Dentin sialophosphoprotein in biomineralization

Abstract

Two of the proteins found in significant quantity in the extracellular matrix (ECM) of dentin are dentin phosphoprotein (DPP) and dentin sialoprotein (DSP). DPP, the most abundant of the non-collagenous proteins in dentin is an unusually polyanionic protein, containing a large number of aspartic acids (Asp) and phosphoserines (Pse) in the repeating sequences of (Asp-Pse)n. and (Asp-Pse-Pse)n. The many negatively charged regions of DPP are thought to promote mineralization by binding calcium and presenting it to collagen fibers at the mineralization front during the formation of dentin. This purported role of DPP is supported by a sizeable pool of in vitro mineralization data showing that DPP is an important initiator and modulator for the formation and growth of hydroxyapatite crystals. Quite differently, DSP is a glycoprotein, with little or no phosphate. DPP and DSP are the cleavage products of dentin sialophosphoprotein (DSPP). Human and mouse genetic studies have demonstrated that mutations in, or knockout of, the Dspp gene result in mineralization defects in dentin and/or bone. The discoveries in the past 40 years with regard to DPP, DSP and DSPP have greatly enhanced our understanding of biomineralization and set a new stage for future studies. In this review, we summarize the important and new developments made in the past four decades regarding the structure and regulation of the DSPP gene, the biochemical characteristics of DSPP, DPP and DSP, as well as the cell/tissue localizations and functions of these molecules.

The Rescue of Dentin Matrix Protein 1 (DMP1)-deficient Tooth Defects by the Transgenic Expression of Dentin Sialophosphoprotein (DSPP) Indicates That DSPP Is a Downstream Effector Molecule of DMP1 in Dentinogenesis

“…Although DMP1 is expressed in teeth, alveolar bone, and long bone, the finding indicates that the mechanism of action of DMP1 involved in the long bone development must differ from that in the formation of dentin and alveolar bone. This view is also supported by two other findings: DSPP expression is more abundant in the alveolar bone compared with that in the long bone (11,39), and inactivation of Dspp leads to severe defects in the alveolar bone but not in the long bone (40,41). Further work is warranted to elucidate the molecular mechanisms by which DMP1 functions differently in the dentin/alveolar bone and in the long bone.…”

Proteolytic Processing of Dentin Sialophosphoprotein (DSPP) Is Essential to Dentinogenesis

“…Based on the abundance of DSPP fragments and scarcity of its full-length form in the dentin, along with the observed roles of DPP in the nucleation and modulation of apatite crystal formation, we hypothesized that the conversion of DSPP to its fragments by proteolytic processing may be an activation event, converting an inactive precursor to active forms, and this activation step may represent one of the controlling mechanisms in dentin formation (16,40,46). In this study, we generated Dspp-KO/D452A-Tg mice lacking the endogenous Dspp gene but expressing the transgenic D452A-DSPP protein, in which Asp 452 , a key cleavage-site residue, was replaced by Ala 452 .…”

“…Studies have shown that significant amounts of DSP, DSP-PG, and DPP are present in the ECM of dentin, whereas a very minor quantity of the full-length form of DSPP is found in the dentin (16,38). The abundance of DSPP fragments, along with the scarcity of fulllength DSPP in the dentin, suggests that the processed fragments of DSPP may be the functional forms directly involved in biomineralization.…”

“…The NH 2 -terminal fragment of DSPP encoded by the 5Ј portion of the DSPP transcript exists in two forms: the core protein form known as "dentin sialoprotein" (DSP) and the proteoglycan form referred to as "DSP-PG" (15)(16)(17)(18)(19). The COOHterminal fragment of DSPP encoded by the 3Ј region of the DSPP transcript is found in only one form, referred to as "dentin phosphoprotein" (DPP).…”

Immunohistological Observation of Milled Teeth in a Rat Mandibular Incisor Extraction Socket

“…Dentin contains non-collagenous proteins such as bone morphogenetic protein 2) , dentin sialophosphoprotein 3) , and dentin matrix protein (DMP-1) 4) . DMP-1 has abundant acidic domains, which are negatively charged at physiological pH.…”