Rictor/mTORC2对Akt/PI3K/FoxO信号通路的调控在骨质疏松症的机制研究

项目名称： Rictor/mTORC2对Akt/PI3K/FoxO信号通路的调控在骨质疏松症的机制研究

项目编号： No.81200647

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 赵琳

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 骨质疏松等增龄性疾病正在影响着加速老龄化进程的中国，这些疾病所造成的社会经济负担也日益显著。Rictor/mTORC2在细胞生长分化中扮演者一个重要的角色，Rictor/mTORC2能激活Akt/PI3K信号通路影响成骨细胞增殖分化，并且通过该通路影响FoxO基因的表达，改变氧化应激状态影响骨量的丢失。通过成骨细胞特异性敲除Rictor的小鼠骨密度，骨强度以及骨组织的凋亡情况的观察比较以及成骨细胞以及骨髓基质干细胞中沉默以及过表达Rictor/mTORC2基因对成骨成脂分化的影响，进一步探讨Rictor/mTORC2与Akt/PI3K信号通路的关系及相互作用的精确位点，以及对FoxO基因以及氧化应激状态的影响。为药物干预治疗骨质疏松症的提供可供开发研究的分子靶点。进一步阐述骨质疏松的发病机制，为寻找骨质疏松的治疗策略寻找契机。

中文关键词： Rictor；mTORC2；成骨细胞；破骨细胞；骨重建

英文摘要： Osteoporosis and other aging diseases are more serious in China, social and economic burden caused by these diseases are increasingly significant. Rictor/mTORC2 is a very important gene in cell growth and differentiation, Rictor/mTORC2 can activate Akt/PI3K signaling pathway, and then stimulate osteoblast proliferation and differentiation, and it also can effect FoxO gene expression through this pathway, then change the oxidative stress status and bone mass loss. We use osteoblast conditionally knockout Rictor mice to observation its effect on bone mineral density, bone strength and bone apoptosis. As well as we use osteoblast and bone marrow stem cells with silence or overexpress Rictor/mTORC2 gene and observe their change of adipogenic differentiation and osteogenic differentiation, in order to determine the interaction of Rictor/mTORC2 and Akt/PI3K pathway, as well as its effect on FoxO genes and oxidative stress. Hope this study can provide for the development of molecular targets for drug intervention in the treatment of osteoporosis.

英文关键词： Rictor；mTORC2；Osteoblasts；Osteoclasts；Bone remodeling