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DSPP contains an IRES element responsible for the translation of dentin phosphophoryn.

ABSTRACT: The major phosphoprotein in dentin is the aspartic acid and serine-rich protein called dentin phosphophoryn (DPP). DPP appears to be synthesized as a part of a larger compound protein, dentin sialophosphoprotein (DSPP). DSPP has never been isolated or detected in dentin extracts. It is now evident that DSPP is a chimeric protein composed of 3 parts: dentin sialoprotein (DSP), DPP, and dentin glycoprotein (DGP). Previous reports have suggested that the BMP1 protease is responsible for processing DSPP. However, unequal amounts of these products are present in the dentin matrix. Here, we provide evidence for an internal ribosome entry site in the DSPP gene that directs the synthesis of DPP. This mechanism would account for unequal amounts of intracellular DSP and DPP. The internal ribosomal entry site (IRES) activity varied in different cell types, suggesting the presence of additional regulatory elements during the translational regulation of DPP. Further, we provide evidence that DPP is transported to the extracellular matrix (ECM) through exosomes. Using tissue recombination and lentivirus-mediated gain-of-function approaches, we also demonstrate that DPP is essential for the formation of well-defined tooth structures with mineralized dentin matrix.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC3895336 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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DSPP contains an IRES element responsible for the translation of dentin phosphophoryn.

Zhang Y Y Song Y Y Ravindran S S Gao Q Q Huang C C CC Ramachandran A A Kulkarni A A George A A

Journal of dental research 20131218 2

The major phosphoprotein in dentin is the aspartic acid and serine-rich protein called dentin phosphophoryn (DPP). DPP appears to be synthesized as a part of a larger compound protein, dentin sialophosphoprotein (DSPP). DSPP has never been isolated or detected in dentin extracts. It is now evident that DSPP is a chimeric protein composed of 3 parts: dentin sialoprotein (DSP), DPP, and dentin glycoprotein (DGP). Previous reports have suggested that the BMP1 protease is responsible for processing ...[more]

PMID: 24352500

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Project description:Dentin Sialoprotein (DSP) and phosphophoryn (PP) are two most dominant non-collagenous proteins in dentin, which are the cleavage products of the DSPP (dentin sialophosphoprotein) precursor protein. The absence of the DSPP gene in DSPP knock-out (KO) mice results in characteristics that are consistent with dentinogenesis imperfecta type III in humans. Symptoms include thin dentin, bigger pulp chamber with frequent pulp exposure as well as abnormal epithelial-mesenchymal interactions, and the appearance of chondrocyte-like cells in dental pulp. To better understand how DSPP influences tooth development and dentin formation, we used a bacterial artificial chromosome transgene construct (BAC-DSPP) that contained the complete DSPP gene and promoter to generate BAC-DSPP transgenic mice directly in a mouse DSPP KO background. Two BAC-DSPP transgenic mouse strains were generated and characterized. DSPP mRNA expression in BAC-DSPP Strain A incisors was similar to that from wild-type (wt) mice. DSPP mRNA expression in BAC-DSPP Strain B animals was only 10% that of wt mice. PP protein content in Strain A incisors was 25% of that found in wt mice, which was sufficient to completely rescue the DSPP KO defect in mineral density, since microCT dentin mineral density analysis in 21-day postnatal animal molars showed essentially identical mineral density in both strain A and wt mice. Strain B mouse incisors, with 5% PP expression, only partially rescued the DSPP KO defect in mineral density, as microCT scans of 21-day postnatal animal molars indicated a reduced dentin mineral density compared to wt mice, though the mineral density was still increased over that of DSPP KO. Furthermore, our findings showed that DSPP dosage in Strain A was sufficient to rescue the DSPP KO defect in terms of epithelial-mesenchymal interactions, odontoblast lineage maintenance, along with normal dentin thickness and normal mineral density while DSPP gene dosage in Strain B only partially rescued the aforementioned DSPP KO defect.

Dataset Information

DSPP contains an IRES element responsible for the translation of dentin phosphophoryn.

Publications

DSPP contains an IRES element responsible for the translation of dentin phosphophoryn.

Similar Datasets

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