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We have previously reported that Axin2\u2010expressing (Axin2<jats:sup>+<\/jats:sup>) mesenchymal cells in periodontal ligament (PDL) are the main cell source for cementum growth, and constitutive activation of Wnt\/\u03b2\u2010catenin signaling in Axin2<jats:sup>+<\/jats:sup> cells results in hypercementosis. Therefore, the aim of the present study was to further evaluate the effects of <jats:italic>\u03b2\u2010catenin<\/jats:italic> deletion in Axin2<jats:sup>+<\/jats:sup> cells on cementogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We generated triple transgenic mice to conditionally delete <jats:italic>\u03b2\u2010catenin<\/jats:italic> in Axin2\u2010lineage cells by crossing <jats:italic>Axin2<\/jats:italic><jats:sup><jats:italic>CreERT2\/+<\/jats:italic><\/jats:sup><jats:italic>; R26R<\/jats:italic><jats:sup><jats:italic>tdTomato\/+<\/jats:italic><\/jats:sup> mice with <jats:italic>\u03b2\u2010catenin<\/jats:italic><jats:sup><jats:italic>flox\/flox<\/jats:italic><\/jats:sup> mice. Multiple approaches, including X\u2010ray analysis, micro\u2010CT, histological stainings, and immunostaining assays, were used to analyze cementum phenotypes and molecular mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our data revealed that loss of <jats:italic>\u03b2\u2010catenin<\/jats:italic> in Axin2<jats:sup>+<\/jats:sup> cells led to a cementum hypoplasia phenotype characterized by a sharp reduction in the formation of both acellular and cellular cementum. Mechanistically, we found that conditional removal of <jats:italic>\u03b2\u2010catenin<\/jats:italic> in Axin2<jats:sup>+<\/jats:sup> cells severely impaired the secretion of cementum matrix proteins, for example, bone sialoprotein (BSP), dentin matrix protein 1 (DMP1) and osteopontin (OPN), and markedly inhibited the differentiation of Axin2<jats:sup>+<\/jats:sup> mesenchymal cells into osterix<jats:sup>+<\/jats:sup> cementoblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings confirm the vital role of Axin2<jats:sup>+<\/jats:sup> mesenchymal PDL cells in cementum growth and demonstrate that Wnt\/\u03b2\u2010catenin signaling shows a positive correlation with cementogenic differentiation of Axin2<jats:sup>+<\/jats:sup> cells.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.13101","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T09:26:23Z","timestamp":1674552383000},"page":"414-421","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Loss of \u03b2\u2010catenin causes cementum hypoplasia by hampering cementogenic differentiation of Axin2\u2010expressing cells"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0144-2914","authenticated-orcid":false,"given":"Rui","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Periodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Med\u2010X Center for Materials, West China Hospital of Stomatology Sichuan University  Chengdu 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Diseases, National Clinical Research Center for Oral Diseases, Med\u2010X Center for Materials, West China Hospital of Stomatology Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yafei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Periodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Med\u2010X Center for Materials, West China Hospital of Stomatology Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5314-8442","authenticated-orcid":false,"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Periodontics, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Med\u2010X Center for Materials, West China Hospital of Stomatology Sichuan University  Chengdu 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