THE ROLE OF ONCOSTATIN-M IN ANIMAL AND HUMAN CONNECTIVE-TISSUE COLLAGEN TURNOVER AND ITS LOCALIZATION WITHIN THE RHEUMATOID JOINT

Objective, To study the interaction of interleukin-1 alpha (IL-1 alpha ) and oncostatin M (OSM) in promoting cartilage collagen destruction. Methods. Bovine, porcine, and human cartilage and human chondrocytes w ere studied in culture. The levels of collagenase (matrix metalloprote inase 1 [MMP-1]) and tissue inhibitor of metalloproteinases 1 (TIMP-1) were measured by bioassay and enzyme-linked immunosorbent assay (ELIS A). The levels of OSM in rheumatoid synovial fluid were measured by EL ISA. Results. When combined with OSM, IL-1 alpha, IL-1 beta, and tumor necrosis factor alpha released proteoglycan and collagen from cartila ge. OSM was the only member of the IL-6 family to have this effect. Hu man tendon also responded to IL-1 alpha and OSM, OSM increased the pro duction of MMP-1 and TIMP-1 but when combined with IL-1 alpha, synergi stically promoted MMP-1 production in human chondrocytes and synovial fibroblasts. High levels of OSM were found in human rheumatoid synovia l fluids, and confocal microscopy showed that OSM was produced by macr ophages in rheumatoid synovial tissue. Conclusion, These results highl ight an important new mechanism by which there is irreversible loss of collagen from cartilage.