Effect of 1,25-dihydroxyvitamin D3 on prostaglandin E2 production in cultured mouse parietal bones

Abstract

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] was tested for its effects on prostaglandin E2 (PGE2) production and bone resorption in cultured mouse parietal bones. We found that at 24 h 1,25-(OH)2D3 increased 45Ca release but did not affect PGE2 production. However, at 48 h 1,25-(OH)2D3 produced a dose-related increase in PGE2 production. PGE2 production was increased with 1,25-(OH)2D3 at 10(-10)-10(-8) M, and 45Ca release was increased with 1,25-(OH)2D3 at 10(-11)-10(-8) M. The effects of 1,25-(OH)2D3 on PGE2 production persisted in the presence of cortisol (10(-8) M), and the effects were greater in the presence of arachidonic acid (10(-5) M) or fetal bovine serum (10%). Human interleukin-1 alpha (IL-1, 1 ng/ml) and bovine parathyroid hormone-(1-34) (PTH, 10 ng/ml) increased PGE2 production earlier and to a greater extent than 1,25-(OH)2D3. The PGE2 response to IL-1 and PTH was not affected by 1,25-(OH)2D3 at 24 h, but at 48 h 1,25-(OH)2D3 (10(-8) M) increased the PGE2 response to both IL-1 and PTH. The stimulation of 45Ca release at 48 h by high concentrations of 1,25-(OH)2D3, PTH, or IL-1 was similar, and there was no evidence for an additive effect. To test for an effect of 1,25-(OH)2D3 on endogenous IL-1 production, experiments were performed in the presence of an IL-1 receptor antagonist (IL-1Ra, 1000 ng/ml), which has been found to block selectively IL-1 effects on bone resorption and PG production.(ABSTRACT TRUNCATED AT 250 WORDS)