Aluminum Enhances the Stimulatory Effect of NaF on Prostaglandin E₂ Synthesis in a Clonal Osteoblast-Like Cell Line, MOB 3-4, In Vitro

Abstract

The effect of NaF on prostaglandin E₂ (PGE₂) synthesis in a clonal osteoblast-like cell line, MOB 3-4, was examined in the presence of Al³⁺. The MOB 3-4 cell line, which was derived from neonatal mouse calvaria, displays many osteoblastic characteristics, including the biosynthesis of PGE₂. In the absence of Al³⁺, 1mM NaF increased PGE₂ synthesis (per well) to about 340% of the control level, whereas NaF at lower concentrations (below 0.1mM) did not show such a significant effect. In the presence of 10μM Al³⁺, NaF concentrations ranging from 0.01 to 1mM increased PGE₂ synthesis in a dose-dependent manner, though 10μM Al³⁺ had no effect by itself. Similar effects were observed on alkaline phosphatase (ALP) activity per well, but a stimulatory effect of NaF on protein synthesis was observed only in the presence of 10μM Al³⁺. These data demonstrated that PGE₂ synthesis per protein was increased by NaF alone, and this effect was markedly enhanced by the addition of AlCl₃. ALP activity per protein was, however, significantly increased by NaF in the absence of AlCl₃. Taken together with our previous finding that Al³⁺ enhances the NaF-induced Ca²⁺ mobilization in MOB 3-4 cells, these results suggest that F-combined with Al³⁺ (i. e., AlF₄^-) is a more potent stimulator of PGE₂ synthesis in cells than F^- alone, and that the AlF₄^--enhanced PGE₂ synthesis may be caused by an increase in cytosolic free Ca²⁺ concentration during activation of the G protein by A1F₄^-.