Prostaglandins E2 and F2α enhance differentiation of cementoblastic cells

Background: The prostaglandins (PG) E-2 and PGF(2 alpha) are important cytokines in periodontal physiology and pathology. PGE(2) and PGF(2 alpha) alter cell function by binding and activating the plasma-membrane G-protein-coupled PG receptors. In this study, we examined the PGE(2) and PGF(2 alpha) effects on the immortalized cementoblastic OCCM cells. Methods: Confluent OCCM cells were treated with PGE(2), PGF(2 alpha), 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: PGE(2) and PGF(2 alpha) significantly increased mineralization of OCCM cells. The EP1 and EP3 PG receptor activators 16,16-dimethyl-prostaglandin E-2 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 PGE(2) and PGF(2 alpha) exert an anabolic effect on OCCM mineralization through activation of PKC signaling.