Selective inhibition of type I collagen synthesis in osteoblastic cells by epidermal growth factor.

We have investigated the effect of epidermal growth factor (EGF) on collagen metabolism in clonal MC3T3-E1 cells, an osteoblastic cell line derived from newborn mouse calvaria. EGF significantly increased DNA synthesis, but decreased collagen production. We analyzed the amount of total collagen synthesis and degradation products of collagen together with the level of the enzyme responsible for extracellular collagen degradation, to investigate whether the decreased collagen production was due to a decrease in total collagen synthesis or to an increase in collagen degradation. Total collagen synthesis, determined by total hydroxyproline synthesized, was significantly decreased in cells cultured in medium containing EGF, but the amount of collagen degradation products and the level of animal collagenase activity were not increased. Analysis of the collagen type produced by the cells in the absence of EGF showed that 95% of the collagen recovered was type I and 3% was type III. The decreased level of collagen accumulated by cells cultured in the presence of EGF was explained only by the decreased rate of type I collagen synthesis. These results indicate that EGF selectively inhibits type I collagen synthesis in the clonal osteoblastic cell line, MC3T3-E1.