Stimulatory effect of prostaglandin F 2α on Na-dependent phosphate transport in osteoblast-like cells

Abstract

Prostaglandin F 2α (PGF 2α) has been reported to activate protein kinase C (PKC) through both phospholipase (PL) C and D, resulting in the proliferation of osteoblast-like cells. In addition, it has also been reported that Erk mitogen-activated protein kinase is also involved in the mechanism of PGF 2α-induced proliferation of these cells. Recently, we have reported that several growth factors stimulate Na-dependent phosphate transport (Pi transport) activity of osteoblast-like cells, which has been recognized to play an important role in their mineralization. In the present study, we investigated the effect of PGF 2α on Pi transport in MC3T3-E1 osteoblast-like cells. PGF 2α stimulated Na-dependent Pi transport dose dependently in the range between 1 nM and 10 μM in MC3T3-E1 cells. The effect was time dependent up to 24 h. Kinetic analysis revealed that PGF 2α induces newly synthesized Pi transporter. Pretreatment with actinomycin D and cycloheximide suppressed PGF 2α-induced enhancement of Pi transport. Combined effect of PMA and PGF 2α was not additive in Pi transport. Calphostin C, a PKC inhibitor, dose-dependently suppressed Pi transport induced by PGF 2α. On the contrary, U0126, which inhibits an upstream kinase of Erk (MEK), did not affect PGF 2α-induced enhancement of Pi transport. In conclusion, PGF 2α stimulates Pi transport through activation of PKC in osteoblast-like cells.