Prostaglandins E₂ and F_2α enhance differentiation of cementoblastic cells

Background: The prostaglandins (PG) E₂ and PGF_2α are important cytokines in periodontal physiology and pathology. PGE₂ and PGF_2α alter cell function by binding and activating the plasma-membrane G-protein-coupled PG receptors. In this study, we examined the PGE₂ and PGF_2α effects on the immortalized cementoblastic OCCM cells. Methods: Confluent OCCM cells were treated with PGE₂, PGF_2α, specific activators/inhibitors of the EP prostanoid receptors, a specific activator of the FP prostanoid receptor, and direct activators/inhibitors of the protein kinase C (PKC) signaling pathway. Mineral nodule formation was assessed by the von Kossa stain. Results: PGE₂ and PGF_2α significantly increased mineralization of OCCM cells. The EP1 and EP3 PG receptor activators 16,16-dimethyl-prostagiandin E₂ and sulprostone, also increased mineralization. In contrast, specific activators of the EP2 or the EP2/EP3/EP4 receptors did not have any effect. Fluprostenol, a specific activator of the FP receptor, significantly increased mineralization of OCCM cells. FP and EP (1 or 3) receptors signal through activation of the protein kinase C (PKC) pathway. Indeed, phorbol 12-myristate 13-acetate (PMA), a direct activator of the PKC pathway, significantly increase OCCM mineralization, while pre-treatment of OCCM cells with the PKC inhibitor GF109203x bisindolylmaleimide) significantly decreased mineralization. Conclusion: We conclude that PGE₂ and PGF_2α exert an anabolic effect on OCCM mineralization through activation of PKC signaling.