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Wnt\/\u03b2\u2010catenin signaling plays critical roles in regulating the skeletal development. Here, we analyzed the role of this pathway in the developing coronal sutures (CS) of a murine Apert syndrome model (<jats:italic>Fgfr2<\/jats:italic><jats:sup><jats:italic>S252W\/+<\/jats:italic><\/jats:sup>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed aberrantly increased mRNA expression of <jats:italic>Lrp5<\/jats:italic> and <jats:italic>Lrp6<\/jats:italic> in CS of <jats:italic>Fgfr2<\/jats:italic><jats:sup><jats:italic>S252W\/+<\/jats:italic><\/jats:sup> mice, whereas both wild type (WT) and <jats:italic>Fgfr2<\/jats:italic><jats:sup><jats:italic>S252W\/+<\/jats:italic><\/jats:sup> mice showed similar expression of other Wnt\/\u03b2\u2010catenin\u2010related genes, such as <jats:italic>Wnt3<\/jats:italic>, <jats:italic>Wnt3a<\/jats:italic>, <jats:italic>Fzd4<\/jats:italic>, <jats:italic>Fzd6<\/jats:italic>, <jats:italic>Axin2<\/jats:italic>, and <jats:italic>Dkk1<\/jats:italic> as evidenced by in situ hybridization. Significantly increased <jats:italic>Lrp5<\/jats:italic> and <jats:italic>Lrp6<\/jats:italic> mRNA expression was observed by quantitative PCR analysis of cultured cells isolated from CS of <jats:italic>Fgfr2<\/jats:italic><jats:sup><jats:italic>S252W\/+<\/jats:italic><\/jats:sup> mice. Phospho\u2010LRP5, phospho\u2010LRP6, and non\u2010phospho\u2010\u03b2\u2010catenin were upregulated in <jats:italic>Fgfr2<\/jats:italic><jats:sup><jats:italic>S252W\/+<\/jats:italic><\/jats:sup> CS compared with that in WT CS. Short\u2010interfering RNA targeting <jats:italic>Lrp5<\/jats:italic> and <jats:italic>Lrp6<\/jats:italic> significantly reduced runt\u2010related transcription factor 2, collagen type 1 alpha 1, and osteocalcin mRNA expression, and alkaline phosphatase activity in cultured cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The Wnt\/\u03b2\u2010catenin pathway was activated in the CS of <jats:italic>Fgfr2<\/jats:italic><jats:sup><jats:italic>S252W\/+<\/jats:italic><\/jats:sup> mice during craniofacial development, suggesting the involvement of the Wnt\/\u03b2\u2010catenin pathway in the pathogenesis of CS synostosis in <jats:italic>Fgfr2<\/jats:italic><jats:sup><jats:italic>S252W\/+<\/jats:italic><\/jats:sup> mice.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.239","type":"journal-article","created":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T09:37:05Z","timestamp":1598002625000},"page":"465-476","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Aberrantly activated Wnt\/\u03b2\u2010catenin pathway co\u2010receptors <scp>LRP5<\/scp> and <scp>LRP6<\/scp> regulate osteoblast differentiation in the developing coronal sutures of an Apert syndrome (<scp><i>Fgfr2<\/i><sup><i>S252W<\/i><\/sup><\/scp><sup><i>\/+<\/i><\/sup>) mouse model"],"prefix":"10.1002","volume":"250","author":[{"given":"Nay Myo","family":"Min Swe","sequence":"first","affiliation":[{"name":"Department of Maxillofacial Orthognathics, Division of Maxillofacial and Neck Reconstruction, Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University  Bunkyo\u2010ku Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5551-2845","authenticated-orcid":false,"given":"Yukiho","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Orthognathics, Division of Maxillofacial and Neck Reconstruction, Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University  Bunkyo\u2010ku Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Kamimoto","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Orthognathics, Division of Maxillofacial and Neck Reconstruction, Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University  Bunkyo\u2010ku Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiji","family":"Moriyama","sequence":"additional","affiliation":[{"name":"Department of Maxillofacial Orthognathics, Division of Maxillofacial and Neck 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