Effect of epidermal growth factor on collagen synthesis in osteoblastic cells derived from newborn mouse calvaria.

We investigated the effect of epidermal growth factor (EGF) on collagen and protein synthesis in clone MC3T30-E1, a cell line which retains osteoblast-like characteristics. EGF at concentrations of 2-50 ng/ml significantly the hydroxyproline content of the cell layer. These effects were completely abolished by the addition of anti-EGF rabbit serum. The addition of indomethacin did not affect these EGF-induced effects. Collagen fiber formation was also reduced by EGF; a fine and unstriated type of fibril was detected compared to the typical cross-striated fibrils seen in control cultures. EGF at concentrations of 2-50 ng/ml significantly decreased collagen synthesis in the cells, whereas protein synthesis was rather stimulated. Thus, the proportion of collagen to protein synthesized decreased markedly with increasing concentrations of EGF. Unrelated to its effect on collagen synthesis, EGF at concentrations of 0.4-50 ng/ml significantly increased the activity of prolyl hydroxylase, an enzyme involved in the biosynthesis of collagen. Since the plasma concentration of EGF in humans is sufficiently high to cause the observed effect, osteoblasts in vivo may be responsive to this peptide in the same manner as those observed in vitro.