The identification of key genes and Pathways in Osteoarthritis-related Inflammatory Synoviocytes by Bioinformatics Analysis

Abstract Background: Osteoarthritis (OA) is characterized as sustained synovial inflammation and progressive cartilage degradation, in which inflammatory synoviocytes play a pivotal role. The purpose is to define key genes and relevant pathways in inflammatory synoviocytes in vivo and vitro. In the current study, the differentially expressed genes from GSE46750 and GSE82107 gene data were overlapped to show the intersection genes in inflammatory synoviocytes in vivo, and from GSE49604 and GSE82107 gene data were used in vitro. Meanwhile, the enrichment analyses and protein-protein interaction were confirmed in the two overlapped DEGs, respectively. Subsequently, meta- enrichment analysis was also performed to discriminate the differences between synoviocytes in vivo and vitro. Finally, analysis of miRNA network and associated pathways in overlapped genes in vitro and vivo were also finished. Results: A total of 36 intersection DEGs, enriched in ‘cell response to oxidative stress’, ‘response to lipopolysaccharide’ and ‘tumor necrosis factor signaling pathway’, were identified in inflammatory synoviocytes in vivo, as well as 35 overlapped DEGs, enriched in ‘mineral absorption’, ‘response to lipopolysaccharide’ and ‘oxidation-reduction process’, were identified in vitro. Additionally, in the meta-enrichment analysis, the results suggested that DEGs in vivo and vitro collectively enriched in ‘immune response’, ‘response to LPS’, ‘chemokine signaling pathway’ and ‘TNF signaling pathway’. However, the ‘regulation of macrophage activation’, ‘positive regulation of neutrophil chemotaxis’, ‘positive regulation of leukocyte chemotaxis’ and ‘leukocyte migration’ were individually enriched in the DEGs from inflammatory synoviocytes in vivo. Finally, the two comparison cohorts shared five intersection genes, including C-X-C chemokine ligand (CXCL) 2, CXCL5, chloride intracellular channel (CLIC) 6, solute carrier family 7 member 2 (SLC7A2) and chromosome 15 open reading frame 48 (C15orf48), and predicted miRNAs mainly enriched in transforming growth factor (TGF)-β, Ras and Wnt signaling pathway. Conclusion: The study demonstrated that OA-related inflammatory synoviocytes is associated with immune response, TNF signaling pathway, chemokine signaling pathway and oxidation-related process. However, compared to inflammatory model in vitro, in OA joint, the synovial inflammation is more complicated, maybe involved neutrophil recruitment, monocyte migration, and macrophage activation. Additionally, the current study also shown that some key genes CLIC6, CXCL2, CXCL5, SLC7A2 and C15orf48, may be related to the disease progression and produce effect as potential therapeutic approach in OA.