Mechanosensitive Yes-Associated Protein/TAZ-cGAS-STING Axis Induces Periodontal Ligament Fibroblasts Senescence and Mediates Compression-Induced Root Resorption

Sep 28, 2026

Uploaded by Sarah

This study investigates how compressive force triggers senescence in periodontal ligament fibroblasts (PDLFs) and how that senescence contributes to orthodontic root resorption. PDLF senescence was assessed using β-galactosidase staining, Western blotting, and immunofluorescence, with functional readouts including Alizarin Red S mineralization and TRAP-based osteoclast differentiation. YAP signaling was analyzed by Western blot and immunofluorescence, including pharmacological modulation with XMU-MP-1 and pathway agonists/inhibitors. Results show compressive forces inactivate mechanosensitive YAP, upregulate cGAS/STING signaling, and impair mineralization, with STING activation exacerbating effects.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Article history

Introduction

Materials and Methods

Results

Conclusion

Scientiﬁc Research Report Mechanosensitive Yes-Associated Protein/TAZ−cGAS −STING Axis Induces Periodontal Ligament Fibroblasts Senescence and Mediates Compression-Induced Root Resorption Zuping Wu a,b,y, Siqi Bao a,y, Qian Chena, Xiao Luc, Guzhe Guana, Ruifeng Song a, Qianming Chena*, Xiaoyan Chen a* a Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, China b Guangxi Key Laboratory of the Rehabilitation and Reconstruction for Oral and Maxillofacial Research, Afﬁliated Hospital of Stomatology, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China c Case Western Reserve University Dental School, Cleveland, Ohio, USA | A R T I C L E I N F O | A B S T R A C T | | --- | --- | | Article history:
Received 1 September 2025
Received in revised form
31 October 2025
Accepted 5 November 2025
Available online 11 December 2025 | 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 b-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 agonistsor inhibitors.
Results: Compressive forces induced senescence in PDLFs, evidenced by SA-b-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.
􀀁 2025 The Authors. Published by Elsevier Inc. on behalf ofFDI World Dental Federation. This is an open access article under the CC BY-NC-ND license
([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)) | | Key words:
Root resorption
YAP
cGAS/STING
Periodontal ligament ﬁbroblasts Senescence | | * Corresponding author. Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China. [E-mail addresses:](E-mail addresses: qmchen@zju.edu.cn)[ qmchen@zju.edu.cn](E-mail addresses: qmchen@zju.edu.cn) (Q. Chen), [ortho_chenxy@zju.edu.cn](ortho_chenxy@zju.edu.cn) (X. Chen). Zuping Wu: [http://orcid.org/0000-0003-3661-8593](http://orcid.org/0000-0003-3661-8593) y Zuping Wu and Siqi Bao contributed equally to this w

FAQs

What is the main objective of the study?

To determine whether compressive forces induce senescence in periodontal ligament fibroblasts and to clarify how this senescence mechanistically drives orthodontic root resorption.

How was PDLF senescence evaluated under compressive forces?

Senescence was assessed using β-galactosidase staining, Western blotting, and immunofluorescence.

What mechanistic pathway links YAP to cGAS/STING in compression-induced effects?

Compressive forces inactivate mechanosensitive YAP, which upregulates cGAS/STING signaling; activating STING worsens senescence and impairs mineralization, while YAP activation reduces senescence and osteoclastogenesis and STING inhibition reverses these effects.

Sep 28, 2026

Uploaded by Sarah