title: Post-natal effect of overexpressed DKK1 on mandibular molar formation.
abstract: Dickkopf-related protein 1 (DKK1) is a potent inhibitor of Wnt/β-catenin signaling. Dkk1-null mutant embryos display severe defects in head induction. Conversely, targeted expression of Dkk1 in dental epithelial cells leads to the formation of dysfunctional enamel knots and subsequent tooth defects during embryonic development. However, its role in post-natal dentinogenesis is largely unknown. To address this issue, we studied the role of DKK1 in post-natal dentin development using 2.3-kb Col1a1-Dkk1 transgenic mice, with the following key findings: (1) The Dkk1 transgene was highly expressed in pulp and odontoblast cells during post-natal developmental stages; (2) the 1(st) molar displayed short roots, an enlarged pulp/root canal region, and a decrease in the dentin formation rate; (3) a small malformed second molar and an absent third molar; (4) an increase of immature odontoblasts, few mature odontoblasts, and sharply reduced dentinal tubules; and (5) a dramatic change in Osx and nestin expression. We propose that DKK1 controls post-natal mandibular molar dentin formation either directly or indirectly via the inhibition of Wnt signaling at the following aspects: (i) post-natal dentin formation, (ii) formation and/or maintenance of the dentin tubular system, (iii) mineralization of the dentin, and (iv) regulation of molecules such as Osx and nestin.
authors.affiliation: Baylor College of Dentistry, Department of Biomedical Sciences, Texas A&M Health Science Center, 3302 Gaston Avenue, Dallas, TX 75246, USA.
authors.forename: X L
authors.initials: XL
authors.lastname: Han
authors.forename: M
authors.initials: M
authors.lastname: Liu
authors.forename: A
authors.initials: A
authors.lastname: Voisey
authors.forename: Y S
authors.initials: YS
authors.lastname: Ren
authors.forename: P
authors.initials: P
authors.lastname: Kurimoto
authors.forename: T
authors.initials: T
authors.lastname: Gao
authors.forename: L
authors.initials: L
authors.lastname: Tefera
authors.forename: P
authors.initials: P
authors.lastname: Dechow
authors.forename: H Z
authors.initials: HZ
authors.lastname: Ke
authors.forename: J Q
authors.initials: JQ
authors.lastname: Feng
mesh_terms: D000818:Animals; D003782:Dental Pulp / Q000378:metabolism; D003804:Dentin / Q000002:abnormalities; D003810:Dentinogenesis / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D007381:Intermediate Filament Proteins / Q000096:biosynthesis; D008334:Mandible / Q000000981:diagnostic imaging; D051379:Mice; D008822:Mice, Transgenic; D008963:Molar / Q000254:growth & development*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D064231:Nestin; D009804:Odontoblasts / Q000378:metabolism; D010513:Periodontal Ligament / Q000254:growth & development; D015398:Signal Transduction; D000076182:Sp7 Transcription Factor; D014071:Tooth Abnormalities / Q000235:genetics*; D014074:Tooth Calcification / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis; D019076:Transgenes; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D051153:Wnt Proteins