Identification of key potential targets for TNF-α/TNFR1-related intervertebral disc degeneration by bioinformatics analysis.

ABSTRACT

BACKGROUND: Bioinformatics analysis was performed on gene expression profile microarray data to identify the key genes activated through the TNF-α/TNFR1 signaling pathway in intervertebral disc degeneration (IDD). The common differentially expressed genes (co-DEGs) were calculated in nucleus pulposus (NP) cells and annulus fibrosus (AF) cells under TNF-α treatment or TNFR1 knockdown, which reveals the potential mechanism of TNF-α involvement in IDD and may provide new therapeutic targets for IDD. METHODS: Differentially expressed genes (DEGs) in TNF-α-treated or TNFR1-knockdown NP cells and AF cells were identified. Further analysis of the gene ontology (GO), signaling pathways and interaction networks of the DEGs or co-DEGs were conducted using the Database for Annotation, Visualization and Integrated Discovery, STRING Database, and Cytoscape software. The relationship between genes and musculoskeletal diseases, including IDD, was assessed with the Comparative Toxicogenomics Database. The predicted microRNAs corresponding to the co-DEGs were also identified by microRNA Data Integration Portal. RESULTS: In NP cells, the DEGs (|log2FoldChange|>2, adj.P < 0.01) were identified including 48 DEGs by TNF-α treatment and 74 DEGs by TNFR1 knockdown; in AF cells, correspondingly, 105 DEGs were identified. The co-DEGs between NP cells and AF cells were calculated including CXCL8, ICAM1, BIRC3, RELB, NFKBIA, and TNFAIP3. They may be the hub genes that were significantly associated with both NP cells and AF cells through the TNF-α/TNFR1 signaling pathway. The co-DEGs and corresponding predicted miRNAs may be potential therapeutic targets for IDD. CONCLUSIONS: CXCL8, ICAM1, BIRC3, RELB, NFKBIA, and TNFAIP3 may have a synergistic effect on TNF-α-induced IDD development.Abbreviations IDD Intervertebral disc degeneration; NP Nucleus pulposus; AF Annulus fibrosus; co-DEG Common differentially expressed gene; GO Gene Ontology; KEGG Kyoto Encyclopedia of Genes and Genomes; PPI Protein-protein interaction.