Interactive effects of basic fibroblast growth factor and heparin on bone in 21-day fetal rat calvariae

We examined the interactive effects of heparin and basic fibroblast growth factor (bFGF) on collagen and DNA synthesis in 21-day fetal rat calvariae. In calvariae treated for 24h with heparin (25 micrograms/ml), a significant inhibition of methyl [3H]thymidine (Tdr) incorporation into DNA and [3H]proline labeling of collagenase-digestible protein (CDP) occurred compared to control. Treatment for 24h with bFGF (10(-11) to 10(-9) M) caused a stimulation of Tdr incorporation. With 96h treatment, bFGF (10(-9) M) inhibited CDP labeling by 61%. Basic FGF in combination with heparin overcame the inhibitory effects of heparin on Tdr incorporation. The combination of bFGF plus heparin produced an even greater inhibition of CDP labeling than either effector alone. To assess the role of prostaglandin E2 (PGE2) in moderating the effects of bFGF, calvariae were treated with bFGF in the presence and absence of indomethacin (10(-6) M), an inhibitor of PGE2 production. Indomethacin did not alter the effects of bFGF on Tdr or CDP. We conclude that heparin and bFGF do interact to modulate collagen synthesis in bone via a PGE2-independent mechanism.