INTERACTIONS OF INSULIN-LIKE GROWTH-FACTO RS (IGFS) AND THEIR BINDING-PROTEINS WITH THE PLASMINOGEN PLASMIN ACTIVATOR SYSTEM IN CULTURED OSTEOBLASTS

In biological media, insulin-like growth factors (IGFs) are bound to s pecific high-affinity binding proteins (IGFBPs). Limited proteolysis o f these IGFBPs by serine proteases facilitates dissociation of the IGF s and their access to receptors. Osteoblasts produce IGFs and IGFBPs a s well as plasminogen activators and inhibitors, and it has been shown that plasmin may be involved in proteolysis of the IGFBPs. The IGFBPs secreted by the human osteoblast cell line, MG63, were analysed by We stern ligand- and immuno-blotting. IGFBP-2, -3 and -4 were found in th e conditioned media in the absence of stimulatory factors. When the ce lls were incubated with IGF-I, IGFBP-3 and -4 concentrations increased , but IGFBP-2 production was much less stimulated. When increasing amo unts of plasminogen were added during the final hours of culture, prot eolysis of IGFBP-3 and -4 was detected. If the cells had been treated with IGF-I, this was minimal or absent and urokinase activity measured in the conditioned media was decreased. This study reveals a feed-bac k mechanism by which IGF-I regulates its own bioavailability, acting s imultaneously on IGFBP secretion and the proteolytic balance.