Genes involved in the osteoarthritis process identified through genome wide expression analysis in articular cartilage; the RAAK study

PLoS One. 2014 Jul 23;9(7):e103056. doi: 10.1371/journal.pone.0103056. eCollection 2014.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology*
  • Cohort Studies
  • Female
  • Gene Expression Regulation
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis / genetics*
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology*
  • Protein Interaction Maps
  • Transcriptome*

Grant support

This study was supported by the Leiden University Medical Center, the Dutch Arthritis Association, the Centre of Medical System Biology and the Netherlands Consortium for Healthy Ageing both in the framework of the Netherlands Genomics Initiative (NGI). The authors also acknowledge support by TreatOA which is funded by the European Commission framework 7 program (PF7/2007) under grant agreement no. 200800, and the European Union’s Seventh Framework Program (FP7/2007-2011) under grant agreement n° 259679. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.