The immunoreactivity, ligand, and cell binding characteristics of rheumatoid synovial fluid fibronectin

Abstract

Fibronectin promotes macrophage adherence and expression of Fc receptors, is chemotactic for fibroblasts, and is an opsonin for fibrin and denatured collagen. These properties suggest a role for fibronectin in the modulation of joint inflammation. Since structural modification of the fibronectin molecule has been shown to result in loss or de novo acquisition of opsonic and chemotactic activity, we determined the functional and immunochemical properties of fibronectin isolated from the inflamed joint. Eighty‐six percent of synovial fluids obtained from patients with active rheumatoid arthritis (RA) contained fibronectin fragments, and 39% of the fluids no longer displayed the dimeric form. Compared with native fibronectin, RA peptides were as active in promoting synoviocyte chemotaxis and in glycosaminoglycan binding, but displayed lower affinity for fibrin and gelatin. Although comparable with intact protein in augmenting monocyte attachment to gelatin, the RA synovial fluid peptides did not augment monocyte attachment to fibrin. Analysis of whole synovial fluid and isolated fibronectins by enzyme immunoassay showed that the increased fibronectin immunoreactivity, previously reported in RA synovial fluid, measures intact and nearly intact protein and does not measure extensively degraded fragments.

Regulation of fibronectin and metalloproteinase expression by Wnt signaling in rheumatoid arthritis synoviocytes

“…As demonstrated here, Wnt-1-like signaling up-regulates the synthesis of the cell adhesion molecule fibronectin in RA FLS. Fibronectin expression is high in the synovial tissues and synovial fluids of RA patients (35,36). Taken together with earlier data, these results suggest that the high fibronectin levels in RA are partly attributable to augmented Wnt-1-like activity in RA FLS.…”

“…Fibronectin promotes the survival of mesenchymal cells by localizing growth factors and by stimulating integrin-mediated signaling pathways (36,41). Consistent with this knowledge, confluent nonproliferating cultures of RA FLS (passage 6), which overexpressed fibronectin, survived better than normal fibroblasts (same passage) when the 10% FBS culture medium (complete medium) was replaced by serum-free medium, conditions in which growth factor concentrations are expected to be low ( Figure 9A).…”

“…The RA specimens came from patients with longstanding disease that progressed despite treatment with methotrexate and low-dose corticosteroids. Although we cannot rule out the possibility that these Since the Wnt signal transducer ␤-catenin promotes fibronectin synthesis in Xenopus fibroblasts (29), and an increased level of fibronectin in the synovium is an indicator of disease progression (35,36), we assessed fibronectin levels in the same FLS. Indeed, both supernatants and extracts of RA FLS contained ϳ2 times and ϳ6 times higher levels of fibronectin protein, respectively, than the corresponding samples collected from normal FLS at equivalent cell densities ( Figures 2D and E).…”

“…Fibronectin facilitates adhesion of FLS and macrophages to the surface of articular cartilage (36). Fibronectin is a potent chemoattractant for fibroblasts and can facilitate chemokine signaling (36,43). Thus, fibronectin may promote the incorporation and retention of mesenchymal cells and blood leukocytes in the RA synovium.…”

JNK1 and JNK2 Oppositely Regulate p53 in Signaling Linked to Apoptosis Triggered by an Altered Fibronectin Matrix

“…Degraded matrix conveys messages that are different from those normally conveyed by an intact or stable matrix, and the degradation increases with the severity of the disease. In periodontal disease and arthritis, FN fragments are most abundant in the most diseased sites (6,(25)(26)(27)(28)(29)(30). Previously, we found that a proteolytic 40-kDa fragment of FN associated with the most advanced disease also induced apoptosis of periodontal ligament fibroblasts in vitro by down-regulating p53 and c-Myc (6, 7).…”