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Effects of acid and basic fibroblast growth factor and heparin on resorption of cultured fetal rat long bones
Author(s) -
Simmons Hollis A.,
Raisz Lawrence G.
Publication year - 1991
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650061206
Subject(s) - heparin , endocrinology , bone resorption , medicine , resorption , basic fibroblast growth factor , fibroblast growth factor , dna synthesis , prostaglandin e2 , growth factor , chemistry , biology , biochemistry , dna , receptor
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 45 Ca from cultured fetal rat long bones in the presence and absence of heparin. Purified low‐molecular‐weight heparin (LMW heparin) at 5–125 μg/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 × 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.