内质网应激介导吡格列酮在趋化素诱导成骨细胞代谢过程中的作用机制
The effect of pioglitazone on the metabolism of osteoblasts in endoplasmic reticulum stress induced by chemerin
  
DOI:10.3969/j.issn.1006-7108.2015.10.020
中文关键词:  吡格列酮  趋化素  成骨细胞  内质网应激
英文关键词:Pioglitazone  Chemerin  Osteoblasts  Endoplasmic reticulum stress
基金项目:国家自然科学基金(81370927);陕西省自然科学基金(2013JM4009)
作者单位
刘军1 甄平1李慎松1 周胜虎1 常彦峰1 陈慧1 张航向2 何晓乐2 李旭升1* 1. 兰州军区总医院全军骨科中心甘肃 兰州 730050 2.第四军医大学西京医院老年病科陕西 西安 710032 
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中文摘要:
      目的 观察吡格列酮(Pioglitazone)对趋化素诱导成骨细胞代谢过程中的影响,探讨吡格列酮改善成骨细胞凋亡的信号转导机制。方法 将成骨细胞随机分组,选取适宜浓度的趋化素(Chemerin)进行诱导后,加入吡格列酮,观察成骨细胞活力变化。ELISA 法检测细胞趋化蛋白1(MCP-1)、E选择素(E-selection)的的影响,采用Western blot法检测成骨细胞黏附分子1(ICAM-1)、需肌醇跨膜激酶/核酸内切酶1(inositol-requiring transmembrane kinase/endonuclease 1,IRE1)、葡萄糖调节蛋白78(Glucose-regulated protein 78,GRP78)的表达变化,探究内质网应激反应在此过程中作用。结果 MTT法检测提示加入Pioglitazone后对成骨细胞活力未见明显影响;与对照组相比,成骨细胞ICAM-1、MCP-1、E-selection、IRE1、GRP78、在Chemerin组的指标较高(P<0.05),而 Pioglitazone呈浓度依赖性地抑制Chemerin所诱导的上述效应,差异具有统计学意义(P<0.05),当吡格列酮浓度为20μmol/L时效果最显著。结论 内质网应激可能参与趋化素诱导成骨细胞代谢中的细胞凋亡过程,吡格列酮可抑制趋化素的作用,对成骨细胞具有保护功能,其机制可能与抑制内质网应激反应相关。
英文摘要:
      Objective To explore the anti-apoptosis mechanism of pioglitazone in chemerin-induced primary osteoblasts under endoplasmic reticulum stress. Methods Calvarial osteoblasts were divided into four groups. The primary osteoblasts induced by chemerin were additioned with pioglitazone. The viability of the osteoblasts was detected. MCP-1 and E-selection were detected using enzyme linked immunosorbent assay (ELISA). The expressions of intercellular cell adhesion molecule-1 (ICAM-1), inositol-requiring transmembrane kinase/endonuclease 1 (IRE1), and glucose-regulated protein 78 (GRP78) were detected using Western blotting. Results MTT detection indicated that the viability of osteoblasts was not changed after addition of pioglitazone. Comparing to those in the control group, the protein expressions of ICAM-1, MCP-1, E-selection, IRE1, and GRP78 increased in chemerin group (P<0.05). These above effects of chemerin were inhibited by pioglitazone in a concentration-dependent manner, with the maximal effect of pioglitazone at a concentration of 20μmol/L. Conclusion Endoplasmic reticulum stress may be involved in cell apoptosis process during chemerin-induced osteoblast metabolism. Pioglitazone has the protect effect on osteoblasts, and the mechanism of its action may be the inhibition of endoplasmic reticulum stress.
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