Gene expression profiling analysis of human intervertebral disc degeneration

Abstract

Objective To reveal the possible genes associated with the pathogenesis of intervertebral disc degeneration by analyzing the microarray data using bioinformatics methods. Methods Six human nucleus pulposus samples were included: three degenerative samples from patients with intervertebral disc degeneration and three non-degenerative as controls. The differentially expressed genes between the disease and disease normal samples were identified using limma packages of R. Gene Ontology function and KEGG pathway enrichment analyses were used to identify differentially expressed genes related biological functions and pathways in intervertebral disc degeneration, respectively. Gene expression values were validated by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). Results A total of 153 differentially expressed genes were screened in nucleus pulposuscells. The differentially expressed genes were mainly associated with the biological processes of programmed cell death, apoptosis; and with the cell cycle signaling pathway. The protein-protein interaction network demonstrated that kinetochore complex component (NDC80), mitotic checkpoint serine/threonine-protein kinase BUB1 beta (BUB1B), and cohesin complex component (RAD21) had high degree in the network. RT-qPCR data confirmed NDC80, BUB1B, and RAD21 were significantly increased in degenerative nucleus pulposus cells. The expression of NDC80, BUB1B and RAD21 were up-regulated (3.23±0.67) times (P=0.016), (3.79±0.91) times (P=0.005) and (2.73±0.51) times (P=0.009) respectively in the degenerated nucleus pulposus tissues. Conclusion These results revealed the involvement of NDC80, BUB1B, and RAD21 in the apoptosis, and cell death of nucleus pulposus cells in the progression of intervertebral disc degeneration. Key words: Intervertebral disc degeneration; Dysregulated genes; Nucleus pulposuscell; Apoptosis