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Updated: Jul 20, 2025
Inducing Apical Periodontitis in Mice
Published on: August 6, 2019
Activation of receptor-interacting protein 3-mediated necroptosis accelerates periodontitis in mice
Yuan Yue1, Weicheng Chan1, Jing Zhang2
1The State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Objective:
To investigate the involvement and role of receptor-interacting protein 3 (RIP3)-mediated necroptosis in periodontitis.
Methods:
A periodontitis murine model was established by oral infection with Porphyromonas gingivalis, and activation of necroptosis pathway was identified by immunohistochemistry. Adeno-associated virus was used to knock down Rip3 and the effect of Rip3 knockdown on periodontal inflammation was examined by Micro-CT, qRT-PCR and histological staining. In vitro, P. gingivalis-LPS was used to infect fibroblast cell line L929 and siRNA was used to knock down Rip3. Necroptosis pathway signalling and inflammation in cells were detected by cell viability and death assay, Western Blot, qRT-PCR and immunofluorescence analysis.
Results:
Phosphorylation of RIP3 and mixed lineage kinase domain-like protein (MLKL) was increased in the periodontal ligament of mice infected with P. gingivalis. RIP3 knockdown reduced osteoclastogenesis and inflammatory cytokines in the periodontal area, and alleviated alveolar bone loss in vivo. In vitro, P. gingivalis-LPS-induced RIP3-mediated necroptosis in L929 cells, and knockdown of RIP3 by siRNA decreased the expression of inflammatory cytokines.
Conclusion:
RIP3-mediated necroptosis is activated in periodontitis and blocking necroptosis alleviates disease progression, indicating that RIP3 may be a potential target for periodontitis treatment.
Insights
Receptor-interacting protein 3 (RIP3)-mediated necroptosis is active in periodontitis. Blocking this process alleviates disease, suggesting RIP3 as a potential therapeutic target for periodontitis treatment.
Area of Science:
- Immunology
- Cell Biology
- Periodontal Disease Research
Background:
- Periodontitis is a chronic inflammatory disease affecting the gums and supporting bone.
- Necroptosis is a programmed cell death pathway implicated in various inflammatory conditions.
Purpose of the Study:
- To investigate the role of receptor-interacting protein 3 (RIP3)-mediated necroptosis in the pathogenesis of periodontitis.
- To evaluate RIP3 as a potential therapeutic target for periodontitis.
Main Methods:
- Established a periodontitis murine model using Porphyromonas gingivalis infection.
- Utilized adeno-associated virus and siRNA for RIP3 knockdown in vivo and in vitro.
- Assessed necroptosis activation, inflammation, and bone loss using immunohistochemistry, Micro-CT, qRT-PCR, Western Blot, and cell assays.
Main Results:
- Increased RIP3 and MLKL phosphorylation observed in periodontitis models.
- RIP3 knockdown reduced osteoclastogenesis, inflammatory cytokines, and alveolar bone loss.
- In vitro studies confirmed P. gingivalis-LPS-induced RIP3-mediated necroptosis and decreased inflammatory cytokine expression upon RIP3 knockdown.
Conclusions:
- RIP3-mediated necroptosis is activated during periodontitis.
- Inhibition of necroptosis via RIP3 targeting demonstrates therapeutic potential for periodontitis.
- RIP3 represents a promising molecular target for managing periodontitis progression.
