{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:19:33Z","timestamp":1792757973996,"version":"4.5.0"},"reference-count":64,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2023\/15750\u20107"],"award-info":[{"award-number":["2023\/15750\u20107"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["25\/09939\u20105"],"award-info":[{"award-number":["25\/09939\u20105"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["24\/15353\u20100"],"award-info":[{"award-number":["24\/15353\u20100"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["25\/01429\u20108"],"award-info":[{"award-number":["25\/01429\u20108"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Clinic Periodontology"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate whether local administration of sodium tanshinone IIA sulfonate (STS) modulates periodontal inflammation, alveolar bone loss, immune response and bone remodelling\u2013related signalling pathways in a ligature\u2010induced murine model of periodontitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Sixty C57BL\/6J male mice were randomly assigned to four groups: control group (C), periodontitis (P), low\u2010dose (1\u2009mg\/kg) tanshinone (STS1) and high\u2010dose (5\u2009mg\/kg) tanshinone treatment (STS5). Experimental periodontitis was induced by bilateral placement of ligatures around the first maxillary molars in the P, STS1 and STS5 groups. STS or vehicle was administered locally to the gingival tissues 2\u2009days before disease induction and continued until the end of the experiment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      STS significantly attenuated periodontal bone loss, preserved bone microarchitecture, reduced inflammatory infiltrate and maintained collagen organisation. Mechanistically, STS suppressed RANKL\u2010dependent osteoclastogenesis by down\u2010regulating RANKL, CTSK, MMP\u20109, OSCAR and NFATc1 mRNA expression while restoring the RANKL\/OPG balance, thereby limiting osteoclast differentiation and activity. In parallel, STS attenuated inflammatory signalling by inhibiting NF\u2010\u03baB pathway activation, as reflected by reduced NF\u2010\u03baB protein levels, stabilisation of its inhibitory regulator I\u03baB\u03b1 as well as suppression of IL\u20106, TNF\u2010\u03b1 and TGF\u2010\u03b2 gene expression, followed by a trend towards reduced IFN\u2010\u03b3 gene levels. STS further modulated macrophage polarisation by reducing M1\u2010like macrophages, as shown by decreased F4\/80\n                      <jats:sup>+<\/jats:sup>\n                      CD80\n                      <jats:sup>+<\/jats:sup>\n                      signal, while CD206 immunoreactivity increased. At the protein level, STS reduced TRAP, CTSK and NFATc1 expression while restoring RUNX2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>STS effectively suppresses periodontal inflammation and alveolar bone destruction by modulating inflammatory signalling and attenuating M1\u2010like macrophage polarisation, inhibiting osteoclastogenesis and partially restoring osteogenic pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jcpe.70159","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T07:41:02Z","timestamp":1783150862000},"page":"1443-1458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Local Sodium Tanshinone\n                    <scp>IIA<\/scp>\n                    Sulfonate Attenuates Periodontal Bone Loss by Modulating Inflammatory, Immune and Osteoclastogenic Signalling"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1110-6233","authenticated-orcid":false,"given":"Rafael Scaf","family":"de Molon","sequence":"first","affiliation":[{"name":"Department of Diagnostic and Surgery, School of Dentistry S\u00e3o Paulo State University (UNESP)  Ara\u00e7atuba S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5068-0268","authenticated-orcid":false,"given":"Raquel Mantuaneli","family":"Scarel\u2010Caminaga","sequence":"additional","affiliation":[{"name":"Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry S\u00e3o Paulo State University\u2010UNESP  Araraquara S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4688-2059","authenticated-orcid":false,"given":"Fran\u00e7ois Isnaldo Dias","family":"Caldeira","sequence":"additional","affiliation":[{"name":"Department of Morphology, Genetics, Orthodontics and Pediatric Dentistry, School of Dentistry S\u00e3o Paulo State University\u2010UNESP  Araraquara S\u00e3o Paulo Brazil"},{"name":"Department of Diagnosis and Surgery, School of Dentistry S\u00e3o Paulo State University\u2010UNESP  Araraquara S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4859-0583","authenticated-orcid":false,"given":"Edilson","family":"Ervolino","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, School of Dentistry S\u00e3o Paulo State University (UNESP)  Ara\u00e7atuba S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6681-1269","authenticated-orcid":false,"given":"Erica Dorigatti","family":"de Avila","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Surgery, School of Dentistry S\u00e3o Paulo State University (UNESP)  Ara\u00e7atuba S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula Aboud","family":"Barbugli","sequence":"additional","affiliation":[{"name":"Department of Dental Materials and Prosthodontics, School of Dentistry S\u00e3o Paulo State University\u2010UNESP  Araraquara S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Ezequiel","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Surgery, School of Dentistry S\u00e3o Paulo State University (UNESP)  Ara\u00e7atuba S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao Pedro","family":"Franco\u2010Moura","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Surgery, School of Dentistry S\u00e3o Paulo State University (UNESP)  Ara\u00e7atuba S\u00e3o Paulo 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