INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS (IGF-BPS) IN BOVINE ARTICULAR AND OVINE GROWTH-PLATE CHONDROCYTE CULTURES - THEIR REGULATION BYIGFS AND MODULATION OF PROTEOGLYCAN SYNTHESIS

Cultured chondrocytes respond to insulin-like growth factors (IGFs) by increasing the production of proteoglycans and insulin-like growth fa ctor binding proteins (IGF-BPs). To investigate the biological effects of IGFs and IGF-BPs, isolated bovine articular and ovine growth-plate chondrocytes were cultured at high density in the presence of IGF-I, and its truncated form, des (1-3) IGF-I. Both growth factors stimulate d the production of IGF-BPs in articular and growth-plate chondrocyte monolayers. Western ligand blots showed that bovine articular chondroc ytes released two forms of IGF-BPs into conditioned medium with molecu lar weights of 29 and 31 kDa. Ovine growth-plate chondrocytes released four different forms of IGF-BPs of approx. 22, 24; 29-30 and 34 kDa. IGF-I and des (1-3) IGF-I stimulated total proteoglycan synthesis by a rticular chondrocytes up to 1.5-fold. The truncated analogue was more potent at lower concentrations, particularly in stimulating incorporat ion of newly synthesized proteoglycans into the cell-layer. The maxima l stimulation of proteoglycan synthesis in ovine growth-plate chondroc yte culture was 3-fold with des (1-3) IGF-I, while IGF-I enhanced prot eoglycan production by only 2-fold over the concentrations used, Our r esults suggest that endogenous IGF-BPs in chondrocyte cultures act as a part of a feed-back mechanism which diminishes the bioactivity of IG F-I.