This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Force-Dependent Presence of Senescent Cells Expressing Vascular Endothelial Growth Factor During Orthodontic Tooth Movement
by
, and
Yohei Morihana
1,
Masato Nakagawa
2,*,†,
Yue Zhou
3,
Hidetoshi Morikuni
1,
Zi Deng
2,
Yoshitomo Honda
2 and
Aki Nishiura
1,*,† 1
Department of Orthodontics, Osaka Dental University, 8-1 Kuzuhahanazono-cho, Hirakata 573-1121, Osaka, Japan
2
Department of Oral Anatomy, Osaka Dental University, 8-1 Kuzuhahanazono-cho, Hirakata 573-1121, Osaka, Japan
3
Stomatological Center, Affiliated Hospital of Yunnan University, No. 176, Qingnian Road, Kunming 650021, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biology 2026, 15(2), 187; https://doi.org/10.3390/biology15020187
Submission received: 17 November 2025
/
Revised: 30 December 2025
/
Accepted: 10 January 2026
/
Published: 19 January 2026
(This article belongs to the Special Issue Cellular Senescence in Development, Regeneration, Aging, and Cancer)
Simple Summary
Mechanical force is an inducer of cellular senescence; however, the influence of orthodontic force magnitude on the presence of senescent cells in angiogenesis during orthodontic tooth movement remains unclear. In this study, we examined the presence of senescent cells and their expression of vascular endothelial growth factor (VEGF) in a rat tooth movement model with different force magnitudes. A moderate force increased both senescent cell abundance and angiogenesis, whereas a stronger force reduced these responses. Senescent cells expressing vascular endothelial growth factor appeared mainly under moderate force. These findings suggest that force magnitude influences the presence of VEGF+ senescent cells during orthodontic tooth movement.
Abstract
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.
