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Hypertrophic Chondrocytes Have a Limited Capacity to Cope with Increases in Endoplasmic Reticulum Stress without Triggering the Unfolded Protein Response
Mutations causing metaphyseal chondrodysplasia type Schmid (MCDS) (e.g., Col10a1p.N617K) induce the pathology by a mechanism involving increased endoplasmic reticulum (ER) stress triggering an unfolded protein response (UPR) in hypertrophic chondrocytes (Rajpar et al. 2009). Here we correlate the ex...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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SAGE Publications
2012
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524565/ https://www.ncbi.nlm.nih.gov/pubmed/22859705 http://dx.doi.org/10.1369/0022155412458436 |
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author | Kung, Louise H. W. Rajpar, M. Helen Briggs, Michael D. Boot-Handford, Raymond P. |
author_facet | Kung, Louise H. W. Rajpar, M. Helen Briggs, Michael D. Boot-Handford, Raymond P. |
author_sort | Kung, Louise H. W. |
collection | PubMed |
description | Mutations causing metaphyseal chondrodysplasia type Schmid (MCDS) (e.g., Col10a1p.N617K) induce the pathology by a mechanism involving increased endoplasmic reticulum (ER) stress triggering an unfolded protein response (UPR) in hypertrophic chondrocytes (Rajpar et al. 2009). Here we correlate the expression of mutant protein with the onset of the UPR and disease pathology (hypertrophic zone [HZ] expansion) in MCDS and ColXTg (cog) mouse lines from E14.5 to E17.5. Embryos homozygous for the Col10a1p.N617K mutation displayed a delayed secretion of mutant collagen X accompanied by a UPR at E14.5, delayed ossification of the primary center at E15.5, and an expanded HZ at E17.5. Heterozygote embryos expressed mutant collagen X from E14.5 but exhibited no evidence of a UPR or an HZ expansion until after E17.5. Embryos positive for the ER stress-inducing ColXTg (cog) allele expressed Tg(cog) at E14.5, but the onset of the UPR was not apparent until E15.5 in homozygous and E17.5 in hemizygous embryos. Only homozygous embryos exhibited an HZ expansion at E17.5. The differential onset of the UPR and pathology, dependent on mutation type and gene dosage, indicates that hypertrophic chondrocytes have a latent capacity to deal with ER stress, which must be exceeded to trigger the UPR and HZ expansion. |
format | Online Article Text |
id | pubmed-3524565 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-35245652013-04-25 Hypertrophic Chondrocytes Have a Limited Capacity to Cope with Increases in Endoplasmic Reticulum Stress without Triggering the Unfolded Protein Response Kung, Louise H. W. Rajpar, M. Helen Briggs, Michael D. Boot-Handford, Raymond P. J Histochem Cytochem Articles Mutations causing metaphyseal chondrodysplasia type Schmid (MCDS) (e.g., Col10a1p.N617K) induce the pathology by a mechanism involving increased endoplasmic reticulum (ER) stress triggering an unfolded protein response (UPR) in hypertrophic chondrocytes (Rajpar et al. 2009). Here we correlate the expression of mutant protein with the onset of the UPR and disease pathology (hypertrophic zone [HZ] expansion) in MCDS and ColXTg (cog) mouse lines from E14.5 to E17.5. Embryos homozygous for the Col10a1p.N617K mutation displayed a delayed secretion of mutant collagen X accompanied by a UPR at E14.5, delayed ossification of the primary center at E15.5, and an expanded HZ at E17.5. Heterozygote embryos expressed mutant collagen X from E14.5 but exhibited no evidence of a UPR or an HZ expansion until after E17.5. Embryos positive for the ER stress-inducing ColXTg (cog) allele expressed Tg(cog) at E14.5, but the onset of the UPR was not apparent until E15.5 in homozygous and E17.5 in hemizygous embryos. Only homozygous embryos exhibited an HZ expansion at E17.5. The differential onset of the UPR and pathology, dependent on mutation type and gene dosage, indicates that hypertrophic chondrocytes have a latent capacity to deal with ER stress, which must be exceeded to trigger the UPR and HZ expansion. SAGE Publications 2012-10 /pmc/articles/PMC3524565/ /pubmed/22859705 http://dx.doi.org/10.1369/0022155412458436 Text en © The Author(s) 2012 http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed under the terms of the Creative Commons Attribution-Non Commercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page(http://www.uk.sagepub.com/aboutus/openaccess.htm). |
spellingShingle | Articles Kung, Louise H. W. Rajpar, M. Helen Briggs, Michael D. Boot-Handford, Raymond P. Hypertrophic Chondrocytes Have a Limited Capacity to Cope with Increases in Endoplasmic Reticulum Stress without Triggering the Unfolded Protein Response |
title | Hypertrophic Chondrocytes Have a Limited Capacity to Cope with Increases in Endoplasmic Reticulum Stress without Triggering the Unfolded Protein Response |
title_full | Hypertrophic Chondrocytes Have a Limited Capacity to Cope with Increases in Endoplasmic Reticulum Stress without Triggering the Unfolded Protein Response |
title_fullStr | Hypertrophic Chondrocytes Have a Limited Capacity to Cope with Increases in Endoplasmic Reticulum Stress without Triggering the Unfolded Protein Response |
title_full_unstemmed | Hypertrophic Chondrocytes Have a Limited Capacity to Cope with Increases in Endoplasmic Reticulum Stress without Triggering the Unfolded Protein Response |
title_short | Hypertrophic Chondrocytes Have a Limited Capacity to Cope with Increases in Endoplasmic Reticulum Stress without Triggering the Unfolded Protein Response |
title_sort | hypertrophic chondrocytes have a limited capacity to cope with increases in endoplasmic reticulum stress without triggering the unfolded protein response |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524565/ https://www.ncbi.nlm.nih.gov/pubmed/22859705 http://dx.doi.org/10.1369/0022155412458436 |
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