Expression of osteopontin protein in the synovial membrane and cartilage-pannus junction in rheumatoid arthritis. Effects on the Release of Collagenas

Journal/Book: Z Rheumatol 1998; 57 Suppl. 1: 47 (P 11). 1998;

Abstract: Zentrum für Experimentelle Rheumatologie Universitätsspital Zürich Aims: Osteopontin (OPN) is a secreted Arg-Gly-Asp (RGD)-containing extracellular matrix protein that interacts with av integrins and capable of promoting cell attachment chemotaxis and signal transduction in several different cell types. As demonstrated previously by us OPN mRNA is strongly expressed in fibroblast-like cells of the rheumatoid synovial lining layer and at the cartilage-pannus junction. This study was designed to examine the expression of OPN protein in rheumatoid arthritis (RA) and to investigate its effect of OPN on the production of collagenase-1 in RA synovial fibroblasts and articular chondrocytes. Methods: Expression of OpN protein in synovial tissue from 8 RA patients was examined by immunogold-silver immunohistochemistry. Synovial fibroblasts from 4 RA patients and articular chondrocytes from 3 patients without joint disease were cultured in the presence of various concentrations of osteopontin (0 - 10 ug/ml). Levels of collagenase-1 in the culture supernatants were measured using a commercially available ELISA kit. Results: All specimen tested (8/8) exhibited strong OPN-specific staining which was localized predominantly to the synovial lining and sublining layer. Strong expression of OPN protein was also found at the interface of cartilage and invading synovium. 3/3 cultures of articular chondrocytes secreted detectable basal amounts of collagenase with a dose dependent increase under OPN stimulation with a maximum at 5 mg/ml. In contrast synovial fibroblast cultures produced 10 - 20 fold lower levels of collagenase with only 2 of 4 fibroblast strains responding in a dose dependent manner. Conclusion: The data suggest that OPN produced by synovial fibroblasts in the synovial lining layer and at the cartilage-pannus junction mediates not only attachment but also contributes to matrix degradation in RA by stimulating the secretion of collagenase-1 in articular chondrocytes. le

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