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

• Published in: Scientific reports 2019-03, Vol.9 (1), p.4257-4257, Article 4257
• Main Authors: Fujii, Shinsuke, Nagata, Kengo, Matsumoto, Shinji, Kohashi, Ken-ichi, Kikuchi, Akira, Oda, Yoshinao, Kiyoshima, Tamotsu, Wada, Naohisa
• Format: Article
• Language: English
• Subjects: 13/109; 13/51; 13/89; 14/19; 38/61; 45/23; 631/67/1534; 631/80/83; 64/60; Adolescent; Animals; beta Catenin - analysis; beta Catenin - genetics; beta Catenin - metabolism; Cell growth; Cell Line; Cell Proliferation; Child; Child, Preschool; Cytoplasm; DNA Mutational Analysis; Down-Regulation - physiology; Embryo, Mammalian; Epithelial cells; Epithelial Cells - physiology; Familial adenomatous polyposis; Gene Knockdown Techniques; Humanities and Social Sciences; Humans; Immunohistochemistry; Kinases; Mice; Morphogenesis; multidisciplinary; Odontogenesis - physiology; Odontoma - genetics; Odontoma - pathology; Odontoma - surgery; Primary Cell Culture; RNA, Small Interfering - metabolism; Science; Science (multidisciplinary); Semaphorin-3A - analysis; Semaphorin-3A - genetics; Semaphorin-3A - metabolism; Semaphorins; Teeth; Tooth Germ - cytology; Tooth Germ - embryology; Wnt protein; Wnt Signaling Pathway - physiology; Young Adult; β-Catenin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-39686-1

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.