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A Zebrafish Model of Diabetes Mellitus and Metabolic Memory
Published on: February 28, 2013
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DHFR-Driven Metabolic Memory Sustains Periodontal Tissue Destruction
1State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Journal of Dental Research
|June 27, 2025
Summary
Hyperglycemia causes lasting damage to periodontal tissues by altering macrophage metabolism via dihydrofolate reductase (DHFR). Restoring DHFR function reversed these harmful effects, suggesting a new therapeutic target for diabetic complications.
Area of Science:
- Endocrinology
- Immunology
- Periodontology
Background:
- Diabetes mellitus is a global metabolic disease with periodontal tissue destruction as a key complication.
- Hyperglycemia contributes to persistent periodontal tissue damage through metabolic and immune dysregulation.
Purpose of the Study:
- To investigate the role of dihydrofolate reductase (DHFR) in hyperglycemia-induced chronic periodontal tissue destruction.
- To explore the concept of metabolic memory in macrophages within the context of diabetic complications.
Main Methods:
- Utilized mouse models including metabolic memory and bone marrow transplantation.
- Employed combined metabolomic and transcriptomic analyses.
- Investigated the impact of hyperglycemia on macrophage phenotype and function.
Main Results:
- Hyperglycemia induced a persistent inflammatory senescent phenotype in macrophages, resistant to glycemic control.
- Reduced DHFR-mediated 1-carbon metabolism, decreased NADP+ and ATP levels were observed under hyperglycemia.
- DHFR overexpression successfully reversed hyperglycemia-induced metabolic and pathological changes in macrophages.
Conclusions:
- DHFR-mediated metabolic memory in macrophages is a critical driver of chronic periodontal tissue destruction in diabetes.
- Targeting DHFR may offer a novel therapeutic strategy for managing diabetic periodontal complications.
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