OBJECTIVE: To identify osteoarthritis (OA) relevant genes and pathways in damaged and undamaged cartilage isolated from the knees of patients with anteromedial gonarthrosis (AMG) - a specific form of knee OA. DESIGN: Cartilage was obtained from nine patients undergoing unicompartmental knee replacement (UKR) for AMG. AMG provides a spatial representation of OA progression; showing a reproducible and histologically validated pattern of cartilage destruction such that damaged and undamaged cartilage from within the same knee can be consistently isolated and examined. Gene expression was analysed by microarray and validated using real-time PCR. RESULTS: Damaged and undamaged cartilage showed distinct gene expression profiles. 754 genes showed significant up- or down-regulation (non-False discovery rate (FDR) P < 0.05) with enrichment for genes involved in cell signalling, Extracellular Matrix (ECM) and inflammatory response. A number of genes previously unreported in OA showed strongly altered expression including RARRES3, ADAMTSL2 and DUSP10. Confirmation of genes previously identified as modulated in OA was also obtained e.g., SFRP3, MMP3 and IGF1. CONCLUSIONS: This is the first study to examine a common and consistent phenotype of OA to allow direct comparison of damaged and undamaged cartilage from within the same joint compartment. We have identified specific gene expression profiles in damaged and undamaged cartilage and have determined relevant genes and pathways in OA progression. Importantly this work also highlights the necessity for phenotypic and microanatomical characterization of cartilage in future studies of OA pathogenesis and therapeutic development.
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Cartilage, Gene expression, Knee, Microarray, Signalling, Aged, Arthroplasty, Replacement, Knee, Cartilage, Articular, Disease Progression, Female, Gene Expression Profiling, Gene Expression Regulation, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Osteoarthritis, Knee, Phenotype, Real-Time Polymerase Chain Reaction, Transcriptome