Soluble glycoprotein 130 (gp130) attenuates OSM- and LIF-induced cartilageproteoglycan catabolism

Oncostatin M (OSM) and leukaemia inhibitory factor (LIF) exhibit pleiotropi c biological activities and share many structural and genetic features. The two cytokines bind with high affinity to the same receptor (LIF/OSM recept or), which consists of the LIF receptor a chain (LIFR alpha) and the signal transduction unit gp130, A soluble form of the beta chain of the receptor complex called soluble gp130 (sgp130) has been cloned. In this study, we so ught to determine whether recombinant sgp130 or anti-gp130 Ab could attenua te the resorption of proteoglycans induced by OSM and LIF in articular cart ilage explants, The results show that at high concentrations sgp130 is capa ble of attenuating both LIF and OSM mediated resorption, In contrast, anti- gp130 Ab selectively inhibited the stimulation of proteoglycan (PG) release by OSM, albeit minimally. The failure of anti-gp130 to attenuate LIF stimu lated PG resorption may be due to the normal interaction of LIF with LIFR a lpha and unfettered heterodimerization of LIFRa with gp130 in the presence of the antibody. The results indicate that sgp130 and anti-gp130 can modula te cartilage PG metabolism in vitro. Whether sgp130 may have therapeutic ac tivity in models of arthritis or indeed in arthritic diseases remains to be determined. (C) 2000 Academic Press.