模拟失重下BMECs外泌体源性lncRNA ODSM介导成骨细胞cyclin B1泛素化降解的机制研究

航天失重导致的骨质丢失对航天员的健康和安全危害极大，促进成骨细胞功能是防治失重性骨丢失的关键手段之一。已有研究证实，骨微血管内皮细胞与成骨细胞之间存在密切的相互作用关系。我们的预研发现，骨微血管内皮细胞可能通过外泌体途径递送lncRNA ODSM干预成骨细胞周期蛋白cyclin B1的泛素化降解，调控成骨细胞增殖功能。但细胞间的信号调控机制、lncRNA ODSM与蛋白的互作机制，以及模拟失重对这些调控通路的影响等关键问题尚未被阐明。因此，本项目将综合采用细胞与分子生物学技术，联合回转器模拟失重，开展正常重力和模拟失重下骨微血管内皮细胞对成骨细胞的胞间调控机制研究，以及lncRNA ODSM调控cyclin B1泛素化降解的分子机制研究。本研究有望阐明骨微血管内皮细胞对成骨细胞的调控作用和机制，深化对失重性骨质丢失发生机制的理解，为今后长期载人航天飞行中骨质丢失防治提供有价值的参考和借鉴。

During the spaceflight, bone loss induced by weightlessness is extremely harmful to the health and safety of astronauts. Promoting the function of osteoblasts is one of the key methods to prevent bone loss. It has been proved that bone microvascular endothelial cells can regulate the function of osteoblasts. Recently, our study shows that microvascular endothelial cells may deliver lncRNA ODSM via exosomes to interfere in the degradation of cyclin B1 through ubiquitination proteasome system and regulate proliferation of osteoblasts. However, the regulation mechanism between microvascular endothelial cells and osteoblasts, the interaction mechanism between lncRNA ODSM and related proteins, and effect of simulated weightlessness on these mechanisms have not been elucidated. In this project, a variety of cellular and molecular biological techniques will be used. We will use clinostat to simulate weightlessness. Then, under normal gravity and simulated weightlessness conditions, we will explore the intercellular regulation mechanism between bone microvascular endothelial cells and osteoblasts and study the interaction mechanism between lncRNA ODSM and related proteins. This project is expected to clarify the regulation mechanism of bone microvascular endothelial cells on osteoblasts, and to deepen the understanding of the mechanism of bone loss induced by weightlessness. The results may provide valuable reference for the prevention and treatment of bone loss during long-term manned space flight.