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

We previously showed that prostaglandin (PG) F_2α stimulates PGE₂ synthesis in osteoblast-like MC3T3-E1 cells, and that the activation of protein kinase C (PKC) amplifies the effect of PGF_2α 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 PGF_2α-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 PGF_2α-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 PGF₂α-induced PGE₂ synthesis in these cells. However, the pretreatment with 1,25-(OH)₂D₃ no longer affected the amplification of PGF_2α-induced PGE₂ synthesis by 12-O-tetradecanoylphorbol-13-acetate, a PKC activator. These results strongly suggest that 1,25-(OH)₂D₃ inhibits PGF_2α-induced PGE₂ synthesis in osteoblast-like cells, however, the activation of PKC reverses this inhibitory effect of 1,25-(OH)₂D₃.