Piezo1 reduces inflammation regulatory ability of periodontal ligament cells to decelerate orthodontic tooth movement in response to heavy mechanical force

Abstract Periodontal ligament (PDL) cells exhibit immunoregulatory characteristics and are being explored as promising therapeutic candidates for accelerating orthodontic tooth movement (OTM). The impact of light or heavy orthodontic mechanical force (MF) on PDL cellular regulatory ability and the modulation of alveolar bone remodeling during OTM is not yet fully understood. Piezo1, a mechanosensitive ion channel, is essential for mediating the conversion in response to MF stimuli. This study aimed to investigate the influence of light and heavy MF on OTM and the consequent remodeling of alveolar bone by altering the immunoregulatory capabilities of PDL cells through Piezo1 modulation. This research represents the initial exploration of the role of Piezo1 activation by either light or heavy MF in the modulation of mitochondrial calcium concentrations through mitochondria-associated endoplasmic reticulum membranes in PDL cells. The study results have validated that heavy MF-induced deregulation of mitochondrial calcium by Piezo1 leads to a decrease in the release of mitochondrial DNA into the cytoplasm, thereby inhibiting the cGAS-STING pathway activation. Inhibition of the cGAS-STING pathway leads to a decrease in the immunoregulatory capacity of PDL cells during OTM, resulting in reduced osteoclast remodeling and deceleration of rat and sting−/− OTM model. The cumulative findings of this study indicate that manipulating the immunoregulatory ability of PDL cells via Piezo1 could potentially offer an effective strategy to shorten the duration of orthodontic treatment.