Mechanosensory ion channels are proteins that are sensitive to mechanical forces. They are found in tissues throughout the body and play an important role in bone remodeling by sensing changes in mechanical stress and transmitting signals to bone-forming cells. Orthodontic tooth movement (OTM) is a prime example of mechanically induced bone remodeling. However, the cell-specific role of the ion channelsPiezo1andPiezo2in OTM has not been investigated yet. Here we first identify the expression of PIEZO1/2 in the dentoalveolar hard tissues. Results showed that PIEZO1 was expressed in odontoblasts, osteoblasts, and osteocytes, while PIEZO2 was localized in odontoblasts and cementoblasts. We therefore used aPiezo1floxed/floxedmouse model in combination withDmp1creto inactivatePiezo1in mature osteoblasts/cementoblasts, osteocytes/cementocytes, and odontoblasts. Inactivation ofPiezo1in these cells did not affect the overall morphology of the skull but caused significant bone loss in the craniofacial skeleton. Histological analysis revealed a significantly increased number of osteoclasts inPiezo1floxed/floxed;Dmp1cremice, while osteoblasts were not affected. Despite this increased number of osteoclasts, orthodontic tooth movement was not altered in these mice. Our results suggest that despitePiezo1being crucial for osteoclast function, it may be dispensable for mechanical sensing of bone remodeling.