Differential Regulation of Chondrocyte Metabolism by Oncostatin M and Interleukin-6

OBJECTIVE: To determine the effects of interleukin (IL)-6 and oncostatin M (OSM) added separately or in combination with IL-1beta on human osteoarthritic (OA) chondrocytes in alginate beads. DESIGN: Human chondrocytes were isolated from OA cartilage and cultured in alginate beads for 12 days, in the absence or in the presence of increasing amounts of IL-6 (20-500ng/ml) with its soluble receptor or OSM (0.1-10ng/ml) and with or without IL-1beta (1.7ng/ml). Aggrecan (AGG), transforming growth factor-beta1 (TGF-beta1), stromelysin-1 [matrix metalloprotease (MMP)-3], tissue inhibitor of metalloproteinases-1 (TIMP-1), macrophage inflammatory protein-1 beta (MIP-1beta), IL-6 and IL-8 productions were assayed by specific enzyme amplified sensitivity immunoassays. Prostaglandin (PG)E(2) was measured by a specific radioimmunoassay and nitrite (NO(2)(-)) by a spectrophotometric method based upon the Griess reaction. RESULTS: OSM, but not IL-6, decreased basal AGG and TGF-beta1 synthesis. Although IL-6 stimulated basal TIMP-1 production, it did not significantly modify MMP-3/TIMP-1 ratio. In contrast, 10ng/ml OSM highly increased TIMP-1 production, and decreased by half the ratio MMP-3/TIMP-1. IL-1beta highly stimulated *NO, IL-8, IL-6, MIP-1beta and PGE(2) synthesis but decreased AGG and TGF-beta1 production. Neither IL-6 nor OSM modulated IL-1beta-inhibitory effect on AGG production. IL-6, but not OSM, reversed IL-1beta-induced TGF-beta1 inhibition. At 1-10ng/ml, OSM significantly decreased IL-1beta-stimulated IL-8, MIP-1beta, PGE(2) and *NO production but amplified IL-1beta stimulating effect on IL-6 production. IL-6 had no effect on these parameters. CONCLUSIONS: OSM and IL-6, two glycoprotein 130 binding cytokines, show different activity profiles on OA chondrocytes, indicating that these cytokines could play different roles in the OA disease process.