Excess NF-κB induces ectopic odontogenesis in embryonic incisor epithelium

J Dent Res. 2015 Jan;94(1):121-8. doi: 10.1177/0022034514556707. Epub 2014 Nov 6.

Abstract

Nuclear factor kappa B (NF-κB) signaling plays critical roles in many physiological and pathological processes, including regulating organogenesis. Down-regulation of NF-κB signaling during development results in hypohidrotic ectodermal dysplasia. The roles of NF-κB signaling in tooth development, however, are not fully understood. We examined mice overexpressing IKKβ, an essential component of the NF-κB pathway, under keratin 5 promoter (K5-Ikkβ). K5-Ikkβ mice showed supernumerary incisors whose formation was accompanied by up-regulation of canonical Wnt signaling. Apoptosis that is normally observed in wild-type incisor epithelium was reduced in K5-Ikkβ mice. The supernumerary incisors in K5-Ikkβ mice were found to phenocopy extra incisors in mice with mutations of Wnt inhibitor, Wise. Excess NF-κB activity thus induces an ectopic odontogenesis program that is usually suppressed under physiological conditions.

Keywords: Ikkβ; Wnt signaling; cervical loop; enamel; tooth development; wise.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ameloblasts / cytology
  • Amelogenin / analysis
  • Animals
  • Apoptosis / physiology
  • Bone Morphogenetic Proteins / genetics
  • Dental Enamel / cytology
  • Epithelium / embryology
  • Hedgehog Proteins / physiology
  • I-kappa B Kinase / physiology
  • Imaging, Three-Dimensional / methods
  • Incisor / abnormalities
  • Incisor / embryology*
  • Keratin-15 / genetics
  • Mice
  • Mice, Mutant Strains
  • Microradiography / methods
  • Mutation / genetics
  • NF-kappa B / physiology*
  • Odontogenesis / physiology*
  • Patched Receptors
  • Phenotype
  • Promoter Regions, Genetic / genetics
  • Receptors, Cell Surface / physiology
  • Tooth Germ / abnormalities
  • Tooth Germ / embryology*
  • Tooth, Supernumerary / etiology
  • Tooth, Supernumerary / genetics
  • Wnt Signaling Pathway / genetics
  • Wnt Signaling Pathway / physiology
  • X-Ray Microtomography / methods

Substances

  • Amelogenin
  • Bone Morphogenetic Proteins
  • Hedgehog Proteins
  • Keratin-15
  • Krt15 protein, mouse
  • NF-kappa B
  • Patched Receptors
  • Receptors, Cell Surface
  • Shh protein, mouse
  • Sostdc1 protein, mouse
  • Chuk protein, mouse
  • I-kappa B Kinase