Wnt与Notch信号协同调控钙磷植入体界面MSCs骨向分化并靶向促进其骨整合的作用及机制研究

项目名称： Wnt与Notch信号协同调控钙磷植入体界面MSCs骨向分化并靶向促进其骨整合的作用及机制研究

项目编号： No.31271032

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 李继华

作者单位： 四川大学

项目金额： 80万元

中文摘要： 钙磷复合物是目前较理想的可植入性硬组织替代材料，在生理或病理状态下有效促进植入体与主体骨形成稳定的骨整合是急需解决的主要问题，运用关键信号因子靶向调控MSCs在钙磷-骨界面上募集、增殖、骨向分化是值得探索的关键路径之一。Wnt和Notch通路是骨组织生长发育和代谢相关的主要调控信号。近年发现：两条通路之间存在着许多直接或间接的串话机制，可表现为互相协同或拮抗的耦合效应，其交互串话机制在成骨细胞系增殖、分化，改建中均起着重要作用。本课题拟将多孔nHA/PA、HA表面喷涂的钛桩植入正常及骨质疏松的SD雌性大鼠股骨，并运用流式细胞仪，RT-PCR，基因抑制消减、RNAi、Westen blot等技术探索通路中关键基因及蛋白的表达及其与MSCs增殖、分化、凋亡的对应关系，探索二通路对钙磷-骨整合的调控方式及作用环节，并运用关键信号因子靶向干预Wnt与Notch通路，发挥协同作用，有效促钙磷骨整合。

中文关键词： Ga/P骨整合；Wnt；Notch；信号通路；间充质干细胞

英文摘要： Calcium phosphate ceramic is an ideal implanted material which can be used to replace the injured hard tissues and organs, but the key point, which needs to be solved immediately, is how to form stable osseointegration in both physiological and pathological conditions. Using the given signal factors to regulate MSCs to aggregate, colonize, proliferate and differentiate into osteoblasts in the interface of bone- ceramic is worthy of exploration. Many findings obtained from detailed analyses of mice having mutations of Wnt or Notch signaling molecules have confirmed that Wnt and Notch signaling has potential roles in bone remodeling. There are two pathways of Wnt signaling: β-catenindependent canonical and independent non-canonical pathways. Wnts act on osteoblast precursor cells and promote their differentiation into mature osteoblasts through the β-catenindependent canonical pathway. Wnt proteins are palmitoylated and glycosylated ligands that play a central role in the development of hard tissues. To date, many studies have shown that some Notch pathway genes such as Lfng, Hes1, Hes5, and Hes7 have been involved in several aspects of bone formation and bone resorption and provide strong evidence that the Notch proteins are necessary for blood and vessel formation. So Wnt and Notch Signal pathway may be the two

英文关键词： Ga/P；osteointegration；Wnt Notch signal pathway；MScs；