Ultrasound Stimulation Induces PGE2 Synthesis Promoting Cementoblastic Differentiation Through EP2/EP4 Receptor Pathway

The present study aims to provide insights into how ultrasound treatment (US) can affect the regenerative response of cementum by evaluating the role of prostaglandin E2 induced by ultrasound stimulation on cementoblastic differentiation. The mouse cementoblast cell line OCCM-30 was exposed to low-intensity ultrasound and the cyclooxygenase-2 (COX-2) mRNA expression and prostaglandin E2 (PGE2) production were quantified. The role of the US-induced PGE2 in mineralization was examined using COX-2 inhibitor and prostaglandin receptors (EP-receptors) agonists and antagonists. In addition, gene expression of differentiation markers related to mineral metabolism was evaluated. Ultrasound significantly enhanced COX-2 mRNA expression and PGE2 production. PGE2 induced by US mediated mineral nodule formation, whereas COX-2 inhibitor treatment eliminated the enhancement of mineralization induced by US stimulation. Mineral deposition was also inhibited by treatment with EP2 or EP4 antagonist. Moreover, up-regulation of differentiation markers induced by US was suppressed by treatment with COX-2 inhibitor. The present findings provide evidence that US stimulation has a positive effect on mineralization ability of cementoblasts through the activation of EP2/EP4 pathway, suggesting that US can be a promising therapeutic tool for cementum repair. (E-mail: emanuelbraga@hiroshima-u.ac.jp)