Insulin-like growth factor binding proteins (IGF-BPs) in bovine articular and ovine growth-plate chondrocyte cultures: their regulation by IGFs and modulation of proteoglycan synthesis

• Published in: Biochimica et biophysica acta Vol. 1245; no. 1; pp. 43 - 48
• Main Authors: Sunic, Damir, Belford, David A., McNeil, Julian D., Wiebkin, Ole W.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 17.08.1995
• Subjects: [ 35S]-sulfate incorporation; Animals; Carrier Proteins - biosynthesis; Cartilage - drug effects; Cartilage - metabolism; Cattle; Cells, Cultured; Des (1–3) IGF-I; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I - pharmacology; Monolayer; Peptide Fragments - pharmacology; Proteoglycan synthesis; Proteoglycans - biosynthesis; Sheep; Monolayer; Des (1–3) IGF-I; Proteoglycan synthesis; [ 35S]-sulfate incorporation
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/0304-4165(95)00076-N

Cultured chondrocytes respond to insulin-like growth factors (IGFs) by increasing the production of proteoglycans and insulin-like growth factor 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 stimulated the production of IGF-BPs in articular and growth-plate chondrocyte monolayers. Western ligand blots showed that bovine articular chondrocytes released two forms of IGF-BPs into conditioned medium with molecular 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 articular chondrocytes up to 1.5-fold. The truncated analogue was more potent at lower concentrations, particularly in stimulating incorporation of newly synthesized proteoglycans into the cell-layer. The maximal stimulation of proteoglycan synthesis in ovine growth-plate chondrocyte culture was 3-fold with des (1–3) IGF-I, while IGF-I enhanced proteoglycan production by only 2-fold over the concentrations used. Our results suggest that endogenous IGF-BPs in chondrocyte cultures act as a part of a feed-back mechanism which diminishes the bioactivity of IGF-I.