Four-Octyl itaconate ameliorates periodontal destruction via Nrf2-dependent antioxidant system  

作　　者：Liangjing Xin Fuyuan Zhou Chuangwei Zhang Wenjie Zhong Shihan Xu Xuan Jing Dong Wang Si Wang Tao Chen Jinlin Song 

机构地区：[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

出　　处：《International Journal of Oral Science》2022年第3期297-308,共12页国际口腔科学杂志（英文版）

基　　金：supported by the National Natural Science Foundation of China (31971282 and 32071362);2019 Chongqing Graduate Tutor Team Construction Project (dstd201903);Scientific and Technological Research Program of Chongqing Municipal Education Commission (KJQN201900415)。

摘　　要：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.

关 键 词：Four-Octyl itaconate ameliorates periodontal destruction via Nrf2-dependent antioxidant system 

分 类 号：R781.42[医药卫生—口腔医学]