Dentin sialoprotein and phosphoprotein have specific roles in dentin mineralization

Objective: Our research is focused on understanding the molecular roles of dentin sialophosphoprotein (DSPP) in dentin mineralization because it is the most abundant noncollagenous protein in dentin and because it is implicated in the most common hereditary dentin disorder, dentinogenesis imperfecta (DGI). The DSPP mRNA is translated into a single protein, DSPP, which is cleaved mainly into 3 peptides, dentin sialoprotein (DSP), dentin glycoprotein (DGP), and dentin phosphoprotein (DPP). Our previous work on DSPP knockout mice (DSPP KO) confirmed the important role of DSPP in dentin mineralization. These mice develop tooth defects similar to those seen in DGI III, with enlarged pulp chambers, a decreased width of the dentin zone along with an increased width of the predentin zone, hypomineralization, and pulp exposure. Our objective for the current work was to delineate the precise molecular roles of DSP and DPP in dentin development and mineralization. Methods: We constructed transgenic vectors that express DSP/DGP under the control of the DSPP promoter and generated independent transgenic lines (DSPTgKO) that express DSP/DGP in odontoblasts and preameloblasts in a DSPP-null background. Results: We have established 2 DSPTgKO transgenic mouse lines that express DSP/DGP at low and high levels. An initial analysis revealed that the spatial and temporal expression patterns of the DSP/DGP transgene were similar to that of endogenous DSPP. SEM analysis revealed that all of the defects seen in the DSPP-null teeth were not rescued in the DSPTgKO teeth. Unlike the incisors, the molars of 3-month-old DSPTgKO mice showed near normal thickness of predentin. However, their pulpal cavity was still abnormally wide. Conclusions: We have successfully generated 2 mouse models in which DSP/DGP is expressed at 2 different levels in dentin in a DSPP-null background. Normal expression of DSP and DPP is required for normal dentin development and mineralization. Supported by NIDCR-DIR Z01DE000698-08CDBR.