Dentin matrix protein 1 regulates dentin sialophosphoprotein gene transcription during early odontoblast differentiation.
Dentin mineralization requires transcriptional mechanisms to induce a cascade of gene expression for progressive develop- ment of the odontoblast phenotype. During cytodifferentiation of odontoblasts there is a constant change of actively tran- scribed genes. Thus, tissue-specific matrix genes that are silenced in early differentiation are expressed during the termi- nal differentiation process. Dentin sialophosphoprotein (DSPP) is an extracellular matrix, prototypical dentin, and a bone-spe- cific gene, however, the molecular mechanisms by which it is temporally and spatially regulated are not clear. In this report, we demonstrate that dentin matrix protein 1 (DMP1), which is localized in the nucleus during early differentiation of odonto- blasts, is able to bind specifically with the DSPP promoter and activate its transcription. We have identified the specific pro- moter sequence that binds specifically to the carboxyl end of DMP1. The DNA binding domain in DMP1 resides between amino acids 420 and 489. A chromatin immunoprecipitation assay confirmed the in vivo association of DMP1 with the DSPP promoter. Interactions between DMP1 and DSPP promoter thus provide the foundation to understand how DMP1 regulates the expression of the DSPP gene.
Two of the proteins found in significant quantity in the extracellular matrix (ECM) of dentin are dentin phosphoprotein (DPP) and dentin sialoprotein (DSP). DPP, the most abundant of the non-collagenous proteins in dentin is an unusually polyanionic protein, containing a large number of aspartic acids (Asp) and phosphoserines (Pse) in the repeating sequences of (Asp-Pse)n. and (Asp-Pse-Pse)n. The many negatively charged regions of DPP are thought to promote mineralization by binding calcium and presenting it to collagen fibers at the mineralization front during the formation of dentin. This purported role of DPP is supported by a sizeable pool of in vitro mineralization data showing that DPP is an important initiator and modulator for the formation and growth of hydroxyapatite crystals. Quite differently, DSP is a glycoprotein, with little or no phosphate. DPP and DSP are the cleavage products of dentin sialophosphoprotein (DSPP). Human and mouse genetic studies have demonstrated that mutations in, or knockout of, the Dspp gene result in mineralization defects in dentin and/or bone. The discoveries in the past 40 years with regard to DPP, DSP and DSPP have greatly enhanced our understanding of biomineralization and set a new stage for future studies. In this review, we summarize the important and new developments made in the past four decades regarding the structure and regulation of the DSPP gene, the biochemical characteristics of DSPP, DPP and DSP, as well as the cell/tissue localizations and functions of these molecules.
Of course, we know what is coming next right? 😉