TGFβ-1 downregulates DMP-1 and DSPP in odontoblasts

A. Unterbrink, M. O'Sullivan, S. Chen, M. MacDougall

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42 Scopus citations

Abstract

Transforming growth factor β-1 (TGFβ-1) is a multifunctional growth factor that is expressed in numerous cell types. It has been shown to induce secretion of dentin extracellular matrix components associated with primary dentinogenesis and to play a role in tertiary or reparative dentinogenesis. In this study, we investigated the potential transcriptional regulation by TGFβ-1 of two dentin matrix proteins: dentin matrix protein 1 (DMP-1), and dentin sialophosphoprotein (DSPP). In vitro promoter studies were performed using plasmid constructs containing mouse DMP-1 and DSPP promoter sequences fused to the luciferase reporter gene. Constructs were transiently transfected in the mouse odontoblast cell line M06-G3 and cultured in the presence or absence of TGFβ-1. The integrity of the TGFβ-1 signaling pathway was investigated in the M06-G3 cells by identifying known key effectors of TGFβ-1 signal transduction. Transient transfection studies demonstrate for the first time that TGFβ-1 downregulates both DMP-1 and DSPP genes. Our findings indicate that the TGFβ-1 type I receptor ALK5 is expressed by odontoblasts as well as the signal transduction proteins Smad2, Smad3, and Smad4. These results suggest that TGFβ-1 regulates two key dentin proteins involved in matrix mineralization most likely mediated through the type I ALK5 receptor and transduced by Smads 2, 3, and 4.

Original languageEnglish (US)
Pages (from-to)354-358
Number of pages5
JournalConnective Tissue Research
Volume43
Issue number2-3
Publication statusPublished - Jul 27 2002

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Keywords

  • ALK5
  • Dentin matrix protein 1
  • Dentin sialophosphoprotein
  • Smads
  • TGFBR1
  • TGFβ-1

ASJC Scopus subject areas

  • Rheumatology
  • Biochemistry
  • Orthopedics and Sports Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Unterbrink, A., O'Sullivan, M., Chen, S., & MacDougall, M. (2002). TGFβ-1 downregulates DMP-1 and DSPP in odontoblasts. Connective Tissue Research, 43(2-3), 354-358.