高糖环境中吡格列酮对MC3T3-E1成骨细胞的作用及其机制  

Effects of pioglitazone on MC3T3-E1 osteoblasts in high glucose condition and its mechanism

作　　者：李美蓉[1,2] 林经安[3] 严孙杰[1] 

机构地区：[1]福建医科大学附属第一医院内分泌科,福建福州350005 [2]晋江市医院内分泌科,福建晋江362200 [3]福建医科大学附属第一医院中心实验室,福建福州350005

出　　处：《中国新药与临床杂志》2011年第1期24-29,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：福建省自然科学基金资助项目(2009J01135)

摘　　要：目的观察高糖环境下吡格列酮对MC3T3-E1成骨细胞的作用并探讨其可能机制。方法高糖(22.5 mmol·L^(-1))环境培养MC3T3-E1细胞,分为对照组,吡格列酮2.5、5、10μmol·L^(-1)组,干预24、48 h。检测细胞增殖活性、凋亡率、骨钙素和碱性磷酸酶(ALP)分泌水平,以及过氧化物酶体增殖物激活受体γ(PPARγ)、成骨因子runt相关基因2(Runx2)和骨形态蛋白2(BMP-2)mRNA的表达水平。并分析PPARγ、Runx2的表达与骨钙素、ALP、BMP-2的相关性。结果在相同干预时限,吡格列酮各组MC3T3-E1成骨细胞增殖活性、骨钙素和ALP的分泌水平、Runx2 mRNA和BMP-2 mRNA的表达均低于对照组,凋亡率和PPARγmRNA的表达高于对照组(P<0.05)。随吡格列酮浓度增加,细胞增殖活性、骨钙素和ALP的分泌、Runx2 mRNA和BMP-2 mRNA的表达均降低,而细胞凋亡率和PPARγmRNA的表达增高(P<0.05)。与干预24 h相比,干预48 h时相同浓度吡格列酮组细胞增殖活性,骨钙素和ALP的分泌水平,PPARγ、Runx2、BMP-2 mRNA的表达或无变化或略增加。结论高糖环境下吡格列酮对成骨细胞有损害作用,促进PPARγ表达、抑制Runx2的表达可能为其作用机制之一。AIM To assess the effects of pioglitazone on MC3T3-E1 osteoblasts which were exposed to constant high glucose condition,and try to explore the possible mechanisms.METHODS The MC3T3-E1 osteoblasts cultured in vitro high glucose condition（22.5 mmol·L^（-1）） were divided into four groups（control group（without pioglitazon）,pioglitazone 2.5,5 and 10μmol·L^（-1） group）,and intervened with different concentrations of pioglitazone for 24 and 48 hours.The cell proliferation ability,cells apoptosis,the levels of osteocalcin and ALP and the transcription of PPARγ,Runx2,BMP-2 mRNA were tested.The relevance of the expression of PPARγand Runx2 with osteocalcin,ALP,BMP-2 was analyzed.RESULTS At the same intervening time,the MC3T3-E1 osteoblast proliferation ability,secretion levels of osteocalcin and ALP, expressions of Runx2 mRNA and BMP-2 mRNA in the pioglitazone groups were lower than the control group （P0.05）.The apoptosis rates and expression of PPARγmRNA of the pioglitazone groups compared with the control group were significantly higher（P0.05）.With the increasing concentrations of pioglitazone,cell proliferation ability,secretion levels of osteocalcin and ALP,expressions of Runx2 mRNA and BMP-2 mRNA decreased,while the apoptosis rates and expression of PPARγmRNA increased（P0.05）.Compared with the intervention 24 hours,cell proliferation ability,secretion levels of osteocalcin and ALP,expressions of PPARγmRNA,Runx2 mRNA,BMP-2 mRNA of the same pioglitazone concentration groups in intervention 48 hours did not change or slightly increased.CONCLUSION Pioglitazone may damage osteoblasts in high glucose condition.Promoting PPARγexpression and inhibiting Runx2 expression may be one of the mechanisms.

关 键 词：吡格列酮 成骨细胞 骨钙素 碱性磷酸酶 骨形态发生蛋白质类 

分 类 号：R977.15[医药卫生—药品]