title: Genes involved in the osteoarthritis process identified through genome wide expression analysis in articular cartilage; the RAAK study.
abstract: OBJECTIVE
  Identify gene expression profiles associated with OA processes in articular cartilage and determine pathways changing during the disease process.
  
  
  METHODS
  Genome wide gene expression was determined in paired samples of OA affected and preserved cartilage of the same joint using microarray analysis for 33 patients of the RAAK study. Results were replicated in independent samples by RT-qPCR and immunohistochemistry. Profiles were analyzed with the online analysis tools DAVID and STRING to identify enrichment for specific pathways and protein-protein interactions.
  
  
  RESULTS
  Among the 1717 genes that were significantly differently expressed between OA affected and preserved cartilage we found significant enrichment for genes involved in skeletal development (e.g. TNFRSF11B and FRZB). Also several inflammatory genes such as CD55, PTGES and TNFAIP6, previously identified in within-joint analyses as well as in analyses comparing preserved cartilage from OA affected joints versus healthy cartilage were among the top genes. Of note was the high up-regulation of NGF in OA cartilage. RT-qPCR confirmed differential expression for 18 out of 19 genes with expression changes of 2-fold or higher, and immunohistochemistry of selected genes showed a concordant change in protein expression. Most of these changes associated with OA severity (Mankin score) but were independent of joint-site or sex.
  
  
  CONCLUSIONS
  We provide further insights into the ongoing OA pathophysiological processes in cartilage, in particular into differences in macroscopically intact cartilage compared to OA affected cartilage, which seem relatively consistent and independent of sex or joint. We advocate that development of treatment could benefit by focusing on these similarities in gene expression changes and/or pathways.
authors: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; The Netherlands Genomics Initiative, sponsored by the NCHA, Leiden-Rotterdam, The Netherlands.
authors: Yolande F M
authors: YF
authors: Ramos
authors: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Wouter
authors: W
authors: den Hollander
authors: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Judith V M G
authors: JV
authors: Bovée
authors: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Nils
authors: N
authors: Bomer
authors: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Ruud
authors: R
authors: van der Breggen
authors: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Nico
authors: N
authors: Lakenberg
authors: Department of Orthopeadics, Leiden University Medical Center, Leiden, The Netherlands.
authors: J Christiaan
authors: JC
authors: Keurentjes
authors: Department of Biostatistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Jelle J
authors: JJ
authors: Goeman
authors: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; The Netherlands Genomics Initiative, sponsored by the NCHA, Leiden-Rotterdam, The Netherlands.
authors: P Eline
authors: PE
authors: Slagboom
authors: Department of Orthopeadics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Rob G H H
authors: RG
authors: Nelissen
authors: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; The Netherlands Genomics Initiative, sponsored by the NCHA, Leiden-Rotterdam, The Netherlands.
authors: Steffan D
authors: SD
authors: Bos
authors: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; The Netherlands Genomics Initiative, sponsored by the NCHA, Leiden-Rotterdam, The Netherlands.
authors: Ingrid
authors: I
authors: Meulenbelt
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D060066:Protein Interaction Maps; D059467:Transcriptome