Bone protection by inhibition of microRNA-182.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Inoue, K; Deng, Z; Chen, Y; Giannopoulou, E; Xu, R; Gong, S; Greenblatt, MB; Mangala, LS; Lopez-Berestein, G; Kirsch, DG; Sood, AK; Zhao, L; Zhao, B

Published Date

  • October 5, 2018

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 4108 -

PubMed ID

  • 30291236

Pubmed Central ID

  • 30291236

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-018-06446-0

Language

  • eng

Conference Location

  • England