Dimethyl fumarate modulates M1/M2 macrophage polarization to ameliorate periodontal destruction by increasing TUFM-mediated mitophagy
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 fun...
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| Language: | English |
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Nature Publishing Group
2025-04-01
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| Series: | International Journal of Oral Science |
| Online Access: | https://doi.org/10.1038/s41368-025-00360-0 |
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| author | Liang Chen Pengxiao Hu Xinhua Hong Bin Li Yifan Ping ShuoMin Chen Tianle Jiang Haofu Jiang Yixin Mao Yang Chen Zhongchen Song Zhou Ye Xiaoyu Sun Shufan Zhao Shengbin Huang |
| author_facet | Liang Chen Pengxiao Hu Xinhua Hong Bin Li Yifan Ping ShuoMin Chen Tianle Jiang Haofu Jiang Yixin Mao Yang Chen Zhongchen Song Zhou Ye Xiaoyu Sun Shufan Zhao Shengbin Huang |
| author_sort | Liang Chen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-329e85a09bdf4939b8e80036d731345b |
| institution | OA Journals |
| issn | 2049-3169 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | International Journal of Oral Science |
| spelling | doaj-art-329e85a09bdf4939b8e80036d731345b2025-08-20T02:17:46ZengNature Publishing GroupInternational Journal of Oral Science2049-31692025-04-0117111410.1038/s41368-025-00360-0Dimethyl fumarate modulates M1/M2 macrophage polarization to ameliorate periodontal destruction by increasing TUFM-mediated mitophagyLiang Chen0Pengxiao Hu1Xinhua Hong2Bin Li3Yifan Ping4ShuoMin Chen5Tianle Jiang6Haofu Jiang7Yixin Mao8Yang Chen9Zhongchen Song10Zhou Ye11Xiaoyu Sun12Shufan Zhao13Shengbin Huang14Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical UniversityInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical UniversityInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical UniversityInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical UniversityInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical UniversityInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical UniversityInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical UniversityInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical UniversityInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical UniversityInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical UniversityDepartment of Periodontology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineApplied Oral Sciences and Community Dental Care, Faculty of Dentistry, University of Hong KongInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical UniversityInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical UniversityInstitute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical UniversityAbstract 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.https://doi.org/10.1038/s41368-025-00360-0 |
| spellingShingle | Liang Chen Pengxiao Hu Xinhua Hong Bin Li Yifan Ping ShuoMin Chen Tianle Jiang Haofu Jiang Yixin Mao Yang Chen Zhongchen Song Zhou Ye Xiaoyu Sun Shufan Zhao Shengbin Huang Dimethyl fumarate modulates M1/M2 macrophage polarization to ameliorate periodontal destruction by increasing TUFM-mediated mitophagy International Journal of Oral Science |
| title | Dimethyl fumarate modulates M1/M2 macrophage polarization to ameliorate periodontal destruction by increasing TUFM-mediated mitophagy |
| title_full | Dimethyl fumarate modulates M1/M2 macrophage polarization to ameliorate periodontal destruction by increasing TUFM-mediated mitophagy |
| title_fullStr | Dimethyl fumarate modulates M1/M2 macrophage polarization to ameliorate periodontal destruction by increasing TUFM-mediated mitophagy |
| title_full_unstemmed | Dimethyl fumarate modulates M1/M2 macrophage polarization to ameliorate periodontal destruction by increasing TUFM-mediated mitophagy |
| title_short | Dimethyl fumarate modulates M1/M2 macrophage polarization to ameliorate periodontal destruction by increasing TUFM-mediated mitophagy |
| title_sort | dimethyl fumarate modulates m1 m2 macrophage polarization to ameliorate periodontal destruction by increasing tufm mediated mitophagy |
| url | https://doi.org/10.1038/s41368-025-00360-0 |
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