title: Temporo-spatial requirement of Smad4 in dentin formation.
abstract: The TGF-β/BMP family plays an important role in multiple stages of tooth development. TGF-β/BMP signaling is required for odontoblast differentiation and dentin formation; however, the precise molecular mechanisms underlying dentin formation remain unclear. To address the role of TGF-β/BMP signaling in dentin formation, we analyzed mice in which Smad4, a key intracellular mediator of TGF-β/BMP signaling, was subjected to tissue-specific ablation under the control of Dspp, OC, or Col1a1 promoters. Three independent Smad4 conditional knockout mice exhibited various dentin defects in the crowns and roots of their molars depending on the transactivator. In all mutant molars, crown dentin thickness was thinner than that of the control. In addition, impaired dentin was found in the cervical region and root furcation area. Although the initial differentiation of odontoblasts was normal, odontoblast polarity abruptly decreased and the expression of Col1a1, OC, and Dspp was reduced in the odontoblasts of mutant molars. In Dspp-Cre-mediated Smad4 disruption mice, primary dentin formation was slightly delayed, while secondary dentin formation was severely affected in the cervical region of the molars. These results indicate that TGF-β/BMP signaling is required for odontoblast maturation and dentin formation in a stage- and site-dependent manner.
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju 561756, South Korea.
authors.forename: Tak-Heun
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju 561756, South Korea.
authors.forename: Cheol-Hyeon
authors.initials: CH
authors.lastname: Bae
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju 561756, South Korea.
authors.forename: Ju-Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju 561756, South Korea.
authors.forename: Jeong-Chae
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju 561756, South Korea.
authors.forename: Seung-O
authors.initials: SO
authors.lastname: Ko
authors.affiliation: Center for Craniofacial Molecular Biology School of Dentistry University of Southern California, 2250 Alcazar Street, CSA 103, Los Angeles, CA 90033, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chai
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju 561756, South Korea. Electronic address: oasis@jbnu.ac.kr.
authors.forename: Eui-Sic
authors.initials: ES
authors.lastname: Cho
mesh_terms: D000818:Animals; D003804:Dentin / Q000254:growth & development*; D051379:Mice; D009804:Odontoblasts / Q000378:metabolism*; D051901:Smad4 Protein / Q000502:physiology*
chemical_list: D051901:Smad4 Protein; C490810:Smad4 protein, mouse
keywords: Dentin formation; Maturation; Mouse; Odontoblast; Smad4