Abstract
BackgroundOsteoarthritis (OA) is one of the most common degenerative diseases of the joints worldwide, but still the pathogenesis of OA is largely unknown. The purpose of our study is to clarify key candidate genes and relevant signaling pathways in a surgical-induced OA rat model.MethodsThe microarray raw data of GSE8077 was downloaded from GEO datasets. GeoDiver were employed to screen differentially-expressed genes (DEGs). Enrichment analyses of DEGs were performed using Metascape. Construction of protein–protein interaction (PPI) network and identification of key genes were conducted using STRING, Cytoscape v3.6.0, and Centiscape2.2. Furthermore, miRDB and Cytoscape v3.6.0 were used for visualization of miRNA-mRNA regulatory network. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for predicted miRNAs was undertaken using DIANA-miRPath v3.0.ResultsSeveral DEGs (188 in comparison between OA and sham-operated group and 160 in comparison between OA and contralateral group) were identified. DEGs mainly enriched in vasculature development, regulation of cell migration, response to growth factor (Gene ontology), and ECM-receptor interaction (KEGG). Two comparison cohorts shared 79 intersection genes, and of these, Ccl2, Col4a1, Col1a1, Aldh1a3, and Itga8 were defined as the hub genes. Predicted miRNAs of seven DEGs from sub-networks mainly enriched in MAPK signaling pathway.ConclusionThe current study shows that some key genes and pathways, such as Ccl2, Col4a1, Col1a1, Aldh1a3, Itga8, ECM-receptor interaction, and MAPK signaling pathway may be associated with OA progression and act as potential biomarkers and therapeutic targets for OA.
Highlights
Osteoarthritis (OA), one of the most important causes leading to joint disability, is associated with increased social and medical burden [1, 2]
Enrichment analysis of differentially expressed genes (DEGs) DEGs in comparison between OA and sham group mainly enriched in urogenital system development, regulation of vasculogenesis, vasculature development, response to growth factor, negative regulation of cell proliferation, skeletal system development (GO), and ECM-receptor interaction (KEGG) (Fig. 3a)
DEGs in comparison between OA and contralateral group mainly enriched in muscle system process, positive regulation of cell migration, regulation of system process, response to growth factor (GO), and ECM-receptor interaction (KEGG) (Fig. 3b)
Summary
Osteoarthritis (OA), one of the most important causes leading to joint disability, is associated with increased social and medical burden [1, 2]. Bioinformatics analysis were widely used to identify DEGs and perform subsequent enrichment analyses, such as Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, which may largely promote the understanding of OA pathogenesis [14, 15]. Previous studies indicated that several ectopically expressed genes, such as AQP-1, GDF5, and TAK1, participated in the development of surgically induced OA in rat models [16,17,18]. Most of researchers merely attached importance to individual OA-related gene, which can hardly have a comprehensive understanding of corresponding molecule mechanisms, which were usually complicated and networked. Bioinformatics analysis may be a powerful way to explore these complicated regulatory networks and molecule mechanisms in a surgical-induced OA rat model. The purpose of our study is to clarify key candidate genes and relevant signaling pathways in a surgical-induced OA rat model
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
