Abstract
Mutations in the dentin sialophosphoprotein (DSPP) gene cause dentinogenesis imperfecta. After synthesis, DSPP is proteolytically processed into NH2- and COOH-terminal fragments. The NH2-terminal fragment of DSPP is highly glycosylated but not phosphorylated, whereas the COOH-terminal fragment (named “dentin phosphoprotein” or “DPP”) is highly phosphorylated but not glycosylated. These two fragments are believed to perform distinct roles in dentin formation. To analyze the functions of DPP in dentinogenesis, we created “Dspp-/-;DPP Tg mice”, which expressed transgenic DPP driven by a Type I collagen promoter but lacked the endogenous Dspp gene. We characterized the dentin of the Dspp-/-;DPP Tg mice using X-ray radiography, histology, scanning electron microscopy, double fluorochrome labeling, immunohistochemistry and in situ hybridization. Micro-computed tomography analyses revealed that at postnatal 6 months, the transgenic expression of DPP increased the dentin thickness of the Dspp-null mice by 97.1% and restored the dentin material density by 29.5%. Histological analyses showed that the Dspp-null mice manifested an abnormal widening of the predentin while the predentin in Dspp-/-;DPP Tg mice was narrower than in the Dspp-null mice. Scanning electron microscopy analyses showed that the dentinal tubules in the Dspp-/-;DPP Tg mice were better organized than in the Dspp-null mice. The double fluorochrome labeling analyses demonstrated that the dentin mineral deposition rate in the Dspp-/-;DPP Tg mice was significantly improved compared to that in the Dspp-null mice. These findings indicate that the transgenic expression of DPP partially rescued the dentin defects of the DSPP-null mice, suggesting that DPP may promote dentin formation and that the coordinated actions between DPP and the NH2-terminal fragment of DSPP may be necessary for dentinogenesis.
Highlights
Dentin is composed of an organic matrix that is primarily made of Type I collagen and a mineral phase that consists of hydroxyapatite crystals
X-ray radiography showed that the mandibular teeth from 3-week-old Dspp+/+;dentin phosphoprotein” (DPP) Tg transgenic mice were slightly smaller than the normal controls, and Hematoxylin and Eosin (H&E) staining of the mandibular first molars revealed that the dentin of Dspp+/+;DPP Tg mice appeared slightly thinner than in the normal control mice
Plain X-ray radiography revealed that the Dspp-/- mice exhibited thinner dentin and enlarged pulp chambers compared with the Dspp+/- mice, and the transgenic expression of HA-DPP markedly improved the dental defects of the Dspp-/- mice (Fig 2)
Summary
Dentin is composed of an organic matrix that is primarily made of Type I collagen and a mineral phase that consists of hydroxyapatite crystals. As the precursor of dentin, predentin lies between the mineralization front and the cells; it is converted to dentin when hydroxyapatite crystals are laid down within and around collagen fibrils. A rather uniform layer of predentin is maintained, suggesting that the rate of predentin formation must equal the rate of mineralization. The uniformity of these rates indicates that balanced mechanisms must be involved to control the site and rate of hydroxyapatite formation and growth. Changes that are well documented include increases in collagen fibril diameters, secretion and removal of proteoglycans and deposition of acidic phosphoproteins at the mineralization front [1]
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