模拟失重下破骨细胞源性外泌体中调节骨形成相关miRNAs的筛选及功能研究

项目名称： 模拟失重下破骨细胞源性外泌体中调节骨形成相关miRNAs的筛选及功能研究

项目编号： No.31500688

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 呼延霆

作者单位： 西北工业大学

项目金额： 20万元

中文摘要： 长期空间飞行中，失重性骨丢失已被列为影响航天员生命健康的首要风险因素。失重环境中，航天员体内骨代谢调控的失衡导致了骨丢失的发生。破骨细胞在骨代谢调控中扮演着重要的角色，申请者前期研究表明破骨细胞在模拟失重下可通过旁分泌途径调节成骨细胞的功能，进一步研究发现破骨细胞外泌体可抑制成骨细胞的骨形成。同时，国内外研究表明外泌体中的miRNAs对骨代谢有重要的调控作用。据此，我们提出了“模拟失重下破骨细胞外泌体miRNAs可能作为一种关键的信使参与骨形成的调控过程”这一科学假设。本项目拟利用尾悬吊、随机回转及抗磁悬浮分别建立模拟失重动物、细胞模型，采用高通量测序、分子细胞生物学等研究方法，从分子—细胞—整体各个层面揭示破骨细胞外泌体miRNAs在模拟失重下调控骨形成的分子机制。该研究将为深入理解空间骨丢失的发生机理提供理论基础和实验依据，并可望为空间失重性骨丢失的防治提供新的思路和药物作用靶点。

中文关键词： 模拟失重；破骨细胞；骨形成；外泌体；微小RNA

英文摘要： During long-term space flight, space bone loss is the primary risk factor which seriously threatens the health of astronauts. Bone loss is induced by regulation of astronauts' bone metabolism imbalance in the weightlessness environment. Osteoclasts are playing a key role in the regulation of bone metabolism. Our previous study showed that the osteoblasts function was regulated by osteoclasts via paracrine signaling under simulated weightlessness, and further results showed that bone formation activity of osteoblasts was inhibited by the exosomes derived from osteoclasts. Meanwhile, it has recently been shown that exosomal miRNAs are the key signal regulatory factors in regulation of bone metabolism. Based on the existing research, we propose the hypothesis that the exosomal miRNAs derived from osteoclasts may be the pivotal messager involved in the regulation of bone formation under simulated weightlessness. The present project aims to investigate the molecular mechanism of the osteoclasts derived exosomal miRNAs in the regulation of bone formation under simulated weightlessness on molecular-cell-animal levels. The experimental approach will be based on high-throughput sequencing and molecular-cell technology. This project will lay the research foundation and experimental evidence for space bone metabolism and prospectively provide new ideas and drug target for the therapy of space bone loss.

英文关键词： simulated weightlessness;osteoclasts;bone formation;exosome;miRNAs