{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:42:30Z","timestamp":1780411350924,"version":"3.54.1"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004799","name":"Australian Dental Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004799","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010909","name":"Young Scientists Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010909","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","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":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Growing evidence suggests that excessive inflammation hampers the regenerative capacity of periodontal ligament cells (PDLCs) and that activation of the Wnt\/\u03b2\u2010catenin pathway is crucial in suppressing immune dysregulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to establish the role of the Wnt\/\u03b2\u2010catenin in regulating the immune microenvironment and its subsequent impact on periodontal regeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Lithium chloride (LiCl, Wnt activator) was administered daily into the standard periodontal defects created in 12\u2010week\u2010old Lewis rats. Harvested at 1\u2010week and 2\u2010week post\u2010surgery, samples were then subjected to histological and immunohistochemical evaluation of macrophage distribution and phenotype (pro\u2010inflammatory M1 and anti\u2010inflammatory M2). A murine macrophage cell line, RAW 264.7, was stimulated with LiCl to activate Wnt\/\u03b2\u2010catenin. Following treatment with the conditioned medium derived from the LiCl\u2010activated macrophages, the expression of bone\u2010 and cementum\u2010related markers of the PDLCs was determined. The involvement of Wnt\/\u03b2\u2010catenin in the immunoregulation and autophagic activity was further investigated with the addition of cardamonin, a commercially available Wnt inhibitor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A significantly increased number of macrophages were detected around the defects during early healing upon receiving the Wnt\/\u03b2\u2010catenin signaling cue. The defect sites in week 2 exhibited fewer M1 and more M2 macrophages along with an enhanced regeneration of alveolar bone and cementum in the Wnt\/\u03b2\u2010catenin activation group. LiCl\u2010induced immunomodulatory effect was accompanied with the activation Wnt\/\u03b2\u2010catenin signaling, which was suppressed in the presence of Wnt inhibitor. Exposure to LiCl could induce autophagy in a dose\u2010dependent manner, thus maintaining macrophages in a regulatory state. The expression level of bone\u2010 and cementum\u2010related markers was significantly elevated in PDLCs stimulated with LiCl\u2010activated macrophages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The application of Wnt activator LiCl facilitates the recruitment of macrophages to defect sites and regulates their phenotypic switching in favor of periodontal regeneration. Suppression of Wnt\/\u03b2\u2010catenin pathway could attenuate the LiCl\u2010induced immunomodulatory effect. Taken together, the Wnt\/\u03b2\u2010catenin pathway may be targeted for therapeutic interventions in periodontal diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.13022","type":"journal-article","created":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T15:33:04Z","timestamp":1654702384000},"page":"835-848","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["<scp>LiCl<\/scp>\u2010induced immunomodulatory periodontal regeneration via the activation of the Wnt\/\u03b2\u2010catenin signaling pathway"],"prefix":"10.1111","volume":"57","author":[{"given":"Xiumei","family":"Zheng","sequence":"first","affiliation":[{"name":"Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment Stomatological Hospital of Xiamen Medical College  Xiamen China"},{"name":"The Australia\u2010China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM) Queensland University of Technology  Brisbane Queensland 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