4.4 Article

Dentin sialophosphoprotein and dentin matrix protein-1: Two highly phosphorylated proteins in mineralized tissues

Journal

ARCHIVES OF ORAL BIOLOGY
Volume 57, Issue 9, Pages 1165-1175

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.archoralbio.2012.03.005

Keywords

DSPP; DMP-1; Genetically engineered mouse models; Cell signalling molecules; Astacin family proteinases

Funding

  1. Grants-in-Aid for Scientific Research [22792040] Funding Source: KAKEN
  2. Intramural NIH HHS [Z01 DE000698-10] Funding Source: Medline

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Dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1) are highly phosphorylated proteins that belong to the family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and are essential for proper development of hard tissues such as teeth and bones. In order to understand how they contribute to tissue organization, DSPP and DMP-1 have been analyzed for over a decade using both in vivo and in vitro techniques. Among the five SIBLINGs, the DSPP and DMP-1 genes are located next to each other and their gene and protein structures are most similar. In this review we examine the phenotypes of the genetically engineered mouse models of DSPP and DMP-1 and also introduce complementary in vitro studies into the molecular mechanisms underlying these phenotypes. DSPP affects the mineralization of dentin more profoundly than DMP-1. In contrast, DMP-1 significantly affects bone mineralization and importantly controls serum phosphate levels by regulating serum FGF-23 levels, whereas DSPP does not show any systemic effects. DMP-1 activates integrin signalling and is endocytosed into the cytoplasm whereupon it is translocated to the nucleus. In contrast, DSPP only activates integrin-dependent signalling. Thus it is now clear that both DSPP and DMP-1 contribute to hard tissue mineralization and the tissues affected by each are different presumably as a result of their different expression levels. In fact, in comparison with DMP-1, the functional analysis of cell signalling by DSPP remains relatively unexplored. (C) 2012 Elsevier LtdElsevier Ltd. All rights reserved.

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