Metformin ameliorates HMGB1-mediated oxidative stress through mTOR pathway in experimental periodontitis
Periodontitis is an oral chronic inflammatory disease. Inhibiting tissue destruction and promoting tissue regeneration are important means for the treatment of periodontitis. Metformin not only has hypoglycemic effect but also has anti-inflammatory effect. Metformin has been shown to inhibit oxidati...
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KeAi Communications Co., Ltd.
2023-03-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304221000830 |
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| author | Boyang Sun Siqi Ying Qian Ma Han Li Jie Li Jinlin Song |
| author_facet | Boyang Sun Siqi Ying Qian Ma Han Li Jie Li Jinlin Song |
| author_sort | Boyang Sun |
| collection | DOAJ |
| description | Periodontitis is an oral chronic inflammatory disease. Inhibiting tissue destruction and promoting tissue regeneration are important means for the treatment of periodontitis. Metformin not only has hypoglycemic effect but also has anti-inflammatory effect. Metformin has been shown to inhibit oxidative stress and activate autophagy through AMPK/mTOR pathway. High mobility group box 1 (HMGB1) has been implicated in the pathogenesis of many inflammatory diseases including periodontitis, it can participate in the induction of oxidative stress. HMGB1 is an autophagy regulator under oxidative stress, which can activate mTOR pathway. However, it is not clear whether metformin is related to HMGB1 and its mechanism in the process of periodontitis. Cell viability and expression of inflammatory cytokines were clarified by Cell Counting Kit-8, real-time PCR and enzyme-linked immunosorbent assay. Western blot and immunofluorescence were conducted to determine HMGB1 intracellular localization and expression of autophagy-associated proteins in vitro. Experimental periodontitis mice model was induced by administering a ligature. Immunohistochemistry was performed to detect the expression and localization of HMGB1 in vivo. The results of CCK-8, real-time PCR, enzyme-linked immunosorbent assay, Western blot and immunofluorescence showed lipopolysaccharide (LPS) treatment inhibited cell viability, and increased HMGB1 expression at a dose-independent manner. Metformin can reduce the effect of LPS. It also improves autophagy pathway inhibited by LPS and down-regulates mTOR expression. In addition, metformin attenuated alveolar bone resorption induced by ligation. This study provides new evidence for that metformin is a potential drug for the treatment of periodontitis and HMGB1 may be a potential target for periodontal intervention. |
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| spelling | doaj.art-4ba4c7ec46df4998b04a11e77c6696cc2023-09-03T11:33:23ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422023-03-01102542553Metformin ameliorates HMGB1-mediated oxidative stress through mTOR pathway in experimental periodontitisBoyang Sun0Siqi Ying1Qian Ma2Han Li3Jie Li4Jinlin Song5College of Stomatology, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 400016, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 400016, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 400016, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 400016, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 400016, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 400016, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 400016, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 400016, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 400016, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 400016, China; Corresponding authors. College of Stomatology, Chongqing Medical University, 426# Songshibei Road, Yubei District, Chongqing 401147, China. Fax: +86 23 8886 0222.College of Stomatology, Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 400016, China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 400016, China; Corresponding authors. College of Stomatology, Chongqing Medical University, 426# Songshibei Road, Yubei District, Chongqing 401147, China. Fax: +86 23 8886 0222.Periodontitis is an oral chronic inflammatory disease. Inhibiting tissue destruction and promoting tissue regeneration are important means for the treatment of periodontitis. Metformin not only has hypoglycemic effect but also has anti-inflammatory effect. Metformin has been shown to inhibit oxidative stress and activate autophagy through AMPK/mTOR pathway. High mobility group box 1 (HMGB1) has been implicated in the pathogenesis of many inflammatory diseases including periodontitis, it can participate in the induction of oxidative stress. HMGB1 is an autophagy regulator under oxidative stress, which can activate mTOR pathway. However, it is not clear whether metformin is related to HMGB1 and its mechanism in the process of periodontitis. Cell viability and expression of inflammatory cytokines were clarified by Cell Counting Kit-8, real-time PCR and enzyme-linked immunosorbent assay. Western blot and immunofluorescence were conducted to determine HMGB1 intracellular localization and expression of autophagy-associated proteins in vitro. Experimental periodontitis mice model was induced by administering a ligature. Immunohistochemistry was performed to detect the expression and localization of HMGB1 in vivo. The results of CCK-8, real-time PCR, enzyme-linked immunosorbent assay, Western blot and immunofluorescence showed lipopolysaccharide (LPS) treatment inhibited cell viability, and increased HMGB1 expression at a dose-independent manner. Metformin can reduce the effect of LPS. It also improves autophagy pathway inhibited by LPS and down-regulates mTOR expression. In addition, metformin attenuated alveolar bone resorption induced by ligation. This study provides new evidence for that metformin is a potential drug for the treatment of periodontitis and HMGB1 may be a potential target for periodontal intervention.http://www.sciencedirect.com/science/article/pii/S2352304221000830AutophagyMetforminOxidative stressPeriodontal ligament cellsPeriodontitis |
| spellingShingle | Boyang Sun Siqi Ying Qian Ma Han Li Jie Li Jinlin Song Metformin ameliorates HMGB1-mediated oxidative stress through mTOR pathway in experimental periodontitis Genes and Diseases Autophagy Metformin Oxidative stress Periodontal ligament cells Periodontitis |
| title | Metformin ameliorates HMGB1-mediated oxidative stress through mTOR pathway in experimental periodontitis |
| title_full | Metformin ameliorates HMGB1-mediated oxidative stress through mTOR pathway in experimental periodontitis |
| title_fullStr | Metformin ameliorates HMGB1-mediated oxidative stress through mTOR pathway in experimental periodontitis |
| title_full_unstemmed | Metformin ameliorates HMGB1-mediated oxidative stress through mTOR pathway in experimental periodontitis |
| title_short | Metformin ameliorates HMGB1-mediated oxidative stress through mTOR pathway in experimental periodontitis |
| title_sort | metformin ameliorates hmgb1 mediated oxidative stress through mtor pathway in experimental periodontitis |
| topic | Autophagy Metformin Oxidative stress Periodontal ligament cells Periodontitis |
| url | http://www.sciencedirect.com/science/article/pii/S2352304221000830 |
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