Genetic evidence for key roles of decorin and biglycan in dentin mineralization

Targeted disruption of the dentin sialophosphoprotein (DSPP) gene in the mice (Dspp^-/-) results in dentin mineralization defects with enlarged predentin phenotype similar to human dentinogenesis imperfecta type III. Using DSPP/biglycan (Dspp^-/-Bgn^-/0) and DSPP/decorin (Dspp^-/-Dcn^-/-) double knockout mice, here we determined that the enlarged predentin layer in Dspp^-/- teeth is rescued in the absence of decorin, but not in the absence of biglycan. However, Fourier transform infrared (FTIR) spectroscopy analysis reveals similar hypomineralization of dentin in both Dspp^-/-Bgn^-/0 and Dspp^-/-Dcn^-/- teeth. Atomic force microscopy (AFM) analysis of collagen fibrils in dentin shows subtle differences in the collagen fibril morphology in these genotypes. The reduction of enlarged predentin in Dspp^-/-Dcn^-/- mice suggests that the elevated level of decorin in Dspp^-/- predentin interferes with the mineralization process at the dentin mineralization front. On the other hand, the lack of DSPP and biglycan leads to the increased number of calcospherites in Dspp^-/-Bgn^-/0 predentin, suggesting that a failure in coalescence of calcospherites was augmented in Dspp^-/-Bgn^-/0 teeth as compared to Dspp^-/- teeth. These findings indicate that normal expression of small leucine rich proteoglycans, such as biglycan and decorin, plays an important role in the highly orchestrated process of dentin mineralization.