REGULATION OF IGF-1 RECEPTORS ON RABBIT ARTICULAR CHONDROCYTES BY INFLAMMATORY MEDIATORS

Insulin-like growth factor 1 (IGF-1) is a known stimulator of proteoglycan synthesis in articular cartilage. However, arthritic cartilage shows a reduced responsiveness to IGF-1, resulting in depletion of proteoglycan moieties. A receptor binding assay for IGF-1 was set up in normal articular chondrocytes to determine whether or not growth factors and cytokines found in inflammatory tissues could influence the response of these cells to IGF-1 through modulation of target receptors. The results of the binding assays show that IGF-1 receptors on rabbit articular chondrocytes are not downregulated by inflammatory cytokines, and are only modulated by high concentrations of IGF-1, insulin and Nu-serum (of which IGF-1 and insulin are constituents). This suggests that if monolayer cultures of chondrocytes behave similarly to chondrocytes in cartilage, reduced responsiveness to IGF-1 is unlikely to be caused by a depletion of IGF-1 receptors.