酸性细胞外基质蛋白对BMSC骨向分化的调节作用及相关机理研究

项目名称： 酸性细胞外基质蛋白对BMSC骨向分化的调节作用及相关机理研究

项目编号： No.81470715

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 孙瑶

作者单位： 同济大学

项目金额： 67万元

中文摘要： 骨髓间充质干细胞（BMSC）在再生医学中有着广阔应用前景，但了解BMSC定向分化的调控机制是重要前提。近来多项重要研究表明，细胞外基质对干细胞的增殖和分化有重要的调控作用。因此，骨细胞外基质蛋白对BMSC的招募及定向分化的调控机制已成为本领域新的研究热点。牙本质基质蛋白１（DMP1）是骨组织中高表达的酸性细胞外基质蛋白，对骨发育和骨矿化有着重要的影响。我们的最新研究发现，包括DMP1在内的几种酸性骨基质蛋白联合应用可以促进ＢＭＳＣ的迁移和成骨向分化，同时该类蛋白可以在体内招募自体细胞以修复大范围骨缺损。本研究聚焦到它们中的DMP1，利用DMP1条件性基因敲除、DMP1相关整合素基因沉默、DMP1缺失后BMSC细胞转录组测序等手段，结合模式动物和体外实验探讨DMP1对BMSC增殖、黏附，迁移、定向分化等过程的调控机制，以及利用DMP1在骨再生过程中促进新骨生成和矿化。

中文关键词： 骨髓间充质干细胞；骨矿化；细胞外基质蛋白

英文摘要： Mesenchymal stem cells (BMSC) has broad applications in the treatment of diseases and tissue regeneration. But understanding the regulatory mechanisms directed differentiation of BMSC is an important prerequisite . Recently, a number of important studies have shown that the extracellular matrix have an important role on the proliferation and differentiation of stem cells. Thus, the regulatory mechanisms of bone extracellular matrix proteins on BMSC recruitment and directed differentiation of has become a new hotspot. Dentin matrix protein 1 (DMP1) is highly expressed in bone tissue, and has an important impact on bone growth and bone mineralization. Our latest research findings shows that, including DMP1, a variety of acidic bone matrix proteins can promote BMSC migration and osteogenic differentiation, and such proteins can also recruit autologous cells in the body to repair a critical size of bone defects. In this study, we focused on DMP1. By using conditional gene knockout of DMP1, DMP1 related integrin gene's silencing, cell transcriptome sequencing of BMSC without DMP1+ matrix, we will test the role of DMP1 on BMSC proliferation, adhesion , migration. Combined with animal models and in vitro experiments, we will try to explain the important roles and mechanisms of the acidic extracellular matrix proteins in bone development and bone regeneration.

英文关键词： BMSC;bone mineralization;ECM proteins