Effect of vitamin D3 on prostaglandin E2 synthesis in osteoblast-like cells

We previously showed that prostaglandin (PG) F2 alpha stimulates PGE2 synthesis in osteoblast-like MC3T3-E1 cells, and that the activation of protein kinase C (PKC) amplifies the effect of PGF2 alpha through the potentiation of phospholipase A2 activity (H. Tokuda, Y. Oiso and O. Kozawa, J Cell Biochem. 48: 262-268, 1992). In the present study, we investigated the effects of vitamin D3 on PGF2 alpha-induced PGE2 synthesis in MC3T3-E1 cells. The pretreatment with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], an active form of vitamin D3, significantly inhibited the PGF2 alpha-induced PGE2 synthesis in a dose-dependent manner in the range between 1 pM and 1 nM. This inhibitory effect of 1,25-(OH)2D3 was dependent on the time of pretreatment up to 8 h. On the contrary, the pretreatment with 24,25-dihydroxyvitamin D3, an inactive form of vitamin D3, had little effect on the PGF2 alpha-induced PGE2 synthesis in these cells. However, the pretreatment with 1,25-(OH)2D3 no longer affected the amplification of PGF2 alpha-induced PGE2 synthesis by 12-O-tetradecanoylphorbol-13-acetate, a PKC activator. These results strongly suggest that 1,25-(OH)2D3 inhibits PGF2 alpha-induced PGE2 synthesis in osteoblast-like cells, however, the activation of PKC reverses this inhibitory effect of 1,25-(OH)2D3.