Piezo channels contribute to the terminal cytodifferentiation of odontoblasts via modulation of canonical Wnt signaling.

Piezo1 and Piezo2 are mechanosensitive ion channels that transduce mechanical stimuli into intracellular biochemical signals in diverse tissues and organ systems. Their functions in odontoblast development are still not well understood. In this study, we showed that Piezo1 and Piezo2 displayed dynamic expression in odontoblasts during terminal cytodifferentiation, suggesting a functional role in this process. However, Piezo1 knockouts in odontoblasts using Wnt1-Cre (Piezo1 cKO) did not cause pronounced structural change in tooth development in a majority of the Piezo1 cKO mice. Piezo2 cKO did not show obvious tooth defect either. Therefore, we pursued a double knockout approach. A phenotype analysis of Wnt1-Cre mediated Piezo1 and Piezo2 double knockout (Piezo1/Piezo2 dKO) mice revealed impaired cytodifferentiation and morphological change in the odontoblasts. Specifically, the heights of odontoblast and ameloblast layers were lower in Piezo1/Piezo2 dKO mice than controls, and expression of markers for odontoblast terminal differentiation, including collagen type 1a and alkaline phosphatase, was delayed. Furthermore, levels of nuclear β-catenin and Wnt10a were remarkably decreased, indicative of compromised Wnt/β-catenin signaling. Notably, the application of the Wnt10a protein rescued the odontoblast phenotype of Piezo1/Piezo2 dKO teeth in an ex vivo organ culture system. Moreover, the intraperitoneal injection of Yoda1, a Piezo1 channel agonist, facilitated odontoblast cytodifferentiation and elevated Wnt/β-catenin signaling in dental pulp tissues at the newborn stage. Altogether, these data suggest that Piezo channels play a role in regulating the terminal differentiation of odontoblasts via modulation of Wnt/β-catenin signaling.