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(HFD) and a single streptozotocin (STZ) dose to induce diabetes mellitus (DM), alongside periodontitis (Perio) induced by ligature placement and oral inoculation with Porphyromonas gingivalis (P. gingivalis). The goal was to mimic human pathological conditions, creating a physiologically relevant environment to study the interplay between DM and Perio. A total of 128 six-week-old male C57BL\/6J mice were randomly divided into four groups: Control, DM, Perio, and DM-P. DM was induced by HFD and STZ injection, and Perio by ligature placement and P. gingivalis infection. Evaluations occurred at baseline and days 7, 14, and 21. Alveolar bone loss was assessed by micro-computed tomography, and inflammation was examined histologically. DM mice showed elevated glucose levels and insulin resistance. Perio and DM-P groups experienced significant bone loss compared with Control and DM groups. The morphometric analysis revealed abundant inflammatory cells and reduced collagen fibers in Perio and DM-P groups, especially at day 7. This dual murine model successfully replicated the key features of DM and Perio, maintaining overall health of the animals, and good tolerability by those subjects to the stress of both interventional procedures.<\/jats:p>","DOI":"10.3390\/ijms26125611","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T11:18:40Z","timestamp":1749640720000},"page":"5611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Establishing a Dual Murine Model to Explore the Interactions Between Diabetes and Periodontitis in Mice"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5521-424X","authenticated-orcid":false,"given":"B\u00e1rbara R.","family":"Silva","sequence":"first","affiliation":[{"name":"Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, S\u00e3o Paulo State University\u2014UNESP, Araraquara 14801-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0161-3872","authenticated-orcid":false,"given":"Marco A. R.","family":"Hidalgo","sequence":"additional","affiliation":[{"name":"Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, S\u00e3o Paulo State University\u2014UNESP, Araraquara 14801-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata C. L.","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, S\u00e3o Paulo State University\u2014UNESP, Araraquara 14801-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica D.","family":"de Avila","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Surgery, School of Dentistry at Ara\u00e7atuba, Sao Paulo State University\u2014UNESP, Ara\u00e7atuba 16015-050, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deivys L. P.","family":"Fuentes","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, School of Pharmaceutical Sciences, S\u00e3o Paulo State University\u2014UNESP, Araraquara 14800-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0084-3468","authenticated-orcid":false,"given":"Iracilda Z.","family":"Carlos","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, School of Pharmaceutical Sciences, S\u00e3o Paulo State University\u2014UNESP, Araraquara 14800-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid D.","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, School of Pharmaceutical Sciences, S\u00e3o Paulo State University\u2014UNESP, Araraquara 14800-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estela S.","family":"Cerri","sequence":"additional","affiliation":[{"name":"Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, S\u00e3o Paulo State University\u2014UNESP, Araraquara 14801-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5756-5828","authenticated-orcid":false,"given":"Paulo S.","family":"Cerri","sequence":"additional","affiliation":[{"name":"Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, S\u00e3o Paulo State University\u2014UNESP, Araraquara 14801-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0987-5295","authenticated-orcid":false,"given":"Amanda M.","family":"Baviera","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, School of Pharmaceutical Sciences, S\u00e3o Paulo State University\u2014UNESP, Araraquara 14800-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1110-6233","authenticated-orcid":false,"given":"Rafael Scaf","family":"de Molon","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Surgery, School of Dentistry at Ara\u00e7atuba, Sao Paulo State University\u2014UNESP, Ara\u00e7atuba 16015-050, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5068-0268","authenticated-orcid":false,"given":"Raquel M.","family":"Scarel-Caminaga","sequence":"additional","affiliation":[{"name":"Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry at Araraquara, S\u00e3o Paulo State University\u2014UNESP, Araraquara 14801-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022). Global Oral Health Status Report: Towards Universal Health Coverage for Oral Health by 2030, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1111\/jcpe.13506","article-title":"Global, regional, and national burden of severe periodontitis, 1990\u20132019: An analysis of the Global Burden of Disease Study 2019","volume":"48","author":"Chen","year":"2021","journal-title":"J. Clin. Periodontol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Van Dyke, T.E., Bartold, P.M., and Reynolds, E.C. (2020). The Nexus Between Periodontal Inflammation and Dysbiosis. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00511"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1111\/jcpe.13769","article-title":"Prevalence of periodontitis in dentate people between 2011 and 2020: A systematic review and meta-analysis of epidemiological studies","volume":"50","author":"Trindade","year":"2023","journal-title":"J. Clin. Periodontol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S183","DOI":"10.1002\/JPER.16-0480","article-title":"Manifestations of systemic diseases and conditions that affect the periodontal attachment apparatus: Case definitions and diagnostic considerations","volume":"89","author":"Albandar","year":"2018","journal-title":"J. Periodontol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S162","DOI":"10.1111\/jcpe.12946","article-title":"Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions","volume":"45","author":"Papapanou","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee (2024). 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care, 47, S20\u2013S42.","DOI":"10.2337\/dc24-S002"},{"key":"ref_8","unstructured":"Atlas, D. (2017). IDF Diabetes Atlas, International Diabetes Federation. [8th ed.]."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1016\/S0140-6736(22)01655-5","article-title":"Type 2 diabetes","volume":"400","author":"Ahmad","year":"2022","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee (2024). 8. Obesity and Weight Management for the Prevention and Treatment of Type 2 Diabetes: Standards of Care in Diabetes-2024. Diabetes Care, 47, S145\u2013S157.","DOI":"10.2337\/dc24-S008"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ruze, R., Liu, T., Zou, X., Song, J., Chen, Y., Xu, R., Yin, X., and Xu, Q. (2023). Obesity and type 2 diabetes mellitus: Connections in epidemiology, pathogenesis, and treatments. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1161521"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/prd.12318","article-title":"The impact of diabetes on periodontal diseases","volume":"82","author":"Graves","year":"2020","journal-title":"Periodontol. 2000"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41368-023-00227-2","article-title":"Periodontitis as a promoting factor of T2D: Current evidence and mechanisms","volume":"15","author":"Su","year":"2023","journal-title":"Int. J. Oral Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Stohr, J., Barbaresko, J., Neuenschwander, M., and Schlesinger, S. (2021). Bidirectional association between periodontal disease and diabetes mellitus: A systematic review and meta-analysis of cohort studies. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-93062-6"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/s41577-020-00488-6","article-title":"Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities","volume":"21","author":"Hajishengallis","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1159\/000329675","article-title":"Animal models to study host-bacteria interactions involved in periodontitis","volume":"15","author":"Graves","year":"2012","journal-title":"Front. Oral Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.patbio.2006.07.045","article-title":"Pathogenic potential of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, the red bacterial complex associated with periodontitis","volume":"55","author":"Bodet","year":"2007","journal-title":"Pathol. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Acqua, Y.D., Hernandez, C., Fogacci, M., Barbirato, D., and Palioto, D. (2022). Local and systemic effects produced in different models of experimental periodontitis in mice: A systematic review. Arch. Oral Biol., 143.","DOI":"10.1016\/j.archoralbio.2022.105528"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"476068","DOI":"10.1155\/2014\/476068","article-title":"Porphyromonas gingivalis: Major periodontopathic pathogen overview","volume":"2014","author":"Mysak","year":"2014","journal-title":"J. Immunol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41368-024-00313-z","article-title":"Gingipain from Porphyromonas gingivalis causes insulin resistance by degrading insulin receptors through direct proteolytic effects","volume":"16","author":"Liu","year":"2024","journal-title":"Int. J. Oral Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e78","DOI":"10.1002\/cpz1.78","article-title":"Streptozotocin-Induced Diabetic Models in Mice and Rats","volume":"1","author":"Furman","year":"2021","journal-title":"Curr. Protoc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"131","DOI":"10.2174\/1573399810666140508121012","article-title":"Leptin- and leptin receptor-deficient rodent models: Relevance for human type 2 diabetes","volume":"10","author":"Wang","year":"2014","journal-title":"Curr. Diabetes Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1111\/j.1476-5381.2012.01911.x","article-title":"The use of animal models in diabetes research","volume":"166","author":"King","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/jdi.12235","article-title":"Modeling type 2 diabetes in rats using high fat diet and streptozotocin","volume":"5","author":"Skovso","year":"2014","journal-title":"J. Diabetes Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1902\/jop.2013.130225","article-title":"Evaluation of the host response in various models of induced periodontal disease in mice","volume":"85","author":"Cirelli","year":"2014","journal-title":"J. Periodontol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1007\/s00784-015-1607-0","article-title":"Long-term evaluation of oral gavage with periodontopathogens or ligature induction of experimental periodontal disease in mice","volume":"20","author":"Mascarenhas","year":"2016","journal-title":"Clin. Oral Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"113896","DOI":"10.1016\/j.intimp.2024.113896","article-title":"Diabetes exacerbates periodontitis by disrupting IL-33-mediated interaction between periodontal ligament fibroblasts and macrophages","volume":"147","author":"Lou","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1080\/01478885.2023.2188705","article-title":"Perturbation of mitochondrial dynamics links to the aggravation of periodontitis by diabetes","volume":"46","author":"Fu","year":"2023","journal-title":"J. Histotechnol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e9","DOI":"10.1902\/jop.2015.150330","article-title":"Obesity and Hyperlipidemia Modulate Alveolar Bone Loss in Wistar Rats","volume":"87","author":"Cavagni","year":"2016","journal-title":"J. Periodontol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ranbhise, J.S., Ju, S., Singh, M.K., Han, S., Akter, S., Ha, J., Choe, W., Kim, S.S., and Kang, I. (2025). Chronic Inflammation and Glycemic Control: Exploring the Bidirectional Link Between Periodontitis and Diabetes. Dent. J., 13.","DOI":"10.3390\/dj13030100"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Chen, X., He, Y., Zhou, Y., Gong, H., Zhang, J., Qiu, G., Shen, Y., and Qin, W. (2025). Modulatory role of exogenous arachidonic acid in periodontitis with type 2 diabetes mellitus mice. BMC Oral Health, 25.","DOI":"10.1186\/s12903-025-05525-1"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/jre.12951","article-title":"Inhibition of acid sphingomyelinase by imipramine abolishes the synergy between metabolic syndrome and periodontitis on alveolar bone loss","volume":"57","author":"Li","year":"2022","journal-title":"J. Periodontal Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7981","DOI":"10.1021\/acsnano.4c15227","article-title":"Bioactive Zn-V-Si-Ca Glass Nanoparticle Hydrogel Microneedles with Antimicrobial and Antioxidant Properties for Bone Regeneration in Diabetic Periodontitis","volume":"19","author":"Li","year":"2025","journal-title":"ACS Nano"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9071","DOI":"10.1038\/s41467-024-53290-6","article-title":"Polyphenol-mediated redox-active hydrogel with H2S gaseous-bioelectric coupling for periodontal bone healing in diabetes","volume":"15","author":"Fang","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gu, Y., Golub, L.M., Lee, H.M., and Walker, S.G. (2025). Diabetes, periodontal disease, and novel therapeutic approaches- host modulation therapy. Front. Clin. Diabetes Healthc., 6.","DOI":"10.3389\/fcdhc.2025.1529086"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2902351","DOI":"10.1155\/2016\/2902351","article-title":"An Overview of Murine High Fat Diet as a Model for Type 2 Diabetes Mellitus","volume":"2016","author":"Heydemann","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.nutres.2024.09.008","article-title":"The high-fat diet and low-dose streptozotocin type-2 diabetes model induces hyperinsulinemia and insulin resistance in male but not female C57BL\/6J mice","volume":"131","author":"Racine","year":"2024","journal-title":"Nutr. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"S215","DOI":"10.2337\/diabetes.53.suppl_3.S215","article-title":"The high-fat diet-fed mouse: A model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes","volume":"53","author":"Winzell","year":"2004","journal-title":"Diabetes"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Costa, M.C., Lima, T.F.O., Arcaro, C.A., Inacio, M.D., Batista-Duharte, A., Carlos, I.Z., Spolidorio, L.C., Assis, R.P., Brunetti, I.L., and Baviera, A.M. (2020). Trigonelline and curcumin alone, but not in combination, counteract oxidative stress and inflammation and increase glycation product detoxification in the liver and kidney of mice with high-fat diet-induced obesity. J. Nutr. Biochem., 76.","DOI":"10.1016\/j.jnutbio.2019.108303"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4840203","DOI":"10.1155\/2016\/4840203","article-title":"Comparison of Experimental Diabetic Periodontitis Induced by Porphyromonas gingivalis in Mice","volume":"2016","author":"Wang","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Huang, K.C., Chuang, P.Y., Yang, T.Y., Tsai, Y.H., Li, Y.Y., and Chang, S.F. (2024). Diabetic Rats Induced Using a High-Fat Diet and Low-Dose Streptozotocin Treatment Exhibit Gut Microbiota Dysbiosis and Osteoporotic Bone Pathologies. Nutrients, 16.","DOI":"10.3390\/nu16081220"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1007\/s00125-021-05509-0","article-title":"HDL and type 2 diabetes: The chicken or the egg?","volume":"64","author":"Xepapadaki","year":"2021","journal-title":"Diabetologia"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Hahn, M., van Krieken, P.P., Nord, C., Alanentalo, T., Morini, F., Xiong, Y., Eriksson, M., Mayer, J., Kostromina, E., and Ruas, J.L. (2020). Topologically selective islet vulnerability and self-sustained downregulation of markers for beta-cell maturity in streptozotocin-induced diabetes. Commun. Biol., 3.","DOI":"10.1038\/s42003-020-01243-2"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1080\/21623945.2020.1721970","article-title":"Transplantation of brown adipose tissue up-regulates miR-99a to ameliorate liver metabolic disorders in diabetic mice by targeting NOX4","volume":"9","author":"Li","year":"2020","journal-title":"Adipocyte"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.biopha.2018.02.084","article-title":"Investigation of insulin resistance in the popularly used four rat models of type-2 diabetes","volume":"101","author":"Chao","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Martinez-Garcia, M., and Hernandez-Lemus, E. (2021). Periodontal Inflammation and Systemic Diseases: An Overview. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.709438"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/jcpe.13151","article-title":"Epigenetic and inflammatory events in experimental periodontitis following systemic microbial challenge","volume":"46","author":"Palioto","year":"2019","journal-title":"J. Clin. Periodontol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Murugaiyan, V., Utreja, S., Hovey, K.M., Sun, Y., LaMonte, M.J., Wactawski-Wende, J., Diaz, P.I., and Buck, M.J. (2024). Defining Porphyromonas gingivalis strains associated with periodontal disease. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-56849-x"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Haugsten, H.R., Kristoffersen, A.K., Haug, T.M., Soland, T.M., Ovstebo, R., Aass, H.C.D., Enersen, M., and Galtung, H.K. (2023). Isolation, characterization, and fibroblast uptake of bacterial extracellular vesicles from Porphyromonas gingivalis strains. Microbiologyopen, 12.","DOI":"10.1002\/mbo3.1388"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1136\/gutjnl-2015-309897","article-title":"Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response","volume":"66","author":"Garidou","year":"2017","journal-title":"Gut"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1177\/0022034520911037","article-title":"Porphyromonas gingivalis Induces Insulin Resistance by Increasing BCAA Levels in Mice","volume":"99","author":"Tian","year":"2020","journal-title":"J. Dent. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e24366","DOI":"10.1016\/j.heliyon.2024.e24366","article-title":"Periodontitis promotes the progression of diabetes mellitus by enhancing autophagy","volume":"10","author":"Cai","year":"2024","journal-title":"Heliyon"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1111\/jre.12912","article-title":"Hyperglycemia modulates M1\/M2 macrophage polarization via reactive oxygen species overproduction in ligature-induced periodontitis","volume":"56","author":"Zhang","year":"2021","journal-title":"J. Periodontal Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.chom.2017.06.014","article-title":"Diabetes Enhances IL-17 Expression and Alters the Oral Microbiome to Increase Its Pathogenicity","volume":"22","author":"Xiao","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_55","unstructured":"Canadian Council on Animal Care (1993). Guide to the Care and Use of Experimental Animals, Canadian Council on Animal Care. [2nd ed.]."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1093\/jn\/123.11.1939","article-title":"AIN-93 purified diets for laboratory rodents: Final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet","volume":"123","author":"Reeves","year":"1993","journal-title":"J. Nutr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.apsusc.2019.05.154","article-title":"Anti-bacterial efficacy via drug-delivery system from layer-by-layer coating for percutaneous dental implant components","volume":"488","author":"Castro","year":"2019","journal-title":"Appl. Surf. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e00335-17","DOI":"10.1128\/IAI.00335-17","article-title":"B10 Cells Alleviate Periodontal Bone Loss in Experimental Periodontitis","volume":"85","author":"Wang","year":"2017","journal-title":"Infect. Immun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"E261","DOI":"10.1152\/ajpendo.00676.2007","article-title":"Comparison between surrogate indexes of insulin sensitivity and resistance and hyperinsulinemic euglycemic clamp estimates in mice","volume":"294","author":"Lee","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/jcpe.12636","article-title":"Contribution of biomechanical forces to inflammation-induced bone resorption","volume":"44","author":"Nogueira","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1902\/jop.2013.130453","article-title":"Cimetidine reduces alveolar bone loss in induced periodontitis in rat molars","volume":"85","author":"Longhini","year":"2014","journal-title":"J. Periodontol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1002\/JPER.21-0375","article-title":"Diacerein-induced interleukin-1beta deficiency reduces the inflammatory infiltrate and immunoexpression of matrix metalloproteinase-8 in periodontitis in rat molars","volume":"93","author":"Silva","year":"2022","journal-title":"J. Periodontol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1111\/jre.12857","article-title":"Chalcone T4, a novel chalconic compound, inhibits inflammatory bone resorption in vivo and suppresses osteoclastogenesis in vitro","volume":"56","author":"Fernandes","year":"2021","journal-title":"J. Periodontal Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e012","DOI":"10.1590\/1807-3107bor-2020.vol34.0012","article-title":"Pam2CSK4 (TLR2 agonist) induces periodontal destruction in mice","volume":"34","author":"Souza","year":"2020","journal-title":"Braz. Oral Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5611\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:50:20Z","timestamp":1760032220000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5611"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,11]]},"references-count":64,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125611"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125611","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,11]]}}}