Nociceptor Neurons Facilitate Orthodontic Tooth Movement via Piezo2 in Mice.

Multiple sensory afferents, including mechanosensitive and nociceptive nerves, are projected to the periodontium. Peptidergic afferents expressing transient receptor potential vanilloid 1 (TRPV1), a receptor for capsaicin, mediate pain caused by orthodontic forces. However, their role in orthodontic force-induced alveolar bone remodeling is poorly understood as is the contribution of mechanosensitive ion channels such as Piezo2 in nociceptive nerves. To investigate this role, we studied orthodontic tooth movement and alveolar bone remodeling using neural manipulations and genetic mouse models. Chemical ablation of TRPV1-expressing afferents localized to the trigeminal ganglia decreased orthodontic force-induced tooth movement and the number of osteoclasts in alveolar bone on the compression side. The extent of the force-induced increase in the ratio of receptor activator of nuclear factor kappa-B ligand/osteoprotegerin in the periodontium was modestly decreased in the chemical ablation group. Furthermore, chemogenetic silencing of TRPV1-lineage afferents reduced orthodontic tooth movement and the number of osteoclasts. Piezo2 was expressed in most periodontal afferents, and chemogenetic inhibition of Piezo2-expressing neurons decreased orthodontic tooth movement and the number of osteoclasts. In addition, the conditional knockout of Piezo2 in TRPV1-lineage afferents decreased orthodontic tooth movement and the number of osteoclasts. Overall, these results suggest that nociceptor neurons play critical roles in orthodontic force-induced alveolar bone remodeling and that the mechanical activation of neuronal Piezo2 in nociceptive nerves facilitates orthodontic tooth movement and associated alveolar bone remodeling.