Oncostatin M (OSM) stimulates resorption and inhibits synthesis of proteoglycan in porcine articular cartilage explants

Oncostatin M (OSM) is structurally and functionally similar to leukaemia inhibitory factor (LIF), interleukin 6 (IL-6), interleukin 11 (IL-11) and ciliary neurotrophic factor (CNTF). We have previously shown that LIF stimulates proteoglycan release and suppresses proteoglycan synthesis in pig and goat cartilage explants. The aim of this study was to determine whether OSM and related cytokines influence proteoglycan metabolism in pig cartilage explants. Slices of pig articluar cartilage were incubated for 6 days in serum free DMEM with or without cytokines. The total proteoglycan content in papain digested cartilage explants and medium was determined by the 1,9 dimethylmethylene blue method. Cytokine activity was assessed by determining the percentage release of total proteoglycan. To evaluate proteoglycan synthesis, cartilage was cultured for 48 h under the same conditions and in the final 6 h the tissue was cultured in sulphate free DMEM containing (SO4)-S-35. The radioactivity in the medium and tissue was determined in cetylpyridinium chloride precipitates. Biosynthetic activity was expressed as DPM per mg wet weight of cartilage. Dose dependent stimulation of proteoglycan release and suppression of proteoglycan synthesis were observed with rhOSM. IL-6, IL-11 and CNTF also inhibited proteoglycan synthesis in a dose dependent manner but the degree of inhibition was less than that for OSM and these cytokines had no significant effect on proteoglycan release. New biological effects have been identified for OSM and the related cytokines CNTF and IL-11. All three of these cytokines, like LIF and IL-6, suppress proteoglycan synthesis in pig cartilage explants. This common effect suggests that the gp130 subunit of the receptors for these cytokines may represent a common signalling pathway whereby proteoglycan synthesis is regulated, Whilst OSM and LIF stimulate proteoglycan catabolism; IL-6 IL-11 and OSM do not. Thus these effects are not always coupled and activation of gp130 alone may not be a sufficient signal for proteoglycan catabolism. (C) 1996 Academic Press Limited