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Publication : Dentin sialoprotein facilitates dental mesenchymal cell differentiation and dentin formation.

First Author  Li W Year  2017
Journal  Sci Rep Volume  7
Issue  1 Pages  300
PubMed ID  28331230 Mgi Jnum  J:316617
Mgi Id  MGI:6838190 Doi  10.1038/s41598-017-00339-w
Citation  Li W, et al. (2017) Dentin sialoprotein facilitates dental mesenchymal cell differentiation and dentin formation. Sci Rep 7(1):300
abstractText  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(aa 363-458) interacts with the occludin extracellular loop 2(aa 194-241). The C-terminal DSP domain induced phosphorylation of occludin Ser(490) and focal adhesion kinase (FAK) Ser(722) and Tyr(576). 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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