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Many studies have identified potential therapeutic targets, yet no effective treatment has been determined. The aim of this study was to identify and rank osteoarthritis-associated genes and micro-RNAs to prioritise those most integral to the disease. A systematic meta-analysis of differentially expressed mRNA and micro-RNAs in human osteoarthritic cartilage was conducted. Ingenuity pathway analysis identified cellular senescence as an enriched pathway, confirmed by a significant overlap (p &lt; 0.01) with cellular senescence drivers (CellAge Database). A co-expression network was built using genes from the meta-analysis as seed nodes and combined with micro-RNA targets and SNP datasets to construct a multi-source information network. This accumulated and connected 1689 genes which were ranked based on node and edge aggregated scores. These bioinformatic analyses were confirmed at the protein level by mass spectrometry of the different zones of human osteoarthritic cartilage (superficial, middle, and deep) compared to normal controls. This analysis, and subsequent experimental confirmation, revealed five novel osteoarthritis-associated proteins (PPIB, ASS1, LHDB, TPI1, and ARPC4-TTLL3). Focusing future studies on these novel targets may lead to new therapies for osteoarthritis.<\/jats:p>","DOI":"10.3390\/ijms23084395","type":"journal-article","created":{"date-parts":[[2022,4,18]],"date-time":"2022-04-18T04:21:28Z","timestamp":1650255688000},"page":"4395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Identifying Novel Osteoarthritis-Associated Genes in Human Cartilage Using a Systematic Meta-Analysis and a Multi-Source Integrated Network"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9431-3742","authenticated-orcid":false,"given":"Emily","family":"Shorter","sequence":"first","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4997-9953","authenticated-orcid":false,"given":"Roberto","family":"Avelar","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8950-4077","authenticated-orcid":false,"given":"Margarita","family":"Zachariou","sequence":"additional","affiliation":[{"name":"Bioinformatics Department, The Cyprus Institute of Neurology & Genetics, Nicosia 23462, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2470-3363","authenticated-orcid":false,"given":"George M.","family":"Spyrou","sequence":"additional","affiliation":[{"name":"Bioinformatics Department, The Cyprus Institute of Neurology & Genetics, Nicosia 23462, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Raina","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aibek","family":"Smagul","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalda","family":"Ashraf Kharaz","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy","family":"Peffers","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasia","family":"Goljanek-Whysall","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK"},{"name":"Department of Physiology, School of Medicine, The Regenerative Medicine Institute (REMEDI), NUI Galway, H91 TK33 Galway, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6363-2465","authenticated-orcid":false,"given":"Jo\u00e3o Pedro","family":"de Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blandine","family":"Poulet","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,15]]},"reference":[{"key":"ref_1","first-page":"37","article-title":"Osteoarthritis pathogenesis\u2014A complex process that involves the entire joint","volume":"7","author":"Lu","year":"2014","journal-title":"J. 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