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Updated: May 17, 2025

Induction of Periodontitis via a Combination of Ligature and Lipopolysaccharide Injection in a Rat Model
Published on: February 17, 2023
Cyclic di-AMP alleviates periodontitis by activating PI3K/Akt/Nrf2 pathways
Kaihua Luo1,2, Qinrui Wu1,2, Zhengyi Li1
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.
Cyclic di-AMP (c-di-AMP), a bacterial molecule, alleviates periodontitis by reducing bone loss and inflammation. It activates the PI3K/Akt pathway, enhancing immune defense and bone homeostasis.
Area of Science:
- Immunology
- Microbiology
- Periodontology
Background:
- Cyclic di-AMP (c-di-AMP) is a bacterial secondary messenger influencing host immunity.
- Periodontitis is a prevalent inflammatory disease affecting tooth-supporting structures.
Purpose of the Study:
- To investigate the role of c-di-AMP in periodontitis.
- To elucidate the molecular mechanisms underlying c-di-AMP's effects on periodontitis.
Main Methods:
- Ligation-induced periodontitis model in mice.
- Transcriptomic sequencing of gingival tissues.
- In vitro studies using gingival epithelial cells.
- Analysis of inflammatory factors and signaling pathways (PI3K/Akt, cGMP/PKG).
Main Results:
- c-di-AMP treatment significantly reduced alveolar bone resorption in vivo.
- c-di-AMP upregulated the PI3K/Akt and cGMP/PKG signaling pathways in gingival tissues.
- c-di-AMP activated the PI3K/Akt pathway in gingival epithelial cells.
- c-di-AMP suppressed inflammatory factor release (IL-6, TNF-α) and upregulated Akt and Nrf2 under LPS-induced inflammation.
Conclusions:
- c-di-AMP demonstrates a therapeutic role in alleviating periodontitis.
- Activation of the PI3K/Akt pathway is a key mechanism for c-di-AMP's anti-periodontitis effects.
- cGMP/PKG pathway involvement and enhanced immune defense/bone homeostasis are highlighted.
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