Role of EP4 Signaling in RANKL/OPG Expression in HPDL Cells

Prostaglandin E2 (PGE2) plays roles in bone resorption via the regulation of receptor activator of nuclear factor kappa B ligand or RANKL, a molecule essential for osteoclastogenesis. It has been shown that PGE2 generated the signal via cell surface receptor, EP1-EP4. Our previous study indicated that human periodontal ligament (HPDL) cells responded to PGE2, however, the detailed mechanism was still unknown. Objective: The aim of this study was to investigate the involvement of EP receptor in PGE2-induced HPDL cells. Materials and Methods: HPDL cells were cultured in the presence or absence of PGE2 for 24 hours. Reverse transcription polymerase chain reaction (RT-PCR) analysis and Western blot/ELISA analysis were used to examine the mRNA and protein expression, respectively. Inhibitors and siRNA were used to examine the involvement of EP receptor. Results: The data from quantitative RT-PCR and Western blot analysis revealed that PGE2 upregulated RANKL mRNA and protein synthesis. However, PGE2 had no effect on osteoprotegerin (OPG) expression and secretion. Induction of RANKL by PGE2 was attenuated by EP4 inhibitor and siRNA. Interestingly, in the presence of EP4 inhibitor, PGE2 decreased the expression of OPG suggesting the role of EP4 in RANKL/OPG homeostasis. Conclusion: The results demonstrate the role of EP4 in RANKL/OPG regulation in HPDL cells. This suggests EP4 as a therapeutic target for the treatment of periodontal disease.