PMID- 25545425 OWN - NLM STAT- MEDLINE DCOM- 20151215 LR - 20220321 IS - 1522-9653 (Electronic) IS - 1063-4584 (Print) IS - 1063-4584 (Linking) VI - 23 IP - 4 DP - 2015 Apr TI - Transcriptional analysis of micro-dissected articular cartilage in post-traumatic murine osteoarthritis. PG - 616-28 LID - S1063-4584(14)01387-9 [pii] LID - 10.1016/j.joca.2014.12.014 [doi] AB - 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. TGFbeta 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 TGFbeta. 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. CI - Copyright (c) 2014 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Gardiner, M D AU - Gardiner MD AD - 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. FAU - Vincent, T L AU - Vincent TL AD - 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. FAU - Driscoll, C AU - Driscoll C AD - 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. FAU - Burleigh, A AU - Burleigh A AD - 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. FAU - Bou-Gharios, G AU - Bou-Gharios G AD - 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. FAU - Saklatvala, J AU - Saklatvala J AD - 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. FAU - Nagase, H AU - Nagase H AD - 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. FAU - Chanalaris, A AU - Chanalaris A AD - 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. LA - eng GR - MR/K006312/1/MRC_/Medical Research Council/United Kingdom GR - 088844/Z/09/Z/WT_/Wellcome Trust/United Kingdom GR - AR40994/AR/NIAMS NIH HHS/United States GR - ARC_/Arthritis Research UK/United Kingdom PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20141226 PL - England TA - Osteoarthritis Cartilage JT - Osteoarthritis and cartilage JID - 9305697 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Calcium-Binding Proteins) RN - 0 (Cell Cycle Proteins) RN - 0 (Extracellular Matrix Proteins) RN - 0 (FMOD protein, human) RN - 0 (Fibronectins) RN - 0 (Fmod protein, mouse) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (JAG1 protein, human) RN - 0 (Jag1 protein, mouse) RN - 0 (Jagged-1 Protein) RN - 0 (Membrane Proteins) RN - 0 (Nbl1 protein, mouse) RN - 0 (Ndr2 protein, mouse) RN - 0 (Nerve Tissue Proteins) RN - 0 (Proteins) RN - 0 (Proteoglycans) RN - 0 (Serrate-Jagged Proteins) RN - 0 (Tenascin) RN - 0 (Tetraspanins) RN - 0 (Transforming Growth Factor beta) RN - 0 (Tspan2 protein, mouse) RN - 0 (tenascin-N protein, mouse) RN - 126468-95-9 (Fibromodulin) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Animals MH - Calcium-Binding Proteins/metabolism MH - Cartilage, Articular/*metabolism/pathology MH - Cell Cycle Proteins MH - Disease Models, Animal MH - Extracellular Matrix Proteins/metabolism MH - Fibromodulin MH - Fibronectins/metabolism MH - Intercellular Signaling Peptides and Proteins/metabolism MH - Jagged-1 Protein MH - Male MH - Membrane Proteins/metabolism MH - Menisci, Tibial/*metabolism/pathology MH - Mice MH - Mice, Inbred C57BL MH - Microarray Analysis/*methods MH - Nerve Tissue Proteins/metabolism MH - Osteoarthritis, Knee/*etiology/*metabolism/pathology MH - Proteins/metabolism MH - Proteoglycans/metabolism MH - Serrate-Jagged Proteins MH - Signal Transduction/genetics/*physiology MH - Tenascin/metabolism MH - Tetraspanins/metabolism MH - Transcription, Genetic/*physiology MH - Transforming Growth Factor beta/metabolism MH - Wounds and Injuries/*complications PMC - PMC4373757 OTO - NOTNLM OT - Destabilisation of the medial meniscus (DMM) OT - Fibromodulin OT - Fibronectin OT - Microarray OT - Osteoarthritis OT - Tenascin EDAT- 2014/12/30 06:00 MHDA- 2015/12/17 06:00 PMCR- 2015/04/01 CRDT- 2014/12/30 06:00 PHST- 2014/06/04 00:00 [received] PHST- 2014/12/03 00:00 [revised] PHST- 2014/12/16 00:00 [accepted] PHST- 2014/12/30 06:00 [entrez] PHST- 2014/12/30 06:00 [pubmed] PHST- 2015/12/17 06:00 [medline] PHST- 2015/04/01 00:00 [pmc-release] AID - S1063-4584(14)01387-9 [pii] AID - 10.1016/j.joca.2014.12.014 [doi] PST - ppublish SO - Osteoarthritis Cartilage. 2015 Apr;23(4):616-28. doi: 10.1016/j.joca.2014.12.014. Epub 2014 Dec 26.