title: Transcriptional analysis of micro-dissected articular cartilage in post-traumatic murine osteoarthritis.
abstract: 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).
  
  
  METHODS
  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.
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Old Road Campus, Roosevelt Drive, Headington, Oxford, OX3 7FY, UK. Electronic address: matthew.gardiner@kennedy.ox.ac.uk.
authors.forename: M D
authors.initials: MD
authors.lastname: Gardiner
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Old Road Campus, Roosevelt Drive, Headington, Oxford, OX3 7FY, UK. Electronic address: tonia.vincent@kennedy.ox.ac.uk.
authors.forename: T L
authors.initials: TL
authors.lastname: Vincent
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Old Road Campus, Roosevelt Drive, Headington, Oxford, OX3 7FY, UK. Electronic address: clare.driscoll@kennedy.ox.ac.uk.
authors.forename: C
authors.initials: C
authors.lastname: Driscoll
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Old Road Campus, Roosevelt Drive, Headington, Oxford, OX3 7FY, UK. Electronic address: aburleigh@rvc.ac.uk.
authors.forename: A
authors.initials: A
authors.lastname: Burleigh
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Old Road Campus, Roosevelt Drive, Headington, Oxford, OX3 7FY, UK. Electronic address: g.bou-gharios@liverpool.ac.uk.
authors.forename: G
authors.initials: G
authors.lastname: Bou-Gharios
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Old Road Campus, Roosevelt Drive, Headington, Oxford, OX3 7FY, UK. Electronic address: jeremy.saklatvala@kennedy.ox.ac.uk.
authors.forename: J
authors.initials: J
authors.lastname: Saklatvala
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Old Road Campus, Roosevelt Drive, Headington, Oxford, OX3 7FY, UK. Electronic address: hideaki.nagase@kennedy.ox.ac.uk.
authors.forename: H
authors.initials: H
authors.lastname: Nagase
authors.affiliation: Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Old Road Campus, Roosevelt Drive, Headington, Oxford, OX3 7FY, UK. Electronic address: anastasios.chanalaris@kennedy.ox.ac.uk.
authors.forename: A
authors.initials: A
authors.lastname: Chanalaris
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D000071235:Fibromodulin; D005353:Fibronectins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008592:Menisci, Tibial / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis / Q000379:methods*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D019063:Tenascin / Q000378:metabolism; D059470:Tetraspanins / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014947:Wounds and Injuries / Q000150:complications*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; D005353:Fibronectins; C000604332:Fmod protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C490089:Nbl1 protein, mouse; C485172:Ndr2 protein, mouse; D009419:Nerve Tissue Proteins; D011506:Proteins; D011509:Proteoglycans; D000072099:Serrate-Jagged Proteins; D019063:Tenascin; D059470:Tetraspanins; D016212:Transforming Growth Factor beta; C512651:Tspan2 protein, mouse; C477504:tenascin-N protein, mouse; D000071235:Fibromodulin
keywords: Destabilisation of the medial meniscus (DMM); Fibromodulin; Fibronectin; Microarray; Osteoarthritis; Tenascin