TGF beta-1 downregulates DMP-1 and DSPP in odontoblasts.
Transforming growth factor beta-1 (TGF beta-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 TGF beta-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 TGF beta-1. The integrity of the TGF beta-1 signaling pathway was investigated in the M06-G3 cells by identifying known key effectors of TGF beta-1 signal transduction. Transient transfection studies demonstrate for the first time that TGF beta-1 downregulates both DMP-1 and DSPP genes. Our findings indicate that the TGF beta-1 type I receptor ALK5 is expressed by odontoblasts as well as the signal transduction proteins Smad2, Smad3, and Smad4. These results suggest that TGF beta-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.
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Department of Pediatric Dentistry, Dental School, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MCS 7888, San Antonio, Texas 78229-3900, USA.
O'Sullivan
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Chen
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MacDougall
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D030201:Activin Receptors, Type I / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins; D007150:Immunohistochemistry; D051379:Mice; D009804:Odontoblasts / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D000099311:Dentin Sialophosphoprotein
D030201:Activin Receptors, Type I; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D011498:Protein Precursors; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000099311:Dentin Sialophosphoprotein; C513308:Dmp1 protein, mouse; C508961:Tgfb1 protein, mouse; C508962:Tgfb1 protein, rat; C000625842:Tgfbr1 protein, mouse; C000625843:Tgfbr1 protein, rat