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

2012; Elsevier BV; Volume: 20; Issue: 9 Linguagem: Inglês

10.1016/j.joca.2012.05.006

1522-9653

Yaobo Xu, Matt J. Barter, Daniel Swan, Kenneth S. Rankin, Andrew D. Rowan, Mauro Santibanez‐Koref, John Loughlin, David A. Young,

Inflammatory mediators and NSAID effects

ObjectiveTo define for the first time the transcriptomes of normal and end-stage osteoarthritis (OA) hip cartilage.Materials and methodsRNA 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.ResultsIn 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 dataset20Karlsson C. Dehne T. Lindahl A. Brittberg M. Pruss A. Sittinger M. et al.Genome-wide expression profiling reveals new candidate genes associated with osteoarthritis.Osteoarthritis Cartilage. 2010; 18: 581-592Abstract Full Text Full Text PDF PubMed Scopus (194) Google Scholar only identified 229 genes similarly differentially expressed although remarkably 34 canonical pathways overlapped between experiments.ConclusionsThis 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.