EFFECTS OF PROSTAGLANDIN-F2-ALPHA ON BONE-FORMATION AND RESORPTION IN CULTURED NEONATAL MOUSE CALVARIAE - ROLE OF PROSTAGLANDIN-E2 PRODUCTION

Although most studies show that prostaglandin E2 (PGE2) is the most potent and effective of the prostanoids in bone, recent data in cell culture suggest that PGF2α may have unique effects, particularly on cell replication. The present study was undertaken to compare the effects of PGF2α and PGE2 in cultured neonatal mouse parietal bones by simultaneous measurement of bone resorption as release of previously incorporated45Ca, bone formation as incorporation of [3H]proline into collagenase- digestible (CDP) and noncollagen protein, and DNA synthesis as incorporation of [3H]thymidine. PGF2α was less effective than PGE2 as a stimulator of bone resorption, and its effects were partially inhibited by indomethacin and markedly inhibited by glucocorticoids. In contrast, the resorptive response to PGE2 was unaffected by indomethacin and only partially inhibited by cortisol. PGF2α had little effect on bone formation, in contrast to the biphasic effect of PGE2, which inhibited labeling of CDP in the absence of cortisol and stimulated CDP labeling in the presence of cortisol. PGF2α increased thymidine incorporation into DNA, but the effect was smaller than that of PGE2 and was inhibited by indomethacin. These observations suggested that PGF2α might act in part by stimulating PGE2 production. By RIA, PGE2 concentrations were increased in the medium of bones treated with PGF2α, and this increase was blocked by indomethacin. By HPLC, bones prelabeled with [3H]arachidonic acid showed an increase in labeled PGE2 release, and RIA showed an increase in PGE2 after PGF2α treatment. These results indicate that PGF2α is a relatively weak agonist in bone compared to PGE2 and that some of the effects of PGF2α on bone resorption, formation, and cell replication may be mediated by an increase in endogenous PGE2 production. © 1990 by The Endocrine Society.