Dentin Sialophosphoprotein (DSPP) and Dentin

Abstract

The revolution in genetics disclosed the types of malformations that occur when expression of a particular gene is lost. In the case of tooth dentin, mutations in the two genes encoding type I collagen cause osteogenesis imperfecta, a bone condition that often includes dentin malformations. Besides collagen, there are a number of non-collagenous proteins in dentin. Among the genes encoding the dentin non-collagenous proteins, only mutations in DSPP (dentin sialophosphoprotein) cause inherited dental malformations. DSPP mutations cause dentinogenesis imperfecta types II and III, and dentin dysplasia type II. DSPP is the most abundant non-collagenous protein in dentin. DSPP protein is necessary for proper dentin formation, and understanding its structure and function should yield important insights into how dentin forms and biomineralization is controlled. DSPP is expressed and secreted by odontoblasts, the cells that make tooth dentin and that also maintain cell processes extending into the mineralized tissue. Following its secretion, DSPP is cleaved into smaller pieces by multiple extracellular proteases. For the last five years I have devoted myself to characterizing DSPP-derived proteins. DSPP is cleaved by proteases into three main parts : dentin sialoprotein (DSP), dentin glycoprotein (DGP), and dentin phosphoprotein (DPP). We have learned that DSP is a proteoglycan that forms covalent dimers, DGP is a phosphorylated glycoprotein, and DPP is a highly phosphorylated intrinsically disordered protein that shows extensive length polymorphisms due to the genetic heterogeneity of its coding region.

Mineralization induction effects of osteopontin, bone sialoprotein, and dentin phosphoprotein on a biomimetic collagen substrate

“…Although OPN is also perceived to play a regulatory role, it has been immunolocalized in the collagen matrix ahead of developing bone and uncertainty remains regarding its mineralization induction properties. DPP has been shown to have the capacity to strongly bind calcium ions, indicating its potential for playing a role in biomineralization 5, 6. Furthermore, OPN and BSP have also been seen to be enriched at bone–implant interfacial sites 1, 2, 7–11.…”

“…DSPP is cleaved into two fragments in bone and dentin, DPP, and DSP 17. DPP is a highly negatively charged molecule composed of 751 amino acids in humans with a molecular weight of 100–140 kDa 2, 5. It also has a high degree of phosphorylation 5, 6, 17.…”

“…DPP is a highly negatively charged molecule composed of 751 amino acids in humans with a molecular weight of 100–140 kDa 2, 5. It also has a high degree of phosphorylation 5, 6, 17. It is the major noncollagenous protein of the dentin extracellular matrix (ECM) and becomes soluble only after the ECM has been demineralized 17.…”

“…The foci of this work are to determine the adsorption characteristics of OPN, BSP, and DPP to an aligned 2D collagen type I fibril matrix that resembles developing bone and to directly compare the mineralization induction effects of OPN, BSP, and DPP when specifically bound to this matrix. Multiple investigations have characterized the adsorption or binding of these proteins to various collagen coatings 1, 3–5, 17. For example, our previous work probed OPN and BSP binding to a collagen type I tropocollagen coating on tissue‐culture polystyrene (TCPS) 19.…”

Nanofibrous Spongy Microspheres Enhance Odontogenic Differentiation of Human Dental Pulp Stem Cells

“…The OCN gene expression level in NF-SMS group was significantly higher than in either NF-MS group or S-MS group at both 2 and 4 wk of induction. As the major non-collagenous dentinal protein, DSPP is essential for dentin mineralization [28] , and is considered to be a highly specific tissue marker for dentin. DSPP gene expression was significantly higher in NF-SMS group than in NF-MS or S-MS group at both 2 and 4 wk of induction.…”