MicroRNA-34a prevents postmenopausal osteoporosis by promoting osteoclasts-induced osteoblasts differentiation and downregulating the proinflammatory cytokines

Reduction of estrogen levels at the menopause causes the increasing of pro-inflammatory cytokines, the enhancing of bone resorption and the impairing of bone formation, leading to osteoporosis. Previous studies showed that microRNA-34a (miR-34a) was associated with the process of postmenopausal osteoporosis (PMOP). However, the exact mechanisms by which miR-34a is involved in PMOP are not fully elucidated. In the present study, western blot, quantitative real-time PCR, tartrate-resistant acid phosphatase staining, alkaline phosphatase staining and alizarin red staining were employed to investigate the role of miR-34a in PMOP. The results showed that miR-34a inhibited RANKL-induced osteoclasts differentiation. Osteoblasts differentiation was further enhanced when osteoblasts were cultured in conditioned medium (CM) from miR-34a-overexpressed osteoclasts compared with CM from miR-NC-transfected osteoclasts. Conversely, osteoblasts differentiation was decreased when osteoblasts were cultured in CM from miR-34a-silenced osteoclasts, suggesting that miR-34a could promote bone formation through indirectly affecting coupling of osteoclasts to bone formation responses. Moreover, miR-34a impaired TNF-α-induced production of pro-inflammatory cytokines in RAW264.7 cells. Taken together, miR-34a might be used as a therapeutic agent for treating PMOP by promoting osteoclasts-induced osteoblasts differentiation and downregulating the proinflammatory cytokines.