Effect of Dibutyryl-Cyclic AMP on Collagen and Non-Collagen Protein Synthesis in Cultured Human Cells

Total cell protein, rate of cell proliferation and the rates of synthesis of collagen and non-collagenous protein were determined in human embryonic bone fibroblasts in the absence and in the presence of dibutyryl-cyclic AMP (DBC) and sodium butyrate. DBC, at a concentration of 1 mM, inhibited cell proliferation almost completely and protein synthesis 30-50% when determined either by the increase in total cell protein content with time or by incorporation of 14C-proline. The synthesis of collagen, however, was stimulated 20-35 %, so that a higher percentage of the newly-synthetized protein was collagen. Stimulation of collagen synthesis was more pronounced in stationary than in proliferating cultures. Butyrate, at comparable concentrations, inhibited cell proliferation completely but had no effect on either collagen or non-collagen protein synthesis.In a cell line derived from a human bone giant cell tumor, DBC caused a more normal fibroblast-like morphology and, as in the case of normal bone cells, inhibited cell proliferation and total protein synthesis but stimulated collagen synthesis. The stimulation of collagen synthesis by DBC was not correlated with or mediated by the inhibition of cell proliferation.DBC, which induces collagen synthesis in an established cell line (Chinese Hamster Ovary) of epithelioid characteristics and, normally, negligible collagen-synthesizing activity, did not induce collagen synthesis in human epithelial cells.