Dspp-independent Effects of Transgenic Trps1 Overexpression on Dentin Formation

Abstract

The Trps1 transcription factor is highly expressed in dental mesenchyme and preodontoblasts, while in mature, secretory odontoblasts, it is expressed at low levels. Previously, we have shown that high Trps1 levels in mature odontoblasts impair their function in vitro and in vivo. Col1a1-Trps1 transgenic (Trps1-Tg) mice demonstrate defective dentin secretion and mineralization, which are associated with significantly decreased Dspp expression due to direct repression of the Dspp gene by Trps1. Here, by crossing Trps1-Tg and Col1a1-Dspp transgenic (Dspp-Tg) mice, we generated Col1a1-Trps1;Col1a1-Dspp double transgenic (double-Tg) mice in which Dspp was restored in odontoblasts overexpressing Trps1. Comparative micro-computed tomography analyses revealed partial correction of the dentin volume and no improvement of dentin mineralization in double transgenic mice in comparison with Trps1-Tg and wild-type (WT) mice. In addition, dentin of double-Tg mice has an irregular mineralization pattern characteristic for dentin in hypophosphatemic rickets. Consistent with this phenotype, decreased levels of Phex, Vdr, and Fam20c proteins are detected in both Trps1-Tg and doubleTg odontoblasts in comparison with WT and Dspp-Tg odontoblasts. This suggests that the Dspp-independent dentin mineralization defects in Trps1-Tg mice are a result of downregulation of a group of proteins critical for mineral deposition within the dentin matrix. In summary, by demonstrating that Trps1 functions as a repressor of later stages of dentinogenesis, we provide functional significance of the dynamic Trps1 expression pattern during dentinogenesis.

Making extra teeth: Lessons from a TRPS1 mutation

“…Overexpression of Trps1 in mice causes dentinogenesis imperfecta, a hereditary defect of dentin. Trps1 functions to maintain the preodontoblast stage of development by restricting the expression of important mineralization proteins [Napierala et al, ; Mobley et al, ].…”

Cancer Secretome May Influence BSP and DSP Expression in Human Salivary Gland Cells

“…89,90-92 DSP, on the contrary, is primarily a glycoprotein with minimal phosphate, but very high levels of sialic acid and carbohydrate, 93 thus playing a role in initiation of mineralization and laying down of matrix. In addition to its expression in mineralized tissue such as bone, dentin, and cementum, 44,49,50,58,83,85-87,94-96 DSP is found in non-mineralized tissues, 52,97-99 and has also been shown to be elevated in several epithelial cancers, of particular note, prostate, 24,30 breast, 21,27 and lung. 27 Expression of DSP has also been related to aggressiveness in human prostate cancers and oral cancers.…”

“…DSPP and its cleaved products, namely, DPP (dentin phosphoprotein) and DSP, play important roles in biomineralization. 47,49,50,58,[83][84][85][86][87] Although cleaved from the same DSPP holoprotein, DPP and DSP are functionally distinct with respect to biomineralization. 88 DPP with its repeated sequences of aspartic acid (Asp) and phosphorylated serine residues (Pse), and relatively long carboxylate and phosphate groups, regulate the rate and location of dentin mineralization by apatite crystal formation.…”