Differential Proteomics Study Of Human Plasma And Synovial Fibroblasts Obtained From Arthritis

Rheumatoid arthritis (RA) is a complex autoimmune disease, which is characterized by chronic inflammation of the synovial tissue of multiple joints. The disease is often progressive and destructive, and can lead to a substantial reduction in the quality of life of the affected individuals. Extensive researches over the last few decades have provided data to support the hypotheses that RA is an antigen-driven, autoimmune disease. However, to date, the complex molecular mechanisms explaining the onset and perpetuation of the inflammation and the broad clinical heterogeneity, including different disease progression and therapy response, are not fully understood. There is growing evidence that activated synovial fibroblasts (SFs), as part of a complex cellular network, play an important role in the pathogenesis of rheumatoid arthritis. In recent years, these cells have been studied intensively, and significant progress has been made in elucidating the specific features of these fibroblasts. One of the most striking features of inflammatory arthritis is the hyperplasia of synovial fibroblasts in the lining layer. Mutations and/or overexpression of proteins that regulate proliferation, or act as oncogenes in other systems, have been documented in RA SFs. Moreover, synovial fibroblasts have the potential to induce synovitis by releasing mediators that attract leukocytes into the joint. The simultaneous production of endogenous anti-inflammatory cytokines highlights the presence of complex regulatory pathways in the inflamed joint. The MMPs collagenase (MMP-1) and stromelysin (MMP-3) are expressed by SFs in situ, and production of these enzymes by cultured SFs can markedly increase under direct contact with T cells or exposure to pro-inflammatory cytokines.Osteoarthritis (OA) is a chronic, degenerative disorder characterized by gradual loss of articular cartilage. It is generally believed to be a disease primarily caused by biomechanical alteration. It is clear now that profound inflammation appears during the course of the disease in many patients and that inflammatory infiltration can be found in the...