不同氧分压下Runx2信号轴与SDF-1信号轴的交叉对话对静脉移植的MSCs定向归巢效应的影响

项目名称： 不同氧分压下Runx2信号轴与SDF-1信号轴的交叉对话对静脉移植的MSCs定向归巢效应的影响

项目编号： No.81472103

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： 李章华

作者单位： 武汉大学

项目金额： 72万元

中文摘要： 本课题拟在前期研究基础上，探讨氧分压与股骨头坏死程度、MSCs定向归巢效应之间的时效关系，以深入了解影响MSCs定向归巢效应和股骨头坏死修复的调控因素及其作用机制，为制定针对性的ANFH治疗方案奠定基础。另外，期望了解Runx2信号轴和SDF-1信号轴的交叉对话增强不同氧分压下MSCs归巢效应的作用机制，为更好地应用MSCs治疗ANFH奠定基础。实验综合运用实时荧光定量PCR、Western blotting分析、激光共聚焦显微镜、流式细胞仪、影像学及组织学等方法，在体内外观察不同氧浓度/氧分压下MSCs增殖、成骨分化、迁移能力及Runx2信号轴和SDF-1信号轴表达；再通过基因转染或拮抗剂激活或阻断两个信号轴的交叉对话，阐明两个信号轴的交叉对话增强不同氧浓度/氧分压下MSCs归巢效应的作用机制，为应用MSCs治疗ANFH提供更有力的实验依据。

中文关键词： 缺血性股骨头坏死；间充质干细胞；氧分压；归巢；迁移

英文摘要： On the base of primary study, this research investigates the time-effect relationship between oxygen pressure and femoral head necrosis and MSCs homing effect, so as to understand the mechanism and regulatory factors of MSCs homing and femoral head necrosis healing, therefore provide the basis for designing the therapeutic schedule of ANFH. On the other hand, we hope to understand the mechanism of strengthen effect on MSCs homing via cross talk between Runx2 and SDF-1 signaling axis under different oxygen pressure, to provide the basis for treatment ANFH through using MSCs.Firstly, through using Real-time PCR, Western blotting, laser scanning confocal microscopy, flow cytometry, radiological imaging and histologic methods, we will observe not only MSCs' proliferation, osteogenic differentiation and migration capacity,but also expression of Runx2 signaling axis and SDF-1 signaling axis under different oxygen concentration/pressure. Then through transfecting or antagonist activated or block the cross talk between Runx2 and SDF-1 signaling axis, we attend to identify the mechanisms of strengthen effect on MSCs homing via cross talk between Runx2 and SDF-1 signaling axis under different oxygen concentration/pressure, so as to provide more powerful experimental basis for the application of MSCs in the treatment of ANFH.

英文关键词： avascular necrosis of femoral head;mesenchymal stem cells;oxygen pressure;homing;migration