{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:10:06Z","timestamp":1791357006031,"version":"4.3.1"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2022\/04466\u20103"],"award-info":[{"award-number":["2022\/04466\u20103"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study aimed to investigate the role of Janus kinase (JAK) signaling in the pathogenesis of periodontitis by evaluating the effects of pharmacological inhibition of JAK isoforms (JAK1 and JAK3) on periodontal inflammation and ligature\u2010induced alveolar bone loss.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Experimental periodontitis (EP) was induced by ligature placement around the mandibular first molars of rats. Concurrently, animals (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200910 per group) received either a JAK1\u20103 inhibitor (JAK1\u20103i group), a JAK3 inhibitor (JAK3i group), or distilled water (EP group) via daily intragastric gavage for 7\u2009days. A control group received only distilled water without ligature placement. Following euthanasia, the mandibles were evaluated using microcomputed tomography for bone loss, stereometric analysis for inflammatory infiltrate and blood vessels, Second Harmonic Generation Microscopy for collagen quantification, and immunohistochemistry to quantify CD45+ and CD3+ cell populations. Gingival tissues were assessed for inflammatory markers by RT\u2010qPCR (\n                      <jats:italic>Il\u20106<\/jats:italic>\n                      ,\n                      <jats:italic>Tnf\u2010\u03b1<\/jats:italic>\n                      , and\n                      <jats:italic>Rankl<\/jats:italic>\n                      ) and ELISA (TNF\u2010\u03b1).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ligature placement resulted in significant alveolar bone loss, increased osteoclast numbers, leukocyte infiltration, extracellular matrix degradation, and elevated expression of inflammatory markers. Treatment with both JAK1\u20103i and JAK3i effectively prevented bone loss and reduced osteoclast numbers. Histological and stereometric analyses showed reduced inflammatory infiltrate and improved tissue organization in both treated groups. JAK1\u20103i preserved collagen content more effectively and significantly reduced the number of CD45+ cells. Compared to the Experimental Periodontitis (EP) group, both inhibitors significantly downregulated the mRNA expression of\n                      <jats:italic>Il\u20106<\/jats:italic>\n                      ,\n                      <jats:italic>Tnf\u2010\u03b1<\/jats:italic>\n                      , and\n                      <jats:italic>Rankl<\/jats:italic>\n                      , and also reduced TNF\u2010\u03b1 protein levels in gingival tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, the findings establish a mechanistic link between JAK signaling and inflammation\u2010driven periodontal tissue destruction, providing new insights into the cellular and molecular events underlying the pathogenesis of experimental periodontitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jre.70042","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T11:36:50Z","timestamp":1759491410000},"page":"1039-1049","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>JAK<\/scp>\n                    Inhibition Prevents Bone Loss and Reduces Inflammation in Experimental Periodontitis"],"prefix":"10.1111","volume":"60","author":[{"given":"Mariely A.","family":"Godoi","sequence":"first","affiliation":[{"name":"Department of Diagnosis and Surgery, School of Dentistry at Araraquara Sao Paulo State University (UNESP)  Araraquara Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1bio R. M.","family":"Leite","sequence":"additional","affiliation":[{"name":"Oral Health Academic Clinical Programme Duke\u2010NUS Medical School  Singapore Singapore"},{"name":"National Dental Research Institute Singapore National Dental Centre Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4985-443X","authenticated-orcid":false,"given":"Angelo C.","family":"Camilli","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Surgery, School of Dentistry at Araraquara Sao Paulo State University (UNESP)  Araraquara Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen G. A.","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Surgery, School of Dentistry at Araraquara Sao Paulo State University (UNESP)  Araraquara Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vit\u00f3ria B.","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Surgery, School of Dentistry at Araraquara Sao Paulo State University (UNESP)  Araraquara Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iolanda A. F.","family":"de Matos","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Surgery, School of Dentistry at Araraquara Sao Paulo State University (UNESP)  Araraquara Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6425-4777","authenticated-orcid":false,"given":"Evangelos","family":"Papathanasiou","sequence":"additional","affiliation":[{"name":"Department of Periodontology Tufts University School of Dental Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1297-9717","authenticated-orcid":false,"given":"Morgana R.","family":"Guimar\u00e3es\u2010Stabili","sequence":"additional","affiliation":[{"name":"Department of Diagnosis and Surgery, School of Dentistry at Araraquara Sao Paulo State University (UNESP)  Araraquara Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12946"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.20-0088"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0328-y"},{"issue":"5","key":"e_1_2_11_5_1","first-page":"139","article-title":"Shifting the Paradigm From Inhibitors of Inflammation to Resolvers of Inflammation in Periodontitis","volume":"176","author":"Van Dyke T. 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