MiRNA-133a is involved in the regulation of postmenopausal osteoporosis through promoting osteoclast differentiation

Abstract

The important role of miR-133a in the progress and development of postmenopausal osteoporosis has been reported, however, the underlying mechanism is not clear yet. In this study, qRT-PCR analysis was performed to assess miR-133 expression in serum isolated from postmenopausal osteoporosis patients (PMOP) and healthy controls. Bone mineral density (BMD) was measured at the lumbar spine by dual-energy X-ray absorptiometry (DXA). The results showed that miR-133a was significantly upregulated and negatively correlated with lumbar spine BMD in serum of postmenopausal osteoporotic women. The miR-133a mimic, miR-133a inhibitor, and the corresponding controls were transfected into RAW264.7 and THP-1 cells, respectively. TRAP-positive cells were counted and the protein expression of NFATc1, c-Fos and TRAP were detected by western blot analysis. We found that MiR-133a was upregulated during osteoclastogenesis, and overexpression of miR-133a promoted RANKL-induced differentiation of RAW264.7 and THP-1 cells into osteoclasts, whereas miR-133a knockdown showed the reversed results. In in vivo experiment, rats were bilaterally ovariectomized (OVX) and injected with antagomiR-133a or antagoNC, and were sacrificed for collecting serum and lumbar spine for ELISA, micro-computed Tomography (CT) and bone histomorphology analysis, respectively. It was found that, in OVX rats, miR-133a knockdown altered the levels of osteoclastogenesis-related factors in serum and increased lumbar spine BMD and changed bone histomorphology. Collectively, miRNA-133a is involved in the regulation of postmenopausal osteoporosis through promoting osteoclast differentiation.