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Related Experiment Video

Updated: Jan 17, 2026

Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils
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GCN2-Mediated Integrated Stress Response Attenuates Periodontitis.

D Huang1, Q Li1,2, S Peng1

  • 1State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

Journal of Dental Research
|September 22, 2025
PubMed
Summary

The integrated stress response (ISR), regulated by general control nonderepressible 2 (GCN2), protects against periodontitis by reducing inflammation and bone loss. Activating GCN2 may be a new therapy for this common gum disease.

Keywords:
immunomodulationinflammasomesinflammationmacrophagesperiodontal diseasesprotein kinases

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Area of Science:

  • Cellular Biology
  • Immunology
  • Oral Biology

Background:

  • The integrated stress response (ISR), regulated by general control nonderepressible 2 (GCN2), is crucial for tissue homeostasis.
  • The specific role of GCN2-mediated ISR in periodontitis pathogenesis is not well understood.

Purpose of the Study:

  • To investigate the role of GCN2-mediated ISR in periodontitis.
  • To explore the therapeutic potential of GCN2 activation in periodontitis.

Main Methods:

  • Transcriptomic analysis and immunohistochemistry of human and mouse gingival biopsies.
  • Utilizing a ligature-induced mouse periodontitis model and Gcn2 knockout mice.
  • Bulk RNA-sequencing and in vitro assays to elucidate molecular mechanisms.

Main Results:

  • GCN2-mediated ISR is activated in human and mouse periodontitis, primarily in macrophages.
  • Gcn2 deficiency exacerbates gingival inflammation and bone loss in experimental periodontitis.
  • Loss of GCN2 impairs autophagy and overactivates the NLRP3/CASPASE1 inflammasome pathway.

Conclusions:

  • GCN2-mediated ISR plays a protective role in the oral mucosa against periodontitis.
  • GCN2 activation, demonstrated by halofuginone treatment, mitigates oral inflammation and tissue destruction.
  • GCN2 represents a potential therapeutic target for periodontitis treatment.