Bone protection by inhibition of microRNA-182. Academic Article uri icon

Overview

abstract

  • Targeting microRNAs recently shows significant therapeutic promise; however, such progress is underdeveloped in treatment of skeletal diseases with osteolysis, such as osteoporosis and rheumatoid arthritis (RA). Here, we identified miR-182 as a key osteoclastogenic regulator in bone homeostasis and diseases. Myeloid-specific deletion of miR-182 protects mice against excessive osteoclastogenesis and bone resorption in disease models of ovariectomy-induced osteoporosis and inflammatory arthritis. Pharmacological treatment of these diseases with miR-182 inhibitors completely suppresses pathologic bone erosion. Mechanistically, we identify protein kinase double-stranded RNA-dependent (PKR) as a new and essential miR-182 target that is a novel inhibitor of osteoclastogenesis via regulation of the endogenous interferon (IFN)-β-mediated autocrine feedback loop. The expression levels of miR-182, PKR, and IFN-β are altered in RA and are significantly correlated with the osteoclastogenic capacity of RA monocytes. Our findings reveal a previously unrecognized regulatory network mediated by miR-182-PKR-IFN-β axis in osteoclastogenesis, and highlight the therapeutic implications of miR-182 inhibition in osteoprotection.

publication date

  • October 5, 2018

Research

keywords

  • Bone Resorption
  • Interferon-beta
  • MicroRNAs
  • Osteogenesis
  • eIF-2 Kinase

Identity

PubMed Central ID

  • PMC6173760

Scopus Document Identifier

  • 85054449932

Digital Object Identifier (DOI)

  • 10.1038/s41467-018-06446-0

PubMed ID

  • 30291236

Additional Document Info

volume

  • 9

issue

  • 1