Journal article
A pituitary homeobox 2 (Pitx2):microRNA-200a-3p:β-catenin pathway converts mesenchymal cells to amelogenin-expressing dental epithelial cells
The Journal of biological chemistry, Vol.289(39), pp.27327-27341
09/26/2014
DOI: 10.1074/jbc.M114.575654
PMCID: PMC4175363
PMID: 25122764
Abstract
Pitx2, Wnt/β-catenin signaling, and microRNAs (miRs) play a critical role in the regulation of dental stem cells during embryonic development. In this report, we have identified a Pitx2:β-catenin regulatory pathway involved in epithelial cell differentiation and conversion of mesenchymal cells to amelogenin expressing epithelial cells via miR-200a. Pitx2 and β-catenin are expressed in the labial incisor cervical loop or epithelial stem cell niche, with decreased expression in the differentiating ameloblast cells of the mouse lower incisor. Bioinformatics analyses reveal that miR-200a-3p expression is activated in the pre-ameloblast cells to enhance epithelial cell differentiation. We demonstrate that Pitx2 activates miR-200a-3p expression and miR-200a-3p reciprocally represses Pitx2 and β-catenin expression. Pitx2 and β-catenin interact to synergistically activate gene expression during odontogenesis and miR-200a-3p attenuates their expression and directs differentiation. To understand how this mechanism controls cell differentiation and cell fate, oral epithelial and odontoblast mesenchymal cells were reprogrammed by a two-step induction method using Pitx2 and miR-200a-3p. Conversion to amelogenin expressing dental epithelial cells involved an up-regulation of the stem cell marker Sox2 and proliferation genes and decreased expression of mesenchymal markers. E-cadherin expression was increased as well as ameloblast specific factors. The combination of Pitx2, a regulator of dental stem cells and miR-200a converts mesenchymal cells to a fully differentiated dental epithelial cell type. This pathway and reprogramming can be used to reprogram mesenchymal or oral epithelial cells to dental epithelial (ameloblast) cells, which can be used in tissue repair and regeneration studies.
Details
- Title: Subtitle
- A pituitary homeobox 2 (Pitx2):microRNA-200a-3p:β-catenin pathway converts mesenchymal cells to amelogenin-expressing dental epithelial cells
- Creators
- Thad Sharp - From the Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242Jianbo Wang - the Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030, andXiao Li - From the Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242Huojun Cao - the Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030, andShan Gao - the Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030, andMyriam Moreno - From the Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242Brad A Amendt - From the Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, the Craniofacial Anomalies Research Center, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242 brad-amendt@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.289(39), pp.27327-27341
- DOI
- 10.1074/jbc.M114.575654
- PMID
- 25122764
- PMCID
- PMC4175363
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- United States
- Grant note
- R01 DE013941 / NIDCR NIH HHS DE13941 / NIDCR NIH HHS
- Language
- English
- Date published
- 09/26/2014
- Academic Unit
- Orthodontics; Anatomy and Cell Biology; Endodontics; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025335502771
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