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

• Published in: Matrix biology 2009-04, Vol.28 (3), p.129-136
• Main Authors: Haruyama, Naoto, Sreenath, Taduru L., Suzuki, Shigeki, Yao, Xiaomei, Wang, Zhigang, Wang, Yong, Honeycutt, Cherlita, Iozzo, Renato V., Young, Marian F., Kulkarni, Ashok B.
• Format: Article
• Language: English
• Subjects: Animals; Biglycan; Collagen - ultrastructure; Decorin; Dentin - diagnostic imaging; Dentin - metabolism; Dentin - pathology; Dentin - ultrastructure; Dentin mineralization; Dentin sialophosphoprotein (DSPP); Dentinogenesis imperfecta (DGI); Dentinogenesis Imperfecta - genetics; Dentinogenesis Imperfecta - pathology; Extracellular Matrix Proteins - genetics; Extracellular Matrix Proteins - metabolism; Humans; Incisor - diagnostic imaging; Incisor - growth & development; Incisor - metabolism; Incisor - pathology; Knockout mouse; Mice; Mice, Inbred Strains; Mice, Knockout; Microradiography; Microscopy, Atomic Force; Microscopy, Electron, Scanning; Odontoblasts - metabolism; Phosphoproteins; Protein Precursors - genetics; Proteoglycans - genetics; Proteoglycans - metabolism; Sialoglycoproteins; Spectroscopy, Fourier Transform Infrared; Tooth Calcification - genetics
• ISSN: 0945-053X; 1569-1802
• DOI: 10.1016/j.matbio.2009.01.005

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.