{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:51:03Z","timestamp":1791996663559,"version":"4.4.0"},"reference-count":48,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T00:00:00Z","timestamp":1758326400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["K12DE027826"],"award-info":[{"award-number":["K12DE027826"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R00DE029756"],"award-info":[{"award-number":["R00DE029756"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE034695"],"award-info":[{"award-number":["R01DE034695"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["P30AR069620"],"award-info":[{"award-number":["P30AR069620"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Periodontitis is a chronic oral inflammatory disease characterized by alveolar bone loss. Other diseases, such as osteoporosis, cardiovascular disease, and diabetes, can exacerbate its progression. These chronic diseases also have systemic effects that vary in frequency in men and women. Thus, this study sought to determine if periodontitis induced sex-specific changes in long bones. Periodontitis was induced by tying a 5-0 silk suture around the second maxillary molar of 6- to 8-wk-old male and female C57BL\/6J mice. Ligatures were left in place for 7\u2009d or 21\u2009d, and the tibia was subsequently collected for characterization using micro\u2013computed tomography, flow cytometry, and proteomics analysis. Female mice exhibited sustained trabecular and cortical bone loss through day 21, whereas males recovered from any bone loss observed at day 7. Flow cytometry and proteomics analysis indicated that an increased neutrophil response contributes to this bone loss by upregulating pathways associated with neutrophil extracellular trap (NET) formation and reactive oxygen species production. Eliminating NET generation using a Padi4-deficient mouse eliminated the bone loss phenotype during periodontitis. This study suggests that the neutrophil-driven pattern of bone loss observed in female mice, as well as the higher prevalence of osteoporosis in women, may highlight a potential mechanism by which periodontitis exacerbates systemic bone loss.<\/jats:p>","DOI":"10.1177\/00220345251360752","type":"journal-article","created":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T12:24:01Z","timestamp":1758371041000},"page":"130-137","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Periodontitis Leads to Systemic Bone Loss through Neutrophil Reprogramming"],"prefix":"10.1177","volume":"105","author":[{"given":"K.","family":"Martin","sequence":"first","affiliation":[{"name":"Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Dabaja","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA"},{"name":"Department of Mechanical Engineering, University of Michigan School of Engineering, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.J.","family":"Mianecki","sequence":"additional","affiliation":[{"name":"Department of Cariology, Restorative Sciences, and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA"},{"name":"Department of Periodontics and Endodontics, Stony Brook School of Dental Medicine, Stony Brook, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8821-4069","authenticated-orcid":false,"given":"V.","family":"Maglaras","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA"},{"name":"Department of Cariology, Restorative Sciences, and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5067-7317","authenticated-orcid":false,"given":"M.H.A.","family":"Saleh","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7914-4741","authenticated-orcid":false,"given":"J.T.","family":"Decker","sequence":"additional","affiliation":[{"name":"Department of Cariology, Restorative Sciences, and Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.M.","family":"Decker","sequence":"additional","affiliation":[{"name":"Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9,20]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218103"},{"key":"e_1_3_3_3_1","doi-asserted-by":"crossref","unstructured":"Azzouz D Khan MA Palaniyar N. 2021. ROS induces NETosis by oxidizing DNA and initiating DNA repair. Cell Death Discov. 7(1):113. https:\/\/doi.org\/10.1038\/s41420-021-00491-3","DOI":"10.1038\/s41420-021-00491-3"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-024-00865-3"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.04.040"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-021-01000-6"},{"key":"e_1_3_3_7_1","doi-asserted-by":"crossref","unstructured":"Conejeros I Vel\u00e1squez ZD Grob D Zhou E Salecker H Hermosilla C Taubert A. 2019. Histone H2A and Bovine Neutrophil Extracellular Traps Induce Damage of Besnoitia besnoiti-Infected Host Endothelial Cells but Fail to Affect Total Parasite Proliferation. Biology (Basel). 8(4). https:\/\/doi.org\/10.3390\/biology8040078","DOI":"10.3390\/biology8040078"},{"key":"e_1_3_3_8_1","doi-asserted-by":"crossref","unstructured":"Dejas L Santoni K Meunier E Lamkanfi M. 2023. Regulated cell death in neutrophils: From apoptosis to NETosis and pyroptosis. Semin Immunol. 70:101849. https:\/\/doi.org\/10.1016\/j.smim.2023.101849","DOI":"10.1016\/j.smim.2023.101849"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-0026"},{"key":"e_1_3_3_10_1","doi-asserted-by":"crossref","unstructured":"Deerhake ME Cardakli ED Shinohara ML. 2022. Dectin-1 signaling in neutrophils up-regulates PD-L1 and triggers ROS-mediated suppression of CD4+ T cells. J Leukoc Biol. 112(6):1413\u20131425. https:\/\/doi.org\/10.1002\/JLB.3A0322-152RR","DOI":"10.1002\/JLB.3A0322-152RR"},{"key":"e_1_3_3_11_1","doi-asserted-by":"crossref","unstructured":"Eke PI Borgnakke WS Genco RJ. 2020. Recent epidemiologic trends in periodontitis in the usa. Periodontology 2000. 82(1):257\u2013267. doi:https:\/\/doi.org\/10.1111\/prd.12323.","DOI":"10.1111\/prd.12323"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034512457373"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.511799"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12131744"},{"key":"e_1_3_3_15_1","doi-asserted-by":"crossref","unstructured":"Gajendran C Fukui Shoichi Sadhu NM Zainuddin M Rajagopal S Gosu R Gutch S Fukui Saeko Sheehy CE Chu L et al. 2023. Alleviation of arthritis through prevention of neutrophil extracellular traps by an orally available inhibitor of protein arginine deiminase 4. Sci Rep. 13(1):3189. https:\/\/doi.org\/10.1038\/s41598-023-30246-2","DOI":"10.1038\/s41598-023-30246-2"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.20-0029"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2025.114477"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00118"},{"key":"e_1_3_3_19_1","doi-asserted-by":"crossref","unstructured":"Huang J Hong W Wan M Zheng L. 2022. Molecular mechanisms and therapeutic target of NETosis in diseases. MedComm (Beijing). 3(3). https:\/\/doi.org\/10.1002\/mco2.162","DOI":"10.1002\/mco2.162"},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1810692116"},{"key":"e_1_3_3_21_1","doi-asserted-by":"crossref","unstructured":"Jurdzi\u0144ski KT Potempa J Grabiec AM. 2020. Epigenetic regulation of inflammation in periodontitis: cellular mechanisms and therapeutic potential. Clin Epigenetics. 12(1):186. https:\/\/doi.org\/10.1186\/s13148-020-00982-7","DOI":"10.1186\/s13148-020-00982-7"},{"key":"e_1_3_3_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12398"},{"key":"e_1_3_3_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034518804185"},{"key":"e_1_3_3_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.03.043"},{"key":"e_1_3_3_25_1","first-page":"625678","article-title":"Neutrophils drive sexual dimorphism in experimental periodontitis","volume":"2027","author":"Martin K","year":"2024","unstructured":"Martin K, Mianecki M, Maglaras V, Sheikh A, Saleh MHA, Decker AM, Decker JT. 2024. Neutrophils drive sexual dimorphism in experimental periodontitis. bioRxiv.2024.2011. 2027.625678.","journal-title":"bioRxiv.2024.2011"},{"key":"e_1_3_3_26_1","doi-asserted-by":"crossref","unstructured":"Oliveira SR de Arruda JAA Schneider AH Bemquerer LM de Souza RMS Barbim P de Mattos-Pereira GH Calderaro DC Machado CC Alves SF et al. 2024. Neutrophil extracellular traps in rheumatoid arthritis and periodontitis: Contribution of PADI4 gene polymorphisms. J Clin Periodontol. 51(4):452\u2013463. https:\/\/doi.org\/10.1111\/jcpe.13921","DOI":"10.1111\/jcpe.13921"},{"key":"e_1_3_3_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-012-2130-7"},{"key":"e_1_3_3_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2022.10.002"},{"key":"e_1_3_3_29_1","doi-asserted-by":"crossref","unstructured":"Reina S Guarino F Magr\u00ec A De Pinto V. 2016. VDAC3 As a Potential Marker of Mitochondrial Status Is Involved in Cancer and Pathology. Front Oncol. 6:264. https:\/\/doi.org\/10.3389\/fonc.2016.00264","DOI":"10.3389\/fonc.2016.00264"},{"key":"e_1_3_3_30_1","doi-asserted-by":"publisher","DOI":"10.5051\/jpis.2006060303"},{"key":"e_1_3_3_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-021-02772-0"},{"key":"e_1_3_3_32_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2010.100044"},{"key":"e_1_3_3_33_1","doi-asserted-by":"crossref","unstructured":"Sela M Tirza G Ravid O Volovitz I Solodeev I Friedman O Zipori D Gur E Krelin Y Shani N. 2015. NOX1-induced accumulation of reactive oxygen species in abdominal fat-derived mesenchymal stromal cells impinges on long-term proliferation. Cell Death Dis. 6(4):e1728\u2013e1728. https:\/\/doi.org\/10.1038\/cddis.2015.84","DOI":"10.1038\/cddis.2015.84"},{"key":"e_1_3_3_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.identj.2025.03.016"},{"key":"e_1_3_3_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031786"},{"key":"e_1_3_3_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.138873"},{"key":"e_1_3_3_37_1","doi-asserted-by":"crossref","unstructured":"Valerio MS Kirkwood KL. 2018. Sexual Dimorphism in Immunity to Oral Bacterial Diseases: Intersection of Neutrophil and Osteoclast Pathobiology. J Dent Res. 97(13):1416\u20131423. https:\/\/doi.org\/10.1177\/0022034518798825","DOI":"10.1177\/0022034518798825"},{"key":"e_1_3_3_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-13825-7"},{"key":"e_1_3_3_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.10357"},{"key":"e_1_3_3_40_1","doi-asserted-by":"crossref","unstructured":"Wang Han Kim SJ Lei Y Wang S Wang Hui Huang H Zhang H Tsung A. 2024. Neutrophil extracellular traps in homeostasis and disease. Signal Transduct Target Ther. 9(1):235. https:\/\/doi.org\/10.1038\/s41392-024-01933-x","DOI":"10.1038\/s41392-024-01933-x"},{"key":"e_1_3_3_41_1","doi-asserted-by":"crossref","unstructured":"Wan H Yang Y Zhang Q Chen Y Hu X Huang Y Shang L Xiong K. 2024. VDAC1 as a downstream molecule of MLKL participates in OGD\/R-induced necroptosis by inducing mitochondrial damage. Heliyon. 10(1):e23426. https:\/\/doi.org\/10.1016\/j.heliyon.2023.e23426","DOI":"10.1016\/j.heliyon.2023.e23426"},{"key":"e_1_3_3_42_1","doi-asserted-by":"crossref","unstructured":"Wigerblad G Kaplan MJ. 2023. Neutrophil extracellular traps in systemic autoimmune and autoinflammatory diseases. Nat Rev Immunol. 23(5):274\u2013288. https:\/\/doi.org\/10.1038\/s41577-022-00787-0","DOI":"10.1038\/s41577-022-00787-0"},{"key":"e_1_3_3_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2010.07.007"},{"key":"e_1_3_3_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2025.103244"},{"key":"e_1_3_3_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15367"},{"key":"e_1_3_3_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare11192649"},{"key":"e_1_3_3_47_1","doi-asserted-by":"crossref","unstructured":"Zhao Y Wang L Zhang X Zhang L Wei F Li S Li Y. 2024. Identification of neutrophil extracellular traps genes as potential biomarkers in psoriasis based on bioinformatics analysis. Sci Rep. 14(1):23848. https:\/\/doi.org\/10.1038\/s41598-024-75069-x","DOI":"10.1038\/s41598-024-75069-x"},{"key":"e_1_3_3_48_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01200"},{"key":"e_1_3_3_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11213380"}],"container-title":["Journal of Dental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345251360752","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/00220345251360752","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00220345251360752","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:09:33Z","timestamp":1777496973000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/00220345251360752"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,20]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1177\/00220345251360752"],"URL":"https:\/\/doi.org\/10.1177\/00220345251360752","relation":{},"ISSN":["0022-0345","1544-0591"],"issn-type":[{"value":"0022-0345","type":"print"},{"value":"1544-0591","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,20]]}}}