Dimethyl fumarate modulates M1/M2 macrophage polarization to ameliorate periodontal destruction by increasing TUFM-mediated mitophagy.
10.1038/s41368-025-00360-0
- Author:
Liang CHEN
1
;
Pengxiao HU
1
;
Xinhua HONG
1
;
Bin LI
1
;
Yifan PING
1
;
ShuoMin CHEN
1
;
Tianle JIANG
1
;
Haofu JIANG
1
;
Yixin MAO
1
;
Yang CHEN
1
;
Zhongchen SONG
2
;
Zhou YE
3
;
Xiaoyu SUN
1
;
Shufan ZHAO
4
;
Shengbin HUANG
5
Author Information
1. Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
2. Department of Periodontology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
3. Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, University of Hong Kong, Hong Kong, China.
4. Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China. sf.zhao@wmu.edu.cn.
5. Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China. huangsb003@wmu.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Dimethyl Fumarate/pharmacology*;
Mitophagy/drug effects*;
Animals;
Mice;
Macrophages/metabolism*;
Periodontitis/prevention & control*;
RAW 264.7 Cells;
Oxidative Stress/drug effects*;
Peptide Elongation Factor Tu/metabolism*;
Mice, Inbred C57BL;
Male;
Mitochondria/drug effects*
- From:
International Journal of Oral Science
2025;17(1):32-32
- CountryChina
- Language:English
-
Abstract:
Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages, with improved mitochondrial function, inhibited oxidative stress, and increased mitophagy in RAW 264.7 cells. Furthermore, DMF increased intracellular mitochondrial Tu translation elongation factor (TUFM) levels to maintain mitochondrial homeostasis, promoted mitophagy, and modulated macrophage polarization, whereas TUFM knockdown decreased the protective effect of DMF. Finally, mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway. Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages, resulting in a shift in the balance of macrophage polarization, thereby attenuating periodontitis. Importantly, this study provides new insights into the prevention of periodontitis.
