Effects of prostaglandin E2 on bone formation in cultured fetal rat calvariae: role of insulin-like growth factor-I.
Prostaglandin E2 (PGE2) can stimulate collagen synthesis in bone at low concentrations or in the presence of cortisol. Moreover, cortisol inhibits and PGE2 stimulates the production of insulin-like growth factor (IGF-I) in cultured osteoblastic cells. Therefore, we examined the role of IGF-I in the response to PGE2. In 96-h fetal rat calvarial organ cultures, PGE2 increased, and cortisol and indomethacin decreased the medium IGF-I concentration, suggesting that both exogenous and endogenous PGs regulate IGF-I production. In the presence of cortisol, the stimulatory effects of PGE2 on medium IGF-I and incorporation of [3H] proline into collagenase-digestible protein were highly correlated (r = 0.95). When exogenous IGF-I (30 nM) was added, the stimulatory effect of PGE2 was abrogated in the absence, but not the presence, of cortisol. When we added IGF-binding proteins, which blocked the effects of IGF-I and IGF-II, collagenase-digestible protein labeling was decreased in control and cortisol-treated cultures, whereas the stimulatory effect of PGE2 was reduced, but not abrogated. We conclude that endogenous IGFs play a role in maintaining bone formation in cultured fetal rat calvariae and may mediate in part the anabolic response to PGE2. However, the PGE2 response probably involves additional IGF-independent pathways.
Raisz
L G
LG
University of Connecticut Health Center, Farmington 06030.
Fall
P M
PM
Gabbitas
B Y
BY
McCarthy
T L
TL
Kream
B E
BE
Canalis
E
E
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D017364:Collagenases; D046508:Culture Techniques; D015232:Dinoprostone / Q000494:pharmacology*; D005333:Fetus / Q000378:metabolism / Q000502:physiology*; D006131:Growth Inhibitors / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000196:embryology / Q000254:growth & development*; D013936:Thymidine / Q000493:pharmacokinetics
D002352:Carrier Proteins; D006131:Growth Inhibitors; D018969:Insulin-Like Growth Factor Binding Proteins; D011506:Proteins; D007334:Insulin-Like Growth Factor I; D017364:Collagenases; D015232:Dinoprostone; D013936:Thymidine; D006854:Hydrocortisone; D007213:Indomethacin