三磷酸腺苷对骨髓间充质干细胞成骨和成脂分化的影响  

Regulating osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells by extracellular adenosine triphosphate

作　　者：李文凯[1] 张英弛 韦盛[1] 杨勇[1] 吴华[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院骨科,湖北省武汉市430030

出　　处：《中国组织工程研究》2015年第32期5085-5091,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金青年基金资助项目(81301552)~~

摘　　要：背景:骨髓间充质干细胞的功能紊乱是骨质疏松的重要病理机制,而适当力学刺激可促进骨生长、提高骨强度,同时也会使细胞分泌腺苷类物质,如三磷酸腺苷。目的:探讨三磷酸腺苷对骨髓间充质干细胞成骨和成脂肪分化的影响及其相关机制。方法:不同浓度(10,50,250μmol/L)的三磷酸腺苷刺激骨髓间充质干细胞,通过RT-qP CR检测成骨和成脂肪相关基因表达、茜素红染色和油红O染色来评估三磷酸腺苷对骨髓间充质干细胞成骨和成脂分化的影响。Western blot检测三磷酸腺苷刺激对ERK1/2通路激活的影响。结果与结论:三磷酸腺苷促进骨髓间充质干细胞成骨相关基因的表达和钙沉积,抑制成脂肪相关基因表达和脂滴生成,但不影响细胞增殖,这些影响呈剂量依赖性。三磷酸腺苷可以激活ERK1/2通路,ERK1/2通路抑制剂U0126抑制了三磷酸腺苷对骨髓间充质干细胞的促成骨抑成脂效应。BACKGROUND：Impaired balance between osteogenesis and adipogenesis of bone marrow mesenchymal stem cels is a crucial pathological mechanism of osteoporosis. Mechanical loads applied to bone tissue can increase bone formation and improve bone strength, and meanwhile lead to the release of extracelular nucleotides, such as adenosine triphosphate. OBJECTIVE： To determine the effects of adenosine triphosphate on the osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cels and to investigate the underlying mechanisms. METHODS：The effect of adenosine triphosphate （10, 50, 250 μmol/L） on differentiation of bone marrow mesenchymal stem cels were measured by osteogenic and adipogenic related genes expression, alizarin red staining and oil red O staining. The activation of ERK1/2 signaling pathway by adenosine triphosphate was tested using western blot assay. RESULTS AND CONCLUSION： Incubation of bone marrow mesenchymal stem cels with adenosine triphosphate resulted in the dose-dependent increase of osteogenic genes expression and calcium deposition, and inhibition of adipogenic genes expression and lipid droplet formation, but had no effects on cel proliferation. Adenosine triphosphate activated ERK1/2 signaling pathway, and U0126 as an ERK1/2 inhibitor restrained the effect of adenosine triphosphate on the differentiation of bone marrow mesenchymal stem cels.

关 键 词：干细胞 骨髓干细胞 三磷酸腺苷 骨髓间充质干细胞 成骨分化 成脂分化 ERK信号通路 国家自然科学基金 

分 类 号：R394.2[医药卫生—医学遗传学]