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
|
Resource |
DNA material |
CSII-CMV-MCS-IRES2-Bsd (RDB04385)
pCMV-VSV-G-RSV-Rev (RDB04393)
pCAG-HIVgp (RDB04394) |