MicroRNA-183 increases osteoclastogenesis by repressing heme oxygenase-1

Bone. 2015 Dec:81:237-246. doi: 10.1016/j.bone.2015.07.006. Epub 2015 Jul 8.

Abstract

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.

Keywords: Heme oxygenase-1; Osteoclast; Piceatannol; Resveratrol; miR-183.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Heme Oxygenase-1 / antagonists & inhibitors*
  • Heme Oxygenase-1 / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / biosynthesis*
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism*
  • Osteogenesis / drug effects
  • Osteogenesis / physiology*
  • RANK Ligand / pharmacology

Substances

  • MicroRNAs
  • Mirn183 microRNA, mouse
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • Heme Oxygenase-1