胞生成及活性的影响[J].江苏农业科学, 2007, 6: 175-178
[88]Suda T, Ueno Y, Fujii K, Shinki T. Vitamin D and bone[J]. Journal of Cellular Biochemistry, 2003, 88(2): 259-266
[89]Lum L, Wong B R, Josien R, Becherer J D, Erdjument-Bromage H, Schl?ndorff J, Tempst P, Choi Y, Blobel C P. Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival[J]. The Journal of Biological Chemistry, 1999, 274: 13613-13618
[90]Zhang Y Y, Chen D C, Lu C Y. Influence of vitamin D on proliferation, differentiation and secretion of OPG and RANKL of cultured marrow mesenchymal cells of rhesus monkey[J]. Abstrants/Bone, 2008, 43: S38-S75
[91]吴小涛,王海军,宋萍. 1,25(OH)2D3对体外培养大鼠成骨细胞RANKL/OPG mRNA表达的影响[J].东南大学学报(医学版), 2007, 26(1): 32-35
[92]王科,王晓雄,石炳毅.实时荧光定量PCR在细胞因子mRNA检测研究中的应用[J].北京生物医学工程, 2006, 25(2): 217-221
[93]陈兆鹏,黄瞻云,张文芳,徐红菊,陈文雨,万海英.荧光定量PCR和ELISA测定乙肝病毒标志物2005例结果分析[J].同济大学学报(医学版), 2003, 24(2): 138-143
[94]Hofbauer L C, Dunstan C R, Spelsberg T C, Riggs B L, Khosla S. Osteoprotegerin production by human osteoblast lineage cells is stimulated by vitamin D, bone morphogenetic protein-2, and cytokines[J]. Biochem Biophys Res Commun, 1998, 250(3): 776–781
[95]Giner M, Rios M J, Montoya M J, Vázquez M A, Naji L, Pérez-Cano. RANKL/OPG in primary cultures of osteoblasts from post-menopausal women. Differences between osteoporotic hip fractures and osteoarthritis[J]. Journal of Steroid Biochemistry & Molecular Biology, 2009, 113(1-2): 46-51
[96]Theoleyre S, Wittrant Y, Tat S K, Fortun Y, Redini F, Heymann D. The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling[J]. Cytokine & Growth Factor Reviews, 2004, 15(6): 457-475
[97]Seriwatanachai D, Thongchote K, Charoenphandhu N, Pandaranandaka J, Tudpor K, Teerapornpuntakit J, Suthiphongchai T, Krishnamra N. Prolactin directly enhances bone turnover by raising osteoblast-expressed receptor activator of nuclear factorκB ligand/osteoprotegerin ratio[J]. Bone, 2008, 42(3): 535-546
[98]Thomas G P, Baker S U K, Eisman J A, Gardiner E M. Changing RANKL/OPG mRNA expression in differentiating murine primary osteoblasts[J]. Journal of Endocrinology, 2001, 170: 451-460
[99]Wiberg K, Ljunghall S, Binderup L, Ljunggren?. Studies on two new vitamin D Analogs, EB 1089 and KH 1060: Effects on bone resorption and osteoclast recruitment in vitro[J]. Bone, 1995, 17(4): 391-395
[100]李新锋,周振雷,张建鹏,侯加法.肉鸡胫骨软骨发育不良研究进展[J].畜牧与兽医, 2008, 40(3): 103-106
[101]Chamber T J, Magnus C J. Calcitonin alters behavior of isolated osteoclasts[J]. The Journal of Pathology, 1982, 137(1): 27
[102]邓力.体外破骨细胞培养及研究进展[J].华西要学杂志, 2000, 15(3): 195-196
[103]Tsuda E, Goto M, Monochizuki S I. Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis[J]. Biochemical and Biophysical Research Communications, 1997, 234(1): 137-142
[104]Lacey D, Timms E, Tan H L, Kelley M J, Dunstan C R, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian Y X, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle W J. Osteoprotegerinligand is a cytokine that regulates osteoclast differentiation and activation[J]. Cell, 1998, 93: 165-176
[105]Kong Y Y, Yoshida H, Sarosi I, Tan H L, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos A J, Van G, Itie A, Khoo W, Wakeham A, Dunstan C R, Lacey D L, Mak T W, Boyle W J, Penninger J M. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis[J]. Nature, 1999, 397(28): 315–323
[106]Quinn J M W, Fujikawa Y, Mcgee J O’D, Athanasou N A. Rodent osteoblast-like cells support osteoclastic differentiation of human cord blood monocytes in the presence of M-CSF and 1,25 dihydroxyvitamin D3[J]. The International Journal of Biochemistry & Cell Biology, 1997, 29(1):173-179
[107]Okahashi N, Koide M, Jimi E, Suda T, Nishihara T. Caspases (interleukin-1β-converting enzyme family proteases) are involved in the regulation of the survival of osteoclasts[J]. Bone, 1998, 23(1): 33-41
[108]Kim J H, Kim K, Jin H M, Youn B U, Song I, Choi H S, Kim N. Upstream stimulatory factors regulate OSCAR gene expression in RANKL-mediated osteoclast differentiation[J]. Journal of Molecular Biology, 2008, 383(3): 502-511
[109]Battaglino R A, Pham L, Morse L R, Vokes M, Sharma A, Odgren P R, Yang M, Sasaki H, Stashenko P. NHA-oc/NHA2: A mitochondrial cation-proton antiporter selectively expressed in osteoclast[J]. Bone, 2008, 42: 180-192
[110]顾建红,刘俊栋,刘海霞,谢献胜,郑中朝,张力,刘宗平.番鸭破骨细胞的培养及鉴定[J].中国兽医学报, 2008, 28(1): 75-78
[111]高建军,顾淑珠,金慰芳,邓华云,王洪复.高纯度破骨细胞分离培养与功能表达[J].中国骨质疏松杂志, 2001, 7(1): 15-17
[112]Anthony J, Janckila, Ruth M. Alternative immunoassay for tartrate-resistant acid phosphatase isoform 5b using the fluorogenic substrate naphthol ASBI-phosphate and heparin[J]. Clinica Chimica Acta , 347, 2004: 157-167
[113]Theoleyre S, Wittrant Y, Couillaud S, Vusio P, Berreur M, Dunstan C, Blanchard F, Rédini F, Heymann D. Cellular activity and signaling induced by ostoprotegerin in osteoclasts: involvement of receptor activator of nuclear factorκB ligand and MAPK[J]. Biochimica et Biophysica Acta, 2004, 1644(1): 1-7
[114]Chung H, Kang Y S, Hwang C S, Moon I K, Yim C H, Choi K H, Han K O, Jang H C, YoonH K, Han I K. Deflazacort Increases Osteoclast Formation in Mouse Bone Marrow Culture and the Ratio of RANKL/OPG mRNA Expression in Marrow Stromal Cells[J]. Journal of Korean Medical Science, 2001, 16(6): 769-773
[115]Horowitz MC, Xi Y, Wimberly Y, Kacena M A. Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands[J]. Cytokine and Growth Factor Reviews, 2001,12(1): 9-18
[116]Kitazawa R, Kitazawa S. Vitamin D3 Augments Osteoclastogenesis via Vitamin D-Responsive Element of Mouse RANKL Gene Promoter[J]. Biochemical and Biophysical Research Communications, 2002, 290: 650-655
[117]Kong Y Y, William J B, Josef M P. Osteoprotegerin ligand: a regulator of immune responses and bone physiology[J]. Immunology Today, 2000, 21(10): 495-502
[118]Tsurukai T, Udagawa N, Matsuzaki K, Takahashi N, Suda T. Roles of macrophage-colony stimulating factor and osteocalast differentiation factor in osteoclastogenesis[J]. Journal of Bone and Mineral Metabolism, 2000, 18(4): 177-184
[119]钱红波,赵建宁,妖静,曾晓峰,陆维举,胡云峰.小鼠破骨细胞骨髓诱导培养体系的建立[J].医学研究生学报, 2006, 19 (8): 692-695
[120]黄红铭,姜华,张慧,侯健.外周血单个核细胞诱导培养破骨细胞[J].国际病理科学与临床杂志, 2008, 28 (1): 10-13
[121]Sato M, Nakamichi Y, Nakamura M, Sato N, Ninomiya T, Muto A, Nakamura H, Ozawa H, Iwasaki Y, Kobayashi E, Shimizu M, Deluca H F, Takahashi N, Udagawa N. New 19-nor-(20S)-1α,25-dihydroxyvitamin D3 analogs strongly stimulate osteoclast formation both in vivo and in vitro[J]. Bone, 2007, 40: 293-304
[122]Hayashi H, Nakaham K I, Sato T, Tuchiya T, Asakawa Y, Maemura T, Tanaka M, Morita M, Morita I. The role of Mac-1 (CD11b/CD118) in osteoclast differentiation induced by receptor activator of nuclear factor-κB[J]. FEBS Letters, 2008, 582: 3234-3248
[123]Lakkakorpi P T, V??n?nen H K. Kinetics of the osteoclast cytoskeleton during the resorption cycle in vitro[J]. Journal of Bone Mineral Research, 1991, 6: 817–826
[124]Burgess T L, Qian Y X, Kaufman S, Ring B D, Van G, Capparelli C, Kelley M, Hsu H, Boyle W J, Dunstan C R, Hu S, Lacey D L. The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts[J]. Journal of Biological Chemistry, 1999, 145(3): 527-538
[125]Fuller K, Owens J M, Tagger C J, Wilson A, Moss R, Chambers T J. Macrophagecolony-stimulating factor stimulates survival and chemotactic behavior in isolated osteoclasts [J]. The Journal of Experimental Medicine, 1993, 178(5): 1733-1744
[126]Fujikawa Y, Sabokbar A, Neale S D, Itonaga I, Torisu T, Athanasou N A. The effect of macrophage-colony stimulating factor and other humoral factors (interleukin-1, -3, -6, and -11, tumor necrosis factor-alpha, and granulocyte macrophage-colony stimulating factor) on human osteoclast formation from circulating cells[J]. Bone, 2001, 28(3): 261-267
[127]Troen B R. Molecular mechanisms underlying osteoclast formation and activation[J]. Experimental Gerontology, 2003, 38(6): 605-614
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