PT - JOURNAL ARTICLE AU - Graham R. S. Ritchie AU - Theodoros I. Roumeliotis AU - Julia Steinberg AU - Abbie L. A. Binch AU - Rachael Coyle AU - Mercedes Pardo AU - Christine L. Le Maitre AU - Jyoti S. Choudhary AU - J. Mark Wilkinson AU - Eleftheria Zeggini TI - Integrated molecular phenotyping identifies genes and pathways disrupted in osteoarthritis AID - 10.1101/038067 DP - 2016 Jan 01 TA - bioRxiv PG - 038067 4099 - http://biorxiv.org/content/early/2016/01/28/038067.short 4100 - http://biorxiv.org/content/early/2016/01/28/038067.full AB - Osteoarthritis (OA) is a degenerative joint disease with substantial global health economic burden and no curative therapy. Here we investigate genes and pathways underpinning disease progression, combining methylation typing, RNA sequencing and quantitative proteomics in chondrocytes from matched damaged and healthy articular cartilage samples from OA patients undergoing knee replacement surgery. Our data highlight 49 genes differentially regulated at multiple levels, identifying 19 novel genes with a potential role in OA progression. An integrated pathway analysis identifies established and emerging biological processes. We perform an in silico search for drugs predicted to target the differentially regulated factors and identify several established therapeutic compounds which now warrant further investigation in OA. Overall this work provides a first integrated view of the molecular landscape of human primary chondrocytes and offers insights into the mechanisms of cartilage degeneration. The results point to new therapeutic avenues, highlighting the translational potential of integrated functional genomics. All data from these experiments are freely available for access in the appropriate repositories.