内质网应激信号在碳纳米管调控BMSC成骨分化与凋亡中的作用及机制研究

项目名称： 内质网应激信号在碳纳米管调控BMSC成骨分化与凋亡中的作用及机制研究

项目编号： No.31300791

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 邱彤

作者单位： 武汉理工大学

项目金额： 25万元

中文摘要： 碳纳米管作为干细胞生长和分化的基质在再生医学领域具有重要的应用前景，了解其对细胞分化和凋亡的影响具有重大的临床意义。目前，碳纳米管影响干细胞凋亡和分化的分子机制研究非常匮乏。申请者前期研究发现，碳纳米管刺激骨髓间充质干细胞产生了内质网应激。内质网应激具有双向介导细胞凋亡和存活的作用。特别是在成骨细胞的研究中，已证实应激能特异性促进细胞的成骨分化。本项目将围绕内质网应激，分析碳纳米管激活内质网应激信号通路调控骨髓间充质干细胞成骨分化与凋亡的作用机制。首先验证碳纳米管刺激下干细胞内质网应激的发生及其与材料剂量和作用时间之间的关系。再在诱导细胞凋亡和细胞分化的条件下，运用定量PCR,蛋白印迹和蛋白质组学方法研究碳纳米管对干细胞凋亡和分化的调控机制，分析内质网应激在调控过程中的作用，揭示纳米材料信号- - 内质网应激信号- - 细胞效应信号之间的信号传递路径，为优化碳纳米管基组织工程支架材料提供实验依据。

中文关键词： 碳纳米管；骨髓间充质干细胞；内质网应激；凋亡；分化

英文摘要： Carbon nanotubes have important application in the field of regenerative medicine, especially as the matrix for stem cell growth and differentiation. It is of great clinical significance to understand the effect on the cell differentiation and apoptosis from carbon nanotubes. So far, the mechanisms underline the effects on differentiation and apoptosis of stem cells derived from carbon nanotubes stimulation are still scarce. We know little about the signal transduction form materials to the cells and the intracellular signal transduction pathway. Our previous study suggested that endoplasmic reticulum stress occurred when the bone marrow mesenchymal stem cells co-cultured with carbon nanotubes. The endoplasmic reticulum stress(ERs) is believed to guide the bi-phasic response - differentiation pathway or the apoptotic pathway dependent on the extent of ERs. In this project, we will study how the ERs derived form carbon nanotubes regulates the bone marrow mesenchymal stem cell osteogenesis differentiation and apoptosis. Firstly, we will identify the occurrence of ERs in cells when co-cultured with carbon nanotubes and further analysis the relationship between the ERs and the time or the dose of carbon nanotubes. Secondly, in the process of cell apoptosis or cell differentiation, real-time PCR, western blot and pro

英文关键词： carbon nanotubes；bone mesenchymal stem cells；endoplasmic reticulum stress；apoptosis；differentiation