Wntless Regulates Dentin Apposition and Root Elongation in the Mandibular Molar

• Published in: Journal of dental research Vol. 94; no. 3; pp. 439 - 445
• Main Authors: Bae, C.H., Kim, T.H., Ko, S.O., Lee, J.C., Yang, X., Cho, E.S.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.03.2015; SAGE PUBLICATIONS, INC
• Subjects: Animals; Apposition; Axin Protein - analysis; beta Catenin - analysis; Cell Differentiation - physiology; Cell Proliferation; Clonal deletion; Collagen (type I); Collagen Type I - analysis; Dental pulp; Dental Pulp Cavity - abnormalities; Dental roots; Dentin; Dentin - abnormalities; Dentin sialoprotein; Dentinogenesis - physiology; Dentistry; Down-Regulation; Elongation; Epithelium; Extracellular Matrix Proteins - analysis; Gene deletion; Immunohistochemistry; Intracellular Signaling Peptides and Proteins - physiology; Laboratories; Ligands; Mandible; Mesenchyme; Mice; Mice, Transgenic; Microscopy, Electron, Scanning; Molar - abnormalities; Molar - growth & development; Molars; Morphogenesis; Nerve Tissue Proteins - analysis; Odontoblasts; Odontoblasts - physiology; Odontogenesis - physiology; Phosphoproteins - analysis; Protein transport; Proteins; Receptors, G-Protein-Coupled - physiology; Research Reports; Roles; Root canals; Sialoglycoproteins - analysis; Signal transduction; Studies; Teeth; Tooth Apex - abnormalities; Tooth Crown - abnormalities; Tooth Root - abnormalities; Tooth Root - growth & development; Wnt protein; Wnt Proteins - analysis; Wnt Signaling Pathway - physiology; X-Ray Microtomography - methods; β-Catenin; United States > US; tooth development; odontoblasts; dentinogenesis; tooth roots; Wnt signaling pathway; mice
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/0022034514567198

Wnt signaling plays an essential role in the dental epithelium and mesenchyme during tooth morphogenesis. However, it remains unclear if Wnt ligands, produced from dental mesenchyme, are necessary for odontoblast differentiation and dentin formation. Here, we show that odontoblast-specific disruption of Wntless (Wls), a chaperon protein that regulates Wnt sorting and secretion, leads to severe defects in dentin formation and root elongation. Dentin thickness decreased remarkably and pulp chambers enlarged in the mandibular molars of OC-Cre;WlsCO/CO mice. Although the initial odontoblast differentiation was normal in the mutant crown, odontoblasts became cuboidal and dentin thickness was reduced. In immunohistochemistry, Wnt10a, β-catenin, type I collagen, and dentin sialoprotein were significantly down-regulated in the odontoblasts of mutant crown. In addition, roots were short and root canals were widened. Cell proliferation was reduced in the developing root apex of mutant molars. Furthermore, Wnt10a and Axin2 expression was remarkably decreased in the odontoblasts of mutant roots. Deletion of the Wls gene in odontoblasts appears to reduce canonical Wnt activity, leading to inhibition of odontoblast maturation and root elongation.