Differential and synergistic actions of somatomedin-like growth factors, fibroblast growth factor and epidermal growth factor in rabbit costal chondrocytes.

Epidermal growth factor (EGF) stimulated DNA synthesis, RNA synthesis and cell division of rabbit costal chondrocytes in culture, but did not stimulate nor inhibit proteoglycan synthesis. Multiplication-stimulating activity (MSA) and cartilage-derived factor (CDF) with somatomedin-like activity had relatively small effects on DNA synthesis and cell division of chondrocytes, but markedly enhanced the synthesis of sulfated proteoglycans. MSA and EGF had additive or synergistic effects on the growth of rabbit chondrocytes. MSA and fibroblast growth factor (FGF) also had additive or synergistic effects on the growth of rabbit chondrocytes. CDF mimicked these effects of MSA; CDF and MSA had similar stimulatory effects on DNA synthesis in rabbit chondrocytes even in the presence of EGF, FGF or both. MSA and CDF did not reduce the concentrations of EGF and FGF required for maximum stimulation of DNA synthesis. In addition, EGF and FGF had additive effects on DNA synthesis and cell division of rabbit costal chondrocytes in culture. These findings suggest that the somatomedin-like factors, EGF and FGF have complementary effects in chondrocytes and provide further evidence that CDF produced by chondrocytes resembles somatomedin in its biological action in chondrocytes.