Force-Dependent Presence of Senescent Cells Expressing Vascular Endothelial Growth Factor During Orthodontic Tooth Movement

Orthodontic force magnitude influences angiogenesis during orthodontic tooth movement (OTM); however, the role of senescent cells remains largely unclear. This study investigated the localization of senescent cells and their expression of vascular endothelial growth factor (VEGF) during angiogenesis using a rat horizontal OTM model with different force magnitudes. Nickel-titanium coil springs exerting 60 g or 180 g of orthodontic force were applied to the maxillary first molar of 15-week-old male Sprague-Dawley rats; untreated rats served as controls. Tooth movement was evaluated by stereomicroscopy and micro-computed tomography. Senescent cells (p21, p16) and angiogenesis (CD31 and VEGF) were evaluated by multiplex immunofluorescence. Tooth movement was observed under both the 60 g and 180 g conditions. The 60 g group showed increased cellularity, vascular density, and VEGF expression, suggesting an optimal mechanical force. In contrast, the 180 g group reduced cellularity and angiogenesis, consistent with excessive force. Senescent cells were more abundant in the 60 g group, with over 40% expressing VEGF. These findings suggest that force magnitude influences the presence of VEGF⁺ senescent cells, which may be associated with the angiogenic process in OTM. This work provides insights into the mechanisms underlying optimal force in orthodontic treatment.