模拟微重力条件下黄芩苷通过β-catenin和Cx43促进骨髓间充质干细胞成骨分化的研究

项目名称： 模拟微重力条件下黄芩苷通过β-catenin和Cx43促进骨髓间充质干细胞成骨分化的研究

项目编号： No.81502980

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李晨睿

作者单位： 西北工业大学

项目金额： 18.5万元

中文摘要： 骨髓间充质干细胞（BMSC）成骨分化能力减弱是导致失重性骨质流失的重要原因。β-catenin是调控成骨分化的重要分子；Cx43是Wnt/β-catenin信号通路的下游靶蛋白，在骨组织细胞重力响应和信号转导中发挥重要作用。本课题组研究发现：模拟微重力降低β-catenin 和Cx43表达；黄芩苷为天然来源的黄酮类单体，正常重力下促进BMSC成骨分化和β-catenin表达。因此推测，模拟微重力下黄芩苷通过调控β-catenin和Cx43信号促进BMSC的成骨分化。本项目拟开展以下研究：①随机回转和抗磁悬浮条件下，黄芩苷对BMSC成骨分化功能的影响；②黄芩苷对后肢去负荷大鼠骨密度、骨微观结构和力学性能的影响；③黄芩苷通过β-catenin和Cx43信号分子调节BMSC成骨分化的机制。本项目将为发掘抗失重性骨质流失的天然药物单体提供实验依据，为揭示失重性骨质流失发生机制提供理论参考。

中文关键词： 黄芩苷；模拟微重力；骨髓间充质干细胞；β-catenin；Cx43

英文摘要： Reduced osteogenic differentiation potential of bone marrow derived mesenchymal stem cells (BMSC) contributes to the induction of weightlessness induced bone loss. β-catenin is an important cell signaling modulator regulating osteogenic differentiation. As a downstream target protein of Wnt/β-catenin pathway, connexin 43 (Cx43) is a key component of the intracellular machinery responsible for signal transduction in bone to response to mechanical stimuli. Based on our previous findings, expression of β-catenin and Cx43 were down-regulated under simulated microgravity. Baicalin could promote osteogenic differentiation of BMSC and increase β-catenin level under normal gravity. Thus, we propose that baicalin could promote the osteogenic differentiation of BMSC under simulated microgravity by regulating β-catenin and Cx43. The current study aims to investigate the impact of baicalin on the BMSC osteogenic differentiation under simulated microgravity by random positioning machine and large gradient high magnetic field and to explore the effect of baicalin to promote the bone mineral density, microstructure and bone biomechanical properties of hind limb suspended rats as well as the potential mechanisms mediated by β-catenin and Cx43. The expected results may contribute to identify potential drug candidate and to reveal the potential pathogenesis of weightlessness induced bone loss.

英文关键词： baicalin;simulated microgravity;bone marrow derived mesenchymal stem cells;β-catenin;Cx43