279 SYNERGISTIC EFFECTS OF EPIDERMAL GROWTH FACTOR AND SOMATOMEDIN IN CHICK CHONDROCYTES

Abstract

Multiple growth factors (GF) have been isolated, characterized and shown to stimulate growth in at least one tissue. Some have been termed competence factors, while others are termed progression factors dependent upon their site of action in the cell cycle of 3T3 cells. Somatomedin (SM) is the major regulator of cartilage growth and glycosaminoglycan (GAGS) biosynthesis. Epidermal, fibroblast, platelet derived growth factors, and multiple stimulating activity (EGF, FGF, PDGF, and MSA) are known to be important for growth of other tissues. The combined effects of these GF factors with SM in cartilage cells have not been defined. We have studied the interaction of these GF with SM-C in embryonic chick cartilage cells using radioactive precursors. The cells are grown in Ham's F-12 nutrient mixture with 6% serum for 4-6 days following which the media is removed and replaced with media containing 0.5% albumin and the factor or factors to be studied. Radioactive precursors were added after one hour and incubation continued for 2-3 hours. In 2-12 hour incubations SM-C is stimulatory for 3 5SO4 uptake, [3H]-thymidine into DNA, [3H]-uridine into RNA, and [1 4CJ-serine into protein with no potentiation by EGF, FGF, PDGF, or MSA. However, when the incubations are extended 24-30 hours, there is a synergistic effect of EGF and FGF on DNA, RNA, and protein synthesis with less potentiation of the SM effect on GAGS biosynthesis. The data suggests a synergistic interaction between SM and other GF for optimal cartilage growth.