title: Wnt5a attenuates Wnt3a-induced alkaline phosphatase expression in dental follicle cells.
abstract: Wnt signaling regulates multiple cellular events such as cell proliferation, differentiation, and apoptosis through β-catenin-dependent canonical and β-catenin-independent noncanonical pathways. Canonical Wnt/β-catenin signaling can promote the differentiation of dental follicle cells, putative progenitor cells for cementoblasts, osteoblasts, and periodontal ligament cells, toward a cementoblast/osteoblast phenotype during root formation, but little is known about the biological significance of noncanonical Wnt signaling in this process. We identified the expression of Wnt5a, a representative noncanonical Wnt ligand, in tooth root lining cells (i.e. precementoblasts/cementoblasts) and dental follicle cells during mouse tooth root development, as assessed by immunohistochemistry. Silencing expression of the Wnt5a gene in a dental follicle cell line resulted in enhancement of the Wnt3a (a representative canonical Wnt ligand)-mediated increase in alkaline phosphatase (ALP) expression. Conversely, treatment with recombinant Wnt5a inhibited the increase in ALP expression, suggesting that Wnt5a signaling functions as a negative regulator of canonical Wnt-mediated ALP expression of dental follicle cells. Wnt5a did not affect the nuclear translocation of β-catenin as well as β-catenin-mediated transcriptional activation of T-cell factor (Tcf) triggered by Wnt3a, suggesting that Wnt5a inhibits the downstream part of the β-catenin-Tcf pathway. These findings suggest the existence of a feedback mechanism between canonical and noncanonical Wnt signaling during the differentiation of dental follicle cells.
authors.affiliation: Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sakisaka
authors.affiliation: Department of Oral Diagnosis, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan; Tohoku Fukushi University, Sendai 989-3201, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuchiya
authors.affiliation: Department of Pediatric Dentistry, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan; Liason Center for Innovative Dentistry, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Biochemistry and Molecular Biology, Hokkaido University Graduate School of Dentistry, Sapporo 060-8586, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tamura
authors.affiliation: Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Shimauchi
authors.affiliation: Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan. Electronic address: e-nemoto@dent.tohoku.ac.jp.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nemoto
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003795:Dental Sac / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051153:Wnt Proteins / Q000494:pharmacology*; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; C438615:Wnt5a protein, mouse; D000469:Alkaline Phosphatase
keywords: Alkaline phosphatase; Cell differentiation; Dental follicle cells; Wnt3a; Wnt5a