骨质疏松严重影响老年人健康生活，但其发生发展机制仍不十分清楚。本课题组前期研究发现Rap1A通过MAPK信号促进成骨细胞分化；而隐花色素基因2(CRY2)3’UTR 区rs2292910位点变异与骨质疏松发生密切相关。预实验表明Rap1A可激活STAT3，而STAT3可促进miR-7-5p表达而下调CRY2基因表达，最终促进成骨细胞分化。针对Rap1A如何调控CRY2参与骨质疏松发生这个科学问题，本课题拟从细胞、动物和人体组织水平研究Rap1A激活STAT3的信号途径、STAT3促进miR-7-5p转录的方式及miR-7-5p降解CRY2的机制，并利用动物模型阐释CRY2 3’UTR区rs2292910位点变异对小鼠成骨/破骨细胞分化和骨质疏松发生的影响。本课题有望揭示Rap1A通过STAT3/miR-7-5p/CRY2信号轴促进成骨细胞分化和骨形成的机制，为老年骨质疏松防治提出新策略。

Osteoporosis (OP) seriously threatens the healthy life of the elder people, but the mechanism of OP occurrence and development is not completely clear. We have found, during the previous study, that Rap1A may promote obsteoblast differentiation through activation of MAPK, and that the genotypic changes of a 3’UTR region rs2292910 from cryptochrome 2 were associated with osteoporosis. While the preliminary data suggest that Rap1A may activate STAT3 to promote the transcription of miR-7-5p, which in turn leads to degradation of CRY2 and eventually to stimulate osteoblast differentiation. To explore the mechanism, this project was designed to investigate the signal pathways that Rap1A activates STAT3, STAT3 starts the transcription of miR-7-5p, and miR-7-5p targets and degrades CRY2 by using cells, animals, and human tissues. We will also study the mechanism of osteobalst and osteoclast differentiation and osteoporosis by using the animal models generated with the CRY2 3’UTR region rs2292910 (A or C). Through this project, we will try to reveal the mechanism that Rap1A stimulates osteobalst differentiation and osteogenesis through the STAT3/miR-7-5p/CRY2 signaling axis, and to provide novel strategies for prevention and treatment of elder people osteoporosis.