[Expression profile of intervertebral disc degeneration-specific genes: a transcriptome sequencing-based analysis]

To identify new therapeutic targets for intervertebral disc degeneration (IDD) by analyzing gene variations in IDD.

We analyzed surgical samples of intervertebral disc from 4 patients with IDD and 3 patients with non-IDD using RNA sequencing (RNA-seq) technology to identify significant differentially expressed genes (DEGs) in IDD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized for gene enrichment studies to acquire the key genes and signal pathways during IDD progression. The differential expressions of the identified genes in IDD were validated in clinical samples with qRT-PCR.

The transcriptome profile revealed 512 significant DEGs, which were enriched in terms of keratinization, extracellular matrix (ECM) components, growth factor binding, and inflammatory chemotaxis in GO analysis. The top 10 terms of KEGG enrichment included amoebiasis, viral protein interaction with cytokine and cytokine receptor, ECM-receptor interaction, IL-17 signaling pathway, cytokine-cytokine receptor interaction, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, chemokine signaling pathway and estrogen signaling pathway. Thirteen DEGs selected as the targets for qRT-PCR validation showed significant differential expressions in IDD (P < 0.001), and their expression trends were all consistent with the results of RNA-seq. Among these genes, 10 genes showed significant intergroup fold change (Log2FoldChange>1).

ECM, growth factors, collagen components, inflammatory chemokines and such signal pathways as TNF-α and PI3K-Akt all have important contributions to IDD progression and may thus serve as new therapeutic targets for treatment of IDD.