miR-17-92家族调控自噬恢复衰老干细胞生物学特性的机制研究

项目名称： miR-17-92家族调控自噬恢复衰老干细胞生物学特性的机制研究

项目编号： No.31200972

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 刘文佳

作者单位： 中国人民解放军第四军医大学

项目金额： 22万元

中文摘要： 骨质疏松是一种衰老相关性疾病，间充质干细胞（MSCs）生物学特性的改变是导致骨质疏松的重要原因。自噬的主要功能是清除细胞内多余的蛋白质或者衰老损伤的细胞器。衰老过程中细胞自噬活动下降，然而自噬是否通过影响MSCs的生物学特性从而引发骨质疏松尚不明确。本课题组前期研究发现miR-17-92家族与MSCs骨向分化及衰老密切相关，且microRNAs能够从转录后水平调控细胞的自噬。因此，本课题拟通过体内、外两部分实验,从自噬与MSCs生物学特性的关系、miR-17-92家族调控自噬的机制、及miR-17-92家族对衰老所致骨质疏松动物模型的治疗三个方面探讨microRNAs、自噬及干细胞生物学特性之间的关系。本研究不但为microRNAs治疗衰老所致骨质疏松提供一定的理论依据，而且能为microRNAs治疗其他衰老相关性疾病提供一定的参考，同时丰富了自噬的相关研究，具有重要的理论与临床意义。

中文关键词： 衰老；骨质疏松；自噬；骨髓间充质干细胞；microRNA

英文摘要： Osteoporosis is a common disease of bones that relates to the senescence. Among the pathogenesis of osteoporosis, the amount and biological characteristic of mesenchymal stem cells (MSCs) are decreased during the senescence is the most important reason. Autophagy is a catabolic process involving the degradation of a cell's own components through the lysosomal machinery. It plays an important role in maintain internal environment stably. Autophagic activity declined during the senescence, however, the relationship between autophagy and biological characteristic of MSCs as well as osteoporosis is not yet fully understood. Our team found that the miR-17-92 cluster regulated osteoblastic differentiation and senescence of MSCs. Furthermore, some researches reported that microRNAs interfered with translation of specific target mRNAs could regulate autophagy from post-transcriptional level. In this study, in vitro and in vivo experiments were used to research the relationship between autophagy and biological characteristic of MSCs; regulatory mechansim between miR-17-92 cluster and autophagy; and the treatment effect of using miR-17-92 cluster in animal model. According to the results, we want to elucidate the regulatory loop among miRNAs, autophagy and biology characteristic of stem cells clearly. Our research not onl

英文关键词： aging；osteoporosis；autophagy；bone marrow-derived mesenchymal stem cells；microRNA