Fibrin deposition associates with cartilage degeneration in arthritis

EBioMedicine

Driss Ehirchiou¹  Alexander So²  Patrick Omoumi³  Sonia Nasi³  Thomas Hügle³  Nathalie Busso³ 

[1] Corresponding author.;Department of Diagnostic and Interventional Radiology, Lausanne University Hospital (CHUV) and University of Lausanne, Rue du Bugnon 46, Lausanne 1010, Switzerland;Department of Rheumatology, Lausanne University Hospital (CHUV) and University of Lausanne, Chemin des Boveresses 155, Epalinges 1066, Switzerland;

关键词: Fibrin;    Fibrinogen;    Arthritis;    Cartilage degradation;    Calcification;    Chondro-synovial adhesion;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary:Background: 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. Methods: 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. Findings: 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. Interpretation: In arthritis, fibrin plaques directly impair cartilage integrity via a triad of catabolism, adhesion, and calcification. Funding: None.

【 授权许可】

Unknown