OBJECTIVE: Identify gene changes in articular cartilage of the medial tibial plateau (MTP) at 2, 4 and 8 weeks after destabilisation of the medial meniscus (DMM) in mice. Compare our data with previously published datasets to ascertain dysregulated pathways and genes in osteoarthritis (OA). DESIGN: RNA was extracted from the ipsilateral and contralateral MTP cartilage, amplified, labelled and hybridized on Illumina WGv2 microarrays. Results were confirmed by real-time polymerase chain reaction (PCR) for selected genes. RESULTS: Transcriptional analysis and network reconstruction revealed changes in extracellular matrix and cytoskeletal genes induced by DMM. TGFβ signalling pathway and complement and coagulation cascade genes were regulated at 2 weeks. Fibronectin (Fn1) is a hub in a reconstructed network at 2 weeks. Regulated genes decrease over time. By 8 weeks fibromodulin (Fmod) and tenascin N (Tnn) are the only dysregulated genes present in the DMM operated knees. Comparison with human and rodent published gene sets identified genes overlapping between our array and eight other studies. CONCLUSIONS: Cartilage contributes a minute percentage to the RNA extracted from the whole joint (<0.2%), yet is sensitive to changes in gene expression post-DMM. The post-DMM transcriptional reprogramming wanes over time dissipating by 8 weeks. Common pathways between published gene sets include focal adhesion, regulation of actin cytoskeleton and TGFβ. Common genes include Jagged 1 (Jag1), Tetraspanin 2 (Tspan2), neuroblastoma, suppression of tumourigenicity 1 (Nbl1) and N-myc downstream regulated gene 2 (Ndrg2). The concomitant genes and pathways we identify may warrant further investigation as biomarkers or modulators of OA.
616 - 628
Destabilisation of the medial meniscus (DMM), Fibromodulin, Fibronectin, Microarray, Osteoarthritis, Tenascin, Adaptor Proteins, Signal Transducing, Animals, Calcium-Binding Proteins, Cartilage, Articular, Cell Cycle Proteins, Disease Models, Animal, Extracellular Matrix Proteins, Fibromodulin, Fibronectins, Intercellular Signaling Peptides and Proteins, Jagged-1 Protein, Male, Membrane Proteins, Menisci, Tibial, Mice, Mice, Inbred C57BL, Microarray Analysis, Nerve Tissue Proteins, Osteoarthritis, Knee, Proteins, Proteoglycans, Serrate-Jagged Proteins, Signal Transduction, Tenascin, Tetraspanins, Transcription, Genetic, Transforming Growth Factor beta, Wounds and Injuries