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Effects of Fibroblast Growth Factors on Deoxyribonucleic Acid and Collagen Synthesis in Rat Parietal Bone Cells^*

Department of Medicine (Endocrine Section) and Research Laboratory, Saint Francis Hospital and Medical Center Hartford, Connecticut 06105 University of Connecticut Health Center Farmington, Connecticut 06032

Address all correspondence and requests for reprints to Dr. Thomas L. McCarthy, Saint Francis Hospital and Medical Center, Research Laboratory, 114 Woodland Street, Hartford, Connecticut 06105.

Abstract

Acidic fibroblast growth factor (aFGF) and basic FGF (bFGF) are related molecules that are extractable from bone matrix and may be important in the maintenance of normal bone physiology. The influence of each agent on DNA and protein synthesis was studied using bone-derived primary cell cultures. Both forms of FGF were relatively more mitogenic for bone cell populations with fewer osteoblastic (Ob) characteristics than for Ob-enriched cultures. However, in the Ob cultures, bFGF was intrinsically 10-fold more stimulatory than aFGF, whereas heparin enhanced the mitotic response only to aFGF. An optimal dose of either aFGF or bFGF (100 ng/ml) decreased alkaline phosphatase activity and increased the rate of noncollagen and collagen protein synthesis in Ob cultures. The stimulatory effect was relatively greater on noncollagen than on collagen synthesis, which resulted in a decrease in percent collagen synthesis. Neither factor altered the rate of collagen degradation. Furthermore, hydroxyurea diminished, but did not prevent, the stimulatory effect of each factor on rates of protein synthesis. In contrast, polyacrylamide gel analysis of newly synthesized protein and Northern blot analysis of steady state l type I procollagen mRNA indicated differential effects by each agent on procollagen synthesis and processing. These studies suggest that the FGFs may produce their effects on Ob cells through both shared and disparate mechanisms, with the net result being a decrease in the expression of the osteoblasticphenotype.

Footnotes

^* This work was supported by Grants AR-21707 and AR-39201 from the NIAMSD.

Received March 22, 1989.

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