miR-25-3p调节破骨细胞在骨质疏松中的作用机制研究

骨吸收增强导致骨形成相对减弱是引起骨质疏松的主要原因。而破骨细胞是人体内唯一一种介导骨吸收的细胞，因此，靶向抑制破骨细胞的功能对于预防和治疗骨质疏松具有非常重要的意义。最近研究发现，miRNA水平靶向调控破骨细胞功能，抑制骨吸收，是防治骨质疏松的可能途径，具有重要的研究价值。而我们的前期研究结果表明，miR-25-3p可能通过NFIX负向调控破骨细胞功能，提示其可用于防治骨质疏松。本项目拟在此基础上采用过表达/沉默技术，明确NFIX对破骨细胞分化、功能的影响；其次通过挽救实验验证miR-25-3p是通过NFIX实现对破骨细胞的调控；最后，建立卵巢切除小鼠骨质疏松模型，通过尾静脉注射pre-miR-25-3p或者同时注射Ad-NFIX，明确以 miR-25-3p/NFIX 信号轴为靶点在防治骨质疏松方面的作用。

Osteoclasts are the only cells in the human body that are capable of bone resorption, and Excessive osteoclast formation and bone resorption are key causes of osteoporosis. Therefore, osteoclasts are favorable targets for the treatment of osteoporosis. Previous studies have demonstrated that miRNAs play critical roles in regulating osteoclastogenesis and are associated with osteoporosis. Based on our previous results, miR-25-3p was supposed to inhibit osteoclast differentiation and function through NFIX, thus might be of great value in treatment of osteoporosis. In our present research, we would use the techniques of mimics/inhibitor to demonstrated the effects of NFIX on osteoclastogenesis and bone resorption. Then, overexpression of both NFIX and miR-25-3p would be used to verify the effect of miR-25-3p/NFIX pathway on osteoclast. At last, we would evaluated the effect of miR-25-3p/NFIX on ovariectomy-induced osteoporosis mice in vivo.