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

Hegewald, Anett B. ; Breitwieser, Kai ; Ottinger, Sarah M. ; Mobarrez, Fariborz ; Korotkova, Marina ; Rethi, Bence ; Jakobsson, Per-Johan ; Catrina, Anca I. ; Wähämaa, Heidi ; Saul, Meike J. (2021):
Extracellular miR-574-5p Induces Osteoclast Differentiation via TLR 7/8 in Rheumatoid Arthritis. (Publisher's Version)
In: Frontiers in Immunology, 11, Frontiers, e-ISSN 1664-3224,
DOI: 10.26083/tuprints-00019253,
[Article]

Abstract

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.

Item Type: Article
Erschienen: 2021
Creators: Hegewald, Anett B. ; Breitwieser, Kai ; Ottinger, Sarah M. ; Mobarrez, Fariborz ; Korotkova, Marina ; Rethi, Bence ; Jakobsson, Per-Johan ; Catrina, Anca I. ; Wähämaa, Heidi ; Saul, Meike J.
Origin: Secondary publication via sponsored Golden Open Access
Status: Publisher's Version
Title: Extracellular miR-574-5p Induces Osteoclast Differentiation via TLR 7/8 in Rheumatoid Arthritis
Language: English
Abstract:

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.

Journal or Publication Title: Frontiers in Immunology
Journal volume: 11
Publisher: Frontiers
Collation: 14 Seiten
Divisions: 10 Department of Biology
10 Department of Biology > Extracellular vesicles / miRNA Research
Date Deposited: 04 Aug 2021 08:05
DOI: 10.26083/tuprints-00019253
Official URL: https://tuprints.ulb.tu-darmstadt.de/19253
URN: urn:nbn:de:tuda-tuprints-192537
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