{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T18:59:38Z","timestamp":1793473178607,"version":"4.5.0"},"reference-count":43,"publisher":"Scientific Scholar","content-domain":{"domain":["cytojournal.com"],"crossmark-restriction":true},"short-container-title":["Cytojournal"],"abstract":"\nObjective:<\/jats:title>\nPeriodontitis, the sixth major complication of diabetes, has a mutually influential and mutually reinforcing relationship with diabetes. Forkhead box protein M1 (FOXM1) is essential for osteoclast differentiation, periodontitis, and diabetes. This study aims to investigate the potential action mechanisms and effects of FOXM1 on diabetes periodontitis.<\/jats:p>\n<\/jats:sec>\n\nMaterial and Methods:<\/jats:title>\nA model of mice with diabetes periodontitis was created. The pathological damage of periodontal tissues in the mandibles of mice was assessed through hematoxylin\u2013eosin staining. The expression of bone resorption-related, cell proliferation transcription, inflammatory, and oxidative stress-related factors in mice with diabetes periodontitis was analyzed through Western blot and quantitative reverse transcription polymerase chain reaction. Oxidative stress level was examined through enzyme-linked immunosorbent assay. Furthermore, plasmids with FOXM1 silencing were constructed using short hairpin RNA. The activity of activator protein-1 (AP-1) binding was measured via electrophoretic mobility shift assay. Reactive oxygen species (ROS) expression was detected using a dichlorodihydrofluorescein diacetate probe.<\/jats:p>\n<\/jats:sec>\n\nResults:<\/jats:title>\nTreatment with the ROS inhibitor N-acetylcysteine ameliorated the degree of bone destruction, attenuated the inflammatory response, and mitigated oxidative stress in mice with diabetes periodontitis. Short hairpin-FOXM1 reduced the levels of FOXM1, increased the levels of C-Jun proto-oncogene and AP-1, enhanced AP-1 binding activity, and increased ROS production in the macrophage cells. sh-FOXM1 increased the mRNA and protein levels of tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), and nuclear factor-activated T-cell c1 (NFATc1). By contrast, JUN-small interfering RNA decreased the mRNA and protein expression of TRAP, OSCAR, and NFATc1. The silencing of FOXM1-regulated ROS production mediated AP-1 activation to promote macrophage osteoclast differentiation.<\/jats:p>\n<\/jats:sec>\n\nConclusion:<\/jats:title>\nFOXM1 plays a key role in diabetes periodontitis, and this study provides theoretical support for the clinical prevention and treatment of diabetes periodontitis in humans.<\/jats:p>\n<\/jats:sec>","DOI":"10.25259\/cytojournal_143_2024","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T17:17:01Z","timestamp":1734974221000},"page":"72","update-policy":"https:\/\/doi.org\/10.25259\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Promotion of inflammatory response in mice with diabetes periodontitis: regulation of forkhead box protein M1 silencing to mediate activator protein-1 via reactive oxygen species production"],"prefix":"10.25259","volume":"21","author":[{"given":"Yang","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongping","family":"Ren","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibo","family":"Peng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingxue","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10894","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"10.25259\/Cytojournal_143_2024\/ref-1","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/978-3-030-96881-6_12","article-title":"Update on the bidirectional link between diabetes and periodontitis","volume":"1373","author":"Salhi","year":"2022","journal-title":"Adv Exp Med Biol"},{"key":"10.25259\/Cytojournal_143_2024\/ref-2","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/s41581-020-0278-5","article-title":"Genetics of diabetes mellitus and diabetes complications","volume":"16","author":"Cole","year":"2020","journal-title":"Nat Rev Nephrol"},{"key":"10.25259\/Cytojournal_143_2024\/ref-3","volume-title":"StatPearls","author":"Mehrotra","year":"2024"},{"key":"10.25259\/Cytojournal_143_2024\/ref-4","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.adaj.2018.04.023","article-title":"Periodontitis in US adults: National health and nutrition examination survey 2009-2014","volume":"149","author":"Eke","year":"2018","journal-title":"J Am Dent Assoc"},{"key":"10.25259\/Cytojournal_143_2024\/ref-5","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1111\/jre.12613","article-title":"Vitamin D attenuates human gingival fibroblast inflammatory cytokine production following advanced glycation end product interaction with receptors for AGE","volume":"54","author":"Elenkova","year":"2019","journal-title":"J Periodontal Res"},{"key":"10.25259\/Cytojournal_143_2024\/ref-6","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1111\/prd.12270","article-title":"Diabetes as a potential risk for periodontitis: Association studies","volume":"83","author":"Genco","year":"2000","journal-title":"Periodontol 2020"},{"key":"10.25259\/Cytojournal_143_2024\/ref-7","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1902\/jop.2016.160140","article-title":"Influence of periodontal disease on changes of glycated hemoglobin levels in patients with type 2 diabetes mellitus: A retrospective cohort study","volume":"88","author":"Costa","year":"2017","journal-title":"J Periodontol"},{"key":"10.25259\/Cytojournal_143_2024\/ref-8","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1007\/s10541-005-0161-9","article-title":"Reactive oxygen species and human inflammatory periodontal diseases","volume":"70","author":"Canak\u00e7i","year":"2005","journal-title":"Biochemistry (Mosc)"},{"key":"10.25259\/Cytojournal_143_2024\/ref-9","first-page":"3189","article-title":"Peroxidative stress and nutrient antioxidant status in periodontal disease","volume":"4","author":"Purohit","year":"2013","journal-title":"Int J Biol Med Res"},{"key":"10.25259\/Cytojournal_143_2024\/ref-10","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/s40495-019-00171-y","article-title":"Role of reactive oxygen species in cancer progression","volume":"5","author":"Kashyap","year":"2019","journal-title":"Curr Pharmacol Rep"},{"key":"10.25259\/Cytojournal_143_2024\/ref-11","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1042\/BJ20071341","article-title":"Genetic aspects of inflammation and cancer","volume":"410","author":"Hold","year":"2008","journal-title":"Biochem J"},{"key":"10.25259\/Cytojournal_143_2024\/ref-12","doi-asserted-by":"publisher","first-page":"28624","DOI":"10.18632\/oncotarget.8721","article-title":"The Mbd4 DNA glycosylase protects mice from inflammation-driven colon cancer and tissue injury","volume":"7","author":"Yu","year":"2016","journal-title":"Oncotarget"},{"key":"10.25259\/Cytojournal_143_2024\/ref-13","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.aat.2015.03.002","article-title":"Clinical implication of perioperative inflammatory cytokine alteration","volume":"53","author":"Hsing","year":"2015","journal-title":"Acta Anaesthesiol Taiwan"},{"key":"10.25259\/Cytojournal_143_2024\/ref-14","doi-asserted-by":"publisher","first-page":"80","DOI":"10.15407\/ubj91.01.080","article-title":"Role of AP-1 transcriptional factor in development of oxidative and nitrosative stress in periodontal tissues during systemic inflammatory response","volume":"91","author":"Yelins'ka","year":"2019","journal-title":"Ukr Biochem J"},{"key":"10.25259\/Cytojournal_143_2024\/ref-15","doi-asserted-by":"publisher","first-page":"125","DOI":"10.3233\/JCB-210044","article-title":"Role of reactive oxygen species and antioxidants in periodontal disease","volume":"7","author":"Saluja","year":"2021","journal-title":"J Cell Biotechnol"},{"key":"10.25259\/Cytojournal_143_2024\/ref-16","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1158\/1535-7163.MCT-12-0712","article-title":"FOX(M1) news--it is cancer","volume":"12","author":"Halasi","year":"2013","journal-title":"Mol Cancer Ther"},{"key":"10.25259\/Cytojournal_143_2024\/ref-17","doi-asserted-by":"publisher","first-page":"804","DOI":"10.2319\/072418-536.1","article-title":"Force-induced decline of FOXM1 in human periodontal ligament cells contributes to osteoclast differentiation","volume":"89","author":"Li","year":"2019","journal-title":"Angle Orthod"},{"key":"10.25259\/Cytojournal_143_2024\/ref-18","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1128\/MCB.00934-12","article-title":"FOXM1 promotes allergen-induced goblet cell metaplasia and pulmonary inflammation","volume":"33","author":"Ren","year":"2013","journal-title":"Mol Cell Biol"},{"key":"10.25259\/Cytojournal_143_2024\/ref-19","doi-asserted-by":"publisher","first-page":"411","DOI":"10.4103\/0972-124X.118306","article-title":"Reactive oxygen species in periodontitis","volume":"17","author":"Dahiya","year":"2013","journal-title":"J Indian Soc Periodontol"},{"key":"10.25259\/Cytojournal_143_2024\/ref-20","doi-asserted-by":"publisher","first-page":"e42610515134","DOI":"10.33448\/rsd-v10i5.15134","article-title":"The effect of N-acetylcysteine on periodontitis: A mini-review of literature","volume":"10","author":"Carvalho","year":"2021","journal-title":"Res Soc Development"},{"key":"10.25259\/Cytojournal_143_2024\/ref-21","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1186\/s13287-019-1500-x","article-title":"Aspirin inhibits RANKL-induced osteoclast differentiation in dendritic cells by suppressing NF-\u03baB and NFATc1 activation","volume":"10","author":"Wu","year":"2019","journal-title":"Stem Cell Res Ther"},{"key":"10.25259\/Cytojournal_143_2024\/ref-22","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/s41415-019-0794-5","article-title":"Periodontitis and diabetes","volume":"227","author":"Preshaw","year":"2019","journal-title":"Br Dent J"},{"key":"10.25259\/Cytojournal_143_2024\/ref-23","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.semcancer.2022.07.009","article-title":"Dysregulated FOXM1 signaling in the regulation of cancer stem cells","volume":"86","author":"Sher","year":"2022","journal-title":"Semin Cancer Biol"},{"key":"10.25259\/Cytojournal_143_2024\/ref-24","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.bcp.2018.05.019","article-title":"Targeting forkhead box M1 transcription factor in breast cancer","volume":"154","author":"O'Regan","year":"2018","journal-title":"Biochem Pharmacol"},{"key":"10.25259\/Cytojournal_143_2024\/ref-25","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1186\/s13287-022-03161-y","article-title":"N-acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging","volume":"13","author":"Meng","year":"2022","journal-title":"Stem Cell Res Ther"},{"key":"10.25259\/Cytojournal_143_2024\/ref-26","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1111\/j.1600-0765.2012.01497.x","article-title":"N-acetylcysteine decreases alveolar bone loss on experimental periodontitis in streptozotocin-induced diabetic rats","volume":"47","author":"Toker","year":"2012","journal-title":"J Periodontal Res"},{"key":"10.25259\/Cytojournal_143_2024\/ref-27","doi-asserted-by":"publisher","first-page":"415","DOI":"10.2174\/187152609788922582","article-title":"Redox status in periodontal and systemic inflammatory conditions including associated neoplasias: Antioxidants as adjunctive therapy?","volume":"9","author":"Soory","year":"2009","journal-title":"Infect Disord Drug Targets"},{"key":"10.25259\/Cytojournal_143_2024\/ref-28","doi-asserted-by":"publisher","first-page":"e35","DOI":"10.1902\/jop.2015.150315","article-title":"The effect of melatonin on bone loss, diabetic control, and apoptosis in rats with diabetes with ligature-induced periodontitis","volume":"87","author":"Balci Yuce","year":"2016","journal-title":"J Periodontol"},{"key":"10.25259\/Cytojournal_143_2024\/ref-29","doi-asserted-by":"publisher","first-page":"781378","DOI":"10.3389\/fimmu.2021.781378","article-title":"Immunomodulation in the treatment of periodontitis: Progress and perspectives","volume":"12","author":"Yang","year":"2021","journal-title":"Front Immunol"},{"key":"10.25259\/Cytojournal_143_2024\/ref-30","doi-asserted-by":"publisher","first-page":"3299","DOI":"10.3892\/mmr.2020.11433","article-title":"Nacetyl cysteine inhibits the lipopolysaccharideinduced inflammatory response in bone marrow mesenchymal stem cells by suppressing the TXNIP\/NLRP3\/IL1\u03b2 signaling pathway","volume":"22","author":"Wang","year":"2020","journal-title":"Mol Med Rep"},{"key":"10.25259\/Cytojournal_143_2024\/ref-31","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1139\/cjpp-2017-0559","article-title":"Beneficial effects of N-acetylcysteine on hepatic oxidative stress in streptozotocin-induced diabetic rats","volume":"96","author":"Rosa","year":"2018","journal-title":"Canadian Journal of Physiology and Pharmacology"},{"key":"10.25259\/Cytojournal_143_2024\/ref-32","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/s41387-021-00177-w","article-title":"N-acetylcysteine supplementation did not reverse mitochondrial oxidative stress, apoptosis, and inflammation in the salivary glands of hyperglycemic rats","volume":"11","author":"Anna","year":"2021","journal-title":"Nutr Diabetes"},{"key":"10.25259\/Cytojournal_143_2024\/ref-33","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.molmed.2019.09.007","article-title":"Nrf2: Redox and metabolic regulator of stem cell state and function","volume":"26","author":"Dai","year":"2020","journal-title":"Trends Mol Med"},{"key":"10.25259\/Cytojournal_143_2024\/ref-34","doi-asserted-by":"publisher","first-page":"8307","DOI":"10.1021\/acsnano.3c12580","article-title":"Melatonin-derived carbon dots with free radical scavenging property for effective periodontitis treatment via the Nrf2\/HO-1 pathway","volume":"18","author":"Xin","year":"2024","journal-title":"ACS Nano"},{"key":"10.25259\/Cytojournal_143_2024\/ref-35","doi-asserted-by":"publisher","first-page":"112598","DOI":"10.1016\/j.yexcr.2021.112598","article-title":"Nrf2 activation is involved in osteogenic differentiation of periodontal ligament stem cells under cyclic mechanical stretch","volume":"403","author":"Xi","year":"2021","journal-title":"Exp Cell Res"},{"key":"10.25259\/Cytojournal_143_2024\/ref-36","doi-asserted-by":"publisher","first-page":"2379","DOI":"10.1002\/ijc.30840","article-title":"FOXO transcription factors at the interface of metabolism and cancer","volume":"141","author":"Link","year":"2017","journal-title":"Int J Cancer"},{"key":"10.25259\/Cytojournal_143_2024\/ref-37","first-page":"673","article-title":"Knockdown of foxM1 strengthens osteogenic differentiation ability of bone marrow mesenchymal stem cells","volume":"23","author":"Chen","year":"2019","journal-title":"Chin J Tissue Eng Res"},{"key":"10.25259\/Cytojournal_143_2024\/ref-38","first-page":"833","author":"Zhang","year":"2019"},{"key":"10.25259\/Cytojournal_143_2024\/ref-39","doi-asserted-by":"publisher","first-page":"785","DOI":"10.3892\/or.2019.7192","article-title":"Activation of AKT\/AP1\/FoxM1 signaling confers sorafenib resistance to liver cancer cells","volume":"42","author":"Yan","year":"2019","journal-title":"Oncol Rep"},{"key":"10.25259\/Cytojournal_143_2024\/ref-40","doi-asserted-by":"publisher","first-page":"e106","DOI":"10.1038\/emm.2014.42","article-title":"APE1\/Ref-1 as an emerging therapeutic target for various human diseases: Phytochemical modulation of its functions","volume":"46","author":"Thakur","year":"2014","journal-title":"Exp Mol Med"},{"key":"10.25259\/Cytojournal_143_2024\/ref-41","doi-asserted-by":"publisher","first-page":"3135","DOI":"10.1158\/0008-5472.CAN-16-3566","article-title":"FOXM1 in Cancer: Interactions and vulnerabilities","volume":"77","author":"Gartel","year":"2017","journal-title":"Cancer Res"},{"key":"10.25259\/Cytojournal_143_2024\/ref-42","doi-asserted-by":"publisher","first-page":"13114","DOI":"10.1038\/srep13114","article-title":"Photodynamic activation as a molecular switch to promote osteoblast cell differentiation via AP-1 activation","volume":"5","author":"Kushibiki","year":"2015","journal-title":"Sci Rep"},{"key":"10.25259\/Cytojournal_143_2024\/ref-43","doi-asserted-by":"publisher","first-page":"104530","DOI":"10.1016\/j.archoralbio.2019.104530","article-title":"Reversine inhibits MMP-3, IL-6 and IL-8 expression through suppression of ROS and JNK\/AP-1 activation in interleukin-1\u03b2-stimulated human gingival fibroblasts","volume":"108","author":"Song","year":"2019","journal-title":"Arch Oral Biol"}],"container-title":["Cytojournal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cytojournal.com\/promotion-of-inflammatory-response-in-mice-with-diabetes-periodontitis-regulation-of-forkhead-box-protein-m1-silencing-to-mediate-activator-protein-1-via-reactive-oxygen-species-production\/","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cytojournal.com\/promotion-of-inflammatory-response-in-mice-with-diabetes-periodontitis-regulation-of-forkhead-box-protein-m1-silencing-to-mediate-activator-protein-1-via-reactive-oxygen-species-production\/","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T17:17:04Z","timestamp":1734974224000},"score":1,"resource":{"primary":{"URL":"https:\/\/cytojournal.com\/promotion-of-inflammatory-response-in-mice-with-diabetes-periodontitis-regulation-of-forkhead-box-protein-m1-silencing-to-mediate-activator-protein-1-via-reactive-oxygen-species-production\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,23]]},"references-count":43,"alternative-id":["10.25259\/Cytojournal_143_2024"],"URL":"https:\/\/doi.org\/10.25259\/cytojournal_143_2024","relation":{},"ISSN":["1742-6413","0974-5963"],"issn-type":[{"value":"1742-6413","type":"electronic"},{"value":"0974-5963","type":"print"}],"subject":[],"published":{"date-parts":[[2024,12,23]]},"article-number":"72"}}