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Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures

Pseudoachondroplasia and multiple epiphyseal dysplasia are genetic skeletal diseases resulting from mutations in cartilage structural proteins. Electron microscopy and immunohistochemistry previously showed that the appearance of the cartilage extracellular matrix (ECM) in targeted mouse models of t...

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Autores principales: Bell, Peter A., Wagener, Raimund, Zaucke, Frank, Koch, Manuel, Selley, Julian, Warwood, Stacey, Knight, David, Boot-Handford, Raymond P., Thornton, David J., Briggs, Michael D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744072/
https://www.ncbi.nlm.nih.gov/pubmed/23951406
http://dx.doi.org/10.1242/bio.20135280
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author Bell, Peter A.
Wagener, Raimund
Zaucke, Frank
Koch, Manuel
Selley, Julian
Warwood, Stacey
Knight, David
Boot-Handford, Raymond P.
Thornton, David J.
Briggs, Michael D.
author_facet Bell, Peter A.
Wagener, Raimund
Zaucke, Frank
Koch, Manuel
Selley, Julian
Warwood, Stacey
Knight, David
Boot-Handford, Raymond P.
Thornton, David J.
Briggs, Michael D.
author_sort Bell, Peter A.
collection PubMed
description Pseudoachondroplasia and multiple epiphyseal dysplasia are genetic skeletal diseases resulting from mutations in cartilage structural proteins. Electron microscopy and immunohistochemistry previously showed that the appearance of the cartilage extracellular matrix (ECM) in targeted mouse models of these diseases is disrupted; however, the precise changes in ECM organization and the pathological consequences remain unknown. Our aim was to determine the effects of matrilin-3 and COMP mutations on the composition and extractability of ECM components to inform how these detrimental changes might influence cartilage organization and degeneration. Cartilage was sequentially extracted using increasing denaturants and the extraction profiles of specific proteins determined using SDS-PAGE/Western blotting. Furthermore, the relative composition of protein pools was determined using mass spectrometry for a non-biased semi-quantitative analysis. Western blotting revealed changes in the extraction of matrilins, COMP and collagen IX in mutant cartilage. Mass spectrometry confirmed quantitative changes in the extraction of structural and non-structural ECM proteins, including proteins with roles in cellular processes such as protein folding and trafficking. In particular, genotype-specific differences in the extraction of collagens XII and XIV and tenascins C and X were identified; interestingly, increased expression of several of these genes has recently been implicated in susceptibility and/or progression of murine osteoarthritis. We demonstrated that mutation of matrilin-3 and COMP caused changes in the extractability of other cartilage proteins and that proteomic analyses of Matn3 V194D, Comp T585M and Comp DelD469 mouse models revealed both common and discrete disease signatures that provide novel insight into skeletal disease mechanisms and cartilage degradation.
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spelling pubmed-37440722013-08-15 Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures Bell, Peter A. Wagener, Raimund Zaucke, Frank Koch, Manuel Selley, Julian Warwood, Stacey Knight, David Boot-Handford, Raymond P. Thornton, David J. Briggs, Michael D. Biol Open Research Article Pseudoachondroplasia and multiple epiphyseal dysplasia are genetic skeletal diseases resulting from mutations in cartilage structural proteins. Electron microscopy and immunohistochemistry previously showed that the appearance of the cartilage extracellular matrix (ECM) in targeted mouse models of these diseases is disrupted; however, the precise changes in ECM organization and the pathological consequences remain unknown. Our aim was to determine the effects of matrilin-3 and COMP mutations on the composition and extractability of ECM components to inform how these detrimental changes might influence cartilage organization and degeneration. Cartilage was sequentially extracted using increasing denaturants and the extraction profiles of specific proteins determined using SDS-PAGE/Western blotting. Furthermore, the relative composition of protein pools was determined using mass spectrometry for a non-biased semi-quantitative analysis. Western blotting revealed changes in the extraction of matrilins, COMP and collagen IX in mutant cartilage. Mass spectrometry confirmed quantitative changes in the extraction of structural and non-structural ECM proteins, including proteins with roles in cellular processes such as protein folding and trafficking. In particular, genotype-specific differences in the extraction of collagens XII and XIV and tenascins C and X were identified; interestingly, increased expression of several of these genes has recently been implicated in susceptibility and/or progression of murine osteoarthritis. We demonstrated that mutation of matrilin-3 and COMP caused changes in the extractability of other cartilage proteins and that proteomic analyses of Matn3 V194D, Comp T585M and Comp DelD469 mouse models revealed both common and discrete disease signatures that provide novel insight into skeletal disease mechanisms and cartilage degradation. The Company of Biologists 2013-06-18 /pmc/articles/PMC3744072/ /pubmed/23951406 http://dx.doi.org/10.1242/bio.20135280 Text en © 2013. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Bell, Peter A.
Wagener, Raimund
Zaucke, Frank
Koch, Manuel
Selley, Julian
Warwood, Stacey
Knight, David
Boot-Handford, Raymond P.
Thornton, David J.
Briggs, Michael D.
Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures
title Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures
title_full Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures
title_fullStr Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures
title_full_unstemmed Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures
title_short Analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures
title_sort analysis of the cartilage proteome from three different mouse models of genetic skeletal diseases reveals common and discrete disease signatures
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744072/
https://www.ncbi.nlm.nih.gov/pubmed/23951406
http://dx.doi.org/10.1242/bio.20135280
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