STAP重编程的骨髓间充质干细胞对激素性股骨头坏死的防治研究

项目名称： STAP重编程的骨髓间充质干细胞对激素性股骨头坏死的防治研究

项目编号： No.81472083

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： 叶树楠

作者单位： 华中科技大学

项目金额： 61万元

中文摘要： 激素性股骨头坏死的确切发病机制尚不明确，有研究表明激素能诱导骨髓间充质干细胞(MSCs) 脂质空泡形成，抑制成骨分化，从而诱发或加重骨坏死。环境诱导获得性多能性(STAP)重编程技术是一项革新性技术，通过表观修饰调控能高效地将体细胞重排为多能干细胞。本项目在明确了激素性股骨头坏死患者MSC基因组DNA存在过甲基化修饰的前期工作基础上(国家自然科学基金面上项目，81171750)，设想激素通过染色质的表观遗传修饰，引起干性基因及成骨相关基因转录沉默，继而MSC丧失干性表型及成骨分化潜能，朝脂肪化转变，引起骨代谢失衡，最终导致股骨头坏死、塌陷。我们拟通过STAP重编程技术改造激素性骨坏死的MSCs，通过免疫沉淀+芯片技术观察STAP重编程过程中DNA甲基化和组蛋白修饰的动态变化，阐明各分子事件间的相互联系，使MSC异常的表观修饰得以逆转（重编），改变MSC的命运选择，恢复成骨与成脂的动态平衡。

中文关键词： 环境诱导获得性多能性；重编程；骨髓间充质干细胞；激素性股骨头坏死；成骨分化

英文摘要： The precious mechanism of steroid induced osteonecrosis of femoral head (ONFH) is unclear. Previous studies suggested steroid initiated or worsed ONFH by inducing lipid vacuoles of MSCs and inhibit osteogenesis. STAP reprogramming, which is innovative, can reprogramme somatic cells to stem cells by modulation of epigenetics. Based on the previous research that genome-wide DNA was hypermethylated in the patients with ONFH, we assume that steroid led to transcription silencing of pluripotent and osteogenic genes by chromosome epigenetic modifications. Subsequently, MSCs lost pluripotency and osteogenic potential, became adipogenic. Finally, the femoral head was necrotic and collapsed. We planned to transform them to STAP stem cells, observe the dynamic process of epigenetic modifications, clarify relationship amoung different molecule events, reverse the aberrant epigenetic modifications and fate determination of MSCs so as to keep osteogenesis and adipogenesis balanced.

英文关键词： STAP;reprogramming;MSC;steroid-induced osteonecrosis of femoral head;osteogenic differentiation