Identifying Novel Osteoarthritis-Associated Genes in Human Cartilage Using a Systematic Meta-Analysis and a Multi-Source Integrated Network



Shorter, Emily, Avelar, Roberto ORCID: 0000-0003-4997-9953, Zachariou, Margarita, Spyrou, George M, Raina, Priyanka, Smagul, Aibek, Ashraf Kharaz, Yalda ORCID: 0000-0003-4925-0206, Peffers, Mandy ORCID: 0000-0001-6979-0440, Goljanek-Whysall, Kasia, de Magalhães, João Pedro
et al (show 1 more authors) (2022) Identifying Novel Osteoarthritis-Associated Genes in Human Cartilage Using a Systematic Meta-Analysis and a Multi-Source Integrated Network. International Journal of Molecular Sciences, 23 (8). 4395 - 4395.

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Abstract

<jats:p>Osteoarthritis, the most common joint disorder, is characterised by deterioration of the articular cartilage. 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>

Item Type: Article
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 20 Apr 2022 10:17
Last Modified: 19 Aug 2022 13:10
DOI: 10.3390/ijms23084395
Open Access URL: https://www.mdpi.com/1422-0067/23/8/4395
URI: https://livrepository.liverpool.ac.uk/id/eprint/3153438