Effect of 1,25‐dihydroxyvitamin D 3 on prostaglandin E 2 production in cultured mouse parietal bones

1,25‐Dihydroxyvitamin D 3 [1,25‐(OH) 2 D 3 ] was tested for its effects on prostaglandin E 2 (PGE 2 ) production and bone resorption in cultured mouse parietal bones. We found that at 24 h 1,25‐(OH) 2 D 3 increased 45 Ca release but did not affect PGE 2 production. However, at 48 h 1,25‐(OH) 2 D 3 produced a dose‐related increase in PGE 2 production. PGE 2 production was increased with 1,25‐(OH) 2 D 3 at 10 −10 ‐10 −8 M, and 45 Ca release was increased with 1,25‐(OH) 2 D 3 at 10 −11 ‐10 −8 M. The effects of 1,25‐(OH) 2 D 3 on PGE 2 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‐1α (IL‐1, 1 ng/ml) and bovine parathyroid hormone‐(1–34) (PTH, 10 ng/ml) increased PGE 2 production earlier and to a greater extent than 1,25‐(OH) 2 D 3 . The PGE 2 response to IL‐1 and PTH was not affected by 1,25‐(OH) 2 D 3 at 24 h, but at 48 h 1,25‐(OH) 2 D 3 (10 −8 M) increased the PGE 2 response to both IL‐1 and PTH. The stimulation of 45 Ca release at 48 h by high concentrations of 1,25‐(OH) 2 D 3 , PTH, or IL‐1 was similar, and there was no evidence for an additive effect. To test for an effect of 1,25‐(OH) 2 D 3 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. We found that IL‐1Ra blocked the stimulatory effect of 1,25‐(OH) 2 D 3 (10 −8 M) on PGE 2 production but not on 45 Ca release. We conclude that 1,25‐(OH) 2 D 3 at high concentrations is a stimulator of PGE 2 release from bone and can enhance the response to PTH and IL‐1. Its effect is smaller and occurs later than that of PTH and IL‐1. The effect of 1,25‐(OH) 2 D 3 on PGE 2 production could be mediated by endogenous IL‐1.