Titre
Fibrin deposition associates with cartilage degeneration in arthritis.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Hügle, T.
Co-première auteure/Co-premier auteur
Nasi, S.
Co-première auteure/Co-premier auteur
Ehirchiou, D.
Auteure/Auteur
Omoumi, P.
Auteure/Auteur
So, A.
Auteure/Auteur
Busso, N.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2352-3964
Statut éditorial
Publié
Date de publication
2022-07
Volume
81
Première page
104081
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
Cartilage damage in inflammatory arthritis is attributed to inflammatory cytokines and pannus infiltration. Activation of the coagulation system is a well known feature of arthritis, especially in rheumatoid arthritis (RA). Here we describe mechanisms by which fibrin directly mediates cartilage degeneration.
Fibrin deposits were stained on cartilage and synovial tissue of RA and osteoarthritis (OA) patients and in murine adjuvant-induced arthritis (AIA) in wild-type or fibrinogen deficient mice. Fibrinogen expression and procoagulant activity in chondrocytes were evaluated using qRT-PCR analysis and turbidimetry. Chondro-synovial adhesion was studied in co-cultures of human RA cartilage and synoviocytes, and in the AIA model. Calcific deposits were stained in human RA and OA cartilage and in vitro in fibrinogen-stimulated chondrocytes.
Fibrin deposits on cartilage correlated with the severity of cartilage damage in human RA explants and in AIA in wild-type mice, whilst fibrinogen deficient mice were protected. Fibrin upregulated Adamts5 and Mmp13 in chondrocytes. Chondro-synovial adhesion only occurred in fibrin-rich cartilage areas and correlated with cartilage damage. In vitro, autologous human synoviocytes, cultured on RA cartilage explants, adhered exclusively to fibrin-rich areas. Fibrin co-localized with calcification in human RA cartilage and triggered chondrocyte mineralization by inducing pro-calcification genes (Anx5, Pit1, Pc1) and the IL-6 cytokine. Similar fibrin-mediated mechanisms were observed in OA models, but to a lesser extent and without pseudo-membranes formation.
In arthritis, fibrin plaques directly impair cartilage integrity via a triad of catabolism, adhesion, and calcification.
None.
Fibrin deposits were stained on cartilage and synovial tissue of RA and osteoarthritis (OA) patients and in murine adjuvant-induced arthritis (AIA) in wild-type or fibrinogen deficient mice. Fibrinogen expression and procoagulant activity in chondrocytes were evaluated using qRT-PCR analysis and turbidimetry. Chondro-synovial adhesion was studied in co-cultures of human RA cartilage and synoviocytes, and in the AIA model. Calcific deposits were stained in human RA and OA cartilage and in vitro in fibrinogen-stimulated chondrocytes.
Fibrin deposits on cartilage correlated with the severity of cartilage damage in human RA explants and in AIA in wild-type mice, whilst fibrinogen deficient mice were protected. Fibrin upregulated Adamts5 and Mmp13 in chondrocytes. Chondro-synovial adhesion only occurred in fibrin-rich cartilage areas and correlated with cartilage damage. In vitro, autologous human synoviocytes, cultured on RA cartilage explants, adhered exclusively to fibrin-rich areas. Fibrin co-localized with calcification in human RA cartilage and triggered chondrocyte mineralization by inducing pro-calcification genes (Anx5, Pit1, Pc1) and the IL-6 cytokine. Similar fibrin-mediated mechanisms were observed in OA models, but to a lesser extent and without pseudo-membranes formation.
In arthritis, fibrin plaques directly impair cartilage integrity via a triad of catabolism, adhesion, and calcification.
None.
Sujets
PID Serval
serval:BIB_51597531A1D0
PMID
Open Access
Oui
Date de création
2022-06-15T08:14:07.793Z
Date de création dans IRIS
2025-05-20T17:32:09Z
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Nom
35660787_BIB_51597531A1D0.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by-nc-nd/4.0
Taille
3.35 MB
Format
Adobe PDF
PID Serval
serval:BIB_51597531A1D0.P001
URN
urn:nbn:ch:serval-BIB_51597531A1D03
Somme de contrôle
(MD5):77fa6b03e1b3a8656639ec703f99d88b