{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:26:32Z","timestamp":1790429192638,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T00:00:00Z","timestamp":1450137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["25463216"],"award-info":[{"award-number":["25463216"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["25670882"],"award-info":[{"award-number":["25670882"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["15H02578"],"award-info":[{"award-number":["15H02578"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["15K15763"],"award-info":[{"award-number":["15K15763"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Objectives<\/jats:title>\n                    <jats:p>\n                      Our previous study demonstrated using an oral gavage model that\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\n                        orphyromonas gingivalis\n                      <\/jats:italic>\n                      could induce various inflammatory changes linked to periodontitis\u2010associated systemic diseases by altering gut microbiota. A ligature\u2010induced periodontitis model is similar to human periodontitis in various aspects: in both cases, alveolar bone resorption depends on oral bacterial load, and gingival tissue becomes infiltrated with inflammatory cells. Therefore, this model may be suitable for the analysis of bacterial burden and gingival tissue inflammation with changes related to systemic diseases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and Methods<\/jats:title>\n                    <jats:p>Periodontal tissue destruction was induced by a 2 wk ligature placement around the bilateral maxillary second molar. We analyzed the expression profile of various genes in several tissues, levels of systemic inflammatory markers and induction of insulin resistance. In addition, we studied changes in gut microbiota composition and bacterial load in the oral cavity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Two weeks after ligature placement gingival inflammation was significantly induced with a disrupted gingival epithelial barrier and alveolar bone resorption accompanied by increased bacterial burden in the oral cavity. Gene expression analysis of the gingival tissue of ligated mice demonstrated that interleukin (\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>\n                        l\n                      <\/jats:italic>\n                      )\n                      <jats:italic>1b<\/jats:italic>\n                      was significantly elevated and\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>\n                        l6\n                      <\/jats:italic>\n                      and\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content>\n                        l17a\n                      <\/jats:italic>\n                      tended to be higher in ligated mice than in untreated mice. Although serum\n                      <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                      \u20106 was significantly elevated and serum amyloid\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      tended to be higher in ligated compared to untreated mice, endotoxin levels did not differ between the two groups. Among the genes whose expressions are closely related to glucose and lipid metabolisms, only phosphoenolpyruvate carboxykinase 1 (\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>\n                        ck1\n                      <\/jats:italic>\n                      ) and acetyl\u2010\n                      <jats:styled-content style=\"fixed-case\">c<\/jats:styled-content>\n                      oenzyme\n                      <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                      carboxylase alpha (\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>\n                        caca\n                      <\/jats:italic>\n                      ) showed significant changes following ligature placement in the liver, with the former upregulated and the latter downregulated. However, insulin sensitivity did not change following ligature placement. Furthermore, ligature placement weakly affected the composition of gut microbiota and gene expression in the intestines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The results suggest that increased oral commensals and gingival inflammation have limited roles in the pathological changes to adipose and liver tissues, which are important organs whose dysfunctions contribute to the development of periodontitis\u2010related systemic diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jre.12344","type":"journal-article","created":{"date-parts":[[2015,12,15]],"date-time":"2015-12-15T01:02:57Z","timestamp":1450141377000},"page":"639-646","source":"Crossref","is-referenced-by-count":61,"title":["Ligature\u2010induced periodontitis in mice induces elevated levels of circulating\n                    <scp>interleukin<\/scp>\n                    \u20106 but shows only weak effects on adipose and liver tissues"],"prefix":"10.1111","volume":"51","author":[{"given":"Y.","family":"Matsuda","sequence":"first","affiliation":[{"name":"Research Unit for Oral\u2010Systemic Connection Division of Oral Science for Health Promotion Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"},{"name":"Division of Periodontology Department of Oral Biological Science Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Kato","sequence":"additional","affiliation":[{"name":"Laboratory for Intestinal Ecosystem RCAI RIKEN Center for Integrative Medical Sciences (IMS\u2010RCAI) Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Research Unit for Oral\u2010Systemic Connection Division of Oral Science for Health Promotion Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"},{"name":"Division of Periodontology Department of Oral Biological Science Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Research Unit for Oral\u2010Systemic Connection Division of Oral Science for Health Promotion Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"},{"name":"Division of Periodontology Department of Oral Biological Science Niigata University Graduate School of Medical and Dental Sciences Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Arimatsu","sequence":"additional","affiliation":[{"name":"Research Unit for Oral\u2010Systemic Connection Division of Oral Science for Health Promotion Niigata University Graduate School of Medical and Dental Sciences 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