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