{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T12:54:59Z","timestamp":1777812899553,"version":"3.51.4"},"reference-count":25,"publisher":"SAGE Publications","issue":"13","license":[{"start":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T00:00:00Z","timestamp":1696550400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"the Advanced Research and Development Programs for Medical Innovation","award":["JP18gm1010010"],"award-info":[{"award-number":["JP18gm1010010"]}]},{"DOI":"10.13039\/100008732","name":"uehara memorial foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JST CREST Program","award":["JPMJCR21N3"],"award-info":[{"award-number":["JPMJCR21N3"]}]},{"DOI":"10.13039\/501100001691","name":"japan society for the promotion of science","doi-asserted-by":"publisher","award":["19K22714, 20H03864, 21K19595, and 23H03081"],"award-info":[{"award-number":["19K22714, 20H03864, 21K19595, and 23H03081"]}],"id":[{"id":"10.13039\/501100001691","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":[[2023,12]]},"abstract":"<jats:p>Periodontitis is a multifactorial disease that progresses via dynamic interaction between bacterial and host-derived genetic factors. The recent trend of omics analyses has discovered many periodontitis-related risk factors. However, how much the individual factor affects the pathogenesis of periodontitis is still unknown. This article aims to identify multiple key factors related to the pathogenesis of periodontitis and quantitatively predict the influence of each factor on alveolar bone resorption by omics analysis and mathematical modeling. First, we induced periodontitis in mice ( n = 3 or 4 at each time point) by tooth ligation. Next, we assessed alveolar bone resorption by micro\u2013computed tomography, alterations in the gene expression by RNA sequencing, and the microbiome of the gingivae by 16S ribosomal RNA sequencing during disease pathogenesis. Omics data analysis identified key players (bacteria and molecules) involved in the pathogenesis of periodontitis. We then constructed a mathematical model of the pathogenesis of periodontitis by employing ordinary differential equations that described the dynamic regulatory interplay between the key players and predicted the alveolar bone integrity as output. Finally, we estimated the model parameters using our dynamic experimental data and validated the model prediction of influence on alveolar bone resorption by in vivo experiments. The model predictions and experimental results revealed that monocyte recruitment induced by bacteria-mediated Toll-like receptor activation was the principal reaction regulating alveolar bone resorption in a periodontitis condition. On the other hand, osteoblast-mediated osteoclast differentiation had less impact on bone integrity in a periodontitis condition.<\/jats:p>","DOI":"10.1177\/00220345231196530","type":"journal-article","created":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T05:36:23Z","timestamp":1696570583000},"page":"1468-1477","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Omics-Based Mathematical Modeling Unveils Pathogenesis of Periodontitis in an Experimental Murine Model"],"prefix":"10.1177","volume":"102","author":[{"given":"C.","family":"Fujihara","sequence":"first","affiliation":[{"name":"Department of Periodontology and Regenerative Dentistry, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Murakami","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Systems, Institute for Protein Research, Osaka University, Suita, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6062-5203","authenticated-orcid":false,"given":"S.","family":"Magi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Division of Cell Physiology, Faculty of Medicine, Toho University, Ota-ku, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Motooka","sequence":"additional","affiliation":[{"name":"Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Nantakeeratipat","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Regenerative Dentistry, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan"},{"name":"Department of Conservative Dentistry and Prothodontics, Faculty of Dentistry, Srinakharinwirot University, Bangkok, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Canela","sequence":"additional","affiliation":[{"name":"The Hakubi Center for Advanced Research, Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0769-9382","authenticated-orcid":false,"given":"R. 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