Excess NF-κB induces ectopic odontogenesis in embryonic incisor epithelium

J Blackburn; K Kawasaki; T Porntaveetus; M Kawasaki; Y Otsuka-Tanaka; Y Miake; M S Ota; M Watanabe; M Hishinuma; T Nomoto; S Oommen; S Ghafoor; F Harada; K Nozawa-Inoue; T Maeda; R Peterková; H Lesot; J Inoue; T Akiyama; R Schmidt-Ullrich; B Liu; Y Hu; A Page; Á Ramírez; P T Sharpe; A Ohazama

doi:10.1177/0022034514556707

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.

Authors

J Blackburn¹, K Kawasaki², T Porntaveetus³, M Kawasaki⁴, Y Otsuka-Tanaka⁵, Y Miake⁶, M S Ota⁷, M Watanabe⁸, M Hishinuma⁹, T Nomoto⁹, S Oommen¹, S Ghafoor¹, F Harada¹, K Nozawa-Inoue¹, T Maeda⁸, R Peterková¹⁰, H Lesot¹¹, J Inoue¹², T Akiyama¹², R Schmidt-Ullrich¹³, B Liu¹⁴, Y Hu¹⁵, A Page¹⁶, Á Ramírez¹⁶, P T Sharpe¹⁷, A Ohazama¹⁸

Affiliations

¹ Craniofacial Development and Stem Cell Biology and Biomedical Research Centre, Kings College London, London, UK.
² Craniofacial Development and Stem Cell Biology and Biomedical Research Centre, Kings College London, London, UK Department of Pediatric Dentistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
³ Craniofacial Development and Stem Cell Biology and Biomedical Research Centre, Kings College London, London, UK Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
⁴ Craniofacial Development and Stem Cell Biology and Biomedical Research Centre, Kings College London, London, UK Division of Bio-Prosthodontics, Department of Oral Health Science, Course for Oral Life Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
⁵ Craniofacial Development and Stem Cell Biology and Biomedical Research Centre, Kings College London, London, UK Department of Special Needs Dentistry, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.
⁶ Department of Ultrastructural Science, Tokyo Dental College, Chiyoda-ku, Tokyo, Japan.
⁷ Laboratory of Food Biological Science, Department of Food and Nutrition, Japan Women's University, Bunkyō, Japan.
⁸ Division of Oral Anatomy, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
⁹ Department of Special Needs Dentistry, Nihon University School of Dentistry at Matsudo, Matsudo, Japan.
¹⁰ Department of Teratology, Institute of Experimental Medicine, Academy of Sciences CR, Prague, Czech Republic.
¹¹ INSERM UMR_S1109, Team "Osteoarticular and Dental Regenerative NanoMedicine," FMTS, Faculté de Médecine, Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France.
¹² Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo, Japan.
¹³ Department of Signal Transduction in Tumor Cells, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
¹⁴ Department of Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, TX, USA.
¹⁵ Laboratory of Experimental Immunology, Inflammation and Tumorigenesis Section, National. Cancer Institute-Frederick, Frederick, MD, USA.
¹⁶ Department of Epithelial Biomedicine, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain.
¹⁷ Craniofacial Development and Stem Cell Biology and Biomedical Research Centre, Kings College London, London, UK [email protected] [email protected].
¹⁸ Craniofacial Development and Stem Cell Biology and Biomedical Research Centre, Kings College London, London, UK Division of Oral Anatomy, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan [email protected] [email protected].

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

Adaptor Proteins, Signal Transducing
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

Adaptor Proteins, Signal Transducing
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