MiR‐503 Regulates Osteoclastogenesis via Targeting RANK

MicroRNAs (miRNAs) play important roles in osteoclastogenesis and bone resorption. However, no study has investigated the role of miRNA in postmenopausal osteoporosis. Here, we report that miR‐503 was markedly reduced in circulating progenitors of osteoclasts–CD14⁺ peripheral blood mononuclear cells (PBMCs) from postmenopausal osteoporosis patients compared with those from postmenopausal healthy women. Overexpression of miR‐503 in CD14⁺ PBMCs inhibited receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclastogenesis. Conversely, silencing of miR‐503 in CD14⁺ PBMCs promoted osteoclastogenesis. RANK, which is activated by the binding of RANKL and inducing osteoclast differentiation, was confirmed to be a target of miR‐503. In vivo, silencing of miR‐503 using a specific antagomir in ovariectomy (OVX) mice increased RANK protein expression, promoted bone resorption, and decreased bone mass, whereas overexpression of miR‐503 with agomir inhibited bone resorption and prevented bone loss in OVX mice. Thus, our study revealed that miR‐503 plays an important role in the pathogenesis of postmenopausal osteoporosis and contributes to a new therapeutic way for osteoporosis. © 2014 American Society for Bone and Mineral Research.