Extracellular miR-574-5p Induces Osteoclast Differentiation via TLR 7/8 in Rheumatoid Arthritis
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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.
In: FRONT IMMUNOL, Vol. 11, 2020, p. 585282.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Extracellular miR-574-5p Induces Osteoclast Differentiation via TLR 7/8 in Rheumatoid Arthritis
AU - Hegewald, Anett B
AU - Breitwieser, Kai
AU - Ottinger, Sarah M
AU - Mobarrez, Fariborz
AU - Korotkova, Marina
AU - Rethi, Bence
AU - Jakobsson, Per-Johan
AU - Catrina, Anca I
AU - Wähämaa, Heidi
AU - Saul, Meike J
N1 - Copyright © 2020 Hegewald, Breitwieser, Ottinger, Mobarrez, Korotkova, Rethi, Jakobsson, Catrina, Wähämaa and Saul.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Arthritis, Rheumatoid/immunology
KW - Cell Differentiation/physiology
KW - Extracellular Vesicles/metabolism
KW - HEK293 Cells
KW - HeLa Cells
KW - Humans
KW - MicroRNAs/metabolism
KW - Osteoclasts/metabolism
KW - Osteogenesis/physiology
KW - Synovial Fluid/metabolism
KW - Toll-Like Receptor 7/metabolism
KW - Toll-Like Receptor 8/metabolism
U2 - 10.3389/fimmu.2020.585282
DO - 10.3389/fimmu.2020.585282
M3 - SCORING: Journal article
C2 - 33154755
VL - 11
SP - 585282
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
ER -