Identification of critical genes in nucleus pulposus cells isolated from degenerated intervertebral discs using bioinformatics analysis

Zhu,Zhuangchen; Chen,Guang; Jiao,Wei; Wang,Defeng; Cao,Yan; Zhang,Qingfu; Wang,Junqin

doi:10.3892/mmr.2017.6662

Identification of critical genes in nucleus pulposus cells isolated from degenerated intervertebral discs using bioinformatics analysis

Authors:
- Zhuangchen Zhu
- Guang Chen
- Wei Jiao
- Defeng Wang
- Yan Cao
- Qingfu Zhang
- Junqin Wang
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Affiliations: Department of Orthopedics, Affiliated Hospital of Taishan Medical University, Tai'an, Shandong 271000, P.R. China
Published online on: May 31, 2017 https://doi.org/10.3892/mmr.2017.6662
Pages: 553-564
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Intervertebral disc (IVD) degeneration is a pathological process, which may lead to lower back pain. The present study aimed to investigate the pathogenesis of IVD degeneration. GSE42611 was downloaded from Gene Expression Omnibus, including 4 nucleus pulposus samples isolated from degenerated IVDs and 4 nucleus pulposus samples separated from normal IVDs. The differentially expressed genes (DEGs) between the degenerated and normal samples were screened using the limma package in R. Functional and pathway enrichment analyses were conducted separately for the upregulated and downregulated genes, using Database for Annotation, Visualization and Integrated Discovery software. In addition, protein‑protein interaction (PPI) networks were constructed using the Search Tool for the Retrieval of Interacting Genes database and Cytoscape software. Finally, module analyses were conducted for the PPI networks using the MCODE plug‑in in Cytoscape. A total of 558 DEGs were identified in the degenerated nucleus pulposus cells: 253 upregulated and 305 downregulated. Pathway enrichment analysis revealed that downregulated thrombospondin 1 (THBS1) was enriched in extracellular matrix‑receptor interaction. Interleukin (IL)‑6 in the PPI network for the upregulated genes and vascular endothelial growth factor A (VEGFA) in the PPI network for the downregulated genes had higher degrees. Additionally, four modules (µM1, µM2, µM3 and µM4) were identified from the PPI network for the upregulated genes. Four modules (dM1, dM2, dM3 and dM4) were identified from the PPI network for the downregulated genes. In the dM2 module, collagen genes and integrin subunit α4 (ITGA4) may interact with each other. Additionally, functional enrichment indicated that collagen genes were enriched in extracellular matrix organization. In conclusion, IL‑6, VEGFA, THBS1, ITGA4 and collagen genes may contribute to the progression of IVD degeneration. These results suggested that the manipulation of these genes and their products may have potential as a novel therapeutic strategy for the treatment of patients with IVD.

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