Differential regulation of chondrocyte metabolism by oncostatin M and interleukin-6

Abstract

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. 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. 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. 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.