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Identification of the pathogenic pathways in osteoarthritic hip cartilage: commonality and discord between hip and knee OA

Lookup NU author(s): Yaobo Xu, Dr Matthew Barter, Dr Daniel Swan, Dr Kenneth RankinORCiD, Emeritus Professor Drew Rowan, Dr Mauro Santibanez Koref, Professor John LoughlinORCiD, Professor David YoungORCiD

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Abstract

Objective: To define for the first time the transcriptomes of normal and end-stage osteoarthritis (OA) hip cartilage. Materials and methods: RNA was isolated from cartilage within 2 h of joint replacement surgery. Gene expression was analyzed using Agilent GeneSpring GX 11 following hybridization to Illumina Human HT-12 V3 microarrays. Real-time reverse-transcription polymerase chain reaction (RT-PCR) was used to validate the expression of six genes identified by microarray as differentially expressed. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) were used to investigate enriched functions or canonical pathways amongst differentially expressed genes respectively. Results: In total we identified 998 differentially expressed genes (fold change >= +/- 1.5, P-value <= 0.01) between neck of femur fracture (NOF) (n = 10) and OA hip (n = 9) patient cartilage. These differentially expressed genes were enriched within 71 canonical pathways. A comparison between a comparable knee dataset(20) only identified 229 genes similarly differentially expressed although remarkably 34 canonical pathways overlapped between experiments. Conclusions: This study is the first to report a comprehensive gene expression analysis of human hip OA cartilage compared to control (NOF) cartilage at the whole-genome level. Our differential gene expression dataset shows excellent correlation with similar defined studies using comparable tissue but reveals discord between hip and knee OA at the individual gene status but with commonality with regards the molecular pathways involved. (c) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.


Publication metadata

Author(s): Xu Y, Barter MJ, Swan DC, Rankin KS, Rowan AD, Santibanez-Koref M, Loughlin J, Young DA

Publication type: Article

Publication status: Published

Journal: Osteoarthritis and Cartilage

Year: 2012

Volume: 20

Issue: 9

Pages: 1029-1038

Print publication date: 01/09/2012

ISSN (print): 1063-4584

ISSN (electronic): 1522-9653

Publisher: Elsevier Ltd

URL: http://dx.doi.org/10.1016/j.joca.2012.05.006

DOI: 10.1016/j.joca.2012.05.006


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Funding

Funder referenceFunder name
JGW Patterson Foundation
Northumberland, Tyne
Wear Comprehensive Local Research Network
Newcastle University Hospitals Special Trustees, UK
UK NIHR Biomedical Research Centre for Ageing and Age Related Disease Award
19485Arthritis Research UK grant

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