Effects of acid and basic fibroblast growth factor and heparin on resorption of cultured fetal rat long bones.
We tested acid and basic fibroblast growth factor (aFGF and bFGF), members of the heparin binding FGF family, for their ability to stimulate bone resorption as measured by the release of previously incorporated 45Ca from cultured fetal rat long bones in the presence and absence of heparin. Purified low-molecular-weight heparin (LMW heparin) at 5-125 micrograms/ml had no direct stimulatory effect. There was little effect from aFGF (10(-11)-10(-8) M) alone, but increased resorption was observed in the presence of LMW heparin. With bFGF, increased bone resorption was observed at 10(-9) M but not at 10(-8) M. The stimulatory effects of aFGF and bFGF in the presence of LMW heparin were not blocked by the addition of indomethacin (10(-6) M), which blocks prostaglandin production, or hydroxyurea (10(-3) M), which blocks DNA synthesis. However, pretreatment with aphidicolin (3 x 10(-5) M), a potent inhibitor of DNA synthesis, blocked the effect of acid FGF and diminished the effect of bFGF. These results indicate that both aFGF and bFGF can stimulate bone resorption by a prostaglandin-independent mechanism, particularly in the presence of heparin. The activation of FGF-mediated bone resorption by heparin could play a role in producing the osteoporosis that has been described with heparin therapy and mastocytosis.
Simmons
H A
HA
Division of Endocrinology and Metabolism, University of Connecticut Health Center, Farmington.
Raisz
L G
LG
D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D001862:Bone Resorption / Q000139:chemically induced*; D001842:Bone and Bones / Q000187:drug effects* / Q000196:embryology; D046508:Culture Techniques; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006918:Hydroxyurea / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D006495:Heparin, Low-Molecular-Weight; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D016590:Aphidicolin; D006918:Hydroxyurea; D007213:Indomethacin