Regulation of prostaglandin production by osteoblast-rich calvarial cells.
The effect of various factors upon prostaglandin (PG) production by the osteoblast was examined using osteoblast-rich populations of cells prepared from newborn rat calvaria. Bradykinin and serum, and to a lesser extent, thrombin, were all shown to stimulate PGE2 and 6-keto-PGF1 alpha (the hydration product of PGI2) secretion by the osteoblastic cells. Several inhibitors of prostanoid synthesis, dexamethasone, indomethacin, dazoxiben and nafazatrom, were tested for their effects on the calvarial cells. All inhibited PGE2 and PGI2 (the major arachidonic acid metabolites of these cells) production with half-maximal inhibition by all four substances occurring at approximately 10(-7) M. For dazoxiben and nafazatrom, this was in contrast to published results from experiments in vivo which have indicated that the compounds stimulated PGI2 production. Finally, since the osteoblast is responsive to bone-resorbing hormones, these were tested. Only epidermal growth factor (EGF) was shown to modify PG production. At early times EGF stimulated PGE2 release, however, the predominant effect of the growth factor was an inhibition of both PGE2 and PGI2 production by the osteoblastic cells. The present results suggest that the bone-resorbing hormones do not act to cause an increase in PG by the osteoblast and that any increase in PG production by these cells may be in response to vascular agents.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn; D001920:Bradykinin / Q000494:pharmacology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone; D004815:Epidermal Growth Factor / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D010006:Osteoblasts / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D011720:Pyrazoles / Q000494:pharmacology; D047069:Pyrazolones; D051381:Rats; D013917:Thrombin / Q000494:pharmacology
D007093:Imidazoles; D011453:Prostaglandins; D011458:Prostaglandins E; D011720:Pyrazoles; D047069:Pyrazolones; C029166:dazoxiben; D015121:6-Ketoprostaglandin F1 alpha; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D013917:Thrombin; D015232:Dinoprostone; C018845:nafazatrom; D001920:Bradykinin; D007213:Indomethacin