PPARγ通路对模拟微重力条件下大鼠骨髓间充质干细胞向成骨细胞分化的影响  

Role of PPARγ signaling pathway in osteogenic differentiation of rat bone marrowderived mesenchymal stem cells in simulated microgravity

作　　者：黄懿文[1] 杨锐[1] 陈思[1] 孙嘉[1] 陈容平[1] 黄震[2] 

机构地区：[1]南方医科大学珠江医院内分泌科,广东广州510282 [2]南方医科大学珠江医院外科教研室,广东广州510282

出　　处：《南方医科大学学报》2013年第4期573-577,共5页Journal of Southern Medical University

基　　金：广东省科技计划项目(2011B031800299)

摘　　要：目的观察过氧化物酶体增殖物激活受体γ(PPARγ)通路对模拟微重力条件下大鼠骨髓间充质干细胞(BMSC)向成骨细胞分化的影响,并通过调节PPARγ信号通路开闭影响这一分化过程。方法以大鼠BMSCs作对象,以回转器模拟微重力效应。将细胞随机分为5组,包括实验组:模拟微重力组、模拟微重力+10μmol/L吡格列酮组、模拟微重力+10μmol/L GW9662组、模拟微重力+10μmol/L吡格列酮+10μmol/L GW9662组;对照组:正常重力组。体外成骨诱导14 d后,利用茜素红进行成骨结节染色、油红-O进行脂肪细胞染色,并计算成脂率;测定各组细胞ALP活性;利用RT-PCR技术检测各组细胞PPARγmRNA表达水平。结果吡格列酮明显抑制BMSCs向成骨细胞分化,GW9662通过抑制PPARγ的激活而增加BMSCs向成骨细胞分化。结论推测PPARγ信号通路的激活是模拟微重力条件下抑制BMSCs向成骨细胞分化的主要因素之一,而通过抑制这条通路的激活可以有效预防及治疗失重导致的骨质疏松症。Objective To explore the role of peroxisome proliferator-activated receptor γ（PPARγ） signaling pathway in osteoblast differentiation of rat bone marrow mesenchymal stem cells（BMSCs） cultured in simulated microgravity.Methods Rat BMSCs were cultured in simulated microgravity（by rotating clinostat） in the presence of 10 μmol/L pioglitazone,10 μmol/L GW9662,or both pioglitazone and GW9662,with the cells cultured in normal gravity as the control group.After osteogenic induction for 14 days,the cells were stained with alizarin red for the bone nodules and with oil red-O for the fat cells,and the fat rate was calculated.ALP activity in the cells was determined in each group,and RT-PCR was performed to detect cellular expressions of PPARγ mRNA.Results Pioglitazone significantly inhibited osteoblast differentiation of the BMSCs,whereas GW9662 promoted the cell differentiation by suppressing the activation of PPARγ.Conclusion We hypothesize that the activation of PPARγ signaling pathway is one of the main mechanisms for inhibited osteoblast differentiation of rat BMSCs in simulated microgravity,and inhibiting PPARγ pathway activation can effectively prevent and treat microgravity-induced osteoporosis.

关 键 词：过氧化物酶体增殖物激活受体Γ 模拟微重力 骨髓间充质干细胞 成骨分化 

分 类 号：R85[医药卫生—航空、航天与航海医学]