MicroRNA-183 increases osteoclastogenesis by repressing heme oxygenase-1.

Emerging evidence suggests that microRNAs (miRs) influence skeletal structure by modulating osteoclastogenesis and bone resorption. We have demonstrated previously that the up-regulation of heme oxygenase-1 (HO-1) attenuated osteoclastogenesis in bone marrow-derived macrophages (BMMs). RANKL-induced osteoclastogenesis elevates microRNA-183 (miR-183) in BMM. We show here that HO-1 is a target gene of miR-183 and that this miRNA binds to the 3'-UTR of HO-1. We find that a synthetic inhibitor that binds to miR-183 decreases osteoclast (OC) differentiation and increases the expression of HO-1, while a mimic of endogenous mature miR-183 has the opposite effect. Moreover, the HO-1 inducers, resveratrol and piceatannol decrease the expression of miR-183, resulting in attenuated osteoclastogenesis. Our findings reveal how miR-183 affects OC formation.