吡格列酮对肥胖小鼠骨髓间充质干细胞分化的影响  

The effects and mechanisms of PPARγ on MSC differentiation in obesity mice

作　　者：吕珊[1] 吴琳[1] 程鹏[1] 张爱森[1] 祁寒梅[1] 俞静[1] 刘娟[1] 王龙[1] 丁国宪[1] 

机构地区：[1]南京医科大学第一附属医院老年医学科,南京210029

出　　处：《中国骨质疏松杂志》2010年第4期239-243,共5页Chinese Journal of Osteoporosis

基　　金：国家自然科学基金青年基金项目(30900505)

摘　　要：目的通过建立饮食诱导的高脂小鼠的模型,观察过氧化物酶体增生物激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)激动剂吡格列酮对肥胖小鼠的骨量变化的影响以及骨髓间充质干细胞(mesenchymal stem cell,MSCs)分化的情况,探讨PPARγ与MSCs分化之间的关系及可能的作用机制。方法建立饮食诱导的肥胖鼠模型,吡格列酮(10mg·kg-1.d-1)对肥胖小鼠进行灌胃,一个月后检测肥胖小鼠及灌胃组肥胖小鼠的葡萄糖耐量,骨密度及骨组织形态学,并取小鼠原代MSC进行培养,提取其RNA,利用实时定量PCR,检测在MSCs分化过程中成骨及成脂特异性基因的表达量。结果吡格列酮灌胃的肥胖小鼠胰岛素抵抗改善的同时,骨密度虽无明显改变,但骨组织形态学中成骨细胞周长百分率明显增加,原代MSCs的成骨分化基因的表达量明显增加而成脂基因明显下降。结论PPARγ改善胰岛素抵抗的同时,促使MSCs向成骨细胞分化的能力增强,向脂肪细胞分化的能力下降,PPARγ除直接参与调节MSCs的分化外,还可能通过间接作用在MSCs的分化过程中起重要作用。Objective To explore the role of peroxisome proliferator-activated receptor γ（PPARγ） in the differentiation of MSCs in obesity mice. Methods Obese mice model was established by high-fat-diet, At sacrifice, BMD in the proximal femur was measured by dual-energy X-ray absorptiometry（DEXA）. Bone histomorphometry was performed in proximal femur with undecalcified sections. The effect of pioglitazone on differentiation of mouse MSCs was assessed by gene expression analysis by real-time quantitative PCR. Results Insulin resistance was improved, Ob. S. Pm in pioglitazone treated mice were significantly greater than those of control mice. The mRNA level of Sox9, Dlx5 and Osterix was significantly higher while PPARγ was significantly lower in MSCs from pioglitazone treated mice versus control mice. Conclusion It is indicated that PPARγ may promote the gene expression of osteogenesis and diminish the expression of adipogenesis in the MSCs through indirect way.

关 键 词：过氧化物酶体增生物激活受体Γ 吡格列酮 间充质干细胞 脂肪细胞 成骨细胞 

分 类 号：R965[医药卫生—药理学]