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 also shown to stimulate PGE₂ and 6-keto-PGF_1α (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 occuring at approximately 10⁻⁷ M. For dazoxiben and nafazatrom, this was in contrast to published results from experiments which have indicated that the compounds stimulated PGI₂ production. Finally, since the osteoblasts is responsive to bone-resorbing hormones, these were tested. Only epidermal growth factor (EGF) was shown to modify PG production. At early time 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 esteoblast and that any increase in PG production by these cells may be in response to vascular agents