Periostin在高糖条件下牙周组织中的表达及胰岛素干预调控的研究
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摘要
糖尿病是最为常见的代谢紊乱综合征，可影响胶原的合成，成熟和降解，甚至影响胶原分子本身的结构。牙周膜细胞是主要产生胶原的纤维样细胞，有建立来源于牙周膜的新附着和参与矿化组织重建的能力。因此，牙周膜细胞参与牙周组织再生的细胞数量和活性是牙周组织再生的关键因素。研究表明牙周膜细胞可参与代谢葡萄糖，是胰岛素作用的靶细胞。胰岛素能部分抑制高糖环境诱发的牙周膜细胞凋亡。Periostin蛋白特异地表达于骨膜和牙周膜组织，在骨及牙齿的形成过程中可能起着独特的作用。Periostin作为一种牙周膜成纤维细胞中高表达的细胞外受体蛋白，与维护牙周疾病中累及的牙周完整性有关。最近证实作为鼠牙周膜的关键成分，periostin与胶原纤维生成和成纤维细胞分化的调节有关。Periostin作为TGF-β1的下游因子，具有趋化心肌纤维细胞，促进胶原的合成和成熟的作用。高糖刺激可促进心肌成纤维细胞中periostin的mRNA和蛋白表达。但是糖尿病大鼠牙周组织中的periostin表达是否与正常大鼠有差异，高糖环境是否影响牙周组织中periostin的表达尚不明确。本课题的研究目的是观察糖尿病大鼠牙周组织中periostin的表达情况。研究高糖对牙周组织中periostin表达的作用，以及胰岛素对这些影响的调控和相关的信号通路。为了periostin的临床应用，已经有一些关于periostin在呼吸系统和心血管系统药物中转录的研究在进行，而我们的研究试图为将periostin应用于牙周疾病的相关治疗提供基础。
一、periostin在糖尿病大鼠牙周膜中的表达
目的：建立I型糖尿病大鼠模型，观察periostin在糖尿病大鼠和正常大鼠牙周膜中表达的差异。方法：采取在成年Wistar大鼠腹膜下一次性注射链脲佐菌素（STZ）的方法，建立稳定的1型糖尿病大鼠模型。通过组织学观察和免疫组织化学的方法，观察建模成功后4周、8周和12周的糖尿病大鼠与正常大鼠牙周膜中periostin蛋白表达的异同。结果：本实验条件下，通过在腹膜下注射STZ诱导1型糖尿病大鼠的建模成功率为94.4%。在整个实验过程中，糖尿病大鼠保持着持续稳定的高血糖状态，显著高于健康对照组（P<0.05）。免疫组织化学结果显示Periostin在所有牙齿的整个牙周膜中均有表达。糖尿病大鼠建模4W和8W时periostin在牙周膜根中区中的表达显著低于正常大鼠中的表达（p＜0.05），建模12周后periostin在牙周膜根中区中的表达显著高于正常大鼠中的表达（p＜0.05）。而糖尿病大鼠建模12W时periostin在根尖部的表达才显著高于正常大鼠（p＜0.05）。结论：本实验中建立的STZ诱导的1型糖尿病大鼠模型建模成功率高，模型稳定性好，简便迅速，适合应用于periostin在糖尿病大鼠牙周膜中表达的研究。组织学研究结果显示periostin在糖尿病大鼠建模初期牙周膜中的表达有暂时性的降低，但在建模12W时的牙周膜中的表达相比正常大鼠显著上调。
二、胰岛素对高糖条件下人牙周膜细胞增殖和periostin表达的影响
目的：研究胰岛素对高糖条件下人牙周膜细胞增殖和periostin表达的影响。方法：采用酶消+组织块法体外原代培养人牙周膜细胞，波形丝蛋白、角蛋白用免疫荧光染色法进行细胞鉴定。MTT检测不同糖浓度和胰岛素条件下人牙周膜细胞的增殖。 Western-blot和RT-PCR分析比较不同条件下人牙周膜细胞中periostin的蛋白和mRNA表达。划痕实验比较不同糖浓度条件下，加入或不加胰岛素刺激条件下人牙周膜细胞的细胞迁移速度。结果：1.体外培养的细胞波形丝蛋白染色阳性，角蛋白、S-100因子染色阴性，证实为人牙周膜细胞。2.与5.5mM组相比，25mM组人牙周膜细胞的增殖活性显著增强，与相同糖浓度组相比，加胰岛素组的细胞增殖活性均显著增加（P＜0.01）。16.5in、25in和35in组中胰岛素对细胞增殖的促进作用在10d时开始减弱，与相同糖浓度不加胰岛素组相比，细胞增殖活性没有显著性差异（P＞0.05）。3.16.5mM、25mM、35mM这三种不同高糖浓度均可以促进periostin的mRNA和蛋白表达，其中25mM糖的刺激作用最为显著，24h时periostin的表达明显高于12h和48h。胰岛素可以逆转这种趋势使periostin表达下调。4.25mM组人牙周膜细胞迁移的速度显著高于其余三组（P＜0.01）。加入胰岛素后，5.5in、16.5in和25in组细胞的迁移速度均呈现显著下降趋势（P＜0.01）。结论：1.酶消+组织块培养法可以获得大量的人牙周膜细胞，细胞活性好，增殖能力强。2.葡萄糖可以影响人牙周膜细胞的增殖活性，胰岛素可以对葡萄糖的作用产生影响。3.25mM糖可能通过促进periostin的mRNA和蛋白过表达，使人牙周膜细胞的迁移能力异常加快。而胰岛素可以拮抗这一作用。
三、胰岛素对高糖环境下人牙周膜细胞增殖及periostin表达影响的机制研究
目的：探讨PI3K/Akt信号通路在胰岛素对高糖条件下人牙周膜细胞增殖和periostin表达影响中可能的作用。方法：加入PI3K/Akt通路特异性抑制剂10μMLY294002进行干预， MTT检测人牙周膜细胞的增殖。 Westernblot分析比较不同条件下处理24h后人牙周膜细胞中periostin和Akt/P-Akt的蛋白表达。RT-PCR检测24h时periostin的mRNA水平变化。划痕实验比较12h时不同条件下人牙周膜细胞的细胞迁移速度。结果：1.从3d开始LY294002对5.5mM和25mM两种糖浓度条件下的细胞增殖活性都有显著抑制作用，且LY294002的这种抑制作用一直持续到第10d。胰岛素对细胞增殖活性的促进作用也可以被LY294002显著性抑制。2.用LY294002对人牙周膜细胞处理24h后，periostin的表达被显著抑制（p＜0.01）。分别将5.5inly和25inly组与5.5in和25in组进行比较发现，periostin和P-Akt的蛋白表达略下降，但没有统计学意义。Periostin的mRNA水平呈现相同趋势。3. LY294002使5.5mM组和25mM组人牙周膜细胞的细胞迁移速度显著性降低（p＜0.01）。5.5ly组和5.5inly组的细胞迁移速率之间无明显差异（p＞0.05），25ly组和25inly组的细胞迁移速率结果也无显著性差异（p＞0.05）。结论：1.高糖和胰岛素可能都是通过影响PI3K激酶促使人牙周膜细胞的增殖活性增加。2.高糖微环境可能通过激活PI3K/Akt通路，促进Akt的磷酸化，进而使periostin在人牙周膜细胞中过表达，从而促进了人牙周膜细胞迁移能力的异常增强。3.胰岛素可能通过影响PI3K使人牙周膜细胞的增殖活性增加。
Diabetes, the most common metabolic disorder syndrome, can affect collagensynthesis, maturation and degradation, and even affect the structure of collagenmolecule. Periodontal ligament cells are fibroblast-like cells mainly producingcollagen, possessing the ability of establishing periodontal new attachmentparticipating in reconstruction of mineralized tissue. Therefore, cells number andactivity of periodontal ligament cells are the key factors in periodontal tissueregeneration. Studies suggested that periodontal ligament cells might be involved inthe metabolism of glucose as the target cells of insulin. Insulin could partially inhibithuman periodontal ligament apoptosis caused by high glucose. Periostin proteinspecifically expressed in periosteum and periodontal ligament tissue, may play aunique role in the formation of bone and teeth. Periostin, a extracellular adapterprotein highly expressed by periodontal ligament fibroblasts, is implicated in themaintenance of periodontal integrity, which is compromised in periodontal diseases.Recently, identified as a key component of murine periodontal ligament (PDL),periostin has been implicated in the regulation of collagen fibrillogenesis andfibroblast differentiation. As the downstream factor of TGF-β1, Periostin ownschemotactic function for myocardial fibroblasts, and could promote collagensynthesis and maturation. High glucose-induced periostin protein expression in adultrat myocardial fibroblasts was decreased significantly. However, whether theexpression of periostin in periodontal tissue are different or not between diabetic ratsand normal rats, and whether the high glucose environment would influence theexpression of Periostin in periodontal tissues or not are totally not clear. Theobjective of this research:1. to observe the expression of Periostin in periodontaltissue of diabetic rats;2. to study the effect of high glucose on the expression ofPeriostin in periodontal tissue, and insulin in the regulation of it. In order to achieve the clinical application of Periostin, there have been some studies about transcriptionof Periostin in respiratory and cardiovascular system drugs. We attempt to provide abasis for the related therapeutic application of Periostin in the periodontal disease.
Periostin expression in the periodontal ligament of diabetes rat
Objective: Establishing type1diabetic rat models, to observe the differences ofperiostin expression in periodontal ligament between diabetes rat and normal rat.
Method: Type1diabetic rat models were induced by an intraperitoneal injection ofhigh dose of streptozotocin. The animals were sacrificed after4,8and12weeksrespectively. The immunohistochemical method was applied to localize and examinethe expression of periostin in periodontal tissue of rats. Results: The success rate ofinducing type1diabetes by an intraperitoneal injection of STZ was up to94.4%.During the whole experimental period, hyperglycemia in the diabetic rat models wasstable. Immunohistochemical results indicated that periostin expression inperiodontium of all teeth. Periostin expression in the middle of periodontal ligamentof diabetic rats was significantly lower than in normal rats at4th and8th week （p＜0.05）. Periostin expression in the middle of the periodontal ligament of diabeticrats was significantly higher than in normal rats at12th week（p＜0.05）.Conclusion: Type1diabetic rat models were established successfully with highsuccess rate and steady high blood glucose level. The present work establishedsuitable animal models to study periostin expression in periodontal ligament of type1diabetic rats. Histological study showed Periostin expression in periodontium ofdiabetic rats reduced temporarily at the early stage, while significantly up-regulatedcompared with normal rats at12W.
Effect of Insulin on cell proliferation and periostin expression in
hyperglycaemia in human periodontal ligament
Objective: To explore the effect of hyperglycaemia and insulin on proliferation andperiostin expression of periodontal ligament. Method: Periodontal ligament wasisolated from normal human premolar teeth and primarily cultured using thecombination of tissue explant and enzymatic digestion. Cell growth and morphology were observed under an inverted microscope. Vimentin and keratin were used toidentify the cells by immunofluorescence. Cell proliferation was valuated throughMTT assay. Periostin protein levels were determined by westernblot analysis andperiostin mRNA levels were tested by RT-PCR. Cell scratch test was performed toobserve the effect of hyperglycaemia and insulin on cell migration. Results:1.Theresults of immunofluorescence showed that vimentin was positive and keratin wasnegative in hPDLc.2.25mM glucose could improve hPDLc proliferatio（np＜0.05）.Insulin could improve hPDLc proliferation （p＜0.01）. In group16.5in,25in and35in, promotion of insulin on cells proliferation began to weaken in10d, and therewas no significant difference of proliferative activity compared with the sameconcentration of glucose without insulin group（P＞0.05）.3. Three different highglucose concentrations could promote periostin mRNA and protein expression, andthe stimulation of25mM was the most significant. Periostin expression wassignificantly higher at24h. Insulin could reverse the promoting effects of glucosewith periostin down-regulated.4. At25mM, human periodontal ligament cellmigration speed was significantly higher than the other three groups (P <0.01).Treated with insulin, migration velocity of5.5in,16.5in and25in were significantlydecreased（P＜0.01）.Conclusion: hPDLc were obtained by tissue explant combinedwith enzymatic digestion method. Hyperglycaemia conditions could effect theproliferation of hPDLc. Insulin may have an impact on the role of glucose.25mMglucose may promote periostin mRNA and protein overexpression of hPDLc,accelerating the migration of hPDLc.
The roll of PI3K/Akt pathway in insulin impact on cell proliferation and
periostin expression in hyperglycaemia in human periodontal ligament
Objective: To explore the role of PI3K/Akt pathway in hyperglycaemia andinsulin on proliferation and periostin expression of hPDLc. Method: hPDLc werecultured in different medium, containing two concentrations of glucose (5.5mM and25mM), with or without insulin or LY294002(10μM). Cell proliferation wasvaluated through MTT assay. Periostin and Akt/P-Akt protein levels were determined by westernblot analysis, periostin mRNA levels were tested by RT-PCR.Cell migration speeds was detected by scratch test. Results:1. LY294002showedsignificant inhibitory effect on cell proliferation activity in5.5mM and25mMgroups from3d till10d. The promoting effect of insulin on cell proliferation activitycould attenuated by LY294002.2. Pretreated with LY294002, the expression ofperiostin mRNA and protein were inhibited （p＜0.05）. There was no significantdifference of Periostin and P-Akt protein expression between5.5inly and25inlygroup and5.5in and25in group, respectively, with only slightly decreasedexpression.3. Pretreated with LY294002, hPDLc migration speed significantlydecreased（p＜0.01）. There was no significant difference of cell migration speedsbetween5.5inly and25inly group and5.5in and25in group, respectively（p＞0.05）.
Conclusion: Hyperglycaemia and insulin could promote hPDLc proliferation viaPI3K. Periostin overexpression in hPDLc induced by high glucose via PI3K/Aktpathway could cause cell migration promotion. hPDLc proliferation activity wasenhanced by insulin, which may be via PI3K.
一、periostin在糖尿病大鼠牙周膜中的表达
目的：建立I型糖尿病大鼠模型，观察periostin在糖尿病大鼠和正常大鼠牙周膜中表达的差异。方法：采取在成年Wistar大鼠腹膜下一次性注射链脲佐菌素（STZ）的方法，建立稳定的1型糖尿病大鼠模型。通过组织学观察和免疫组织化学的方法，观察建模成功后4周、8周和12周的糖尿病大鼠与正常大鼠牙周膜中periostin蛋白表达的异同。结果：本实验条件下，通过在腹膜下注射STZ诱导1型糖尿病大鼠的建模成功率为94.4%。在整个实验过程中，糖尿病大鼠保持着持续稳定的高血糖状态，显著高于健康对照组（P<0.05）。免疫组织化学结果显示Periostin在所有牙齿的整个牙周膜中均有表达。糖尿病大鼠建模4W和8W时periostin在牙周膜根中区中的表达显著低于正常大鼠中的表达（p＜0.05），建模12周后periostin在牙周膜根中区中的表达显著高于正常大鼠中的表达（p＜0.05）。而糖尿病大鼠建模12W时periostin在根尖部的表达才显著高于正常大鼠（p＜0.05）。结论：本实验中建立的STZ诱导的1型糖尿病大鼠模型建模成功率高，模型稳定性好，简便迅速，适合应用于periostin在糖尿病大鼠牙周膜中表达的研究。组织学研究结果显示periostin在糖尿病大鼠建模初期牙周膜中的表达有暂时性的降低，但在建模12W时的牙周膜中的表达相比正常大鼠显著上调。
二、胰岛素对高糖条件下人牙周膜细胞增殖和periostin表达的影响
目的：研究胰岛素对高糖条件下人牙周膜细胞增殖和periostin表达的影响。方法：采用酶消+组织块法体外原代培养人牙周膜细胞，波形丝蛋白、角蛋白用免疫荧光染色法进行细胞鉴定。MTT检测不同糖浓度和胰岛素条件下人牙周膜细胞的增殖。 Western-blot和RT-PCR分析比较不同条件下人牙周膜细胞中periostin的蛋白和mRNA表达。划痕实验比较不同糖浓度条件下，加入或不加胰岛素刺激条件下人牙周膜细胞的细胞迁移速度。结果：1.体外培养的细胞波形丝蛋白染色阳性，角蛋白、S-100因子染色阴性，证实为人牙周膜细胞。2.与5.5mM组相比，25mM组人牙周膜细胞的增殖活性显著增强，与相同糖浓度组相比，加胰岛素组的细胞增殖活性均显著增加（P＜0.01）。16.5in、25in和35in组中胰岛素对细胞增殖的促进作用在10d时开始减弱，与相同糖浓度不加胰岛素组相比，细胞增殖活性没有显著性差异（P＞0.05）。3.16.5mM、25mM、35mM这三种不同高糖浓度均可以促进periostin的mRNA和蛋白表达，其中25mM糖的刺激作用最为显著，24h时periostin的表达明显高于12h和48h。胰岛素可以逆转这种趋势使periostin表达下调。4.25mM组人牙周膜细胞迁移的速度显著高于其余三组（P＜0.01）。加入胰岛素后，5.5in、16.5in和25in组细胞的迁移速度均呈现显著下降趋势（P＜0.01）。结论：1.酶消+组织块培养法可以获得大量的人牙周膜细胞，细胞活性好，增殖能力强。2.葡萄糖可以影响人牙周膜细胞的增殖活性，胰岛素可以对葡萄糖的作用产生影响。3.25mM糖可能通过促进periostin的mRNA和蛋白过表达，使人牙周膜细胞的迁移能力异常加快。而胰岛素可以拮抗这一作用。
三、胰岛素对高糖环境下人牙周膜细胞增殖及periostin表达影响的机制研究
目的：探讨PI3K/Akt信号通路在胰岛素对高糖条件下人牙周膜细胞增殖和periostin表达影响中可能的作用。方法：加入PI3K/Akt通路特异性抑制剂10μMLY294002进行干预， MTT检测人牙周膜细胞的增殖。 Westernblot分析比较不同条件下处理24h后人牙周膜细胞中periostin和Akt/P-Akt的蛋白表达。RT-PCR检测24h时periostin的mRNA水平变化。划痕实验比较12h时不同条件下人牙周膜细胞的细胞迁移速度。结果：1.从3d开始LY294002对5.5mM和25mM两种糖浓度条件下的细胞增殖活性都有显著抑制作用，且LY294002的这种抑制作用一直持续到第10d。胰岛素对细胞增殖活性的促进作用也可以被LY294002显著性抑制。2.用LY294002对人牙周膜细胞处理24h后，periostin的表达被显著抑制（p＜0.01）。分别将5.5inly和25inly组与5.5in和25in组进行比较发现，periostin和P-Akt的蛋白表达略下降，但没有统计学意义。Periostin的mRNA水平呈现相同趋势。3. LY294002使5.5mM组和25mM组人牙周膜细胞的细胞迁移速度显著性降低（p＜0.01）。5.5ly组和5.5inly组的细胞迁移速率之间无明显差异（p＞0.05），25ly组和25inly组的细胞迁移速率结果也无显著性差异（p＞0.05）。结论：1.高糖和胰岛素可能都是通过影响PI3K激酶促使人牙周膜细胞的增殖活性增加。2.高糖微环境可能通过激活PI3K/Akt通路，促进Akt的磷酸化，进而使periostin在人牙周膜细胞中过表达，从而促进了人牙周膜细胞迁移能力的异常增强。3.胰岛素可能通过影响PI3K使人牙周膜细胞的增殖活性增加。
Diabetes, the most common metabolic disorder syndrome, can affect collagensynthesis, maturation and degradation, and even affect the structure of collagenmolecule. Periodontal ligament cells are fibroblast-like cells mainly producingcollagen, possessing the ability of establishing periodontal new attachmentparticipating in reconstruction of mineralized tissue. Therefore, cells number andactivity of periodontal ligament cells are the key factors in periodontal tissueregeneration. Studies suggested that periodontal ligament cells might be involved inthe metabolism of glucose as the target cells of insulin. Insulin could partially inhibithuman periodontal ligament apoptosis caused by high glucose. Periostin proteinspecifically expressed in periosteum and periodontal ligament tissue, may play aunique role in the formation of bone and teeth. Periostin, a extracellular adapterprotein highly expressed by periodontal ligament fibroblasts, is implicated in themaintenance of periodontal integrity, which is compromised in periodontal diseases.Recently, identified as a key component of murine periodontal ligament (PDL),periostin has been implicated in the regulation of collagen fibrillogenesis andfibroblast differentiation. As the downstream factor of TGF-β1, Periostin ownschemotactic function for myocardial fibroblasts, and could promote collagensynthesis and maturation. High glucose-induced periostin protein expression in adultrat myocardial fibroblasts was decreased significantly. However, whether theexpression of periostin in periodontal tissue are different or not between diabetic ratsand normal rats, and whether the high glucose environment would influence theexpression of Periostin in periodontal tissues or not are totally not clear. Theobjective of this research:1. to observe the expression of Periostin in periodontaltissue of diabetic rats;2. to study the effect of high glucose on the expression ofPeriostin in periodontal tissue, and insulin in the regulation of it. In order to achieve the clinical application of Periostin, there have been some studies about transcriptionof Periostin in respiratory and cardiovascular system drugs. We attempt to provide abasis for the related therapeutic application of Periostin in the periodontal disease.
Periostin expression in the periodontal ligament of diabetes rat
Objective: Establishing type1diabetic rat models, to observe the differences ofperiostin expression in periodontal ligament between diabetes rat and normal rat.
Method: Type1diabetic rat models were induced by an intraperitoneal injection ofhigh dose of streptozotocin. The animals were sacrificed after4,8and12weeksrespectively. The immunohistochemical method was applied to localize and examinethe expression of periostin in periodontal tissue of rats. Results: The success rate ofinducing type1diabetes by an intraperitoneal injection of STZ was up to94.4%.During the whole experimental period, hyperglycemia in the diabetic rat models wasstable. Immunohistochemical results indicated that periostin expression inperiodontium of all teeth. Periostin expression in the middle of periodontal ligamentof diabetic rats was significantly lower than in normal rats at4th and8th week （p＜0.05）. Periostin expression in the middle of the periodontal ligament of diabeticrats was significantly higher than in normal rats at12th week（p＜0.05）.Conclusion: Type1diabetic rat models were established successfully with highsuccess rate and steady high blood glucose level. The present work establishedsuitable animal models to study periostin expression in periodontal ligament of type1diabetic rats. Histological study showed Periostin expression in periodontium ofdiabetic rats reduced temporarily at the early stage, while significantly up-regulatedcompared with normal rats at12W.
Effect of Insulin on cell proliferation and periostin expression in
hyperglycaemia in human periodontal ligament
Objective: To explore the effect of hyperglycaemia and insulin on proliferation andperiostin expression of periodontal ligament. Method: Periodontal ligament wasisolated from normal human premolar teeth and primarily cultured using thecombination of tissue explant and enzymatic digestion. Cell growth and morphology were observed under an inverted microscope. Vimentin and keratin were used toidentify the cells by immunofluorescence. Cell proliferation was valuated throughMTT assay. Periostin protein levels were determined by westernblot analysis andperiostin mRNA levels were tested by RT-PCR. Cell scratch test was performed toobserve the effect of hyperglycaemia and insulin on cell migration. Results:1.Theresults of immunofluorescence showed that vimentin was positive and keratin wasnegative in hPDLc.2.25mM glucose could improve hPDLc proliferatio（np＜0.05）.Insulin could improve hPDLc proliferation （p＜0.01）. In group16.5in,25in and35in, promotion of insulin on cells proliferation began to weaken in10d, and therewas no significant difference of proliferative activity compared with the sameconcentration of glucose without insulin group（P＞0.05）.3. Three different highglucose concentrations could promote periostin mRNA and protein expression, andthe stimulation of25mM was the most significant. Periostin expression wassignificantly higher at24h. Insulin could reverse the promoting effects of glucosewith periostin down-regulated.4. At25mM, human periodontal ligament cellmigration speed was significantly higher than the other three groups (P <0.01).Treated with insulin, migration velocity of5.5in,16.5in and25in were significantlydecreased（P＜0.01）.Conclusion: hPDLc were obtained by tissue explant combinedwith enzymatic digestion method. Hyperglycaemia conditions could effect theproliferation of hPDLc. Insulin may have an impact on the role of glucose.25mMglucose may promote periostin mRNA and protein overexpression of hPDLc,accelerating the migration of hPDLc.
The roll of PI3K/Akt pathway in insulin impact on cell proliferation and
periostin expression in hyperglycaemia in human periodontal ligament
Objective: To explore the role of PI3K/Akt pathway in hyperglycaemia andinsulin on proliferation and periostin expression of hPDLc. Method: hPDLc werecultured in different medium, containing two concentrations of glucose (5.5mM and25mM), with or without insulin or LY294002(10μM). Cell proliferation wasvaluated through MTT assay. Periostin and Akt/P-Akt protein levels were determined by westernblot analysis, periostin mRNA levels were tested by RT-PCR.Cell migration speeds was detected by scratch test. Results:1. LY294002showedsignificant inhibitory effect on cell proliferation activity in5.5mM and25mMgroups from3d till10d. The promoting effect of insulin on cell proliferation activitycould attenuated by LY294002.2. Pretreated with LY294002, the expression ofperiostin mRNA and protein were inhibited （p＜0.05）. There was no significantdifference of Periostin and P-Akt protein expression between5.5inly and25inlygroup and5.5in and25in group, respectively, with only slightly decreasedexpression.3. Pretreated with LY294002, hPDLc migration speed significantlydecreased（p＜0.01）. There was no significant difference of cell migration speedsbetween5.5inly and25inly group and5.5in and25in group, respectively（p＞0.05）.
Conclusion: Hyperglycaemia and insulin could promote hPDLc proliferation viaPI3K. Periostin overexpression in hPDLc induced by high glucose via PI3K/Aktpathway could cause cell migration promotion. hPDLc proliferation activity wasenhanced by insulin, which may be via PI3K.
引文
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