[Interactions of insulin-like growth factors (IGF) and their binding proteins with the plasminogen/plasmin activator system in cultured osteoblasts].
In biological media, insulin-like growth factors (IGFs) are bound to specific high-affinity binding proteins (IGFBPs). Limited proteolysis of these IGFBPs by serine proteases facilitates dissociation of the IGFs and their access to receptors. Osteoblasts produce IGFs and IGFBPs as 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 Western ligand- and immuno-blotting. IGFBP-2, -3 and -4 were found in the conditioned media in the absence of stimulatory factors. When the cells were incubated with IGF-I, IGFBP-3 and -4 concentrations increased, but IGFBP-2 production was much less stimulated. When increasing amounts of plasminogen were added during the final hours of culture, proteolysis 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-back mechanism by which IGF-I regulates its own bioavailability, acting simultaneously on IGFBP secretion and the proteolytic balance.
Lalou
C
C
INSERM U 142 Hôpital Saint-Antoine, Paris.
Silve
C
C
Segovia
B
B
Binoux
M
M
D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D004347:Drug Interactions; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D010960:Plasminogen Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D002352:Carrier Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D010960:Plasminogen Activators; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator
Interactions des insulin-like growth factors (IGF) et de leurs protéines de liaison avec le système activateur du plasminogène/plasmine dans les cellules ostéoblastiques en culture.