International Dental Journal · Published 2026-02-01 · Available online 11 Dec 2025 · Journal article · DOI 10.1016/j.identj.2025.109303 · PMID: 41385921 · PMC · Cited by 2 (Crossref)
Zuping Wu, Siqi Bao, Qian Chen, Xiao Lu, Guzhe Guan, Ruifeng Song, Qianming Chen, Xiaoyan Chen
Objective: This study investigates compressive force-induced senescence in periodontal ligament fibroblasts (PDLFs) and its mechanistic role in orthodontic root resorption. Materials and Methods: PDLFs senescence under compressive forces was evaluated using β-galactosidase staining, Western blotting, and immunofluorescence. Functional consequences of senescence were assessed via Alizarin Red S for mineralization and TRAP staining for osteoclast differentiation. Yes-associated protein (YAP) signalling dynamics were analysed through Western blot and immunofluorescence, with pharmacological activation by XMU-MP-1. The interplay between YAP and the cGAS/STING pathway was investigated using pharmacological interventions. Finally, senescence-mediated effects on mineralization and osteoclastogenesis were evaluated post-treatment with pathway-specific agonists or inhibitors. Results: Compressive forces induced senescence in PDLFs, evidenced by SA-β-gal activation and reduced mineralization capacity. Coculture with osteoclast precursors amplified osteoclast differentiation. Mechanistically, compressive forces inactivated mechanosensitive YAP, triggering senescence, rescued by YAP agonist XMU-MP-1. The YAP/cGAS/STING axis was identified as central: YAP inactivation upregulated cGAS/STING signalling, while STING agonist c-di-GMP exacerbated senescence and impaired mineralization. Pharmacological validation confirmed bidirectional regulation – YAP activation reduced senescence/osteoclastogenesis, whereas STING inhibition reversed these effects. Conclusion: Mechanical stress-induced YAP dysfunction drives PDLF senescence via cGAS/STING pathway activation, establishing a novel mechanobiological axis in root resorption.
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Wu, Z., Bao, S., Chen, Q., et al. (2026). Mechanosensitive Yes-Associated Protein/TAZ–cGAS–STING Axis Induces Periodontal Ligament Fibroblasts Senescence and Mediates Compression-Induced Root Resorption. International Dental Journal. https://doi.org/10.1016/j.identj.2025.109303