冲击波通过嘌呤受体调节骨髓间充质干细胞向成骨细胞分化增殖的机制

项目名称： 冲击波通过嘌呤受体调节骨髓间充质干细胞向成骨细胞分化增殖的机制

项目编号： No.31470932

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 于铁成

作者单位： 吉林大学

项目金额： 98万元

中文摘要： 冲击波，作为一种物理刺激，不需要其他化学诱导剂辅助，可直接诱导骨髓间充质干细胞（MSCs）向成骨细胞分化。这点是与众不同的，可能是冲击波治疗骨不连的机制所在。前期工作显示：冲击波引起的三磷酸腺苷（ATP）向细胞外释放，能够有效激活P2X7受体（一种嘌呤受体）信号传导通路，引起MSCs向成骨细胞分化。但是，另有研究显示：腺苷（ATP的降解产物）能够通过激活腺苷受体（另一种嘌呤受体），有效增加已经骨分化的MSCs增殖。这暗示：冲击波通过P2X7受体信号通路诱导MSCs向成骨细胞分化，再通过腺苷受体信号通路调节已分化细胞的增殖，分化和增殖是由不同信号通路控制的。国内外未见这方面的报道。本课题以此为切入点，通过体内和体外实验，研究在冲击波诱导MSCs向成骨细胞分化增殖过程中，嘌呤受体的变化和作用。这将扩大冲击波对骨科疾病的治疗潜能，为开发促进骨折愈合和防治异位骨化的新药提供理论依据。

中文关键词： 骨髓间充质干细胞；骨折愈合；体外冲击波；嘌呤受体

英文摘要： Shockwaves, acting as a kind of mechanical stimulation, can induce the osteogenic differentiation of mesenchymal stem cells (MSCs) without other osteogenic inductive reagents. This is unique, which may be the mechanism by which shockwaves promotes bone healing of nonunion fractures. Our preliminary data indicated that shockwaves released cellular ATP that activated P2X7 receptors (a kind of purinoceptors ) and downstream signaling events that caused osteogenic differentiation of hMSCs. But other researches showed that adenosine (degradation product of ATP) was able to enhance the osteogenic differentiation of MSCs by activation the P1 receptors (another purinoceptors). Those results imply that shockwave may trigger the osteogenic differentiation of MSCs via activation of P2X7 receptors, and enhance the osteogenic differentiation by the activation of P1 receptors. It is not reported whether and how shockwaves induce the osteogenic differentiation of MSCs via both activation of P2X7 receptors and P1 receptors. Our project aims to investigate the mechanism throughly, which might underscore the therapeutic potential of shockwave therapy for the treatment of orthopedic diseases and give a hand in finding new medical therapy to cure nonunion fractures or prevent the heterotopic ossification.

英文关键词： purinoceptors;oestogenic differentiation;shockwaves;mesenchymal stem cells