Metabolic Syndrome Promotes Periodontal Inflammation Through Oxidative Modification

To investigate the role of metabolic syndrome (MS) in the promotion of periodontitis through oxidative modification of cysteine. We recruited patients with or without metabolic syndrome and studied their periodontal parameters, oxidative metabolites, and tissue inflammation levels (ethical approval number: PJ2023-057-001,2023.01-2024.12). Immunofluorescence staining was used to detect the abundance of nitrosylated and sulfenated proteins in periodontal tissues of each group. Development of MS and periodontitis models using Gli1-CreERT2-tdtomao (Ethical Approval No.IACUC-2404075), and the oxidative modification inhibitor N-Acetylcysteine was injected locally. Micro-CT and immunofluorescence were used to detect the tissue damage and the oxidative modification of cysteine. 1. MS aggravated the BOP positive rate and attachment loss (p < 0.001). The abundance of protein nitrosylation modification and sulfonation modification in MS group was significantly higher than that in healthy control group (p < 0.0001, p < 0.001). 2. Gli1 lineage stem cells in the periodontal tissues of the MS group were depleted compared with the HC group (p < 0.0001), and the nitrosylation and sulfenation signals in the MS group were significantly increased (p < 0.0001). In the periodontitis model, MS significantly aggravated periodontal destruction. 3.Topical application of N-Acetylcysteine significantly increased the number of stem cells and promoted tissue repair under periodontitis in MS model mice. Metabolic syndrome aggravates periodontal inflammation, accompanied by an increase in the abundance of oxidation-modified proteins. The periodontal tissue damage can be alleviated by topical application of oxidative modification inhibitors.