Background/Purpose:

Pannus infiltration and inflammatory cytokines are the main responsible factors for cartilage damage in rheumatoid arthritis (RA). Moreover, the crosstalk between inflammation and coagulation amplifies and maintains chronic inflammation. Whilst extravascular fibrin deposits in synovial fluid and synovial membrane being hallmarks of RA, there are no reports on direct fibrin deposition and its relation to cartilage damage in RA so far. The first aim is to investigate if fibrin deposition occurs in murine and human RA cartilage, and if there is a direct relation with cartilage degradation. Moreover, we want to determine the possible mechanism by which fibrin could play a role in the pathogenesis of RA.

Methods:

Full-thickness cartilage explants were obtained from RA patients undergoing total knee replacement. Immunohistochemistry was performed on paraffin sections to study fibrin deposition, while Safranin-O staining was used to investigate cartilage damage. An in vitro model of chondrosynovial adhesion was established using primary human RA synoviocytes seeded on human RA cartilage explants. Adherent synoviocytes to cartilage were evaluated on H&E-stained histological sections and fibrin immunohistochemistry was performed on consecutive sections. An experimental RA model (antigen induced arthritis -AIA-) was applied in wild-type (WT) and fibrinogen knock-out mice and paraffin sections of knee joints assessed for fibrin deposition, cartilage damage, and chondrosynovial adhesion

Results:

In human RA cartilage, the amount of fibrin deposits positively correlated with the degree of cartilage degradation. In knees from WT mice fibrin deposition was preferentially found on damaged cartilage and on cartilage areas in direct contact with synovial membrane (i.e chondrosynovial adhesions). In contrast, cartilage degradation and chondrosynovial adhesion were significantly lower in fibrin deficient mice. Mechanical stripping of superficial cartilage layers by fibrin was observed in regions of chondrosynovial adhesion, indicating waxing properties of fibrin. Finally, fibrin-mediated chondrosynovial adhesion was confirmed in the in vitro model, where synoviocytes were found to adhere to human OA cartilage especially in severely damaged and fibrin-rich areas.

Conclusion:

Our results demonstrate that fibrin deposition on cartilage is highly associated with chondrosynovial adhesion and subsequent cartilage damage in RA. We hypothesize that fibrin mediates chondrosynovial adhesion especially during joint resting periods (i.e night-time), leading to mechanical stripping of superficial cartilage layers following motion.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/fibrin-triggered-chondrosynovial-adhesion-as-a-novel-mechanism-of-cartilage-damage-in-rheumatoid-arthritis/