高铁环境对人成骨细胞功能的影响及铁调素对人成骨细胞内钙离子的影响
|
摘要
第一部分高铁环境对人成骨细胞功能的影响
目的：探讨高铁环境（枸橼酸铁铵）对人成骨细胞（hFOB1.19）活性指标（增殖、分化、矿化）及OPG/RANKL系统的影响。
方法：人成骨细胞（hFOB1.19）培养后，用不同终浓度的枸橼酸铁铵（0umol/L、50umol/L、100umol/L、200umol/L）加入细胞培养基中，MTT法检测成骨细胞增殖活性；碱性磷酸酶活性试剂盒检测碱性磷酸酶活性；Von kossa染色法行钙结节染色；用RT-PCR和Western blot法分别检测RANKL、OPG的基因和蛋白表达变化。
结果：在FAC干预48h后，50umol/L FAC使成骨细胞增殖活性显著下降（P﹤0.05），100umol/L和200umol/L FAC使成骨细胞增殖活性下降更为显著（P﹤0.01）；在FAC干预10d后，成骨细胞的碱性磷酸酶活性随着干预浓度的增加而下降（P＜0.01）；在FAC干预15d后，代表成骨细胞矿化能力的钙结节显著减少；在FAC干预48h后，50umol/L FAC对成骨细胞RANKL/OPG mRNA和蛋白表达之比无显著影响（P﹤0.05），100umol/L和200umol/L FAC使成骨细胞RANKL/OPG mRNA和蛋白表达之比显著增加（P﹤0.01）。
结论：高铁环境不仅可以抑制成骨细胞增殖、分化和矿化，从而抑制骨形成；而且还可以促进人成骨细胞RANKL/OPG mRNA和蛋白的表达。因此，铁过载在骨质疏松症的发病机制中，不仅直接抑制了成骨细胞的骨形成作用，而且间接促进了破骨细胞的形成、活化，从而促进骨吸收。
第二部分铁调素对人成骨细胞内钙离子的影响
目的：研究铁调素在正常和不同浓度高铁环境下对成骨细胞内钙离子的影响，并探讨其中的作用机制。
方法:人成骨细胞株（hFOB1.19）分别在正常和不同浓度高铁环境（10、200umol/L）下培养，然后用不同终浓度铁调素干预24h，细胞经钙离子荧光剂（fluo-3/AM）染色后用流式细胞仪检测成骨细胞内钙离子荧光强度。此外，在正常环境下，分别用10umol/L的丹曲林和20umol/L的尼莫地平预处理人成骨细胞25min和10min，然后观察铁调素100nmol/L干预24h后对人成骨细胞内钙离子的影响。
结果:在正常环境下，铁调素10nmol/L时成骨细胞内钙离子荧光无显著变化（P>0.05），30nmol/L时成骨细胞内钙离子荧光开始增加（P<0.05），100nmol/L时显著增加（P<0.01），300nmol/L时无显著变化（P>0.05）；在10umol/L高铁环境下，铁调素的作用与其在正常环境下相似，只是30nmol/L时成骨细胞内钙离子增加较正常环境下更为显著（P<0.01）；在200umol/L高铁环境下，铁调素在10nmol/L至100nmol/L范围之间使成骨细胞内钙离子荧光强度均显著增加（P<0.01），300nmol/L时无变化。此外，当人成骨细胞分别用10umol/L的丹曲林和20umol/L的尼莫地平预处理后，铁调素（100nmol/L）对其胞内的钙离子增加作用不再显著（P>0.05）。
结论:铁调素浓度不超过100nmol/L时，在正常和高铁环境下均可使成骨细胞内钙离子增加，并且在高铁环境下增加更为显著；其机制可能与铁调素干预后胞内钙库释放有关，而钙库钙离子释放通道的激活是由L型钙通道介导的钙离子内流引起的。
PartI Effects of high iron environment on human osteoblastic functions
Objective:To investigate the effects of high iron environment (Ferric AmmoniumCitrate) on osteoblastic functions and OPG/RANKL system in vitro.
Methods:Human osteoblast cells (hFOB1.19) were incubated in media supplementedwith0–200umol/L of Ferric Ammonium Citrate (FAC). Proliferation viability ofosteoblasts were evaluated by MTT assay at48h. Alkaline phosphatase (ALP) activity wasmeasured using ALP viability kit at10d. Von-kossa staining assay were used to evaluatemineralized bone nodules at15d. The gene and protein expression of OPG and RANKLwas detected by RT-PCR and western blot at48h after treatment with FAC.
Results:After treatment with FAC for48h, FAC significantly inhibited cellproliferation (P﹤0.05) at50umol/L, which is more obvious at100umol/L and200umol/LFAC (P﹤0.01). After treatment with FAC for10d, the ALP activity of osteoblasts weresignificantly suppressed by iron overload dose-dependently (P﹤0.01). The number ofmineralized nodules was significantly reduced by FAC at15d. In addition, FAC at100umol/L and200umol/L significantly increased the mRNA and protein expression ofRANKL/OPG (P﹤0.01).
Conclusions: High iron environment not only significantly inhibited cell proliferation,differentiation and mineralizaiotn of human osteoblasts, but also increased the mRNA andprotein expression of RANKL/OPG. Therefore, iron overload not only inhibited boneformation directly, but also increased bone resorption indirectly in the pathogenesis ofosteoporosis.
PartII Effects of hepcidin on intracellular calcium of human osteoblasts
Objective:To study the effects of hepcidin on intracellular calium of humanosteoblasts exposed to normal or high iron environment and explore the underlyingmechanism.
Methods:Human osteoblast cells (hFOB1.19) were cultured in normal and differentconcentrations of iron environment (10、50、200umol/L）. After treatment with hepcidinfor24h, flow cytometry was used to detect the fluorescent intensity of human osteoblastspretreated with Fluo-3/AM. In addition, under normal environment, we also observed theeffect of hepcidin (100nmol/L) on human osteoblasts pretreated with10umol/Ldantrolene and20umol/L nimodipine for25min and10min, respectively.
Results:In normal environment, fluorescent intensity of intracellular calcium didn’tchange by hepcidin at10nmol/L, started to increase at30nmol/L （P<0.05）, increasedsignificantly at100nmol/L （P<0.01）, no difference was observed by hepcidin at300nmol/L. In10umol/L iron environment, similar results was observed compared to normalenvironment, except for more significantly increased intracellular calcium intensity byhepcidin at30nmol/L （P<0.01）. In200umol/L iron environment, hepcidin increased thefluorescent intensity of intracellular calcium at the concentrations ranging from10nmol/Lto100nmol/L （P<0.01）, no difference was observed by hepcidin at300nmol/L. Inaddition, the increase of intracellular calcium of human osteoblasts by hepcidin (100nmol/L) was completely blocked by pretreatment with either dantrolene or nimodipine.
Conclusions: Hepcidin could increase intracellular calcium both at normal and highiron environment when not higher than100nmol/L, which is more obvious in high ironenvironment. Furthermore, these findings indicate that the increase of intracellular calciumis probably due to calcium release from endoplasmic reticulum, which is triggered bycalcium influx.
目的：探讨高铁环境（枸橼酸铁铵）对人成骨细胞（hFOB1.19）活性指标（增殖、分化、矿化）及OPG/RANKL系统的影响。
方法：人成骨细胞（hFOB1.19）培养后，用不同终浓度的枸橼酸铁铵（0umol/L、50umol/L、100umol/L、200umol/L）加入细胞培养基中，MTT法检测成骨细胞增殖活性；碱性磷酸酶活性试剂盒检测碱性磷酸酶活性；Von kossa染色法行钙结节染色；用RT-PCR和Western blot法分别检测RANKL、OPG的基因和蛋白表达变化。
结果：在FAC干预48h后，50umol/L FAC使成骨细胞增殖活性显著下降（P﹤0.05），100umol/L和200umol/L FAC使成骨细胞增殖活性下降更为显著（P﹤0.01）；在FAC干预10d后，成骨细胞的碱性磷酸酶活性随着干预浓度的增加而下降（P＜0.01）；在FAC干预15d后，代表成骨细胞矿化能力的钙结节显著减少；在FAC干预48h后，50umol/L FAC对成骨细胞RANKL/OPG mRNA和蛋白表达之比无显著影响（P﹤0.05），100umol/L和200umol/L FAC使成骨细胞RANKL/OPG mRNA和蛋白表达之比显著增加（P﹤0.01）。
结论：高铁环境不仅可以抑制成骨细胞增殖、分化和矿化，从而抑制骨形成；而且还可以促进人成骨细胞RANKL/OPG mRNA和蛋白的表达。因此，铁过载在骨质疏松症的发病机制中，不仅直接抑制了成骨细胞的骨形成作用，而且间接促进了破骨细胞的形成、活化，从而促进骨吸收。
第二部分铁调素对人成骨细胞内钙离子的影响
目的：研究铁调素在正常和不同浓度高铁环境下对成骨细胞内钙离子的影响，并探讨其中的作用机制。
方法:人成骨细胞株（hFOB1.19）分别在正常和不同浓度高铁环境（10、200umol/L）下培养，然后用不同终浓度铁调素干预24h，细胞经钙离子荧光剂（fluo-3/AM）染色后用流式细胞仪检测成骨细胞内钙离子荧光强度。此外，在正常环境下，分别用10umol/L的丹曲林和20umol/L的尼莫地平预处理人成骨细胞25min和10min，然后观察铁调素100nmol/L干预24h后对人成骨细胞内钙离子的影响。
结果:在正常环境下，铁调素10nmol/L时成骨细胞内钙离子荧光无显著变化（P>0.05），30nmol/L时成骨细胞内钙离子荧光开始增加（P<0.05），100nmol/L时显著增加（P<0.01），300nmol/L时无显著变化（P>0.05）；在10umol/L高铁环境下，铁调素的作用与其在正常环境下相似，只是30nmol/L时成骨细胞内钙离子增加较正常环境下更为显著（P<0.01）；在200umol/L高铁环境下，铁调素在10nmol/L至100nmol/L范围之间使成骨细胞内钙离子荧光强度均显著增加（P<0.01），300nmol/L时无变化。此外，当人成骨细胞分别用10umol/L的丹曲林和20umol/L的尼莫地平预处理后，铁调素（100nmol/L）对其胞内的钙离子增加作用不再显著（P>0.05）。
结论:铁调素浓度不超过100nmol/L时，在正常和高铁环境下均可使成骨细胞内钙离子增加，并且在高铁环境下增加更为显著；其机制可能与铁调素干预后胞内钙库释放有关，而钙库钙离子释放通道的激活是由L型钙通道介导的钙离子内流引起的。
PartI Effects of high iron environment on human osteoblastic functions
Objective:To investigate the effects of high iron environment (Ferric AmmoniumCitrate) on osteoblastic functions and OPG/RANKL system in vitro.
Methods:Human osteoblast cells (hFOB1.19) were incubated in media supplementedwith0–200umol/L of Ferric Ammonium Citrate (FAC). Proliferation viability ofosteoblasts were evaluated by MTT assay at48h. Alkaline phosphatase (ALP) activity wasmeasured using ALP viability kit at10d. Von-kossa staining assay were used to evaluatemineralized bone nodules at15d. The gene and protein expression of OPG and RANKLwas detected by RT-PCR and western blot at48h after treatment with FAC.
Results:After treatment with FAC for48h, FAC significantly inhibited cellproliferation (P﹤0.05) at50umol/L, which is more obvious at100umol/L and200umol/LFAC (P﹤0.01). After treatment with FAC for10d, the ALP activity of osteoblasts weresignificantly suppressed by iron overload dose-dependently (P﹤0.01). The number ofmineralized nodules was significantly reduced by FAC at15d. In addition, FAC at100umol/L and200umol/L significantly increased the mRNA and protein expression ofRANKL/OPG (P﹤0.01).
Conclusions: High iron environment not only significantly inhibited cell proliferation,differentiation and mineralizaiotn of human osteoblasts, but also increased the mRNA andprotein expression of RANKL/OPG. Therefore, iron overload not only inhibited boneformation directly, but also increased bone resorption indirectly in the pathogenesis ofosteoporosis.
PartII Effects of hepcidin on intracellular calcium of human osteoblasts
Objective:To study the effects of hepcidin on intracellular calium of humanosteoblasts exposed to normal or high iron environment and explore the underlyingmechanism.
Methods:Human osteoblast cells (hFOB1.19) were cultured in normal and differentconcentrations of iron environment (10、50、200umol/L）. After treatment with hepcidinfor24h, flow cytometry was used to detect the fluorescent intensity of human osteoblastspretreated with Fluo-3/AM. In addition, under normal environment, we also observed theeffect of hepcidin (100nmol/L) on human osteoblasts pretreated with10umol/Ldantrolene and20umol/L nimodipine for25min and10min, respectively.
Results:In normal environment, fluorescent intensity of intracellular calcium didn’tchange by hepcidin at10nmol/L, started to increase at30nmol/L （P<0.05）, increasedsignificantly at100nmol/L （P<0.01）, no difference was observed by hepcidin at300nmol/L. In10umol/L iron environment, similar results was observed compared to normalenvironment, except for more significantly increased intracellular calcium intensity byhepcidin at30nmol/L （P<0.01）. In200umol/L iron environment, hepcidin increased thefluorescent intensity of intracellular calcium at the concentrations ranging from10nmol/Lto100nmol/L （P<0.01）, no difference was observed by hepcidin at300nmol/L. Inaddition, the increase of intracellular calcium of human osteoblasts by hepcidin (100nmol/L) was completely blocked by pretreatment with either dantrolene or nimodipine.
Conclusions: Hepcidin could increase intracellular calcium both at normal and highiron environment when not higher than100nmol/L, which is more obvious in high ironenvironment. Furthermore, these findings indicate that the increase of intracellular calciumis probably due to calcium release from endoplasmic reticulum, which is triggered bycalcium influx.
引文
[1] North American Menopause Society. Management of osteoporosis in postmenopausalwomen:2006position statement of The North American Menopause Society.Menopause2006,13:340-367;quiz368-369.
[2] Choo WL, Loh FH, Ng SC. Osteoporosis in relation to menopause. Ann Acad MedSingapore,2002,31:30-36.
[3] Ravn P,Bidstrup M, Wasnich RD,et al. Alendronate and estrogen-progestin in thelong-term prevention of bone loss: four-year results from the early postmenopausalintervention cohort study A randomized, controlled trial. Ann Intern Med,1999,131:935-942.
[4]李光飞,徐又佳,钱忠明.铁过载与骨质疏松关系的研究进展.中国骨质疏松杂志,2010,16:88-91.
[5] Weinberg ED. Iron loading: a risk factor for osteoporosis. Biometals,2006,19:633-635.
[6] Weinberg ED. Role of iron in osteoporosis. Pediatr Endocrinol Rev,2008,6Suppl1:81-85.
[7] Jian J, Pelle E, Huang Xi. Iron and menopause: does increased iron affect the healthof postmenopausal women? Antioxid Redox Signal,2009,11(12):2939-2943.
[8] Hamdi Kara I, Aydin S, Gemalmaz A, et al. Habitual tea drinking and bone mineraldensity in postmenopausal Turkish women: investigation of prevalence ofpostmenopausal osteoporosis in Turkey(IPPOT Study).Int J Vitam Nutr Res,2007,77:389-397.
[9] Sheng Z, Xu K,Ou Y,etal.Relationship of body composition and prevalence ofosteoporosis in central south Chinese postmenopausal women. Clin Endocrinol(Oxf),2011,74(3):319-324.
[10] Youjia Xu,Pierre Sirois,Kai Li.Iron overload plays a unique role in osteoporosis.Blood,2010,9: E-letter.
[11] Isomura H,Fujie K,Shibata K,etal.Bone metabolism and oxidative stress inpostmenopausal rats with iron overload.Toxicology,2004,197:93-100.
[12] Kudo H,Suzuki S,Watanabe A,etal.Effects of colloidal iron overload on renal andhepatic siderosis and the femur in male rats.Toxicology,2008,246(2-3):143-147.
[13] Tsay J,Yang Z,Ross FP,Cunningham-Rundles S,Lin H,Coleman R,et al.Bone losscaused by iron overload in a murine model: importance of oxidative stress. Blood,2010,116(14):2582-2589.
[14] Guggenbuhl P, Filmon R, Mabilleau G, et al. Iron inhibits hydroxyapatite crystalgrowth in vitro.Metabolism,2008,57(7):903-910.
[15] Yamasaki K,Hagiwara H.Excess iron inhibits osteoblast metabolism. ToxicolLett,2009,191(2-3):211-215.
[16] Zarjou A,Jeney V,Arosio P,etal.Ferritin-Ferroxidase Activity:A Potent Inhibitor ofOsteogenesis.JBone Miner Res,2010,25(1):164-172.
[17] Liu G, Men P, Kenner GH, et al.Age-associated iron accumulation in bone:implications for postmenopausal osteoporosis and a new target for prevention andtreatment by chelation. Biometals,2006,19:245-251.
[18] Liu G, Men P, Kenner GH, et al. Therapeutic effects of an oral chelator targetingskeletal tissue damage in experimental postmenopausal osteoporosis in rats.Hemoglobin,2008,32:181-190.
[19] Ganz T.Hepcidin--a regulator of intestinal iron absorption and iron recycling bymacrophages. Best Pract Res Clin Haematol,2005,18:171-182.
[20] Collins JF, Wessling-Resnick M, Knutson MD. Hepcidin regulation of iron transport.JNutr,2008,138:2284-2288.
[21] De Domenico I,Kushner JP. Reconstitution of normal hepcidin expression inHfe-deficient mice after liver transplantation: a new role of HFE in Kupffercells?Gastroenterology,2010,139:25-27.
[22] Nemeth E,Tuttle MS, Powelson J,et al.Hepcidin regulates cellular iron efflux bybinding to ferroportin and inducing its internalization. Science,2004,306:2090-2093.
[23] Rivera S,Nemeth E, Gabayan V,etal.Synthetic hepcidin causes rapid dose-dependenthypoferremia and is concentrated in ferroportin-containing organs. Blood,2005,106:2196-2199.
[24] Yong Ma, Youjia Xu. Research on relationship between FPN1content and effect ofhepcidin on intracellular calcium and iron change in osteoblasts. Bone,2010,47(S):406.
[25]张鹏,徐又佳,赵东阳,等.铁调素及铁离子对人成骨细胞(hFOB1.19)内钙离子转运影响的初步报告.中国骨质疏松杂志.2008,14(7):504-507.
[1]李光飞,徐又佳,钱忠明.铁过载与骨质疏松关系的研究进展.中国骨质疏松杂志,2010,16:88-91.
[2] Weinberg ED.Iron loading: a risk factor for osteoporosis. Biometals,2006,19:633-635.
[3] Weinberg ED.Role of iron in osteoporosis. Pediatr Endocrinol Rev,2008,6Suppl1:81-85.
[4] Jian J, Pelle E, Huang Xi. Iron and menopause: does increased iron affect the healthof postmenopausal women? Antioxid Redox Signal,2009,11(12):2939-2943.
[5] Youjia Xu, Pierre Sirois, Kai Li. Iron overload plays a unique role inosteoporosis.Blood,2010,9: E-letter.
[6] Yamasaki K,Hagiwara H. Excess iron inhibits osteoblast metabolism. Toxicol Lett,2009,191(2-3):211-215.
[7] Zarjou A, Jeney V, Arosio P, et al. Ferritin-Ferroxidase Activity: A Potent Inhibitorof Osteogenesis.J Bone Miner Res,2010,25(1):164-172.
[8] Kudo H, Suzuki S, Watanabe A, et al. Effects of colloidal iron overload on renaland hepatic siderosis and the femur in male rats. Toxicology,2008,246(2-3):143-147.
[9] Tsay J, Yang Z, Ross FP, Cunningham-Rundles S, Lin H, Coleman R, et al. Boneloss caused by iron overload in a murine model: importance of oxidative stress.Blood,2010,116(14):2582-2589.
[10] Guggenbuhl P, Filmon R, Mabilleau G, et al. Iron inhibits hydroxyapatite crystalgrowth in vitro. Metabolism,2008,57(7):903-910.
[11] Kiyo-aki Ishii,Toshio Fumoto,Kazuhiro Iwai, et al. Coordination of PGC-1b andiron uptake in mitochondrial biogenesis and osteoclast activation. Nature Medicine.2009,15:259-266.
[12]王建忠,王坤正,周荣兴,等.阿仑膦酸钠干预人骨髓基质细胞OPG/RANKL的体外实验研究.中华关节外科杂志(电子版),2011,(05):625-632.
[13] Abdallah BM,Stilgren LS, Nissen N, et al. Increased RANKL/OPG mRNA ratio iniliac bone biopsies from women with hip fractures. Calcif Tissue Int,2005,76(2):90-7.
[14] Bord S,Ireland DC,Beavan SR,etal.The effects of estrogen on osteoprotegerin,ANKL,and estrogen receptor expression in human osteoblasts.Bone,2003,32(2):136-41.
[15] Boyce BF,Xing L.Functions of RANKL/RANK/OPG in bone modeling andremodeling.Arch Biochem Biophys,2008,473(2):139-46.
[16] Aubin JE, Bonnelye E.Osteoprotegerin and its ligand: a new paradigm forregulation of osteoclastogenesis and bone resorption. Osteoporos Int,2000,11(11):905-13.
[17] Kong YY, Yoshida H,Sarosi I,etal.OPGL is a key regulator of osteoclastogenesis,lymphocyte development and lymph-node organogenesis.Nature,1999,397(6717):315-23.
[1] Weinberg ED. Iron loading: a risk factor for osteoporosis. Biometals,2006,19:633-635.
[2] Liu G, Men P, Kenner GH, et al.. Age-associated iron accumulation in bone:implications for postmenopausal osteoporosis and a new target for prevention andtreatment by chelation. Biometals,2006,19:245-251.
[3] Qu ZH, Zhang XL, Tang TT, et al.. Promotion of osteogenesis through beta-cateninsignaling by desferrioxamine. Biochem Biophys Res Commun,2008,370:332-337.
[4] Jian J, Pelle E, Huang X. Iron and menopause: does increased iron affect the healthof postmenopausal women. Antioxid Redox Signal,2009,11:2939-2943.
[5] Youjia Xu, Pierre Sirois, Kai Li. Iron overload plays a unique role in osteoporosis.Blood,2010,9:E-letter.
[6] De Domenico I, Ward DM, Langelier C, et al.. The molecular mechanism ofhepcidin-mediated ferroportin down-regulation. Mol Biol Cell,2007,18:2569-2578.
[7] Rivera S, Nemeth E, Gabayan V, et al.. Synthetic hepcidin causes rapiddose-dependent hypoferremia and is concentrated in ferroportin-containing organs.Blood,2005,106:2196-2199.
[8] Park CH, Valore EV, Waring AJ, et al.. Hepcidin, a urinary antimicrobial peptidesynthesized in the liver. J Biol Chem,2001,276:7806-7810.
[9] Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia ofinflammation. Blood,2003,102:783-788.
[10] Nemeth E, Tuttle MS, Powelson J, et al.. Hepcidin regulates cellular iron efflux bybinding to ferroportin and inducing its internalization. Science (80-),2004,306:2090-2093.
[11] Zhang P, Xu YJ, Zhao DY, et al.. Increased intracellular iron and mineralization ofcultured hFOB1.19cells following hepcidin activation through ferroportin-1.Saudi Med J,2010,31:1303-1308.
[12] Ganz T. Hepcidin and its role in regulating systemic iron metabolism. HematologyAm Soc Hematol Educ Program,2006:29-35,507.
[13]王莉,段相林.铁离子对Caco-2细胞内钙离子转运的影响及钙离子浓度变化与细胞凋亡关系的研究.解剖学报,2005,36:177-181.
[14] Hallberg L, Brune M, Erlandsson M, et al.. Calcium: effect of different amounts onnonheme-and heme-iron absorption in humans. Am J Clin Nutr,1991,53:112-119.
[15] Berridge MJ, Lipp P, Bootman MD. Signal transduction. The calcium entry pas dedeux. Science (80-),2000,287:1604-1605.
[16]田万里,陶天遵,李磊.降钙素对体外培养大鼠成骨细胞内钙及钙通道电流影响的研究.中国骨质疏松杂志,2006,12:262-266.
[17] Labelle D, Jumarie C, Moreau R. Capacitative calcium entry and proliferation ofhuman osteoblast-like MG-63cells. Cell Prolif,2007,40:866-884.
[18]华坤,黄民.氟对成骨细胞样细胞胞内钙和钙通道电流的影响.中国应用生理学杂志,2003,19:179-181.
[19] Lauckner JE, Hille B, Mackie K. The cannabinoid agonist WIN55,212-2increasesintracellular calcium via CB1receptor coupling to Gq/11G proteins. Proc NatlAcad Sci U S A2005;102(52):19144-9.
[20] Varadi A, Rutter GA. Ca2+-induced Ca2+release in pancreatic islet beta-cells:critical evaluation of the use of endoplasmic reticulum-targeted "cameleons".Endocrinology2004;145(10):4540-9.
[21] Lemmens R, Larsson O, Berggren PO, Islam MS. Ca2+-induced Ca2+release fromthe endoplasmic reticulum amplifies the Ca2+signal mediated by activation ofvoltage-gated L-type Ca2+channels in pancreatic beta-cells. J Biol Chem2001;276(13):9971-7.
[22] Graves TK, Hinkle PM. Ca(2+)-induced Ca(2+) release in the pancreatic beta-cell:direct evidence of endoplasmic reticulum Ca(2+) release. Endocrinology2003;144(8):3565-74.
[23] Choi KJ, Cho DS, Kim JY, Kim BJ, Lee KM, Kim SH, et al. Ca-induced CaRelease from Internal Stores in INS-1Rat Insulinoma Cells. Korean J PhysiolPharmacol2011;15(1):53-9.
1Delbarre F.Osteoporosis in hemochromatosis.Sem Hop1960;36:3279-3294.
2Delbarre F. Osteoarticular Manifestations of Hemochromatosis. Presse Med1964;72:2973-2978.
3Duquenne M,Rohmer V,Legrand E, Chappard D, Wion Barbot N, Basle MF,Audran M,Bigorgne JC.Spontaneous multiple vertebral fractures revealed primaryhaemochromatosis.Osteoporos Int1996;6(4):338-340.
4Eyres KS, McCloskey EV,Fern ED,Rogers S, Beneton M, Aaron JE, KanisJA.Osteoporotic fractures: an unusual presentation of haemochromatosis. Bone1992;13(6):431-433.
5Kagan IE, Settarova DA, Tokarev Iu N, Burdina LM. Roentgenologic studies ofchanges of the osteoarticular system in patients with hereditary hemochromatosis.Gematol Transfuziol1989;34(10):19-24.
6Sella EJ,Goodman AH.Arthropathy secondary totransfusion hemochromatosis.J Bone Joint Surg Am1973;55(5):1077-1081.
7Wardle EN, Patton JT. Bone and joint changes in haemochromatosis. Ann RheumDis1969;28(1):15-23.
8Nicolino J,Lucciani JM. Apropos of osteoarthropathies inidiopathic hemochromatoses. Diabete1967;15(3):196-200.
9Du Lac Y,Deloux G,Deuil R.Arthropathies and chondrocalcinosis duringhemochromatosis. Rev Rhum Mal Osteoartic1967;34(12):758-769.
10Dorfmann H, Solnica J, Mitrovic D, Dreyfus P. Changes of bones and joints inhemochromatosis. Munch Med Wochenschr1969;111(25):1396-1401.
11Lynch SR, Seftel HC, Wapnick AA, Charlton RW, Bothwell TH. Some aspects ofcalcium metabolism in normal and osteoporotic Bantu subjects with specialreference to the effects of iron overload and ascorbic acid depletion. S Afr J MedSci1970;35(2):45-56.
12de Seze S, Solnica J, Mitrovic D, Miravet L, Dorfmann H. Joint and bone disordersand hypoparathyroidism in hemochromatosis. Semin Arthritis Rheum1972;2(1):71-94.
13Sabando P, Miravet L, Dorfman H, Kahn MF, Tun Chot S, Bordier P, Hioco D, DeSeze S. The osteopathy of hemochromatosis. Clinical and biological study. RevClin Esp1973;129(6):545-550.
14Urbina B, de Miguel Mendieta E, Gijon-Banos JG. Joint disease in idiopathichemochromatosis. Rev Rhum Mal Osteoartic1983;50(8-9):585-587.
15Diamond T, Stiel D, Posen S. Osteoporosis in hemochromatosis: iron excess,gonadal deficiency, or other factors? Ann Intern Med1989;110(6):430-436.
16Conte D, Caraceni MP, Duriez J, Mandelli C, Corghi E, Cesana M, Ortolani S,Bianchi PA. Bone involvement in primary hemochromatosis and alcoholic cirrhosis.Am J Gastroenterol1989;84(10):1231-1234.
17Axford JS. Rheumatic manifestations of haemochromatosis. Baillieres ClinRheumatol1991;5(2):351-365.
18Sinigaglia L,Fargion S,Fracanzani AL,Binelli L, Battafarano N, Varenna M,PipernoA,Fiorelli G.Bone and joint involvement ingenetic hemochromatosis: role of cirrhosis and iron overload. J Rheumatol1997;24(9):1809-1813.
19Zeevaert B, Crielaard JM. Osteoarticular hemochromatosis. Rev Med Liege1999;54(3):169-174.
20Vaiopoulos G,Papanikolaou G,Politou M,Jibreel I,Sakellaropoulos N, LoukopoulosD.Arthropathy in juvenile hemochromatosis. Arthritis Rheum2003;48(1):227-230.
21Rollot F, Wechsler B, du Boutin le TH, De Gennes C, Amoura Z, Hachulla E, PietteJC. Hemochromatosis and femoral head aseptic osteonecrosis: a nonfortuitousassociation? J Rheumatol2005;32(2):376-378.
22Guggenbuhl P, Deugnier Y, Boisdet JF, Rolland Y, Perdriger A, Pawlotsky Y,Chales G. Bone mineral density in men with genetic hemochromatosis and HFEgene mutation. Osteoporos Int2005;16(12):1809-1814.
23Chales G, Guggenbuhl P, Pawlotsky Y. Iron overload and arthropathy. Rev Prat2006;56(19):2135-2140.
24Valenti L, Varenna M, Fracanzani AL, Rossi V, Fargion S, Sinigaglia L. Associationbetween iron overload and osteoporosis in patients with hereditaryhemochromatosis. Osteoporos Int2009;20(4):549-555.
25Richette P, Ottaviani S, Vicaut E, Bardin T. Musculoskeletal complications ofhereditary hemochromatosis: a case-control study. J Rheumatol2010;37(10):2145-2150.
26Guggenbuhl P, Fergelot P, Doyard M, Libouban H, Roth MP, Gallois Y, Chales G,Loreal O, Chappard D. Bone status in a mouse model of genetic hemochromatosis.Osteoporos Int2011;22(8):2313-2319.
27Guggenbuhl P, Brissot P, Loreal O. Haemochromatosis: The bone and the joint.Best Pract Res Clin Rheumatol2011;25(5):649-664.
28Lorincz G, Traub NE, Chuke PO, Hussain SF. African haemosiderosis associatedwith osteoporosis and vertebral collapse. East Afr Med J1974;51(6):488-495.
29Schnitzler CM, Macphail AP, Shires R, Schnaid E, Mesquita JM, Robson HJ.Osteoporosis in African hemosiderosis: role of alcohol and iron. J Bone Miner Res1994;9(12):1865-1873.
30Schnitzler CM, Schnaid E, MacPhail AP, Mesquita JM, Robson HJ. Ascorbic aciddeficiency, iron overload and alcohol abuse underlie the severe osteoporosis inblack African patients with hip fractures--a bone histomorphometric study. CalcifTissue Int2005;76(2):79-89.
31Rioja L, Girot R, Garabedian M, Cournot-Witmer G. Bone disease in children withhomozygous beta-thalassemia. Bone Miner1990;8(1):69-86.
32Mahachoklertwattana P, Sirikulchayanonta V, Chuansumrit A, Karnsombat P,Choubtum L, Sriphrapradang A, Domrongkitchaiporn S, Sirisriro R, Rajatanavin R.Bone histomorphometry in children and adolescents with beta-thalassemia disease:iron-associated focal osteomalacia. J Clin Endocrinol Metab2003;88(8):3966-3972.
33Voskaridou E, Terpos E. New insights into the pathophysiology and management ofosteoporosis in patients with beta thalassaemia. Br J Haematol2004;127(2):127-139.
34Salama OS, Al-Tonbary YA, Shahin RA, Eldeen OA. Unbalanced bone turnover inchildren with beta-thalassemia. Hematology2006;11(3):197-202.
35Haidar R, Mhaidli H, Musallam K, Taher AT. The spine in beta thalassemiasyndromes. Spine (Phila Pa1976)2011.
36Sarrai M, Duroseau H, D'Augustine J, Moktan S, Bellevue R. Bone mass density inadults with sickle cell disease. Br J Haematol2007;136(4):666-672.
37Sadat-Ali M, Sultan O, Al-Turki H, Alelq A. Does high serum iron level induce lowbone mass in sickle cell anemia? Biometals2011;24(1):19-22.
38Wibaux C, Legroux-Gerot I, Dharancy S, Boleslawski E, Declerck N, Canva V,Mathurin P, Pruvot FR, Cortet B. Assessing bone status in patients awaiting livertransplantation. Joint Bone Spine2011;78(4):387-391.
39Topcheeva ON. Hepatic osteodystrophy in patients with liver cirrhosis. Eksp KlinGastroenterol2010(6):89-94.
40Loria I, Albanese C, Giusto M, Galtieri PA, Giannelli V, Lucidi C, Di Menna S,Pirazzi C, Corradini SG, Mennini G, Rossi M, Berloco P, Merli M. Bone disordersin patients with chronic liver disease awaiting liver transplantation. Transplant Proc2010;42(4):1191-1193.
41Goral V, Simsek M, Mete N. Hepatic osteodystrophy and liver cirrhosis. World JGastroenterol2010;16(13):1639-1643.
42Smith DL, Shire NJ, Watts NB, Schmitter T, Szabo G, Zucker SD.Hyperbilirubinemia is not a major contributing factor to altered bone mineraldensity in patients with chronic liver disease. J Clin Densitom2006;9(1):105-113.
43Diamond T, Stiel D, Lunzer M, Wilkinson M, Roche J, Posen S. Osteoporosis andskeletal fractures in chronic liver disease. Gut1990;31(1):82-87.
44Long RG, Meinhard E, Skinner RK, Varghese Z, Wills MR, Sherlock S. Clinical,biochemical, and histological studies of osteomalacia, osteoporosis, andparathyroid function in chronic liver disease. Gut1978;19(2):85-90.
45Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptidesynthesized in the liver. J Biol Chem2001;276(11):7806-7810.
46Youjia Xu, Pierre Sirois, Kai Li. Iron overload plays a unique role in osteoporosis.Blood2010; published online September9.
47Xi Huang. Treatment of osteoporosis in peri-and post-menopausal women withhepcidin. United States Patent Application Publication, Pub.No.: US2010/0204122A1.
48Xu Y, Li G, Du B, Zhang P, Xiao L, Sirois P, Li K. Hepcidin increases intracellularCa2+of osteoblast hFOB1.19through L-type Ca2+channels. Regul Pept2011;172(1-3):58-61.
49Xu Y, Zhang W, Zhang P, Xiao L, Wang A, Sirois P, Li K. Down Regulation ofFerroportin1Expression in hFOB1.19Osteoblasts by Hepcidin. Inflammation2011; accepted.
50Merono T, Sorroche P, Brites FD.[Increased iron store and its relationship withcardiovascular disease]. Medicina (B Aires)2011;71(6):566-572.
51Sipe JC, Lee P, Beutler E. Brain iron metabolism and neurodegenerative disorders.Dev Neurosci2002;24(2-3):188-196.
52Aamodt AH, Stovner LJ, Thorstensen K, Lydersen S, White LR, Aasly JO.Prevalence of haemochromatosis gene mutations in Parkinson's disease. J NeurolNeurosurg Psychiatry2007;78(3):315-317.
53Gille G, Reichmann H. Iron-dependent functions of mitochondria--relation toneurodegeneration. J Neural Transm2011;118(3):349-359.
54Guggenbuhl P, Filmon R, Mabilleau G, Basle MF, Chappard D. Iron inhibitshydroxyapatite crystal growth in vitro. Metabolism2008;57(7):903-910.
55Yamasaki K, Hagiwara H. Excess iron inhibits osteoblast metabolism. Toxicol Lett2009;191(2-3):211-215.
56Zarjou A, Jeney V, Arosio P, Poli M, Zavaczki E, Balla G, Balla J.Ferritin-Ferroxidase Activity: A Potent Inhibitor of Osteogenesis. J Bone Miner Res2009.
57Halliwell B, Gutteridge JM. Role of free radicals and catalytic metal ions in humandisease: an overview. Methods Enzymol1990;186:1-85.
58Fridovich I. The biology of oxygen radicals. Science1978;201(4359):875-880.
59Almeida M, Han L, Martin-Millan M, O'Brien CA, Manolagas SC. Oxidative stressantagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from Tcell factor-to forkhead box O-mediated transcription. J Biol Chem2007;282(37):27298-27305.
60Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, BirchmeierW. Functional interaction of beta-catenin with the transcription factor LEF-1.Nature1996;382(6592):638-642.
61Ishii KA, Fumoto T, Iwai K, Takeshita S, Ito M, Shimohata N, Aburatani H,Taketani S, Lelliott CJ, Vidal-Puig A, Ikeda K. Coordination of PGC-1beta and ironuptake in mitochondrial biogenesis and osteoclast activation. Nat Med2009;15(3):259-266.
62Tsay J, Yang Z, Ross FP, Cunningham-Rundles S, Lin H, Coleman R,Mayer-Kuckuk P, Doty SB, Grady RW, Giardina PJ, Boskey AL, Vogiatzi MG.Bone loss caused by iron overload in a murine model: importance of oxidativestress. Blood2010;116(14):2582-2589.
63Isomura H, Fujie K, Shibata K, Inoue N, Iizuka T, Takebe G, Takahashi K,Nishihira J, Izumi H, Sakamoto W. Bone metabolism and oxidative stress inpostmenopausal rats with iron overload. Toxicology2004;197(2):93-100.
64Kudo H, Suzuki S, Watanabe A, Kikuchi H, Sassa S, Sakamoto S. Effects ofcolloidal iron overload on renal and hepatic siderosis and the femur in male rats.Toxicology2008;246(2-3):143-147.
65Morabito N, Russo GT, Gaudio A, Lasco A, Catalano A, Morini E, Franchina F,Maisano D, La Rosa M, Plota M, Crifo A, Meo A, Frisina N. The "lively" cytokinesnetwork in beta-Thalassemia Major-related osteoporosis. Bone2007;40(6):1588-1594.
66Jian J, Pelle E, Huang X. Iron and menopause: does increased iron affect the healthof postmenopausal women? Antioxid Redox Signal2009;11(12):2939-2943.
67Krause A, Neitz S, Magert HJ, Schulz A, Forssmann WG, Schulz-Knappe P,Adermann K. LEAP-1, a novel highly disulfide-bonded human peptide, exhibitsantimicrobial activity. FEBS Lett2000;480(2-3):147-150.
68Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, Loreal O. A newmouse liver-specific gene, encoding a protein homologous to human antimicrobialpeptide hepcidin, is overexpressed during iron overload. J Biol Chem2001;276(11):7811-7819.
69Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A, Vaulont S.Lack of hepcidin gene expression and severe tissue iron overload in upstreamstimulatory factor2(USF2) knockout mice. Proc Natl Acad Sci U S A2001;98(15):8780-8785.
70Nicolas G, Bennoun M, Porteu A, Mativet S, Beaumont C, Grandchamp B, Sirito M,Sawadogo M, Kahn A, Vaulont S. Severe iron deficiency anemia in transgenic miceexpressing liver hepcidin. Proc Natl Acad Sci U S A2002;99(7):4596-4601.
71Fleming RE, Sly WS. Hepcidin: a putative iron-regulatory hormone relevant tohereditary hemochromatosis and the anemia of chronic disease. Proc Natl Acad SciU S A2001;98(15):8160-8162.
72Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T,Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin andinducing its internalization. Science2004;306(5704):2090-2093.
73Nemeth E, Ganz T. Regulation of iron metabolism by hepcidin. Annu Rev Nutr2006;26:323-342.
74Ganz T, Nemeth E. Iron imports. IV. Hepcidin and regulation of body ironmetabolism. Am J Physiol Gastrointest Liver Physiol2006;290(2): G199-203.
75De Domenico I, Ward DM, Langelier C, Vaughn MB, Nemeth E, Sundquist WI,Ganz T, Musci G, Kaplan J. The molecular mechanism of hepcidin-mediatedferroportin down-regulation. Mol Biol Cell2007;18(7):2569-2578.
76Rivera S, Nemeth E, Gabayan V, Lopez MA, Farshidi D, Ganz T. Synthetichepcidin causes rapid dose-dependent hypoferremia and is concentrated inferroportin-containing organs. Blood2005;106(6):2196-2199.
77Yong Ma, Youjia Xu, Aidong Wang, et al. A preliminary report of expression ofhepcidin gene in SD rats osteoporosis model. Suzhou University Journal of MedicalScience,2006,26:367-369.
78Zhang P, Xu YJ, Zhao DY, Ma Y, Xiao L, Feng YS, Du BC, Qian ZM, Li K.Increased intracellular iron and mineralization of cultured hFOB1.19cellsfollowing hepcidin activation through ferroportin-1. Saudi Med J2010;31(12):1303-1308.
79Yong Ma, Youjia Xu. Research on relationship between FPN1content and effect ofhepcidin on intracellular calcium and iron change in osteoblasts. Bone,2010,47(S):406.
80Liu G, Men P, Kenner GH, Miller SC. Age-associated iron accumulation in bone:implications for postmenopausal osteoporosis and a new target for prevention andtreatment by chelation. Biometals2006;19(3):245-251.
81Weinberg ED. Iron loading: a risk factor for osteoporosis. Biometals2006;19(6):633-635.
82Wu CH, Yang YC, Yao WJ, Lu FH, Wu JS, Chang CJ. Epidemiological evidence ofincreased bone mineral density in habitual tea drinkers. Arch Intern Med2002;162(9):1001-1006.
83Liu G, Men P, Kenner GH, Miller SC. Therapeutic effects of an oral chelatortargeting skeletal tissue damage in experimental postmenopausal osteoporosis inrats. Hemoglobin2008;32(1-2):181-190.
84Qu ZH, Zhang XL, Tang TT, Dai KR. Promotion of osteogenesis throughbeta-catenin signaling by desferrioxamine. Biochem Biophys Res Commun2008;370(2):332-337.
85Cornish J, Palmano K, Callon KE, Watson M, Lin JM, Valenti P, Naot D, Grey AB,Reid IR. Lactoferrin and bone; structure-activity relationships. Biochem Cell Biol2006;84(3):297-302.
[1] Xi Huang. Treatment of osteoporosis in peri-and post-menopausal women withhepcidin. United States Patent Application Publication, Pub.No.: US2010/0204122A1.
[2]徐又佳,钱忠明,俞晨.铁调素(Hepcidin)在骨质矿化中的作用[J].中国骨质疏松杂志,2005,11:541-543.
[3] Hamdi Kara I, Aydin S, Gemalmaz A, et al. Habitual tea drinking and bone mineraldensity in postmenopausal Turkish women: investigation of prevalence ofpostmenopausal osteoporosis in Turkey(IPPOT Study)[J]. Int J Vitam Nutr Res,2007,77:389-397.
[4] Sheng Z, Xu K, Ou Y, et al. Relationship of body composition and prevalence ofosteoporosis in central south Chinese postmenopausal women [J]. ClinEndocrinol(Oxf),2010Nov26. doi:10.1111/j.1365-2265.2010.03941.x.[Epubahead of print]
[5] North American Menopause Society. Management of osteoporosis inpostmenopausal women:2006position statement of The North AmericanMenopause Society [J]. Menopause,2006,13:340-367; quiz368-369.
[6] Choo WL, Loh FH, Ng SC. Osteoporosis in relation to menopause [J]. Ann AcadMed Singapore,2002,31:30-36.
[7] Ravn P, Bidstrup M, Wasnich RD, et al. Alendronate and estrogen-progestin in thelong-term prevention of bone loss: four-year results from the early postmenopausalintervention cohort study. A randomized, controlled trial [J]. Ann Intern Med,1999,131:935-942.
[8]李光飞,徐又佳,钱忠明.铁过载与骨质疏松关系的研究进展[J].中国骨质疏松杂志,2010,16:88-91.
[9] Jian J, Pelle E, Huang X. Iron and menopause: does increased iron affect the healthof postmenopausal women [J]? Antioxid Redox Signal,2009,11:2939-2943.
[10] Genazzani AR, Bernardi F, Pluchino N, et al. Endocrinology of menopausaltransition and its brain implications [J]. CNS Spectr,2005,10:449-457.
[11] Prior JC. Ovarian aging and the perimenopausal transition: the paradox ofendogenous ovarian hyperstimulation [J]. Endocrine,2005,26:297-300.
[12] Youjia Xu, Pierre Sirois, Kai Li. Iron overload plays a unique role in osteoporosis.Blood,2010,9: E-letter.
[13] Isomura H, Fujie K, Shibata K, et al. Bone metabolism and oxidative stress inpostmenopausal rats with iron overload [J]. Toxicology,2004,197:93-100.
[14] Ganz T. Hepcidin--a regulator of intestinal iron absorption and iron recycling bymacrophages [J]. Best Pract Res Clin Haematol,2005,18:171-182.
[15] Collins JF, Wessling-Resnick M, Knutson MD. Hepcidin regulation of irontransport [J]. J Nutr,2008,138:2284-2288.
[16] De Domenico I, Kushner JP. Reconstitution of normal hepcidin expression inHfe-deficient mice after liver transplantation: a new role of HFE in Kupffercells [J]? Gastroenterology,2010,139:25-27.
[17] Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux bybinding to ferroportin and inducing its internalization [J]. Science,2004,306:2090-2093.
[18] Zhang P, Xu YJ, Zhao DY, et al. Increased intracellular iron and mineralization ofcultured hFOB1.19cells following hepcidin activation through ferroportin-1[J].Saudi Med J,2010,31:1303-1308.
[19] Rivera S, Nemeth E, Gabayan V, et al. Synthetic hepcidin causes rapiddose-dependent hypoferremia and is concentrated in ferroportin-containing organs[J]. Blood,2005,106:2196-2199.
[20] Yong Ma, Youjia Xu. Research on relationship between FPN1content and effect ofhepcidin on intracellular calcium and iron change in osteoblasts [J]. Bone,2010,47(S):406.
[21] Weinberg ED. Iron loading: a risk factor for osteoporosis [J]. Biometals,2006,19:633-635.
[22] Weinberg ED. Role of iron in osteoporosis [J]. Pediatr Endocrinol Rev,2008,6Suppl1:81-85.
[23] Liu G, Men P, Kenner GH, et al. Age-associated iron accumulation in bone:implications for postmenopausal osteoporosis and a new target for prevention andtreatment by chelation [J]. Biometals,2006,19:245-251.
[24] Liu G, Men P, Kenner GH, et al. Therapeutic effects of an oral chelator targetingskeletal tissue damage in experimental postmenopausal osteoporosis in rats [J].Hemoglobin,2008,32:181-190.
[25]赵理平,张伟,刘虎,等.铁调素对成骨细胞骨相关基因表达的影响[J].中国骨质疏松杂志,2010,16:14-18.
[26]贾鹏,徐又佳,林华.铁调素与骨形态发生蛋白相互关系的研究进展[J].中华骨质疏松和骨矿盐疾病杂志,2010,3:128-132.
[1] Isomura H, Fujie K, Shibata K, et al. Bone metabolism and oxidative stress inpostmenopausal rats with iron overload. Toxicology,2004,197(2):93-100.
[2] Fox SW, Haque SJ, Lovibond AC, et al. The possible role of TGF-beta-inducedsuppressors of cytokine signaling expression in osteoclast/macrophage lineagecommitment in vitro. J Immunol,2003,170(7):3679-3687.
[3] Yamamoto N, Sakai F, Kon S, et al. Essential role of the cryptic epitope SLAYGLRwithin osteopontin in a murine model of rheumatoid arthritis. J Clin Invest,2003,112(2):181-188.
[4] Liu G, Men P, Kenner GH, et al. Age-associated iron accumulation in bone:implications for postmenopausal osteoporosis and a new target for prevention andtreatment by chelation. Biometals,2006,19(3):245-251.
[5] Kudo H, Suzuki S, Watanabe A, et al. Effects of colloidal iron overload on renaland hepatic siderosis and the femur in male rats. Toxicology,2008,246(2-3):143-147.
[6] Liu G, Men P, Kenner GH, et al. Therapeutic effects of an oral chelator targetingskeletal tissue damage in experimental postmenopausal osteoporosis in rats.Hemoglobin2008,32(1-2):181-190.
[7] Guggenbuhl P, Filmon R, Mabilleau G, et al. Iron inhibits hydroxyapatite crystalgrowth in vitro. Metabolism,2008,57(7):903-910.
[8] Yamasaki K, Hagiwara H. Excess iron inhibits osteoblast metabolism. Toxicol Lett,2009,191(2-3):211-215.
[9] Zarjou A, Jeney V, Arosio P, et al. Ferritin-Ferroxidase Activity: A Potent Inhibitorof Osteogenesis. J Bone Miner Res,2010,25(1):164-172.
[10] Lorget F, Clough J, Oliveira M, et al. Lactoferrin reduces in vitro osteoclastdifferentiation and resorbing activity. Biochem Biophys Res Commun,2002,296(2):261-266.
[11] Cornish J, Palmano K, Callon KE, et al. Lactoferrin and bone; structure-activityrelationships. Biochem Cell Biol,2006,84(3):297-302.
[12] Kato I, Dnistrian AM, Schwartz M, et al. Risk of iron overload among middle-agedwomen. Int J Vitam Nutr Res,2000,70(3):119-125.
[13] Zacharski LR, Ornstein DL, Woloshin S, et al. Association of age, sex, and racewith body iron stores in adults: analysis of NHANES III data. Am Heart J,2000,140(1):98-104.
[14] Sampson HW. Alcohol and other factors affecting osteoporosis risk in women.Alcohol Res Health,2002,26(4):292-298.
[15] Duane P, Raja KB, Simpson RJ, et al. Intestinal iron absorption in chronicalcoholics. Alcohol Alcohol,1992,27(5):539-544.
[16] Ioannou GN, Dominitz JA, Weiss NS, et al. The effect of alcohol consumption onthe prevalence of iron overload, iron deficiency, and iron deficiency anemia.Gastroenterology,2004,126(5):1293-1301.
[17] Harrison-Findik DD, Schafer D, Klein E, et al. Alcohol metabolism-mediatedoxidative stress down-regulates hepcidin transcription and leads to increasedduodenal iron transporter expression. J Biol Chem,2006,281(32):22974-22982.
[18] Fatima M, Nawaz H, Kassi M, et al. Determining the risk factors and prevalence ofosteoporosis using quantitative ultrasonography in Pakistani adult women.Singapore Med J,2009,50(1):20-28.
[19] Weinberg ED. Tobacco smoke iron: an initiator/promoter of multiple diseases.Biometals,2009,22(2):207-210.
[20] Sinigaglia L, Fargion S, Fracanzani AL, et al. Bone and joint involvement ingenetic hemochromatosis: role of cirrhosis and iron overload. J Rheumatol,1997,24(9):1809-1813.
[21] Guggenbuhl P, Deugnier Y, Boisdet JF, et al. Bone mineral density in men withgenetic hemochromatosis and HFE gene mutation. Osteoporos Int,2005,16(12):1809-1814.
[22] Valenti L, Varenna M, Fracanzani AL, et al. Association between iron overload andosteoporosis in patients with hereditary hemochromatosis. Osteoporos Int,2009,20(4):549-555.
[23] Gordeuk VR. African iron overload. Semin Hematol,2002,39(4):263-269.
[24] Gangaidzo IT, Moyo VM, Saungweme T, et al. Iron overload in urban Africans inthe1990s. Gut,1999,45(2):278-283.
[25] Schnitzler CM, Schnaid E, MacPhail AP, et al. Ascorbic acid deficiency, ironoverload and alcohol abuse underlie the severe osteoporosis in black Africanpatients with hip fractures--a bone histomorphometric study. Calcif Tissue Int,2005,76(2):79-89.
[26] Voskaridou E, Kyrtsonis MC, Terpos E, et al. Bone resorption is increased in youngadults with thalassaemia major. Br J Haematol,2001,112(1):36-41.
[27] Morabito N, Russo GT, Gaudio A, et al. The "lively" cytokines network inbeta-Thalassemia Major-related osteoporosis. Bone,2007,40(6):1588-1594.
[28] Shah FT, Chatterjee R, Owuso-Asante M, et al. Adults with severe sickle cellanaemia and iron overload have a high incidence of osteopenia and osteoporosis.Blood (ASH Annual Meeting Abstr),2004,104:1684.
[29] Sarrai M, Duroseau H, D'Augustine J, et al. Bone mass density in adults with sicklecell disease. Br J Haematol,2007,136(4):666-672.
[2] Choo WL, Loh FH, Ng SC. Osteoporosis in relation to menopause. Ann Acad MedSingapore,2002,31:30-36.
[3] Ravn P,Bidstrup M, Wasnich RD,et al. Alendronate and estrogen-progestin in thelong-term prevention of bone loss: four-year results from the early postmenopausalintervention cohort study A randomized, controlled trial. Ann Intern Med,1999,131:935-942.
[4]李光飞,徐又佳,钱忠明.铁过载与骨质疏松关系的研究进展.中国骨质疏松杂志,2010,16:88-91.
[5] Weinberg ED. Iron loading: a risk factor for osteoporosis. Biometals,2006,19:633-635.
[6] Weinberg ED. Role of iron in osteoporosis. Pediatr Endocrinol Rev,2008,6Suppl1:81-85.
[7] Jian J, Pelle E, Huang Xi. Iron and menopause: does increased iron affect the healthof postmenopausal women? Antioxid Redox Signal,2009,11(12):2939-2943.
[8] Hamdi Kara I, Aydin S, Gemalmaz A, et al. Habitual tea drinking and bone mineraldensity in postmenopausal Turkish women: investigation of prevalence ofpostmenopausal osteoporosis in Turkey(IPPOT Study).Int J Vitam Nutr Res,2007,77:389-397.
[9] Sheng Z, Xu K,Ou Y,etal.Relationship of body composition and prevalence ofosteoporosis in central south Chinese postmenopausal women. Clin Endocrinol(Oxf),2011,74(3):319-324.
[10] Youjia Xu,Pierre Sirois,Kai Li.Iron overload plays a unique role in osteoporosis.Blood,2010,9: E-letter.
[11] Isomura H,Fujie K,Shibata K,etal.Bone metabolism and oxidative stress inpostmenopausal rats with iron overload.Toxicology,2004,197:93-100.
[12] Kudo H,Suzuki S,Watanabe A,etal.Effects of colloidal iron overload on renal andhepatic siderosis and the femur in male rats.Toxicology,2008,246(2-3):143-147.
[13] Tsay J,Yang Z,Ross FP,Cunningham-Rundles S,Lin H,Coleman R,et al.Bone losscaused by iron overload in a murine model: importance of oxidative stress. Blood,2010,116(14):2582-2589.
[14] Guggenbuhl P, Filmon R, Mabilleau G, et al. Iron inhibits hydroxyapatite crystalgrowth in vitro.Metabolism,2008,57(7):903-910.
[15] Yamasaki K,Hagiwara H.Excess iron inhibits osteoblast metabolism. ToxicolLett,2009,191(2-3):211-215.
[16] Zarjou A,Jeney V,Arosio P,etal.Ferritin-Ferroxidase Activity:A Potent Inhibitor ofOsteogenesis.JBone Miner Res,2010,25(1):164-172.
[17] Liu G, Men P, Kenner GH, et al.Age-associated iron accumulation in bone:implications for postmenopausal osteoporosis and a new target for prevention andtreatment by chelation. Biometals,2006,19:245-251.
[18] Liu G, Men P, Kenner GH, et al. Therapeutic effects of an oral chelator targetingskeletal tissue damage in experimental postmenopausal osteoporosis in rats.Hemoglobin,2008,32:181-190.
[19] Ganz T.Hepcidin--a regulator of intestinal iron absorption and iron recycling bymacrophages. Best Pract Res Clin Haematol,2005,18:171-182.
[20] Collins JF, Wessling-Resnick M, Knutson MD. Hepcidin regulation of iron transport.JNutr,2008,138:2284-2288.
[21] De Domenico I,Kushner JP. Reconstitution of normal hepcidin expression inHfe-deficient mice after liver transplantation: a new role of HFE in Kupffercells?Gastroenterology,2010,139:25-27.
[22] Nemeth E,Tuttle MS, Powelson J,et al.Hepcidin regulates cellular iron efflux bybinding to ferroportin and inducing its internalization. Science,2004,306:2090-2093.
[23] Rivera S,Nemeth E, Gabayan V,etal.Synthetic hepcidin causes rapid dose-dependenthypoferremia and is concentrated in ferroportin-containing organs. Blood,2005,106:2196-2199.
[24] Yong Ma, Youjia Xu. Research on relationship between FPN1content and effect ofhepcidin on intracellular calcium and iron change in osteoblasts. Bone,2010,47(S):406.
[25]张鹏,徐又佳,赵东阳,等.铁调素及铁离子对人成骨细胞(hFOB1.19)内钙离子转运影响的初步报告.中国骨质疏松杂志.2008,14(7):504-507.
[1]李光飞,徐又佳,钱忠明.铁过载与骨质疏松关系的研究进展.中国骨质疏松杂志,2010,16:88-91.
[2] Weinberg ED.Iron loading: a risk factor for osteoporosis. Biometals,2006,19:633-635.
[3] Weinberg ED.Role of iron in osteoporosis. Pediatr Endocrinol Rev,2008,6Suppl1:81-85.
[4] Jian J, Pelle E, Huang Xi. Iron and menopause: does increased iron affect the healthof postmenopausal women? Antioxid Redox Signal,2009,11(12):2939-2943.
[5] Youjia Xu, Pierre Sirois, Kai Li. Iron overload plays a unique role inosteoporosis.Blood,2010,9: E-letter.
[6] Yamasaki K,Hagiwara H. Excess iron inhibits osteoblast metabolism. Toxicol Lett,2009,191(2-3):211-215.
[7] Zarjou A, Jeney V, Arosio P, et al. Ferritin-Ferroxidase Activity: A Potent Inhibitorof Osteogenesis.J Bone Miner Res,2010,25(1):164-172.
[8] Kudo H, Suzuki S, Watanabe A, et al. Effects of colloidal iron overload on renaland hepatic siderosis and the femur in male rats. Toxicology,2008,246(2-3):143-147.
[9] Tsay J, Yang Z, Ross FP, Cunningham-Rundles S, Lin H, Coleman R, et al. Boneloss caused by iron overload in a murine model: importance of oxidative stress.Blood,2010,116(14):2582-2589.
[10] Guggenbuhl P, Filmon R, Mabilleau G, et al. Iron inhibits hydroxyapatite crystalgrowth in vitro. Metabolism,2008,57(7):903-910.
[11] Kiyo-aki Ishii,Toshio Fumoto,Kazuhiro Iwai, et al. Coordination of PGC-1b andiron uptake in mitochondrial biogenesis and osteoclast activation. Nature Medicine.2009,15:259-266.
[12]王建忠,王坤正,周荣兴,等.阿仑膦酸钠干预人骨髓基质细胞OPG/RANKL的体外实验研究.中华关节外科杂志(电子版),2011,(05):625-632.
[13] Abdallah BM,Stilgren LS, Nissen N, et al. Increased RANKL/OPG mRNA ratio iniliac bone biopsies from women with hip fractures. Calcif Tissue Int,2005,76(2):90-7.
[14] Bord S,Ireland DC,Beavan SR,etal.The effects of estrogen on osteoprotegerin,ANKL,and estrogen receptor expression in human osteoblasts.Bone,2003,32(2):136-41.
[15] Boyce BF,Xing L.Functions of RANKL/RANK/OPG in bone modeling andremodeling.Arch Biochem Biophys,2008,473(2):139-46.
[16] Aubin JE, Bonnelye E.Osteoprotegerin and its ligand: a new paradigm forregulation of osteoclastogenesis and bone resorption. Osteoporos Int,2000,11(11):905-13.
[17] Kong YY, Yoshida H,Sarosi I,etal.OPGL is a key regulator of osteoclastogenesis,lymphocyte development and lymph-node organogenesis.Nature,1999,397(6717):315-23.
[1] Weinberg ED. Iron loading: a risk factor for osteoporosis. Biometals,2006,19:633-635.
[2] Liu G, Men P, Kenner GH, et al.. Age-associated iron accumulation in bone:implications for postmenopausal osteoporosis and a new target for prevention andtreatment by chelation. Biometals,2006,19:245-251.
[3] Qu ZH, Zhang XL, Tang TT, et al.. Promotion of osteogenesis through beta-cateninsignaling by desferrioxamine. Biochem Biophys Res Commun,2008,370:332-337.
[4] Jian J, Pelle E, Huang X. Iron and menopause: does increased iron affect the healthof postmenopausal women. Antioxid Redox Signal,2009,11:2939-2943.
[5] Youjia Xu, Pierre Sirois, Kai Li. Iron overload plays a unique role in osteoporosis.Blood,2010,9:E-letter.
[6] De Domenico I, Ward DM, Langelier C, et al.. The molecular mechanism ofhepcidin-mediated ferroportin down-regulation. Mol Biol Cell,2007,18:2569-2578.
[7] Rivera S, Nemeth E, Gabayan V, et al.. Synthetic hepcidin causes rapiddose-dependent hypoferremia and is concentrated in ferroportin-containing organs.Blood,2005,106:2196-2199.
[8] Park CH, Valore EV, Waring AJ, et al.. Hepcidin, a urinary antimicrobial peptidesynthesized in the liver. J Biol Chem,2001,276:7806-7810.
[9] Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia ofinflammation. Blood,2003,102:783-788.
[10] Nemeth E, Tuttle MS, Powelson J, et al.. Hepcidin regulates cellular iron efflux bybinding to ferroportin and inducing its internalization. Science (80-),2004,306:2090-2093.
[11] Zhang P, Xu YJ, Zhao DY, et al.. Increased intracellular iron and mineralization ofcultured hFOB1.19cells following hepcidin activation through ferroportin-1.Saudi Med J,2010,31:1303-1308.
[12] Ganz T. Hepcidin and its role in regulating systemic iron metabolism. HematologyAm Soc Hematol Educ Program,2006:29-35,507.
[13]王莉,段相林.铁离子对Caco-2细胞内钙离子转运的影响及钙离子浓度变化与细胞凋亡关系的研究.解剖学报,2005,36:177-181.
[14] Hallberg L, Brune M, Erlandsson M, et al.. Calcium: effect of different amounts onnonheme-and heme-iron absorption in humans. Am J Clin Nutr,1991,53:112-119.
[15] Berridge MJ, Lipp P, Bootman MD. Signal transduction. The calcium entry pas dedeux. Science (80-),2000,287:1604-1605.
[16]田万里,陶天遵,李磊.降钙素对体外培养大鼠成骨细胞内钙及钙通道电流影响的研究.中国骨质疏松杂志,2006,12:262-266.
[17] Labelle D, Jumarie C, Moreau R. Capacitative calcium entry and proliferation ofhuman osteoblast-like MG-63cells. Cell Prolif,2007,40:866-884.
[18]华坤,黄民.氟对成骨细胞样细胞胞内钙和钙通道电流的影响.中国应用生理学杂志,2003,19:179-181.
[19] Lauckner JE, Hille B, Mackie K. The cannabinoid agonist WIN55,212-2increasesintracellular calcium via CB1receptor coupling to Gq/11G proteins. Proc NatlAcad Sci U S A2005;102(52):19144-9.
[20] Varadi A, Rutter GA. Ca2+-induced Ca2+release in pancreatic islet beta-cells:critical evaluation of the use of endoplasmic reticulum-targeted "cameleons".Endocrinology2004;145(10):4540-9.
[21] Lemmens R, Larsson O, Berggren PO, Islam MS. Ca2+-induced Ca2+release fromthe endoplasmic reticulum amplifies the Ca2+signal mediated by activation ofvoltage-gated L-type Ca2+channels in pancreatic beta-cells. J Biol Chem2001;276(13):9971-7.
[22] Graves TK, Hinkle PM. Ca(2+)-induced Ca(2+) release in the pancreatic beta-cell:direct evidence of endoplasmic reticulum Ca(2+) release. Endocrinology2003;144(8):3565-74.
[23] Choi KJ, Cho DS, Kim JY, Kim BJ, Lee KM, Kim SH, et al. Ca-induced CaRelease from Internal Stores in INS-1Rat Insulinoma Cells. Korean J PhysiolPharmacol2011;15(1):53-9.
1Delbarre F.Osteoporosis in hemochromatosis.Sem Hop1960;36:3279-3294.
2Delbarre F. Osteoarticular Manifestations of Hemochromatosis. Presse Med1964;72:2973-2978.
3Duquenne M,Rohmer V,Legrand E, Chappard D, Wion Barbot N, Basle MF,Audran M,Bigorgne JC.Spontaneous multiple vertebral fractures revealed primaryhaemochromatosis.Osteoporos Int1996;6(4):338-340.
4Eyres KS, McCloskey EV,Fern ED,Rogers S, Beneton M, Aaron JE, KanisJA.Osteoporotic fractures: an unusual presentation of haemochromatosis. Bone1992;13(6):431-433.
5Kagan IE, Settarova DA, Tokarev Iu N, Burdina LM. Roentgenologic studies ofchanges of the osteoarticular system in patients with hereditary hemochromatosis.Gematol Transfuziol1989;34(10):19-24.
6Sella EJ,Goodman AH.Arthropathy secondary totransfusion hemochromatosis.J Bone Joint Surg Am1973;55(5):1077-1081.
7Wardle EN, Patton JT. Bone and joint changes in haemochromatosis. Ann RheumDis1969;28(1):15-23.
8Nicolino J,Lucciani JM. Apropos of osteoarthropathies inidiopathic hemochromatoses. Diabete1967;15(3):196-200.
9Du Lac Y,Deloux G,Deuil R.Arthropathies and chondrocalcinosis duringhemochromatosis. Rev Rhum Mal Osteoartic1967;34(12):758-769.
10Dorfmann H, Solnica J, Mitrovic D, Dreyfus P. Changes of bones and joints inhemochromatosis. Munch Med Wochenschr1969;111(25):1396-1401.
11Lynch SR, Seftel HC, Wapnick AA, Charlton RW, Bothwell TH. Some aspects ofcalcium metabolism in normal and osteoporotic Bantu subjects with specialreference to the effects of iron overload and ascorbic acid depletion. S Afr J MedSci1970;35(2):45-56.
12de Seze S, Solnica J, Mitrovic D, Miravet L, Dorfmann H. Joint and bone disordersand hypoparathyroidism in hemochromatosis. Semin Arthritis Rheum1972;2(1):71-94.
13Sabando P, Miravet L, Dorfman H, Kahn MF, Tun Chot S, Bordier P, Hioco D, DeSeze S. The osteopathy of hemochromatosis. Clinical and biological study. RevClin Esp1973;129(6):545-550.
14Urbina B, de Miguel Mendieta E, Gijon-Banos JG. Joint disease in idiopathichemochromatosis. Rev Rhum Mal Osteoartic1983;50(8-9):585-587.
15Diamond T, Stiel D, Posen S. Osteoporosis in hemochromatosis: iron excess,gonadal deficiency, or other factors? Ann Intern Med1989;110(6):430-436.
16Conte D, Caraceni MP, Duriez J, Mandelli C, Corghi E, Cesana M, Ortolani S,Bianchi PA. Bone involvement in primary hemochromatosis and alcoholic cirrhosis.Am J Gastroenterol1989;84(10):1231-1234.
17Axford JS. Rheumatic manifestations of haemochromatosis. Baillieres ClinRheumatol1991;5(2):351-365.
18Sinigaglia L,Fargion S,Fracanzani AL,Binelli L, Battafarano N, Varenna M,PipernoA,Fiorelli G.Bone and joint involvement ingenetic hemochromatosis: role of cirrhosis and iron overload. J Rheumatol1997;24(9):1809-1813.
19Zeevaert B, Crielaard JM. Osteoarticular hemochromatosis. Rev Med Liege1999;54(3):169-174.
20Vaiopoulos G,Papanikolaou G,Politou M,Jibreel I,Sakellaropoulos N, LoukopoulosD.Arthropathy in juvenile hemochromatosis. Arthritis Rheum2003;48(1):227-230.
21Rollot F, Wechsler B, du Boutin le TH, De Gennes C, Amoura Z, Hachulla E, PietteJC. Hemochromatosis and femoral head aseptic osteonecrosis: a nonfortuitousassociation? J Rheumatol2005;32(2):376-378.
22Guggenbuhl P, Deugnier Y, Boisdet JF, Rolland Y, Perdriger A, Pawlotsky Y,Chales G. Bone mineral density in men with genetic hemochromatosis and HFEgene mutation. Osteoporos Int2005;16(12):1809-1814.
23Chales G, Guggenbuhl P, Pawlotsky Y. Iron overload and arthropathy. Rev Prat2006;56(19):2135-2140.
24Valenti L, Varenna M, Fracanzani AL, Rossi V, Fargion S, Sinigaglia L. Associationbetween iron overload and osteoporosis in patients with hereditaryhemochromatosis. Osteoporos Int2009;20(4):549-555.
25Richette P, Ottaviani S, Vicaut E, Bardin T. Musculoskeletal complications ofhereditary hemochromatosis: a case-control study. J Rheumatol2010;37(10):2145-2150.
26Guggenbuhl P, Fergelot P, Doyard M, Libouban H, Roth MP, Gallois Y, Chales G,Loreal O, Chappard D. Bone status in a mouse model of genetic hemochromatosis.Osteoporos Int2011;22(8):2313-2319.
27Guggenbuhl P, Brissot P, Loreal O. Haemochromatosis: The bone and the joint.Best Pract Res Clin Rheumatol2011;25(5):649-664.
28Lorincz G, Traub NE, Chuke PO, Hussain SF. African haemosiderosis associatedwith osteoporosis and vertebral collapse. East Afr Med J1974;51(6):488-495.
29Schnitzler CM, Macphail AP, Shires R, Schnaid E, Mesquita JM, Robson HJ.Osteoporosis in African hemosiderosis: role of alcohol and iron. J Bone Miner Res1994;9(12):1865-1873.
30Schnitzler CM, Schnaid E, MacPhail AP, Mesquita JM, Robson HJ. Ascorbic aciddeficiency, iron overload and alcohol abuse underlie the severe osteoporosis inblack African patients with hip fractures--a bone histomorphometric study. CalcifTissue Int2005;76(2):79-89.
31Rioja L, Girot R, Garabedian M, Cournot-Witmer G. Bone disease in children withhomozygous beta-thalassemia. Bone Miner1990;8(1):69-86.
32Mahachoklertwattana P, Sirikulchayanonta V, Chuansumrit A, Karnsombat P,Choubtum L, Sriphrapradang A, Domrongkitchaiporn S, Sirisriro R, Rajatanavin R.Bone histomorphometry in children and adolescents with beta-thalassemia disease:iron-associated focal osteomalacia. J Clin Endocrinol Metab2003;88(8):3966-3972.
33Voskaridou E, Terpos E. New insights into the pathophysiology and management ofosteoporosis in patients with beta thalassaemia. Br J Haematol2004;127(2):127-139.
34Salama OS, Al-Tonbary YA, Shahin RA, Eldeen OA. Unbalanced bone turnover inchildren with beta-thalassemia. Hematology2006;11(3):197-202.
35Haidar R, Mhaidli H, Musallam K, Taher AT. The spine in beta thalassemiasyndromes. Spine (Phila Pa1976)2011.
36Sarrai M, Duroseau H, D'Augustine J, Moktan S, Bellevue R. Bone mass density inadults with sickle cell disease. Br J Haematol2007;136(4):666-672.
37Sadat-Ali M, Sultan O, Al-Turki H, Alelq A. Does high serum iron level induce lowbone mass in sickle cell anemia? Biometals2011;24(1):19-22.
38Wibaux C, Legroux-Gerot I, Dharancy S, Boleslawski E, Declerck N, Canva V,Mathurin P, Pruvot FR, Cortet B. Assessing bone status in patients awaiting livertransplantation. Joint Bone Spine2011;78(4):387-391.
39Topcheeva ON. Hepatic osteodystrophy in patients with liver cirrhosis. Eksp KlinGastroenterol2010(6):89-94.
40Loria I, Albanese C, Giusto M, Galtieri PA, Giannelli V, Lucidi C, Di Menna S,Pirazzi C, Corradini SG, Mennini G, Rossi M, Berloco P, Merli M. Bone disordersin patients with chronic liver disease awaiting liver transplantation. Transplant Proc2010;42(4):1191-1193.
41Goral V, Simsek M, Mete N. Hepatic osteodystrophy and liver cirrhosis. World JGastroenterol2010;16(13):1639-1643.
42Smith DL, Shire NJ, Watts NB, Schmitter T, Szabo G, Zucker SD.Hyperbilirubinemia is not a major contributing factor to altered bone mineraldensity in patients with chronic liver disease. J Clin Densitom2006;9(1):105-113.
43Diamond T, Stiel D, Lunzer M, Wilkinson M, Roche J, Posen S. Osteoporosis andskeletal fractures in chronic liver disease. Gut1990;31(1):82-87.
44Long RG, Meinhard E, Skinner RK, Varghese Z, Wills MR, Sherlock S. Clinical,biochemical, and histological studies of osteomalacia, osteoporosis, andparathyroid function in chronic liver disease. Gut1978;19(2):85-90.
45Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptidesynthesized in the liver. J Biol Chem2001;276(11):7806-7810.
46Youjia Xu, Pierre Sirois, Kai Li. Iron overload plays a unique role in osteoporosis.Blood2010; published online September9.
47Xi Huang. Treatment of osteoporosis in peri-and post-menopausal women withhepcidin. United States Patent Application Publication, Pub.No.: US2010/0204122A1.
48Xu Y, Li G, Du B, Zhang P, Xiao L, Sirois P, Li K. Hepcidin increases intracellularCa2+of osteoblast hFOB1.19through L-type Ca2+channels. Regul Pept2011;172(1-3):58-61.
49Xu Y, Zhang W, Zhang P, Xiao L, Wang A, Sirois P, Li K. Down Regulation ofFerroportin1Expression in hFOB1.19Osteoblasts by Hepcidin. Inflammation2011; accepted.
50Merono T, Sorroche P, Brites FD.[Increased iron store and its relationship withcardiovascular disease]. Medicina (B Aires)2011;71(6):566-572.
51Sipe JC, Lee P, Beutler E. Brain iron metabolism and neurodegenerative disorders.Dev Neurosci2002;24(2-3):188-196.
52Aamodt AH, Stovner LJ, Thorstensen K, Lydersen S, White LR, Aasly JO.Prevalence of haemochromatosis gene mutations in Parkinson's disease. J NeurolNeurosurg Psychiatry2007;78(3):315-317.
53Gille G, Reichmann H. Iron-dependent functions of mitochondria--relation toneurodegeneration. J Neural Transm2011;118(3):349-359.
54Guggenbuhl P, Filmon R, Mabilleau G, Basle MF, Chappard D. Iron inhibitshydroxyapatite crystal growth in vitro. Metabolism2008;57(7):903-910.
55Yamasaki K, Hagiwara H. Excess iron inhibits osteoblast metabolism. Toxicol Lett2009;191(2-3):211-215.
56Zarjou A, Jeney V, Arosio P, Poli M, Zavaczki E, Balla G, Balla J.Ferritin-Ferroxidase Activity: A Potent Inhibitor of Osteogenesis. J Bone Miner Res2009.
57Halliwell B, Gutteridge JM. Role of free radicals and catalytic metal ions in humandisease: an overview. Methods Enzymol1990;186:1-85.
58Fridovich I. The biology of oxygen radicals. Science1978;201(4359):875-880.
59Almeida M, Han L, Martin-Millan M, O'Brien CA, Manolagas SC. Oxidative stressantagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from Tcell factor-to forkhead box O-mediated transcription. J Biol Chem2007;282(37):27298-27305.
60Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, BirchmeierW. Functional interaction of beta-catenin with the transcription factor LEF-1.Nature1996;382(6592):638-642.
61Ishii KA, Fumoto T, Iwai K, Takeshita S, Ito M, Shimohata N, Aburatani H,Taketani S, Lelliott CJ, Vidal-Puig A, Ikeda K. Coordination of PGC-1beta and ironuptake in mitochondrial biogenesis and osteoclast activation. Nat Med2009;15(3):259-266.
62Tsay J, Yang Z, Ross FP, Cunningham-Rundles S, Lin H, Coleman R,Mayer-Kuckuk P, Doty SB, Grady RW, Giardina PJ, Boskey AL, Vogiatzi MG.Bone loss caused by iron overload in a murine model: importance of oxidativestress. Blood2010;116(14):2582-2589.
63Isomura H, Fujie K, Shibata K, Inoue N, Iizuka T, Takebe G, Takahashi K,Nishihira J, Izumi H, Sakamoto W. Bone metabolism and oxidative stress inpostmenopausal rats with iron overload. Toxicology2004;197(2):93-100.
64Kudo H, Suzuki S, Watanabe A, Kikuchi H, Sassa S, Sakamoto S. Effects ofcolloidal iron overload on renal and hepatic siderosis and the femur in male rats.Toxicology2008;246(2-3):143-147.
65Morabito N, Russo GT, Gaudio A, Lasco A, Catalano A, Morini E, Franchina F,Maisano D, La Rosa M, Plota M, Crifo A, Meo A, Frisina N. The "lively" cytokinesnetwork in beta-Thalassemia Major-related osteoporosis. Bone2007;40(6):1588-1594.
66Jian J, Pelle E, Huang X. Iron and menopause: does increased iron affect the healthof postmenopausal women? Antioxid Redox Signal2009;11(12):2939-2943.
67Krause A, Neitz S, Magert HJ, Schulz A, Forssmann WG, Schulz-Knappe P,Adermann K. LEAP-1, a novel highly disulfide-bonded human peptide, exhibitsantimicrobial activity. FEBS Lett2000;480(2-3):147-150.
68Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, Loreal O. A newmouse liver-specific gene, encoding a protein homologous to human antimicrobialpeptide hepcidin, is overexpressed during iron overload. J Biol Chem2001;276(11):7811-7819.
69Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A, Vaulont S.Lack of hepcidin gene expression and severe tissue iron overload in upstreamstimulatory factor2(USF2) knockout mice. Proc Natl Acad Sci U S A2001;98(15):8780-8785.
70Nicolas G, Bennoun M, Porteu A, Mativet S, Beaumont C, Grandchamp B, Sirito M,Sawadogo M, Kahn A, Vaulont S. Severe iron deficiency anemia in transgenic miceexpressing liver hepcidin. Proc Natl Acad Sci U S A2002;99(7):4596-4601.
71Fleming RE, Sly WS. Hepcidin: a putative iron-regulatory hormone relevant tohereditary hemochromatosis and the anemia of chronic disease. Proc Natl Acad SciU S A2001;98(15):8160-8162.
72Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T,Kaplan J. Hepcidin regulates cellular iron efflux by binding to ferroportin andinducing its internalization. Science2004;306(5704):2090-2093.
73Nemeth E, Ganz T. Regulation of iron metabolism by hepcidin. Annu Rev Nutr2006;26:323-342.
74Ganz T, Nemeth E. Iron imports. IV. Hepcidin and regulation of body ironmetabolism. Am J Physiol Gastrointest Liver Physiol2006;290(2): G199-203.
75De Domenico I, Ward DM, Langelier C, Vaughn MB, Nemeth E, Sundquist WI,Ganz T, Musci G, Kaplan J. The molecular mechanism of hepcidin-mediatedferroportin down-regulation. Mol Biol Cell2007;18(7):2569-2578.
76Rivera S, Nemeth E, Gabayan V, Lopez MA, Farshidi D, Ganz T. Synthetichepcidin causes rapid dose-dependent hypoferremia and is concentrated inferroportin-containing organs. Blood2005;106(6):2196-2199.
77Yong Ma, Youjia Xu, Aidong Wang, et al. A preliminary report of expression ofhepcidin gene in SD rats osteoporosis model. Suzhou University Journal of MedicalScience,2006,26:367-369.
78Zhang P, Xu YJ, Zhao DY, Ma Y, Xiao L, Feng YS, Du BC, Qian ZM, Li K.Increased intracellular iron and mineralization of cultured hFOB1.19cellsfollowing hepcidin activation through ferroportin-1. Saudi Med J2010;31(12):1303-1308.
79Yong Ma, Youjia Xu. Research on relationship between FPN1content and effect ofhepcidin on intracellular calcium and iron change in osteoblasts. Bone,2010,47(S):406.
80Liu G, Men P, Kenner GH, Miller SC. Age-associated iron accumulation in bone:implications for postmenopausal osteoporosis and a new target for prevention andtreatment by chelation. Biometals2006;19(3):245-251.
81Weinberg ED. Iron loading: a risk factor for osteoporosis. Biometals2006;19(6):633-635.
82Wu CH, Yang YC, Yao WJ, Lu FH, Wu JS, Chang CJ. Epidemiological evidence ofincreased bone mineral density in habitual tea drinkers. Arch Intern Med2002;162(9):1001-1006.
83Liu G, Men P, Kenner GH, Miller SC. Therapeutic effects of an oral chelatortargeting skeletal tissue damage in experimental postmenopausal osteoporosis inrats. Hemoglobin2008;32(1-2):181-190.
84Qu ZH, Zhang XL, Tang TT, Dai KR. Promotion of osteogenesis throughbeta-catenin signaling by desferrioxamine. Biochem Biophys Res Commun2008;370(2):332-337.
85Cornish J, Palmano K, Callon KE, Watson M, Lin JM, Valenti P, Naot D, Grey AB,Reid IR. Lactoferrin and bone; structure-activity relationships. Biochem Cell Biol2006;84(3):297-302.
[1] Xi Huang. Treatment of osteoporosis in peri-and post-menopausal women withhepcidin. United States Patent Application Publication, Pub.No.: US2010/0204122A1.
[2]徐又佳,钱忠明,俞晨.铁调素(Hepcidin)在骨质矿化中的作用[J].中国骨质疏松杂志,2005,11:541-543.
[3] Hamdi Kara I, Aydin S, Gemalmaz A, et al. Habitual tea drinking and bone mineraldensity in postmenopausal Turkish women: investigation of prevalence ofpostmenopausal osteoporosis in Turkey(IPPOT Study)[J]. Int J Vitam Nutr Res,2007,77:389-397.
[4] Sheng Z, Xu K, Ou Y, et al. Relationship of body composition and prevalence ofosteoporosis in central south Chinese postmenopausal women [J]. ClinEndocrinol(Oxf),2010Nov26. doi:10.1111/j.1365-2265.2010.03941.x.[Epubahead of print]
[5] North American Menopause Society. Management of osteoporosis inpostmenopausal women:2006position statement of The North AmericanMenopause Society [J]. Menopause,2006,13:340-367; quiz368-369.
[6] Choo WL, Loh FH, Ng SC. Osteoporosis in relation to menopause [J]. Ann AcadMed Singapore,2002,31:30-36.
[7] Ravn P, Bidstrup M, Wasnich RD, et al. Alendronate and estrogen-progestin in thelong-term prevention of bone loss: four-year results from the early postmenopausalintervention cohort study. A randomized, controlled trial [J]. Ann Intern Med,1999,131:935-942.
[8]李光飞,徐又佳,钱忠明.铁过载与骨质疏松关系的研究进展[J].中国骨质疏松杂志,2010,16:88-91.
[9] Jian J, Pelle E, Huang X. Iron and menopause: does increased iron affect the healthof postmenopausal women [J]? Antioxid Redox Signal,2009,11:2939-2943.
[10] Genazzani AR, Bernardi F, Pluchino N, et al. Endocrinology of menopausaltransition and its brain implications [J]. CNS Spectr,2005,10:449-457.
[11] Prior JC. Ovarian aging and the perimenopausal transition: the paradox ofendogenous ovarian hyperstimulation [J]. Endocrine,2005,26:297-300.
[12] Youjia Xu, Pierre Sirois, Kai Li. Iron overload plays a unique role in osteoporosis.Blood,2010,9: E-letter.
[13] Isomura H, Fujie K, Shibata K, et al. Bone metabolism and oxidative stress inpostmenopausal rats with iron overload [J]. Toxicology,2004,197:93-100.
[14] Ganz T. Hepcidin--a regulator of intestinal iron absorption and iron recycling bymacrophages [J]. Best Pract Res Clin Haematol,2005,18:171-182.
[15] Collins JF, Wessling-Resnick M, Knutson MD. Hepcidin regulation of irontransport [J]. J Nutr,2008,138:2284-2288.
[16] De Domenico I, Kushner JP. Reconstitution of normal hepcidin expression inHfe-deficient mice after liver transplantation: a new role of HFE in Kupffercells [J]? Gastroenterology,2010,139:25-27.
[17] Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux bybinding to ferroportin and inducing its internalization [J]. Science,2004,306:2090-2093.
[18] Zhang P, Xu YJ, Zhao DY, et al. Increased intracellular iron and mineralization ofcultured hFOB1.19cells following hepcidin activation through ferroportin-1[J].Saudi Med J,2010,31:1303-1308.
[19] Rivera S, Nemeth E, Gabayan V, et al. Synthetic hepcidin causes rapiddose-dependent hypoferremia and is concentrated in ferroportin-containing organs[J]. Blood,2005,106:2196-2199.
[20] Yong Ma, Youjia Xu. Research on relationship between FPN1content and effect ofhepcidin on intracellular calcium and iron change in osteoblasts [J]. Bone,2010,47(S):406.
[21] Weinberg ED. Iron loading: a risk factor for osteoporosis [J]. Biometals,2006,19:633-635.
[22] Weinberg ED. Role of iron in osteoporosis [J]. Pediatr Endocrinol Rev,2008,6Suppl1:81-85.
[23] Liu G, Men P, Kenner GH, et al. Age-associated iron accumulation in bone:implications for postmenopausal osteoporosis and a new target for prevention andtreatment by chelation [J]. Biometals,2006,19:245-251.
[24] Liu G, Men P, Kenner GH, et al. Therapeutic effects of an oral chelator targetingskeletal tissue damage in experimental postmenopausal osteoporosis in rats [J].Hemoglobin,2008,32:181-190.
[25]赵理平,张伟,刘虎,等.铁调素对成骨细胞骨相关基因表达的影响[J].中国骨质疏松杂志,2010,16:14-18.
[26]贾鹏,徐又佳,林华.铁调素与骨形态发生蛋白相互关系的研究进展[J].中华骨质疏松和骨矿盐疾病杂志,2010,3:128-132.
[1] Isomura H, Fujie K, Shibata K, et al. Bone metabolism and oxidative stress inpostmenopausal rats with iron overload. Toxicology,2004,197(2):93-100.
[2] Fox SW, Haque SJ, Lovibond AC, et al. The possible role of TGF-beta-inducedsuppressors of cytokine signaling expression in osteoclast/macrophage lineagecommitment in vitro. J Immunol,2003,170(7):3679-3687.
[3] Yamamoto N, Sakai F, Kon S, et al. Essential role of the cryptic epitope SLAYGLRwithin osteopontin in a murine model of rheumatoid arthritis. J Clin Invest,2003,112(2):181-188.
[4] Liu G, Men P, Kenner GH, et al. Age-associated iron accumulation in bone:implications for postmenopausal osteoporosis and a new target for prevention andtreatment by chelation. Biometals,2006,19(3):245-251.
[5] Kudo H, Suzuki S, Watanabe A, et al. Effects of colloidal iron overload on renaland hepatic siderosis and the femur in male rats. Toxicology,2008,246(2-3):143-147.
[6] Liu G, Men P, Kenner GH, et al. Therapeutic effects of an oral chelator targetingskeletal tissue damage in experimental postmenopausal osteoporosis in rats.Hemoglobin2008,32(1-2):181-190.
[7] Guggenbuhl P, Filmon R, Mabilleau G, et al. Iron inhibits hydroxyapatite crystalgrowth in vitro. Metabolism,2008,57(7):903-910.
[8] Yamasaki K, Hagiwara H. Excess iron inhibits osteoblast metabolism. Toxicol Lett,2009,191(2-3):211-215.
[9] Zarjou A, Jeney V, Arosio P, et al. Ferritin-Ferroxidase Activity: A Potent Inhibitorof Osteogenesis. J Bone Miner Res,2010,25(1):164-172.
[10] Lorget F, Clough J, Oliveira M, et al. Lactoferrin reduces in vitro osteoclastdifferentiation and resorbing activity. Biochem Biophys Res Commun,2002,296(2):261-266.
[11] Cornish J, Palmano K, Callon KE, et al. Lactoferrin and bone; structure-activityrelationships. Biochem Cell Biol,2006,84(3):297-302.
[12] Kato I, Dnistrian AM, Schwartz M, et al. Risk of iron overload among middle-agedwomen. Int J Vitam Nutr Res,2000,70(3):119-125.
[13] Zacharski LR, Ornstein DL, Woloshin S, et al. Association of age, sex, and racewith body iron stores in adults: analysis of NHANES III data. Am Heart J,2000,140(1):98-104.
[14] Sampson HW. Alcohol and other factors affecting osteoporosis risk in women.Alcohol Res Health,2002,26(4):292-298.
[15] Duane P, Raja KB, Simpson RJ, et al. Intestinal iron absorption in chronicalcoholics. Alcohol Alcohol,1992,27(5):539-544.
[16] Ioannou GN, Dominitz JA, Weiss NS, et al. The effect of alcohol consumption onthe prevalence of iron overload, iron deficiency, and iron deficiency anemia.Gastroenterology,2004,126(5):1293-1301.
[17] Harrison-Findik DD, Schafer D, Klein E, et al. Alcohol metabolism-mediatedoxidative stress down-regulates hepcidin transcription and leads to increasedduodenal iron transporter expression. J Biol Chem,2006,281(32):22974-22982.
[18] Fatima M, Nawaz H, Kassi M, et al. Determining the risk factors and prevalence ofosteoporosis using quantitative ultrasonography in Pakistani adult women.Singapore Med J,2009,50(1):20-28.
[19] Weinberg ED. Tobacco smoke iron: an initiator/promoter of multiple diseases.Biometals,2009,22(2):207-210.
[20] Sinigaglia L, Fargion S, Fracanzani AL, et al. Bone and joint involvement ingenetic hemochromatosis: role of cirrhosis and iron overload. J Rheumatol,1997,24(9):1809-1813.
[21] Guggenbuhl P, Deugnier Y, Boisdet JF, et al. Bone mineral density in men withgenetic hemochromatosis and HFE gene mutation. Osteoporos Int,2005,16(12):1809-1814.
[22] Valenti L, Varenna M, Fracanzani AL, et al. Association between iron overload andosteoporosis in patients with hereditary hemochromatosis. Osteoporos Int,2009,20(4):549-555.
[23] Gordeuk VR. African iron overload. Semin Hematol,2002,39(4):263-269.
[24] Gangaidzo IT, Moyo VM, Saungweme T, et al. Iron overload in urban Africans inthe1990s. Gut,1999,45(2):278-283.
[25] Schnitzler CM, Schnaid E, MacPhail AP, et al. Ascorbic acid deficiency, ironoverload and alcohol abuse underlie the severe osteoporosis in black Africanpatients with hip fractures--a bone histomorphometric study. Calcif Tissue Int,2005,76(2):79-89.
[26] Voskaridou E, Kyrtsonis MC, Terpos E, et al. Bone resorption is increased in youngadults with thalassaemia major. Br J Haematol,2001,112(1):36-41.
[27] Morabito N, Russo GT, Gaudio A, et al. The "lively" cytokines network inbeta-Thalassemia Major-related osteoporosis. Bone,2007,40(6):1588-1594.
[28] Shah FT, Chatterjee R, Owuso-Asante M, et al. Adults with severe sickle cellanaemia and iron overload have a high incidence of osteopenia and osteoporosis.Blood (ASH Annual Meeting Abstr),2004,104:1684.
[29] Sarrai M, Duroseau H, D'Augustine J, et al. Bone mass density in adults with sicklecell disease. Br J Haematol,2007,136(4):666-672.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |