Molecular mechanism of osteoarthritis by multi-chip combination analysis

doi:10.12307/2021.125

Abstract

Abstract:

BACKGROUND: Osteoarthritis is the most common chronic joint disease. Its pathogenesis is closely related to the complex gene regulatory network, but its underlying network has not been fully clarified.

OBJECTIVE: To identify hub genes, important pathways, miRNA-mRNA regulatory network and immune infiltration in the synovial tissue of osteoarthritis by bioinformatics analysis, with fully clarifying the pathogenesis of osteoarthritis.
METHODS: The gene expression microarrays of GSE1919, GSE55235 and GSE12021 were obtained from GEO database, with differentially expressed genes screened out and enriched by R software. Then, protein-protein interaction network and miRNA-mRNA network were constructed based on upstream regulatory miRNAs of predicted differentially expressed genes to screen out hub genes and miRNAs. Finally, immune infiltration of synovial tissue in osteoarthritis and normal control groups was analyzed by CIBERSORT.
RESULTS AND CONCLUSION: In total 64 up-regulated genes and 23 down-regulated genes were obtained, which were mainly involved in response to steroid hormone, response to corticosteroid, response to lipopolysaccharide and leukocyte migration. The important pathways closely related to osteoarthritis mainly included interleukin-17 signaling pathway, nuclear factor-κB signaling pathway, tumor necrosis factor signaling pathway and mitogen-activated protein kinase signaling pathway. MiRNA-mRNA network analysis showed that 10 hub genes, such as interleukin-6, VEGFA, MYC and miR-21-5p and miR-142-3p, were identified in osteoarthritis. Results of immune infiltration showed that there were significant differences in six kinds of immune cells, such as naïve B cells, plasma cells and regulatory T cells, between osteoarthritic synovium and normal synovium. The study constructed miRNA-mRNA regulatory network and investigated the difference of immune infiltration in synovial tissues, providing a theoretical basis for understanding the pathogenesis of osteoarthritis from the perspective of synovial tissue.

Key words: osteoarthritis, gene, microarray, database, bioinformatics, molecular mechanism, immune infiltration, synovial tissue

CLC Number:

Rong Weiming, Yuan Changshen, Duan Kan, Lu Zhixian, Mei Qijie, Guo Jinrong. Molecular mechanism of osteoarthritis by multi-chip combination analysis[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(26): 4223-4229.

Figures/Tables 7

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