EFFECT OF VITAMIN-D-3 ON PROSTAGLANDIN-E(2) SYNTHESIS IN OSTEOBLAST-LIKE CELLS

We previously showed that prostaglandin (PG) F-2 alpha stimulates PGE(2) synthesis in osteoblast-like MC3T3-E1 cells, and that the activation of protein kinase C (PKC) amplifies the effect of PGF(2 alpha), through the potentiation of phospholipase A(2) 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 D-3 on PGF(2 alpha)-induced PGE(2) synthesis in MC3T3-E1 cells. The pretreatment with 1,25-dihydroxyvitamin D-3 [1,25-(OH)(2)D-3], an active form of vitamin D-3, significantly inhibited the PGF(2 alpha)-induced PGE(2) synthesis in a dose-dependent manner in the range between 1 pM and 1 nM. This inhibitory effect of 1,25-(OH)(2)D-3 was dependent on the time of pretreatment up to 8 h. On the contrary, the pretreatment with 24,25-dihydroxyvitamin D-3, an inactive form of vitamin D-3, had little effect on the PGF(2) alpha -induced PGE(2) synthesis in these cells. However, the pretreatment with 1,25(OH)(2)D-3 no longer affected the amplification of PGF(2 alpha)-induced PGE(2) synthesis by 12-($) under bar O-tetradecanoylphorbol-13-acetate, a PKC activator. These results strongly suggest that 1,25-(OH)(2)D-3 inhibits PGF(2 alpha)-induced PGE(2) synthesis in osteoblast-like cells, however, the activation of PKC reverses this inhibitory effect of 1,25-(OH)(2)D-3.