Cargando…
Disrupted Protein Expression and Altered Proteolytic Events in Hypophosphatemic Dentin Can Be Rescued by Dentin Matrix Protein 1
Dentin, one of the four mineralized tissues of the craniofacial complex, forms sequentially from the deposition of an organic matrix to the nucleation of an inorganic phase within the matrix scaffold. Several promoters and inhibitors of mineralization support and regulate mineral nucleation. Clinica...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034300/ https://www.ncbi.nlm.nih.gov/pubmed/32116788 http://dx.doi.org/10.3389/fphys.2020.00082 |
_version_ | 1783499849927229440 |
---|---|
author | Guirado, Elizabeth Chen, Yinghua Ross, Ryan D. Zhang, Youbin Chaussain, Catherine George, Anne |
author_facet | Guirado, Elizabeth Chen, Yinghua Ross, Ryan D. Zhang, Youbin Chaussain, Catherine George, Anne |
author_sort | Guirado, Elizabeth |
collection | PubMed |
description | Dentin, one of the four mineralized tissues of the craniofacial complex, forms sequentially from the deposition of an organic matrix to the nucleation of an inorganic phase within the matrix scaffold. Several promoters and inhibitors of mineralization support and regulate mineral nucleation. Clinical and experimental evidence suggest that dentin matrix protein 1 (DMP1) and phosphate-regulating neutral endopeptidase (PHEX) cooperate and are necessary for the formation of a cohesive dentin layer. The following study investigates the effect of PHEX loss-of-function on dentin matrix formation preceding mineralization. Using the Hyp mouse, an animal model for X-linked hypophosphatemia (XLH), we identified an irregular distribution of dentin extracellular matrix proteins. Likewise, dental pulp stem cells (DPSCs) from XLH patients exhibited altered proteolytic events with disrupted extracellular matrix deposition. Further differentiation assays demonstrated that XLH DPSCs exhibited impaired matrix mineralization. Overexpression of DMP1 in XLH DPSCs restored the irregular protein processing patterns to near-physiological levels. Our results support the hypothesis that hypophosphatemia resulting from PHEX loss-of-function affects the integrity of the organization of the dentin matrix and suggests that exogenous DMP1 can restore physiological processing of matrix proteins, in addition to its canonical role in mineralization. |
format | Online Article Text |
id | pubmed-7034300 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70343002020-02-28 Disrupted Protein Expression and Altered Proteolytic Events in Hypophosphatemic Dentin Can Be Rescued by Dentin Matrix Protein 1 Guirado, Elizabeth Chen, Yinghua Ross, Ryan D. Zhang, Youbin Chaussain, Catherine George, Anne Front Physiol Physiology Dentin, one of the four mineralized tissues of the craniofacial complex, forms sequentially from the deposition of an organic matrix to the nucleation of an inorganic phase within the matrix scaffold. Several promoters and inhibitors of mineralization support and regulate mineral nucleation. Clinical and experimental evidence suggest that dentin matrix protein 1 (DMP1) and phosphate-regulating neutral endopeptidase (PHEX) cooperate and are necessary for the formation of a cohesive dentin layer. The following study investigates the effect of PHEX loss-of-function on dentin matrix formation preceding mineralization. Using the Hyp mouse, an animal model for X-linked hypophosphatemia (XLH), we identified an irregular distribution of dentin extracellular matrix proteins. Likewise, dental pulp stem cells (DPSCs) from XLH patients exhibited altered proteolytic events with disrupted extracellular matrix deposition. Further differentiation assays demonstrated that XLH DPSCs exhibited impaired matrix mineralization. Overexpression of DMP1 in XLH DPSCs restored the irregular protein processing patterns to near-physiological levels. Our results support the hypothesis that hypophosphatemia resulting from PHEX loss-of-function affects the integrity of the organization of the dentin matrix and suggests that exogenous DMP1 can restore physiological processing of matrix proteins, in addition to its canonical role in mineralization. Frontiers Media S.A. 2020-02-14 /pmc/articles/PMC7034300/ /pubmed/32116788 http://dx.doi.org/10.3389/fphys.2020.00082 Text en Copyright © 2020 Guirado, Chen, Ross, Zhang, Chaussain and George. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Guirado, Elizabeth Chen, Yinghua Ross, Ryan D. Zhang, Youbin Chaussain, Catherine George, Anne Disrupted Protein Expression and Altered Proteolytic Events in Hypophosphatemic Dentin Can Be Rescued by Dentin Matrix Protein 1 |
title | Disrupted Protein Expression and Altered Proteolytic Events in Hypophosphatemic Dentin Can Be Rescued by Dentin Matrix Protein 1 |
title_full | Disrupted Protein Expression and Altered Proteolytic Events in Hypophosphatemic Dentin Can Be Rescued by Dentin Matrix Protein 1 |
title_fullStr | Disrupted Protein Expression and Altered Proteolytic Events in Hypophosphatemic Dentin Can Be Rescued by Dentin Matrix Protein 1 |
title_full_unstemmed | Disrupted Protein Expression and Altered Proteolytic Events in Hypophosphatemic Dentin Can Be Rescued by Dentin Matrix Protein 1 |
title_short | Disrupted Protein Expression and Altered Proteolytic Events in Hypophosphatemic Dentin Can Be Rescued by Dentin Matrix Protein 1 |
title_sort | disrupted protein expression and altered proteolytic events in hypophosphatemic dentin can be rescued by dentin matrix protein 1 |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034300/ https://www.ncbi.nlm.nih.gov/pubmed/32116788 http://dx.doi.org/10.3389/fphys.2020.00082 |
work_keys_str_mv | AT guiradoelizabeth disruptedproteinexpressionandalteredproteolyticeventsinhypophosphatemicdentincanberescuedbydentinmatrixprotein1 AT chenyinghua disruptedproteinexpressionandalteredproteolyticeventsinhypophosphatemicdentincanberescuedbydentinmatrixprotein1 AT rossryand disruptedproteinexpressionandalteredproteolyticeventsinhypophosphatemicdentincanberescuedbydentinmatrixprotein1 AT zhangyoubin disruptedproteinexpressionandalteredproteolyticeventsinhypophosphatemicdentincanberescuedbydentinmatrixprotein1 AT chaussaincatherine disruptedproteinexpressionandalteredproteolyticeventsinhypophosphatemicdentincanberescuedbydentinmatrixprotein1 AT georgeanne disruptedproteinexpressionandalteredproteolyticeventsinhypophosphatemicdentincanberescuedbydentinmatrixprotein1 |