Integrative Bioinformatics Analysis Revealed Mitochondrial Dysfunction-Related Genes Underlying Intervertebral Disc Degeneration

Zhengya Zhu; Zhongyuan He; Tao Tang; Fuan Wang; Hongkun Chen; Baoliang Li; Guoliang Chen; Jianmin Wang; Wei Tian; Dafu Chen; Xinbao Wu; Xizhe Liu; Zhiyu Zhou; Shaoyu Liu

doi:10.1155/2022/1372483

Integrative Bioinformatics Analysis Revealed Mitochondrial Dysfunction-Related Genes Underlying Intervertebral Disc Degeneration

Oxid Med Cell Longev. 2022 Oct 11:2022:1372483. doi: 10.1155/2022/1372483. eCollection 2022.

Authors

Zhengya Zhu¹, Zhongyuan He^{1

2}, Tao Tang^{1

2}, Fuan Wang^{1

2}, Hongkun Chen¹, Baoliang Li^{1

2}, Guoliang Chen^{1

2}, Jianmin Wang¹, Wei Tian³, Dafu Chen³, Xinbao Wu³, Xizhe Liu², Zhiyu Zhou^{1

2}, Shaoyu Liu^{1

2}

Affiliations

¹ Innovation Platform of Regeneration and Repair of Spinal Cord and Nerve Injury, Department of Orthopaedic Surgery, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China.
² Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Orthopaedic Research Institute/Department of Spinal Surgery, The First Affiliated Hospital of sun Yat-Sen University, Guangzhou 510080, China.
³ Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, Beijing Research Institute of Orthopaedics and Traumatology, Beijing Jishuitan Hospital, Beijing 100035, China.

Abstract

Objective: Mitochondrial dysfunction plays an important role in intervertebral disc degeneration (IDD). We aim to explore the pathways and key genes that cause mitochondrial dysfunction during IDD and to further reveal the pathogenesis of IDD based on bioinformatic analyses.

Methods: Datasets GSE70362 and GSE124272 were downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) of mitochondrial dysfunction between IDD patients and healthy controls were screened by package limma package. Critical genes were identified by adopting gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathways, and protein-protein interaction (PPI) networks. We collected both degenerated and normal disc tissues obtained surgically, and we performed western blot and qPCR to verify the key DEGs identified in intervertebral disc tissues.

Results: In total, 40 cases of IDD and 24 healthy controls were included. We identified 152 DEGs, including 67 upregulated genes and 85 downregulated genes. Four genes related to mitochondrial dysfunction (SOX9, FLVCR1, NR5A1 and UCHL1) were screened out. Of them, SOX9, FLVCR1, and UCHL1 were down-regulated in peripheral blood and intervertebral disc tissues of IDD patients, while NR5A1 was up-regulated. The analysis of immune infiltration showed the concentrations of mast cells activated were significantly the highest in IDD patients. Compared with the control group, the level of T cells CD4 memory resting was the lowest in the patients. In addition, 24 cases of IDD tissues and 12 cases of normal disc tissues were obtained to verify the results of bioinformatics analysis. Both western blot and qPCR results were consistent with the results of bioinformatics analysis.

Conclusion: We identified four genes (SOX9, FLVCR1, NR5A1 and UCHL1) associated with mitochondrial dysfunction that play an important role in the progress of disc degeneration. The identification of these differential genes may provide new insights for the diagnosis and treatment of IDD.

MeSH terms

Computational Biology / methods
Gene Expression Profiling / methods
Gene Ontology
Humans
Intervertebral Disc Degeneration* / pathology
Intervertebral Disc* / metabolism
MicroRNAs* / metabolism
Mitochondria / metabolism

Substances

MicroRNAs