1. Academic Validation
  2. Glycolytic reprogramming controls periodontitis-associated macrophage pyroptosis via AMPK/SIRT1/NF-κB signaling pathway

Glycolytic reprogramming controls periodontitis-associated macrophage pyroptosis via AMPK/SIRT1/NF-κB signaling pathway

  • Int Immunopharmacol. 2023 Apr 15;119:110192. doi: 10.1016/j.intimp.2023.110192.
Yani He 1 Yuting Wang 1 Xiangbin Jia 1 Yingxue Li 1 Yao Yang 1 Lifei Pan 1 Rui Zhao 1 Yue Han 1 Feng Wang 2 Xiaoyue Guan 3 Tiezhou Hou 4
Affiliations

Affiliations

  • 1 Key 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.
  • 2 Experimental Center of Stomatology, School of Stomatology, Xi'an Medical College, Xi'an, Shaanxi, China.
  • 3 Key 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. Electronic address: wangchuqiaowcq@xjtu.edu.cn.
  • 4 Key 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. Electronic address: tiezhou@mail.xjtu.edu.cn.
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.

Keywords

2-Deoxy-d-glucose; Glycolysis; Hexokinase; Macrophages; Periodontitis; Pyroptosis.

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