title: Wnt-RhoA signaling is involved in dental enamel development.
abstract: Transgenic mice that express dominant-negative RhoA (RhoA(DN) ) in ameloblasts have hypoplastic enamel with defects in molar cusps. β-catenin and Wnt5a were up-regulated in enamel organs of RhoA(DN) transgenic mice, which indicated that both canonical and non-canonical Wnt pathways are implicated in the process of enamel defect formation. It was hypothesized that expression of RhoA(DN) in ameloblasts interfered with normal enamel development through the pathways that were induced by fluoride. The Wnt and RhoA pathways were further investigated in an ameloblast-lineage cell line (ALC) by treatment with sodium fluoride (NaF). The activities of RhoA and Rho-associated protein kinase (ROCK) II decreased significantly by 8-12 hours, similar to decreased activity in RhoA(DN) transgenic mice. Both canonical and non-canonical Wnt pathways were activated by treatment with NaF, which was verified by western blotting and the β-catenin-TCF/LEF (T cell factor lymphanoid/enhancer factor) reporter gene (TOPflash) assay. β-catenin localization to both cytoplasm and nucleus was up-regulated in NaF-treated ALC, while Gsk-3β, the negative regulator of the Wnt pathway, showed a decreased pattern of expression. The current results indicate that both Wnt and RhoA pathways are implicated in fluoride-induced signaling transductions in the ALC as well as in the development of enamel defects in RhoA(DN) transgenic mice.
authors.affiliation: Department of Anatomy and Cell Biology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104-6030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Peng
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Kate
authors.initials: K
authors.lastname: Shusterman
authors.forename: Melissa
authors.initials: M
authors.lastname: Kuehl
authors.forename: Carolyn W
authors.initials: CW
authors.lastname: Gibson
mesh_terms: D000565:Ameloblasts / Q000187:drug effects / Q000502:physiology*; D000566:Amelogenesis / Q000235:genetics*; D053523:Amelogenin / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002460:Cell Line; D003744:Dental Enamel Hypoplasia / Q000235:genetics*; D004658:Enamel Organ / Q000187:drug effects / Q000502:physiology; D020555:GTP-Binding Protein Regulators / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D012969:Sodium Fluoride / Q000494:pharmacology; D051153:Wnt Proteins / Q000096:biosynthesis / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000187:drug effects* / Q000235:genetics*; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000502:physiology; D054460:rho-Associated Kinases / Q000235:genetics*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000502:physiology*
chemical_list: D053523:Amelogenin; D020555:GTP-Binding Protein Regulators; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D051176:beta Catenin; D012969:Sodium Fluoride; D054460:rho-Associated Kinases; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein