Effect of fibroblast growth factor on cultured fetal rat calvaria

Normal rat or human serum causes a greater incorporation of 3H-proline into bone collagenase digestible protein (CDP) and noncollagen protein (NCP) than does serum from hypophysectomized animals or hypopituitary humans. In the present study, we have tested fibroblast growth factor (FGF), a peptide isolated from bovine pituitary glands that has been shown to stimulate RNA and DNA synthesis in various mesodermal cells, for its effects on cultured fetal rat calvaria. The major effect of FGF appeared to be a stimulation of periosteal fibroblastic cell proliferation. Incorporation of 3H-thymidine into DNA was increased at concentrations of 10--1000 ng/ml; the effect appeared after 12 hr, was sustained for 96 hr, and could not be ascribed to an effect on 3H-thymidine uptake. Total DNA content was increased and histologic sections showed an increase in the number of mitoses in periosteal fibroblasts after colemid arrest. These effects were accompanied by an increase in the uptake and incorporation of 3H-uridine, a decrease in the incorporation of labeled proline into CDP, and a small and variable increase in the incorporation of proline into NCP. Cortisol opposed the effects of FGF on 3H-thymidine and 3H-uridine incorporation. Insulin did not alter the effect of FGF on 3H-thymidine incorporation, but FGF decreased the stimulatory effect of insulin on the labeling of CDP. The effect of FGF on thymidine incorporation and collagen synthesis was not altered by indomethacin. The major effect of FGF in calvaria is to increase DNA synthesis and stimulate the proliferation of periosteal fibroblasts. It does not appear to be the pituitary-dependent factor in serum that stimulates 3H-proline incorporation into CDP and NCP in calvaria.