MicroRNA-151a-3p Functions in the Regulation of Osteoclast Differentiation: Significance to Postmenopausal Osteoporosis

Background: Studies have found the pivotal role of miRNAs in the progression of post-menopausal osteoporosis (OP). However, the function of miRNAs in OP is unclear. This study aimed to explore the biological functions of microRNA-151a-3p in OP. Methods: RT-qPCR was employed to assess the expression of microRNA-151a-3p in serum isolated from OP patients and healthy controls. Dual-energy X-ray absorptiometry (DXA) was used to measure the bone mineral density (BMD) of the lumbar spine. The expression levels of c-Fos, NFATc1, and TRAP were tested by Western blot. Ovariectomized (OVX) rats were treated with antago microRNA-151a-3p or antago NC, and then serum and lumbar vertebrae were collected for ELISA and bone histomorphology analysis. Results: The expression of microRNA-151a-3p in postmenopausal women with osteoporosis was significantly up-regulated, and microRNA-151a-3p level was negatively correlated with BMD. During osteoclastogenesis, microRNA-151a-3p level was obviously increased. Overexpression of microRNA-151a-3p promoted the differentiation of RANKL-induced THP-1 and RAW264.7 cells into osteoclasts, whereas silencing of microRNA-151a-3p resulted in the opposite results. Silencing of microRNA-151a-3p in OVX rats altered osteoclastogenesis-related factors and raised BMD. Conclusion: MicroRNA-151a-3p could partly regulate osteoporosis by promoting osteoclast differentiation, and miRNA-151a-3p could be a potential therapeutic target for post-menopausal osteoporosis. Keywords: miRNA-151a-3p, postmenopausal osteoporosis, osteoclast differentiation, RAW264.7 cells, THP-1 cells