Identification of the pathogenic pathways in osteoarthritic hip cartilage: commonality and discord between hip and knee OA.
OBJECTIVE
To define for the first time the transcriptomes of normal and end-stage osteoarthritis (OA) hip cartilage.


METHODS
RNA was isolated from cartilage within 2h 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.
Musculoskeletal Research Group, Institute of Cellular Medicine, 4th Floor, Cookson Building, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Y
Y
Xu
M J
MJ
Barter
D C
DC
Swan
K S
KS
Rankin
A D
AD
Rowan
M
M
Santibanez-Koref
J
J
Loughlin
D A
DA
Young
D000368:Aged; D002358:Cartilage, Articular / Q000378:metabolism*; D005260:Female; D006801:Humans; D015207:Osteoarthritis, Hip / Q000235:genetics*; D020370:Osteoarthritis, Knee / Q000235:genetics*; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics*; D060449:Wnt Signaling Pathway
D012313:RNA