Four-Octyl itaconate ameliorates periodontal destruction via Nrf2-dependent antioxidant system.
10.1038/s41368-022-00177-1
- Author:
Liangjing XIN
1
;
Fuyuan ZHOU
1
;
Chuangwei ZHANG
1
;
Wenjie ZHONG
1
;
Shihan XU
1
;
Xuan JING
1
;
Dong WANG
2
;
Si WANG
1
;
Tao CHEN
3
;
Jinlin SONG
4
Author Information
1. College of Stomatology, Chongqing Medical University, Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China.
2. Department of Ultrasound, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
3. College of Stomatology, Chongqing Medical University, Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China. chentao1985@hospital.cqmu.edu.cn.
4. College of Stomatology, Chongqing Medical University, Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China. Songjinlin@hospital.cqmu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Alveolar Bone Loss/prevention & control*;
Animals;
Antioxidants/pharmacology*;
Inflammation;
Kelch-Like ECH-Associated Protein 1/metabolism*;
Mice;
Mice, Inbred C57BL;
Molecular Docking Simulation;
NF-E2-Related Factor 2/metabolism*;
Periodontitis/prevention & control*;
Succinates
- From:
International Journal of Oral Science
2022;14(1):27-27
- CountryChina
- Language:English
-
Abstract:
Periodontitis is a widespread oral disease characterized by continuous inflammation of the periodontal tissue and an irreversible alveolar bone loss, which eventually leads to tooth loss. Four-octyl itaconate (4-OI) is a cell-permeable itaconate derivative and has been recognized as a promising therapeutic target for the treatment of inflammatory diseases. Here, we explored, for the first time, the protective effect of 4-OI on inhibiting periodontal destruction, ameliorating local inflammation, and the underlying mechanism in periodontitis. Here we showed that 4-OI treatment ameliorates inflammation induced by lipopolysaccharide in the periodontal microenvironment. 4-OI can also significantly alleviate inflammation and alveolar bone loss via Nrf2 activation as observed on samples from experimental periodontitis in the C57BL/6 mice. This was further confirmed as silencing Nrf2 blocked the antioxidant effect of 4-OI by downregulating the expression of downstream antioxidant enzymes. Additionally, molecular docking simulation indicated the possible mechanism under Nrf2 activation. Also, in Nrf2-/- mice, 4-OI treatment did not protect against alveolar bone dysfunction due to induced periodontitis, which underlined the importance of the Nrf2 in 4-OI mediated periodontitis treatment. Our results indicated that 4-OI attenuates inflammation and oxidative stress via disassociation of KEAP1-Nrf2 and activation of Nrf2 signaling cascade. Taken together, local administration of 4-OI offers clinical potential to inhibit periodontal destruction, ameliorate local inflammation for more predictable periodontitis.
