吡格列酮对小鼠成骨细胞增殖和凋亡的影响

摘要

目的:观察吡格列酮(PIO)对小鼠成骨细胞增殖和凋亡的影响.方法:将小鼠成骨MC3T3-E1细胞分为对照组和不同浓度(10 μmol/L、20μmol/L、40 μmol/L)PIO组,药物作用一定时间后,MTT法检测各组细胞的增殖活性,流式细胞仪测定细胞凋亡率,western blotting检测Wnt信号通路亡相关蛋白[β-catenin、GSK-3β和磷酸化(p)-GSK-3β]的表达情况.结果:20 μmol/L和40 μmol/L PIO作用于MC3T3-E1细胞24 h和48 h,均可抑制细胞的增殖活性(均P＜0.05);干预细胞24 h后,20 μmol/L和40 μmol/L PIO组的细胞凋亡率明显高于对照组和10 μmol/L PIO组(均P＜0.05);westem blotting结果显示,PIO作用24 h时可使β-catenin蛋白的表达下调,p-GSK-3β蛋白的表达上调(均P＜0.05).结论:PIO可以抑制小鼠成骨细胞增殖,促进小鼠成骨细胞的凋亡,该作用可能是通过抑制Wnt/β-catenin信号通路来完成的.%Objective:To observe the effects of pioglitazone (PIO) on proliferation and apoptosis of osteoblasts.Methods:Rats MC3T3-E1 cells were divided into control group and different concentrations of PIO (0,10,20,40 μmol/L)groups.The proliferation ability of cells was measured by MTT.Cell apoptosis was detected by flow cytometry.The expressions of Wnt signaling pathway related proteins was detected by western blotting.Results:The proliferation activity of MC3T3-E1 cells was inhibited by treated with 20 μmol/L and 40 μmol/L PIO for 24 h and 48 h(P＜0.05).The apoptosis rate of cells in 20 μmol/L and 40 μmol/L PIO group were higher than that in the control group and 10 μmol/L PIO group after 24 h intervention (P＜ 0.05).The protein expression of β-catenin was down-regulated,while GSK-3β expression was up-regulated by PIO treatment for 24 h.Conclusion:PIO could suppress osteoblasts proliferation and promote cell apoptosis.The effects of PIO might be related to the inhibition of Wnt/β-catenin signaling pathway.