RRC ID 55035
Author Fujii S, Nagata K, Matsumoto S, Kohashi KI, Kikuchi A, Oda Y, Kiyoshima T, Wada N.
Title Wnt/β-catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development.
Journal Sci Rep
Abstract 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.
Volume 9(1)
Pages 4257
Published 2019-3-12
DOI 10.1038/s41598-019-39686-1
PII 10.1038/s41598-019-39686-1
PMID 30862786
PMC PMC6414619
MeSH Adolescent Animals Cell Line Cell Proliferation Child Child, Preschool DNA Mutational Analysis Down-Regulation / physiology Embryo, Mammalian Epithelial Cells / physiology Gene Knockdown Techniques Humans Immunohistochemistry Mice Odontogenesis / physiology* Odontoma / genetics Odontoma / pathology* Odontoma / surgery Primary Cell Culture RNA, Small Interfering / metabolism Semaphorin-3A / analysis Semaphorin-3A / genetics Semaphorin-3A / metabolism* Tooth Germ / cytology Tooth Germ / embryology* Wnt Signaling Pathway / physiology* Young Adult beta Catenin / analysis beta Catenin / genetics beta Catenin / metabolism
IF 4.011
Times Cited 4
DNA material CSII-CMV-MCS-IRES2-Bsd (RDB04385) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394)