PRODUCTION OF BINDING-PROTEINS AND ROLE OF THE INSULIN-LIKE GROWTH-FACTOR-I BINDING-PROTEIN-3 IN HUMAN ARTICULAR-CARTILAGE EXPLANTS

The aim of this study was to determine the production of insulin-like growth factor binding proteins (IGFBP) and the role of the IGFBP-3 in human normal (n = 2) and osteoarthritic (OA) articular cartilage (n = 14) explants. Binding proteins were studied in the medium by Western l igand blotting and Western blotting. Proteoglycan synthesis under insu lin-like growth factor I (IGF-I) stimulation was studied after a pulse of (SO42-)-S-35 in the presence or absence of added IGFBP-3. Osteoart hritic explants released a doubler of IGFBPs with a 39/43 kDa M(r) cor responding to the binding protein 3. Constitutive production from unst imulated OA cartilage was higher than from normal cartilage. IGF-I ind uced a 20-fold increase and IL-1 a 2-fold increase in IGFBP-3 release. A minor band around 30 kDa was also detectable. Studies of proteoglyc an (PG) synthesis showed that the majority of OA cartilage explant sam ples responded weakly to IGF-I (100 ng/ml) stimulation (+33%), while t he others were high responders (+180%). Co-incubation of IGF-I with re combinant (r) IGFBP-3 did not affect the rate of PG synthesis. However , while pre-incubation with rIGFBP3 for 72 h did not change the rate o f PG synthesis in the high-responder group, it strongly increased PG s ynthesis in the low-responder group. this study demonstrates that the ability of IGF-I to enhance proteoglycan synthesis varied among the OA samples and may in part be dependent on the local level of IGFBP-3. T his implies pathophysiological considerations in the limits of IGF-I a ction during the OA process.