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Updated: Aug 2, 2025
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Published on: November 28, 2015
Glycolytic reprogramming controls periodontitis-associated macrophage pyroptosis via AMPK/SIRT1/NF-κB signaling
Yani He1, Yuting Wang1, Xiangbin Jia1
1Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Department of Cariology and Endodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Abstract:
Glycolysis has been demonstrated as a crucial metabolic process in bacteria infected diseases via modulating the activity of pyroptosis. Macrophages are the most abundant immune cells that infiltrated in the infected periodontal tissues, which significantly influence the outcome of periodontitis (PD). However, the effect of glycolysis in regulating macrophage pyroptosis during PD development remains unknown. This study aimed to explore the role of glycolysis in PD-associated macrophage pyroptosis and periodontal degeneration. Clinical specimens were used to determine the emergence of macrophage pyroptosis and glycolysis in periodontal tissues by immunohistochemical analysis and western blot. For an in-depth understanding of the regulatory effect of glycolysis in the progression of macrophage pyroptosis associated periodontitis, both in vivo PD model and in vitro PD model were treated with 2-DG (2-Deoxy-d-glucose), a glycolysis inhibitor. The data showed that the blockade of glycolysis could significantly suppress the lipopolysaccharide (LPS) induced macrophage pyroptosis, resulting in an attenuation of the inflammatory response and bone resorption in periodontal lesions. Furthermore, we revealed that the regulatory effect of glycolysis on macrophage pyroptosis can be mediated via AMPK/SIRT1/NF-κB signaling pathway. Our study unveiled that suppressed glycolysis restrains the activity of PD-associated macrophage pyroptosis, osteoclastogenesis, and subsequent periodontal tissue destruction. These findings extend our knowledge of glycolysis in regulating PD-associated macrophage pyroptosis and provide a potential novel target for PD therapy.
Insights
In periodontitis, inhibiting glycolysis reduces macrophage pyroptosis, inflammation, and bone loss. This metabolic pathway offers a new therapeutic target for treating periodontal disease.
Area of Science:
- Immunology
- Metabolic pathways
- Periodontal disease
Background:
- Macrophages are key immune cells in periodontal tissues.
- Periodontitis (PD) involves inflammation and bone loss.
- The role of glycolysis in macrophage pyroptosis during PD is unclear.
Purpose of the Study:
- Investigate glycolysis's role in PD-associated macrophage pyroptosis.
- Explore glycolysis's effect on periodontal degeneration.
- Identify potential therapeutic targets for PD.
Main Methods:
- Analyzed clinical specimens using immunohistochemistry and Western blot.
- Utilized in vivo and in vitro PD models treated with 2-deoxy-D-glucose (2-DG), a glycolysis inhibitor.
- Investigated the AMPK/SIRT1/NF-κB signaling pathway.
Main Results:
- Glycolysis blockade suppressed lipopolysaccharide (LPS)-induced macrophage pyroptosis.
- Inhibiting glycolysis attenuated inflammatory responses and bone resorption in periodontal lesions.
- The regulatory effect of glycolysis on pyroptosis is mediated by the AMPK/SIRT1/NF-κB pathway.
Conclusions:
- Suppressed glycolysis restrains PD-associated macrophage pyroptosis, osteoclastogenesis, and periodontal tissue destruction.
- Glycolysis inhibition presents a potential therapeutic strategy for periodontitis.
- Findings deepen understanding of glycolysis in regulating macrophage pyroptosis in PD.
