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Metabolic Signature of Articular Cartilage Following Mechanical Injury: An Integrated Transcriptomics and Metabolomics Analysis

Mechanical injury to the articular cartilage is a key risk factor in joint damage and predisposition to osteoarthritis. Integrative multi-omics approaches provide a valuable tool to understand tissue behavior in response to mechanical injury insult and help to identify key pathways linking injury to...

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Autores principales: Southan, Jennifer, McHugh, Emily, Walker, Heather, Ismail, Heba M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773849/
https://www.ncbi.nlm.nih.gov/pubmed/33392255
http://dx.doi.org/10.3389/fmolb.2020.592905
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author Southan, Jennifer
McHugh, Emily
Walker, Heather
Ismail, Heba M.
author_facet Southan, Jennifer
McHugh, Emily
Walker, Heather
Ismail, Heba M.
author_sort Southan, Jennifer
collection PubMed
description Mechanical injury to the articular cartilage is a key risk factor in joint damage and predisposition to osteoarthritis. Integrative multi-omics approaches provide a valuable tool to understand tissue behavior in response to mechanical injury insult and help to identify key pathways linking injury to tissue damage. Global or untargeted metabolomics provides a comprehensive characterization of the metabolite content of biological samples. In this study, we aimed to identify the metabolic signature of cartilage tissue post injury. We employed an integrative analysis of transcriptomics and global metabolomics of murine epiphyseal hip cartilage before and after injury. Transcriptomics analysis showed a significant enrichment of gene sets involved in regulation of metabolic processes including carbon metabolism, biosynthesis of amino acids, and steroid biosynthesis. Integrative analysis of enriched genes with putatively identified metabolite features post injury showed a significant enrichment for carbohydrate metabolism (glycolysis, galactose, and glycosylate metabolism and pentose phosphate pathway) and amino acid metabolism (arginine biosynthesis and tyrosine, glycine, serine, threonine, and arginine and proline metabolism). We then performed a cross analysis of global metabolomics profiles of murine and porcine ex vivo cartilage injury models. The top commonly modulated metabolic pathways post injury included arginine and proline metabolism, arginine biosynthesis, glycolysis/gluconeogenesis, and vitamin B6 metabolic pathways. These results highlight the significant modulation of metabolic responses following mechanical injury to articular cartilage. Further investigation of these pathways would provide new insights into the role of the early metabolic state of articular cartilage post injury in promoting tissue damage and its link to disease progression of osteoarthritis.
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spelling pubmed-77738492021-01-01 Metabolic Signature of Articular Cartilage Following Mechanical Injury: An Integrated Transcriptomics and Metabolomics Analysis Southan, Jennifer McHugh, Emily Walker, Heather Ismail, Heba M. Front Mol Biosci Molecular Biosciences Mechanical injury to the articular cartilage is a key risk factor in joint damage and predisposition to osteoarthritis. Integrative multi-omics approaches provide a valuable tool to understand tissue behavior in response to mechanical injury insult and help to identify key pathways linking injury to tissue damage. Global or untargeted metabolomics provides a comprehensive characterization of the metabolite content of biological samples. In this study, we aimed to identify the metabolic signature of cartilage tissue post injury. We employed an integrative analysis of transcriptomics and global metabolomics of murine epiphyseal hip cartilage before and after injury. Transcriptomics analysis showed a significant enrichment of gene sets involved in regulation of metabolic processes including carbon metabolism, biosynthesis of amino acids, and steroid biosynthesis. Integrative analysis of enriched genes with putatively identified metabolite features post injury showed a significant enrichment for carbohydrate metabolism (glycolysis, galactose, and glycosylate metabolism and pentose phosphate pathway) and amino acid metabolism (arginine biosynthesis and tyrosine, glycine, serine, threonine, and arginine and proline metabolism). We then performed a cross analysis of global metabolomics profiles of murine and porcine ex vivo cartilage injury models. The top commonly modulated metabolic pathways post injury included arginine and proline metabolism, arginine biosynthesis, glycolysis/gluconeogenesis, and vitamin B6 metabolic pathways. These results highlight the significant modulation of metabolic responses following mechanical injury to articular cartilage. Further investigation of these pathways would provide new insights into the role of the early metabolic state of articular cartilage post injury in promoting tissue damage and its link to disease progression of osteoarthritis. Frontiers Media S.A. 2020-12-17 /pmc/articles/PMC7773849/ /pubmed/33392255 http://dx.doi.org/10.3389/fmolb.2020.592905 Text en Copyright © 2020 Southan, McHugh, Walker and Ismail. 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 Molecular Biosciences
Southan, Jennifer
McHugh, Emily
Walker, Heather
Ismail, Heba M.
Metabolic Signature of Articular Cartilage Following Mechanical Injury: An Integrated Transcriptomics and Metabolomics Analysis
title Metabolic Signature of Articular Cartilage Following Mechanical Injury: An Integrated Transcriptomics and Metabolomics Analysis
title_full Metabolic Signature of Articular Cartilage Following Mechanical Injury: An Integrated Transcriptomics and Metabolomics Analysis
title_fullStr Metabolic Signature of Articular Cartilage Following Mechanical Injury: An Integrated Transcriptomics and Metabolomics Analysis
title_full_unstemmed Metabolic Signature of Articular Cartilage Following Mechanical Injury: An Integrated Transcriptomics and Metabolomics Analysis
title_short Metabolic Signature of Articular Cartilage Following Mechanical Injury: An Integrated Transcriptomics and Metabolomics Analysis
title_sort metabolic signature of articular cartilage following mechanical injury: an integrated transcriptomics and metabolomics analysis
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773849/
https://www.ncbi.nlm.nih.gov/pubmed/33392255
http://dx.doi.org/10.3389/fmolb.2020.592905
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