经典Wnt及Wnt/BMP交互信号通路在续断皂苷Ⅵ防治失重导致的骨丢失中的可能分子机制

项目名称： 经典Wnt及Wnt/BMP交互信号通路在续断皂苷Ⅵ防治失重导致的骨丢失中的可能分子机制

项目编号： No.81201517

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 张蓉

作者单位： 中国人民解放军第四军医大学

项目金额： 23万元

中文摘要： 失重导致的骨丢失是航天员长期飞行面临的健康问题之一，发病机制主要为成骨细胞（OB）发生及骨形成减少。我们前期研究发现中药续断活性成分续断皂苷VI（ASA VI）在正常和失重条件下均显著促进OB分化和成熟。经典Wnt/β-catenin、BMP及Wnt/BMP交互信号通路在骨形成的过程中发挥着重要调控作用，文献和我们前期研究工作表明失重可能抑制Wnt和BMP信号通路激活。本课题拟在此基础上，采用3-D回转器模拟失重培养细胞、尾悬吊复制大鼠失重骨丢失模型，从整体动物和细胞水平证实ASA VI抗失重所致骨丢失作用；深入研究ASA VI对经典Wnt和BMP信号通路的活化作用及Wnt/BMP交互信号通路在ASA VI促进骨形成中的生物学意义。本研究将为ASA VI防治骨丢失提供实验依据，为靶向Wnt或BMP信号途径治疗骨丢失提供理论指导，为创制高效、低毒的骨丢失防治药物奠定基础，具有理论和实际意义。

中文关键词： 骨质疏松；BMP信号通路；Wnt信号通路；续断皂苷Ⅵ；模拟失重

英文摘要： Significant bone loss is one of the most serious medical concerns during long-term space flight， space flight-induced bone loss has been attributed to a decrease in osteoblast (OB) function and bone formation. Our research showed that ASA VI induce osteoblast differentiation and maturation in normal or modeled weightlessness condition. Canonical Wnt//β-catenin, BMP and cross-talk signaling between Wnt and BMP play important roles in the process of bone formation, our previous research and documentations showed that modeled weightlessness may could inhibited activation of Wnt and BMP signaling. Consequently, the aim of the present study was to systematically investigate the protective effects of ASA VI on weightlessness induced-bone loss in hindlimb unloading rats and clinorotation-induced cell, and study molecular mechanisms of Wnt/β-catenin, BMP signaling and cross-talk signaling between Wnt and BMP in antiosteoporotic effect of ASA Ⅵ under weightlessness condition. Our study will provide experiment data for ASA VI prevention and treatment of bone-loss; and provide theory guidance for treatment of bone-loss targeting signaling, and settle basis for founding new effective harmfulless antiosteoporosis agents. In a word, our study will possess theory and practical significance.

英文关键词： osteoporosis；BMP signaling；Wnt/β-catenin；ASA Ⅵ；Modeled weightlessness