First Author | Inoue K | Year | 2018 |
Journal | Nat Commun | Volume | 9 |
Issue | 1 | Pages | 4108 |
PubMed ID | 30291236 | Mgi Jnum | J:268581 |
Mgi Id | MGI:6267989 | Doi | 10.1038/s41467-018-06446-0 |
Citation | Inoue K, et al. (2018) Bone protection by inhibition of microRNA-182. Nat Commun 9(1):4108 |
abstractText | 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)-beta-mediated autocrine feedback loop. The expression levels of miR-182, PKR, and IFN-beta 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-beta axis in osteoclastogenesis, and highlight the therapeutic implications of miR-182 inhibition in osteoprotection. |