Integrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis

Abstract Osteoarthritis (OA) is a common disease characterized by cartilage degeneration and joint remodeling. The underlying molecular changes underpinning disease progression are incompletely understood. We investigated genes and pathways that mark OA progression in isolated primary chondrocytes t...

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Autores principales:	Julia Steinberg, Graham R. S. Ritchie, Theodoros I. Roumeliotis, Raveen L. Jayasuriya, Matthew J. Clark, Roger A. Brooks, Abbie L. A. Binch, Karan M. Shah, Rachael Coyle, Mercedes Pardo, Christine L. Le Maitre, Yolande F. M. Ramos, Rob G. H. H. Nelissen, Ingrid Meulenbelt, Andrew W. McCaskie, Jyoti S. Choudhary, J. Mark Wilkinson, Eleftheria Zeggini
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1131f568f3274d8e84be794049aae9e8
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spelling	oai:doaj.org-article:1131f568f3274d8e84be794049aae9e82021-12-02T15:05:38ZIntegrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis10.1038/s41598-017-09335-62045-2322https://doaj.org/article/1131f568f3274d8e84be794049aae9e82017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09335-6https://doaj.org/toc/2045-2322Abstract Osteoarthritis (OA) is a common disease characterized by cartilage degeneration and joint remodeling. The underlying molecular changes underpinning disease progression are incompletely understood. We investigated genes and pathways that mark OA progression in isolated primary chondrocytes taken from paired intact versus degraded articular cartilage samples across 38 patients undergoing joint replacement surgery (discovery cohort: 12 knee OA, replication cohorts: 17 knee OA, 9 hip OA patients). We combined genome-wide DNA methylation, RNA sequencing, and quantitative proteomics data. We identified 49 genes differentially regulated between intact and degraded cartilage in at least two –omics levels, 16 of which have not previously been implicated in OA progression. Integrated pathway analysis implicated the involvement of extracellular matrix degradation, collagen catabolism and angiogenesis in disease progression. Using independent replication datasets, we showed that the direction of change is consistent for over 90% of differentially expressed genes and differentially methylated CpG probes. AQP1, COL1A1 and CLEC3B were significantly differentially regulated across all three –omics levels, confirming their differential expression in human disease. Through integration of genome-wide methylation, gene and protein expression data in human primary chondrocytes, we identified consistent molecular players in OA progression that replicated across independent datasets and that have translational potential.Julia SteinbergGraham R. S. RitchieTheodoros I. RoumeliotisRaveen L. JayasuriyaMatthew J. ClarkRoger A. BrooksAbbie L. A. BinchKaran M. ShahRachael CoyleMercedes PardoChristine L. Le MaitreYolande F. M. RamosRob G. H. H. NelissenIngrid MeulenbeltAndrew W. McCaskieJyoti S. ChoudharyJ. Mark WilkinsonEleftheria ZegginiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julia Steinberg Graham R. S. Ritchie Theodoros I. Roumeliotis Raveen L. Jayasuriya Matthew J. Clark Roger A. Brooks Abbie L. A. Binch Karan M. Shah Rachael Coyle Mercedes Pardo Christine L. Le Maitre Yolande F. M. Ramos Rob G. H. H. Nelissen Ingrid Meulenbelt Andrew W. McCaskie Jyoti S. Choudhary J. Mark Wilkinson Eleftheria Zeggini Integrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis
description	Abstract Osteoarthritis (OA) is a common disease characterized by cartilage degeneration and joint remodeling. The underlying molecular changes underpinning disease progression are incompletely understood. We investigated genes and pathways that mark OA progression in isolated primary chondrocytes taken from paired intact versus degraded articular cartilage samples across 38 patients undergoing joint replacement surgery (discovery cohort: 12 knee OA, replication cohorts: 17 knee OA, 9 hip OA patients). We combined genome-wide DNA methylation, RNA sequencing, and quantitative proteomics data. We identified 49 genes differentially regulated between intact and degraded cartilage in at least two –omics levels, 16 of which have not previously been implicated in OA progression. Integrated pathway analysis implicated the involvement of extracellular matrix degradation, collagen catabolism and angiogenesis in disease progression. Using independent replication datasets, we showed that the direction of change is consistent for over 90% of differentially expressed genes and differentially methylated CpG probes. AQP1, COL1A1 and CLEC3B were significantly differentially regulated across all three –omics levels, confirming their differential expression in human disease. Through integration of genome-wide methylation, gene and protein expression data in human primary chondrocytes, we identified consistent molecular players in OA progression that replicated across independent datasets and that have translational potential.
format	article
author	Julia Steinberg Graham R. S. Ritchie Theodoros I. Roumeliotis Raveen L. Jayasuriya Matthew J. Clark Roger A. Brooks Abbie L. A. Binch Karan M. Shah Rachael Coyle Mercedes Pardo Christine L. Le Maitre Yolande F. M. Ramos Rob G. H. H. Nelissen Ingrid Meulenbelt Andrew W. McCaskie Jyoti S. Choudhary J. Mark Wilkinson Eleftheria Zeggini
author_facet	Julia Steinberg Graham R. S. Ritchie Theodoros I. Roumeliotis Raveen L. Jayasuriya Matthew J. Clark Roger A. Brooks Abbie L. A. Binch Karan M. Shah Rachael Coyle Mercedes Pardo Christine L. Le Maitre Yolande F. M. Ramos Rob G. H. H. Nelissen Ingrid Meulenbelt Andrew W. McCaskie Jyoti S. Choudhary J. Mark Wilkinson Eleftheria Zeggini
author_sort	Julia Steinberg
title	Integrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis
title_short	Integrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis
title_full	Integrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis
title_fullStr	Integrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis
title_full_unstemmed	Integrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis
title_sort	integrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1131f568f3274d8e84be794049aae9e8
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Integrative epigenomics, transcriptomics and proteomics of patient chondrocytes reveal genes and pathways involved in osteoarthritis

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