Wnt/β-catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development

Odontomas, developmental anomalies of tooth germ, frequently occur in familial adenomatous polyposis patients with activated Wnt/β-catenin signaling. However, roles of Wnt/β-catenin signaling in odontomas or odontogenic cells are unclear. Herein, we investigated β-catenin expression in odontomas and...

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Autores principales: Fujii, Shinsuke, Nagata, Kengo, Matsumoto, Shinji, Kohashi, Ken-ichi, Kikuchi, Akira, Oda, Yoshinao, Kiyoshima, Tamotsu, Wada, Naohisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414619/
https://www.ncbi.nlm.nih.gov/pubmed/30862786
http://dx.doi.org/10.1038/s41598-019-39686-1
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author Fujii, Shinsuke
Nagata, Kengo
Matsumoto, Shinji
Kohashi, Ken-ichi
Kikuchi, Akira
Oda, Yoshinao
Kiyoshima, Tamotsu
Wada, Naohisa
author_facet Fujii, Shinsuke
Nagata, Kengo
Matsumoto, Shinji
Kohashi, Ken-ichi
Kikuchi, Akira
Oda, Yoshinao
Kiyoshima, Tamotsu
Wada, Naohisa
author_sort Fujii, Shinsuke
collection PubMed
description Odontomas, developmental anomalies of tooth germ, frequently occur in familial adenomatous polyposis patients with activated Wnt/β-catenin signaling. However, roles of Wnt/β-catenin signaling in odontomas or odontogenic cells are unclear. Herein, we investigated β-catenin expression in odontomas and functions of Wnt/β-catenin signaling in tooth germ development. β-catenin frequently accumulated in nucleus and/or cellular cytoplasm of odontogenic epithelial cells in human odontoma specimens, immunohistochemically. Wnt/β-catenin signaling inhibited odontogenic epithelial cell proliferation in both cell line and tooth germ development, while inducing immature epithelial bud formation. We identified Semaphorin 3A (Sema3A) as a downstream molecule of Wnt/β-catenin signaling and showed that Wnt/β-catenin signaling-dependent reduction of Sema3A expression resulted in suppressed odontogenic epithelial cell proliferation. Sema3A expression is required in appropriate epithelial budding morphogenesis. These results suggest that Wnt/β-catenin signaling negatively regulates odontogenic epithelial cell proliferation and tooth germ development through decreased-Sema3A expression, and aberrant activation of Wnt/β-catenin signaling may associate with odontoma formation.
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spelling pubmed-64146192019-03-14 Wnt/β-catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development Fujii, Shinsuke Nagata, Kengo Matsumoto, Shinji Kohashi, Ken-ichi Kikuchi, Akira Oda, Yoshinao Kiyoshima, Tamotsu Wada, Naohisa Sci Rep Article Odontomas, developmental anomalies of tooth germ, frequently occur in familial adenomatous polyposis patients with activated Wnt/β-catenin signaling. However, roles of Wnt/β-catenin signaling in odontomas or odontogenic cells are unclear. Herein, we investigated β-catenin expression in odontomas and functions of Wnt/β-catenin signaling in tooth germ development. β-catenin frequently accumulated in nucleus and/or cellular cytoplasm of odontogenic epithelial cells in human odontoma specimens, immunohistochemically. Wnt/β-catenin signaling inhibited odontogenic epithelial cell proliferation in both cell line and tooth germ development, while inducing immature epithelial bud formation. We identified Semaphorin 3A (Sema3A) as a downstream molecule of Wnt/β-catenin signaling and showed that Wnt/β-catenin signaling-dependent reduction of Sema3A expression resulted in suppressed odontogenic epithelial cell proliferation. Sema3A expression is required in appropriate epithelial budding morphogenesis. These results suggest that Wnt/β-catenin signaling negatively regulates odontogenic epithelial cell proliferation and tooth germ development through decreased-Sema3A expression, and aberrant activation of Wnt/β-catenin signaling may associate with odontoma formation. Nature Publishing Group UK 2019-03-12 /pmc/articles/PMC6414619/ /pubmed/30862786 http://dx.doi.org/10.1038/s41598-019-39686-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Fujii, Shinsuke
Nagata, Kengo
Matsumoto, Shinji
Kohashi, Ken-ichi
Kikuchi, Akira
Oda, Yoshinao
Kiyoshima, Tamotsu
Wada, Naohisa
Wnt/β-catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development
title Wnt/β-catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development
title_full Wnt/β-catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development
title_fullStr Wnt/β-catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development
title_full_unstemmed Wnt/β-catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development
title_short Wnt/β-catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development
title_sort wnt/β-catenin signaling, which is activated in odontomas, reduces sema3a expression to regulate odontogenic epithelial cell proliferation and tooth germ development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414619/
https://www.ncbi.nlm.nih.gov/pubmed/30862786
http://dx.doi.org/10.1038/s41598-019-39686-1
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