成骨前体细胞迁移相关LncPMIF与HuR相互作用参与失重性骨质流失发生新机制

成骨前体细胞迁移下降导致骨形成减少可能是失重性骨质流失发生的重要原因之一，然而，细胞迁移的具体机制还不清楚。申请者前期获得一条成骨前体细胞迁移相关长链非编码RNA — LncPMIF，并发现其通过与肌动蛋白（actin）竞争性结合人抗原R（HuR）调节成骨前体细胞迁移，且其在模拟失重条件下表达升高。因此，提出LncPMIF可能通过与HuR结合，干扰actin与HuR相互作用影响成骨前体细胞迁移，进而影响骨形成导致失重性骨质流失发生。本项目拟采用随机回转和小鼠尾悬吊模拟失重模型，研究：（1）模拟失重对成骨前体细胞迁移、LncPMIF、HuR和Actin定位和表达的影响，以及对LncPMIF和HuR相互作用的影响及机制；（2）LncPMIF低表达对模拟失重导致的成骨前体细胞迁移下降和骨质流失的挽救作用。为深入理解失重性骨质流失发生的机制提供新的理论，并为航天员和地面人群的骨骼健康防护提供基础。

Reduction of bone formation caused by the decrease in migration ability of pre-osteoblast is one of the major reasons of bone loss induced by weightlessness. However, the mechanism of pre-osteoblast migration is still unclear. Previously, we identified a long noncoding RNA (named LncPMIF), which is related to pre-osteoblast migration. What’s more, LncPMIF competitively binds to human antigen R (HuR) with actin to regulate pre-osteoblast migration. Besides, simulated weightlessness up-regulated the expression of LncPMIF. Therefore, we propose that LncPMIF may interact with HuR to regulate actin cytoskeleton, thereby affecting pre-osteoblast migration and participating in the occurrence of weightless bone loss. This project will further intend to use random positioning machine (RPM) and hindlimb unloading (HLU) mice model to simulate weightlessness. To investigate the following content: (1) The effects of simulated weightlessness on pre-osteoblast migration, localization and expression of LncPMIF ,HuR and actin, and the interaction between LncPMIF and HuR. (2) The rescue effects and mechanism of inhibition of LncPMIF on the decreased pre-osteoblast migration and bone loss induced by simulated weightlessness. The objective of this project is to provide some new theoretical and experimental evidence for deeply understanding the molecular mechanism of bone loss induced by weightlessness, and also to provide a theoretical basis for the protection of bone health of astronauts and people on the ground.