Piezo1 Is Related to the Enamel Matrix Formation in Mouse Tooth Germ Development

ABSTRACT Cellular responses to mechanical stimulation are involved in tissue development and the maintenance of biological functions. Teeth function as receptors for mastication and occlusal pressure. During tooth development, the tooth germ begins with an invagination of the epithelium, and its morphology matures through dynamic interactions between epithelial cells and mesenchymal cells, suggesting that mechanosensors may play an important role in this process. We analyzed the expression and function of Piezo1, a mechanically activated ion channel, during tooth development and clarified the involvement of Piezo1 in tooth morphogenesis. The expression of Piezo1 was observed in both the enamel organ and the surrounding mesenchymal cells at the early stage and in the ameloblasts and odontoblasts during enamel and dentin matrix formation. Yoda1, a Piezo1 activator, inhibited cell proliferation in mouse dental epithelial (mDE6) cells and E15 tooth germs, and suppressed cell migration in mDE6 cells. Meanwhile, GsMTx4, a Piezo1 inactivator, showed opposite results. Furthermore, in the organ culture of E15 tooth germs, the activation and inactivation of Piezo1 were found to affect the expression of ameloblast differentiation marker genes and control the arrangement of ameloblasts. Interestingly, the expression of E‐cadherin was reduced in the cell membrane of ameloblasts at the cusp in the GsMTx4‐treated tooth germs of organ culture, and enamel formation was significantly decreased. Yoda1‐treated mDE6 cells showed upregulated E‐cadherin expression, which was downregulated by calpain inhibitor. These findings suggest that Piezo1 may be involved in tooth morphogenesis during ameloblast development by playing an essential role in cell proliferation, migration, arrangement, differentiation, and mineralization.