Innate Mechanisms of Synovitis – Fibrin Deposits Contribute to Invasion

Sánchez‐Pernaute, Olga; Gabucio, Antonio; Jüngel, Astrid; Neidhart, Michel; Comazzi, María; Herrero‐Beaumont, Gabriel

doi:10.5772/25831

Cited by 1 publication

(2 citation statements)

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“…Using joint explants from patients undergoing prosthetic surgery, deposition of fibrin was shown at fronts of bone and cartilage invasion. In addition, fibrin co-localised with metalloproteinases 1 and 3, particularly at these sites [20]. All these facts led to propose a fibrin-based model for the development of synovitis based on the direct interaction between the fibrin networks and the resident fibroblasts [21].…”

Section: Fibrin Involvement In the Development Of Synovitismentioning

confidence: 99%

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Targets Hidden by Fibrin Networks Still Need to Find Their Place in the Armamentarium for Rheumatoid Arthritis

Gabucio¹,

Sánchez‐Pernaute²

2016

HealthCare Current Reviews

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HCCR, an open access journal Page 3 of 4 modification of peptides facilitates their recognition as auto antigens [32]. Moreover, the development of antibodies to citrullinated peptides is relatively restricted to the disease. Citrullination is carried out by the family of peptidyl deiminases (PAD), out of which PAD2 emerges as an attractive therapeutic target. Of all isoforms, PAD2 shows the higher affinity for fibrin domains in vitro, and it has been found to be enriched in the synovial fluid of patients with rheumatoid arthritis and spondyloarthritis, as compared to osteoarthritis [33,34]. An increase in PAD has been put in relationship with erosive disease, and the presence of anti citrullinated antibodies is currently considered a marker of severe disease [35]. Altogether, this suggests that particular subgroups of patients would benefit from the inhibition of PAD2 activity. Limitations to the Development of Fibrin-Based TherapiesTwo major criticisms have hindered the progression of fibrin research in rheumatoid arthritis. The first one derived from the extrapolation of histopathological findings in synovial tissues from end-stage disease. Fibrin was for a long time considered a bystander product of inflammation. This hurdle was overcome with the studies performed in experimental models, and more recently, when fibrin was shown to be a major auto antigen of the disease. The second point raised was the lack of specificity of intra-articular fibrin deposition. This drawback is shared by most studies approaching the invasive phenotype of rheumatoid synovial fibroblasts, which have failed to show intrinsic alterations. In concordance, our group has found a similar profile of gene induction in fibroblasts from osteoarthritic joints to the one depicted by rheumatoid fibroblasts upon exposure to fibrin (unpublished data). This rather supports that fibrin networks provide a micro environmental imprinting, as responsible for the aggressive features of these cells. Besides, we did observe differences in the magnitude of the cell response between both conditions, probably due to the higher expression level of TLR4 in rheumatoid as compared to osteoarthritic synovial fibroblasts, as has been observed [25,26].In conclusion, complexity of rheumatoid arthritis warrants a multi-target approach in order to shut down mechanisms involved in disease progression. In the next future, a better characterization of each phenotype will facilitate the use of tailored strategies, in which a place for fibrin-based therapies can be forecasted. AcknowledgementThe authors' work was supported by the Conchita Rabago Foundation.

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Section: Fibrin Involvement In the Development Of Synovitismentioning

confidence: 99%

“…Fibrin networks provide sites for crosslinking of additional matrix proteins, such as fibronectin (Figures 2 and 3) [18,20]. The resulting multimolecular scaffold greatly enhances opportunities for cell attachment.…”

Section: Fibrin Operates Ahead Of the Cytokine Networkmentioning

confidence: 99%