title: Molecular mechanisms of osteoarthritis using gene microarrays.
abstract: This study aimed to investigate the molecular mechanisms of osteoarthritis (OA) by microarray analysis. Three gene expression datasets GSE1919, 19664 and 55235 were downloaded from the Gene Expression Omnibus, and data of OA samples and healthy controls were used. After data preprocessing, differential expression analysis between the OA group and controls was performed using LIMMA (Linear Models for Microarray Data) package and genes with |log2FC (fold change)|>1 and P<0.05 were screened as DEGs (differentially expressed genes). The screened DEGs were then subject to functional annotation and pathway enrichment analysis using DAVID (Database for Annotation Visualization and Integrated Discovery). Next, gene-set enrichment analysis was performed using Enrichment map Cytoscape plug-in, followed by detecting sub-networks using clusterONE. Finally, risk subpathways were screened using iSubpathwayMiner package. A total of 141 DEGs were screened, including 52 up-regulated ones and 89 down-regulated ones. These DEGs were enriched in 48 GO terms that were mainly related to locomotory behavior, taxis, adhesion, and 11 pathways that were related to cytokine-cytokine receptor interaction, ECM-receptor interaction, focal adhesion, as well as several signaling pathways. The enrichment map enriched gene-sets mainly related to cell death and apoptosis, and extracellular components. The risk pathways up-regulated DEGs were exclusively related to arachidonic acid metabolism and glycosphingolipid biosynthesis, and the top two risk pathways were tyrosine metabolism for the down-regulated ones. From this study we conclude that genes involved in cell death and apoptosis, as well as cell-extracellular matrix interaction, may be essential for OA pathogenesis by altering multiple signaling pathways.
authors.affiliation: Microsurgical Ward Section, The First Affiliated Hospital of the Henan University of Science and Technology, Jinghua Road No. 24, Luoyang 471000, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Cui
authors.affiliation: Microsurgical Ward Section, The First Affiliated Hospital of the Henan University of Science and Technology, Jinghua Road No. 24, Luoyang 471000, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Microsurgical Ward Section, The First Affiliated Hospital of the Henan University of Science and Technology, Jinghua Road No. 24, Luoyang 471000, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Hai
authors.affiliation: Microsurgical Ward Section, The First Affiliated Hospital of the Henan University of Science and Technology, Jinghua Road No. 24, Luoyang 471000, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.affiliation: Microsurgical Ward Section, The First Affiliated Hospital of the Henan University of Science and Technology, Jinghua Road No. 24, Luoyang 471000, China.
authors.forename: Yongcai
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Microsurgical Ward Section, The First Affiliated Hospital of the Henan University of Science and Technology, Jinghua Road No. 24, Luoyang 471000, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Microsurgical Ward Section, The First Affiliated Hospital of the Henan University of Science and Technology, Jinghua Road No. 24, Luoyang 471000, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Tong
authors.affiliation: Microsurgical Ward Section, The First Affiliated Hospital of the Henan University of Science and Technology, Jinghua Road No. 24, Luoyang 471000, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Lu
authors.affiliation: Microsurgical Ward Section, The First Affiliated Hospital of the Henan University of Science and Technology, Jinghua Road No. 24, Luoyang 471000, China. Electronic address: ozjiangyuan@163.com.
authors.forename: Zhengjiang
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D030541:Databases, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000235:genetics* / Q000378:metabolism*
keywords: Differentially expressed genes; Functional annotation; Gene-set enrichment analysis; Osteoarthritis; Screening of risk subpathways