Dentin Sialoprotein Facilitates Dental Mesenchymal Cell Differentiation and Dentin Formation

Overview

Journal Sci Rep

Specialty Science

Date 2017 Mar 24

PMID 28331230

Citations 13

Authors

Wentong Li

Lei Chen

Zhuo Chen

Lian Wu

Junsheng Feng

Feng Wang

Lisa Shoff

Xin Li

Kevin J Donly

Mary Macdougall

Shuo Chen

Affiliations

Soon will be listed here.

Abstract

Dentin sialoprotein (DSP) is a dentin extracellular matrix protein. It is involved in dental mesenchymal cell lineages and dentin formation through regulation of its target gene expression. DSP mutations cause dentin genetic diseases. However, mechanisms of DSP in controlling dental mesenchymal cell differentiation are unknown. Using DSP as bait, we screened a protein library from mouse odontoblastic cells and found that DSP is a ligand and binds to cell surface receptor, occludin. Further study identified that the C-terminal DSP domain interacts with the occludin extracellular loop 2. The C-terminal DSP domain induced phosphorylation of occludin Ser and focal adhesion kinase (FAK) Ser and Tyr. Coexpression of DSP, occludin and FAK was detected in dental mesenchymal cells during tooth development. Occludin physically interacts with FAK, and occludin and FAK phosphorylation can be blocked by DSP and occludin antibodies. This DSP domain facilitates dental mesenchymal cell differentiation and mineralization. Furthermore, transplantation and pulp-capping procedures revealed that this DSP domain induces endogenous dental pulp mesenchymal cell proliferation, differentiation and migration, while stimulating blood vessel proliferation. This study elucidates the mechanism of DSP in dental mesenchymal lineages and implies that DSP may serve as a therapeutic agent for dentin-pulp complex regeneration in dental caries.

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