PGE2 Activates Cementoclastogenesis by Cementoblasts via EP4

Abstract

Destruction of cementum and alveolar bone is the main causative event for the exfoliation of teeth as a consequence of periodontitis. Prostaglandin E2 (PGE2) and PGE receptor subtypes (EPs) play an important role in modulating osteoblast-mediated osteoclastogenesis; however, no information is available on the role of PGE2 and EPs in regulating cementoblast-mediated cementoclastogenesis. We hypothesized that the PGE2-EPs pathway also regulates cementoblasts’ ability to activate cementoclasts. For these studies, OCCM-30 cells (a mouse cementoblast cell line) were exposed to PGE2 and specific EP agonists. PGE2 (100 ng/mL) and EP4 agonist (1 μM) up-regulated RANKL and IL-6 mRNA levels, while they down-regulated OPG mRNA expression. The EP4 antagonist (1 μM) eliminated these effects of PGE2. PGE2 treatment of co-cultures of OCCM-30 cells with bone marrow cells induced TRAP-positive cells via the EP4 pathway. These findings suggest that PGE2 promotes cementoblast-mediated cementoclastogenesis by regulating the expression of RANKL and OPG via the EP4 pathway.