Objective. To investigate the effects of the interleukind (IL-6) family cytokines, such as IL-6, IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OSM), on the production of tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) in human articular cartilage.
Methods. Effects of IL-6 family cytokines and growth factors on TIMP-1 production were studied in human articular chondrocytes, grown as monolayer and cartilage explant culture. TIMP-1 protein levels in the cultured medium were measured by sandwich enzyme immunoassay. TIMP-1 messenger RNA levels in the cultured chondrocytes were analyzed by Northern blotting. Western blot analysis was performed to evaluate the release of matrix metalloproteinases (MMPs) in the cultured medium. Cell proliferation of chondrocytes was determined by 3H-thymidine uptake.
Results. IL-6 family cytokines induced TIMP-1 expression in monolayer and explant culture, and the production of TIMP-1 was most stimulated by OSM. In contrast, OSM did not modulate the release of MMPs and cell proliferation.
Conclusion. These results suggest that OSM may be characterized as one of the chondroprotective mediators in cartilage destruction.
Osteoarthritis (OA) is one of the most common disorders of the human joints. It is characterized by a gradual loss of the extracellular matrices of articular cartilage, such as proteoglycan (PG) and type I1 collagen (1,2). It is well known that extracellular matrices -~-Supported in part by the Research Grant for Rheumatoid Arthritis from the Ministry of Health and Welfare of Japan.