Hyperglycaemia-associated macrophage pyroptosis accelerates periodontal inflamm-aging
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Updated: Oct 30, 2025
Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils
Published on: January 21, 2020
Pengfei Zhao1,2, Ziqi Yue1,2, Lulingxiao Nie1,2
1State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Aim:
Pyroptosis and inflamm-aging have been newly identified to be involved in diabetic periodontitis. This study aimed to elucidate whether macrophage pyroptosis plays a role in periodontal inflamm-aging by impacting the senescence of fibroblasts, as well as the potential mechanism via NLR family CARD domain-containing protein 4 (NLRC4) phosphorylation.
Materials And Methods:
Diabetes was induced in mice using streptozotocin. Periodontal pyroptosis and senescence were detected using immunohistochemical analysis. Prior to evaluating senescence in human gingival fibroblasts cultured with conditioned medium derived from macrophages, RAW 264.7 macrophages were confirmed to undergo pyroptosis by scanning electron microscopy and gasdermin D (GSDMD) detection. The NLRC4-related pathway was examined under hyperglycaemic conditions.
Results:
Our data showed that macrophage pyroptosis induced the expression of senescent markers in vivo and in vitro. Importantly, clearance of pyroptotic macrophages rescued senescence in fibroblasts. Furthermore, GSDMD activation and pyroptosis in hyperglycaemia were found to be mediated by NLRC4 phosphorylation.
Conclusions:
Hyperglycaemia could initially induce macrophage pyroptosis and lead to cellular senescence, thereby critically contributing to periodontal pathogenesis in diabetes. In particular, NLRC4 phosphorylation could be a potential therapeutic target for the inhibition of this process.
Insights
Macrophage pyroptosis drives fibroblast senescence in diabetic periodontitis. Targeting NLRC4 phosphorylation may inhibit this process, offering a potential therapeutic strategy for diabetes-related gum disease.
Area of Science:
- Immunology
- Cell Biology
- Periodontology
Background:
- Diabetic periodontitis involves pyroptosis and inflamm-aging.
- Macrophage pyroptosis's role in fibroblast senescence is unclear.
Purpose of the Study:
- Investigate macrophage pyroptosis's impact on fibroblast senescence in diabetic periodontitis.
- Elucidate the mechanism involving NLRC4 phosphorylation.
Main Methods:
- Streptozotocin-induced diabetes in mice.
- Immunohistochemistry for pyroptosis and senescence.
- In vitro studies with human gingival fibroblasts and RAW 264.7 macrophages.
- Analysis of the NLRC4 pathway under hyperglycemia.
Main Results:
- Macrophage pyroptosis induced fibroblast senescence in vivo and in vitro.
- Clearing pyroptotic macrophages reversed fibroblast senescence.
- NLRC4 phosphorylation mediated GSDMD activation and pyroptosis under hyperglycemia.
Conclusions:
- Hyperglycemia induces macrophage pyroptosis and fibroblast senescence, contributing to diabetic periodontitis.
- NLRC4 phosphorylation is a potential therapeutic target to inhibit this pathway.
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