Heavy mechanical force decelerates orthodontic tooth movement via Piezo1-induced mitochondrial calcium down-regulation

influx by inhibiting ITPR3 expression in mitochondria-associated membranes. Decreased mitochondrial calcium uptake led to reduced cytoplasmic release of mitochondrial DNA and inhibited the activation of the cGAS‒STING signaling cascade, subsequently inhibiting monocyte-to-osteoclast differentiation. Inhibition of Piezo1 or up-regulation of STING expression under heavy MF conditions significantly increased osteoclast activity and accelerated OTM. These findings suggest that heavy MF-induced Piezo1 expression in PDLCs is closely related to the control of osteoclast activity during OTM and plays an essential role in alveolar bone remodeling. This mechanism may be a potential therapeutic target for accelerating OTM.