Dentin sialoprotein facilitates dental mesenchymal cell differentiation and dentin formation

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 mesench...

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Autores principales:	Wentong Li, Lei Chen, Zhuo Chen, Lian Wu, Junsheng Feng, Feng Wang, Lisa Shoff, Xin Li, Kevin J. Donly, Mary MacDougall, Shuo Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7089c98de33742ee9bf40aa95d84647d
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spelling	oai:doaj.org-article:7089c98de33742ee9bf40aa95d84647d2021-12-02T12:30:36ZDentin sialoprotein facilitates dental mesenchymal cell differentiation and dentin formation10.1038/s41598-017-00339-w2045-2322https://doaj.org/article/7089c98de33742ee9bf40aa95d84647d2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00339-whttps://doaj.org/toc/2045-2322Abstract 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 domainaa 363–458 interacts with the occludin extracellular loop 2aa 194–241. The C-terminal DSP domain induced phosphorylation of occludin Ser490 and focal adhesion kinase (FAK) Ser722 and Tyr576. 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.Wentong LiLei ChenZhuo ChenLian WuJunsheng FengFeng WangLisa ShoffXin LiKevin J. DonlyMary MacDougallShuo ChenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-18 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wentong Li Lei Chen Zhuo Chen Lian Wu Junsheng Feng Feng Wang Lisa Shoff Xin Li Kevin J. Donly Mary MacDougall Shuo Chen Dentin sialoprotein facilitates dental mesenchymal cell differentiation and dentin formation
description	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 domainaa 363–458 interacts with the occludin extracellular loop 2aa 194–241. The C-terminal DSP domain induced phosphorylation of occludin Ser490 and focal adhesion kinase (FAK) Ser722 and Tyr576. 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.
format	article
author	Wentong Li Lei Chen Zhuo Chen Lian Wu Junsheng Feng Feng Wang Lisa Shoff Xin Li Kevin J. Donly Mary MacDougall Shuo Chen
author_facet	Wentong Li Lei Chen Zhuo Chen Lian Wu Junsheng Feng Feng Wang Lisa Shoff Xin Li Kevin J. Donly Mary MacDougall Shuo Chen
author_sort	Wentong Li
title	Dentin sialoprotein facilitates dental mesenchymal cell differentiation and dentin formation
title_short	Dentin sialoprotein facilitates dental mesenchymal cell differentiation and dentin formation
title_full	Dentin sialoprotein facilitates dental mesenchymal cell differentiation and dentin formation
title_fullStr	Dentin sialoprotein facilitates dental mesenchymal cell differentiation and dentin formation
title_full_unstemmed	Dentin sialoprotein facilitates dental mesenchymal cell differentiation and dentin formation
title_sort	dentin sialoprotein facilitates dental mesenchymal cell differentiation and dentin formation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7089c98de33742ee9bf40aa95d84647d
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Dentin sialoprotein facilitates dental mesenchymal cell differentiation and dentin formation

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