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.