Extracellular miR-574-5p Induces Osteoclast Differentiation via TLR 7/8 in Rheumatoid Arthritis

Autor: Anett B. Hegewald, Kai Breitwieser, Sarah M. Ottinger, Fariborz Mobarrez, Marina Korotkova, Bence Rethi, Per-Johan Jakobsson, Anca I. Catrina, Heidi Wähämaa, Meike J. Saul
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Frontiers in Immunology, Vol 11 (2020)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2020.585282
Popis: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Cell-derived small extracellular vesicles (sEV) mediate cell-to-cell communication in the synovial microenvironment by carrying microRNAs (miRs), a class of small non-coding RNAs. Herein, we report that sEV from synovial fluid promote osteoclast differentiation which is attributed to high levels of extracellular miR-574-5p. Moreover, we demonstrate for the first time that enhanced osteoclast maturation is mediated by Toll-like receptor (TLR) 7/8 signaling which is activated by miR-574-5p binding. This is a novel mechanism by which sEV and miRs contribute to RA pathogenesis and indicate that pharmacological inhibition of extracellular miR-574-5p might offer new therapeutic strategies to protect osteoclast-mediated bone destruction in RA.
Databáze: Directory of Open Access Journals