title: Dual role of the Trps1 transcription factor in dentin mineralization.
abstract: TRPS1 (tricho-rhino-phalangeal syndrome) is a unique GATA-type transcription factor that acts as a transcriptional repressor. TRPS1 deficiency and dysregulated TRPS1 expression result in skeletal and dental abnormalities implicating TRPS1 in endochondral bone formation and tooth development. Moreover, patients with tricho-rhino-phalangeal syndrome frequently present with low bone mass indicating TRPS1 involvement in bone homeostasis. In addition, our previous data demonstrated accelerated mineralization of the perichondrium in Trps1 mutant mice and impaired dentin mineralization in Col1a1-Trps1 transgenic mice, implicating Trps1 in the mineralization process. To understand the role of Trps1 in the differentiation and function of cells producing mineralized matrix, we used a preodontoblastic cell line as a model of dentin mineralization. We generated both Trps1-deficient and Trps1-overexpressing stable cell lines and analyzed the progression of mineralization by alkaline phosphatase and alizarin red staining. As predicted, based on our previous in vivo data, delayed and decreased mineralization of Trps1-overexpressing odontoblastic cells was observed when compared with control cells. This was associated with down-regulation of genes regulating phosphate homeostasis. Interestingly, Trps1-deficient cells lost the ability to mineralize and demonstrated decreased expression of several genes critical for initiating the mineralization process, including Alpl and Phospho1. Based on these data, we have concluded that Trps1 serves two critical and context-dependent functions in odontoblast-regulated mineralization as follows: 1) Trps1 is required for odontoblast maturation by supporting expression of genes crucial for initiating the mineralization process, and 2) Trps1 represses the function of mature cells and, consequently, restricts the extent of extracellular matrix mineralization.
authors.affiliation: From the Institute of Oral Health Research, Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Maria
authors.initials: M
authors.lastname: Kuzynski
authors.affiliation: From the Institute of Oral Health Research, Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Morgan
authors.initials: M
authors.lastname: Goss
authors.affiliation: the Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California 92037, the Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bottini
authors.affiliation: the Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California 92037.
authors.forename: Manisha C
authors.initials: MC
authors.lastname: Yadav
authors.affiliation: From the Institute of Oral Health Research, Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Callie
authors.initials: C
authors.lastname: Mobley
authors.affiliation: From the Institute of Oral Health Research, Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Tony
authors.initials: T
authors.lastname: Winters
authors.affiliation: the EA2496 UFR d'Odontologie, Université Paris Descartes, 92120 Montrouge, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Poliard
authors.affiliation: INSERM UMR-S 1124, Université René Descartes Paris 5, Centre Universitaire des Saints-Pères, 75270 Paris Cedex 06, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Kellermann
authors.affiliation: the Department of Molecular and Human Genetics, Baylor College of Medicine, and the Howard Hughes Medical Institute, Houston, Texas 77030.
authors.forename: Brendan
authors.initials: B
authors.lastname: Lee
authors.affiliation: the Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California 92037.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Millan
authors.affiliation: From the Institute of Oral Health Research, Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Alabama at Birmingham, Birmingham, Alabama 35294, dobrawan@uab.edu.
authors.forename: Dobrawa
authors.initials: D
authors.lastname: Napierala
mesh_terms: D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003804:Dentin / Q000254:growth & development* / Q000378:metabolism*; D003810:Dentinogenesis; D006801:Humans; D009804:Odontoblasts / Q000166:cytology / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C108387:TRPS1 protein, human; D014157:Transcription Factors
keywords: Biomineralization; Dentin; Differentiation; Extracellular Matrix; Gene Expression; Odontoblast; Trps1