Abstract
Background: Emerging research demonstrates the regulatory effects of c-di-AMP, a bacterial-derived small molecule secondary messenger, on host immune responses and promoting resistance against infection-related diseases. This study aims to elucidate the role of c-di-AMP in the occurrence and development of periodontitis.
Methods: We established ligation-induced periodontitis in mice and assessed the impact of c-di-AMP on alveolar bone resorption. Transcriptomic sequencing of mouse gingival tissues post-c-di-AMP treatment revealed the potential PI3K/Akt pathway. Gingival epithelial cells were treated with c-di-AMP to validate PI3K/Akt pathway activation. Under inflammatory conditions induced by LPS, we evaluated the inflammatory factor release, as well as the Akt and NrF2 activation. 16S rRNA gene sequencing of gingival microbiota in mice assessed microbial composition changes post-c-di-AMP treatment. Data were analyzed via one-way ANOVA.
Results: C-di-AMP effectively reduced alveolar bone resorption in mice. Transcriptomic analysis revealed a significant upregulation of the PI3K/Akt pathway, as well as an increase in the cGMP/PKG signaling pathway. In vitro, c-di-AMP suppressed inflammatory factor release (e.g., IL-6 and TNF-α) from gingival epithelial cells and activated Akt and NrF2, the key components of the PI3K/Akt pathway.
Conclusion: This study demonstrates that c-di-AMP definitely plays a role in alleviating periodontitis. These findings shed light on the mechanisms through which c-di-AMP can activate the PI3K/Akt pathway and potentially involve the cGMP/PKG pathway, ultimately contributing to improved immune defense and maintenance of bone homeostasis.