{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T13:01:22Z","timestamp":1777813282653,"version":"3.51.4"},"reference-count":33,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100023885","name":"All of Us Research Program","doi-asserted-by":"publisher","award":["1R01DE031270-01A1"],"award-info":[{"award-number":["1R01DE031270-01A1"]}],"id":[{"id":"10.13039\/100023885","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023885","name":"All of Us Research Program","doi-asserted-by":"publisher","award":["3R01DE031270-02S1"],"award-info":[{"award-number":["3R01DE031270-02S1"]}],"id":[{"id":"10.13039\/100023885","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":[[2025,11]]},"abstract":"<jats:p>\n                    The molecular mechanisms mediating barrier functions of the junctional epithelium (JE) are incompletely understood. The aim of this study was to gain mechanistic insights into how reduced Wnt\/\u03b2-catenin signaling affects the metabolism, turnover, and attachment of JE cells to the tooth surface. A membrane-permeable selective inhibitor of the Wntless protein, C59, was topically delivered to the JE. Wnt pathway suppression was verified by using\n                    <jats:italic toggle=\"yes\">\n                      Axin2\n                      <jats:sup>LacZ\/+<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">\n                      Axin2Cre\n                      <jats:sup>ERT2\/+<\/jats:sup>\n                      ;\n                    <\/jats:italic>\n                    <jats:italic toggle=\"yes\">\n                      R26R\n                      <jats:sup>mTmG\/+<\/jats:sup>\n                    <\/jats:italic>\n                    strains of mice. Quantitative analyses were carried out at multiple time points to assess mitotic activity, apoptosis, expression of hemidesmosomal attachment proteins, distribution of immune cells, collagen remodeling, and alveolar bone resorption. To complement these studies, Wntless was genetically deleted in osteocalcin-expressing cells, including those in the JE, after which the same quantitative analyses were performed. C59 caused a dose-dependent inhibition in Wnt signaling, which led to reduced mitotic activity and increased apoptosis in the JE. Continued dosing of C59 was accompanied by downregulation of the hemidesmosome attachment proteins laminin 5, plectin, and integrin \u03b24 and a disruption in collagen orientation. A genetic approach in which Wntless function was inhibited in osteocalcin-expressing JE cells yielded similar inhibitory effects on Wnt signaling, mitotic activity, the JE\u2019s attachment to the tooth surface, and an increase in immune cells within the connective tissue. Wnt\/\u03b2-catenin signaling is required for JE homeostasis, and disruptions to the pathway are sufficient to cause JE breakdown and attachment loss. Methods to modulate Wnt\/\u03b2-catenin signaling may prove beneficial in restoring JE homeostasis after injury or disease.\n                  <\/jats:p>","DOI":"10.1177\/00220345251336168","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T07:36:27Z","timestamp":1749540987000},"page":"1405-1414","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["The Junctional Epithelium Attachment Is Regulated by Wnt Signaling"],"prefix":"10.1177","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8854-4253","authenticated-orcid":false,"given":"F.","family":"Aellos","sequence":"first","affiliation":[{"name":"Department of Surgery, Stanford School of Medicine, Stanford University, Stanford, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.L.","family":"Cuevas","sequence":"additional","affiliation":[{"name":"Department of Surgery, Stanford School 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