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Objective To investigate the effect of the Piezo1 channel on tension-side angiogenesis and osteogenic remodeling during orthodontic tooth movement, so as to provide an experimental basis for accelerating orthodontic periodontal tissue remodeling. Methods This study was approved by the Animal Ethics Committee. Sixty healthy male Sprague-Dawley rats with bilateral maxillary incisors as the anchorage were selected, and nickel titanium tension springs were used to apply 0.5 N of force to the right maxillary first molar of the rats and construct an orthodontic tooth movement model. The rats were randomly divided into three groups (n = 20 per group). On Days 0 and 8 of force application, equal volumes of saline (control group), 100 μmol/L Piezo1 channel agonist (Yoda1 group), and 48 μmol/L Piezo1 channel inhibitor (GsMTx4 group) were injected into the buccal and palatal submucosa of the right maxillary first molar. Tooth movement distances were recorded on Days 1, 3, 7, and 14. Five rats from each group were sacrificed at each time point to obtain maxillary tissue samples. Hematoxylin and eosin (HE) staining was performed to observe the histophysiological changes in the tension-side periodontal tissues. Immunohistochemical staining was used to mark and count CD31-positive cells (microvascular quantification) and to detect the expression of osteocalcin (OCN) in the tension side. Results Measurements of tooth movement distance showed that the Yoda1 group exhibited significantly increased tooth movement distances on Days 3, 7, and 14 (0.238 ± 0.008 mm, 0.406 ± 0.011 mm, and 0.746 ± 0.013 mm, respectively) compared to the control group (PPPPPP |