Identification and experimental validation of key extracellular proteins as potential targets in intervertebral disc degeneration.

Abstract

Aims:

This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

Methods:

The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.

Results:

A total of 56 EP-DEGs were identified in the differential expression analysis. EP-DEGs were enriched in the extracellular structure organization, ageing, collagen-activated signalling pathway, PI3K-Akt signalling pathway, and AGE-RAGE signalling pathway. PPI network analysis showed that the top ten hub EP-DEGs are closely related to IDD. Correlation analysis also demonstrated a significant correlation between the ten hub EP-DEGs (p＜0.05), which were selected to construct TF-gene interaction and TF-miRNA coregulatory networks. In addition, ten candidate drugs were screened for the treatment of IDD.

Conclusion:

The findings clarify the roles of extracellular proteins in IDD and highlight their potential as promising novel therapeutic targets.

• Authors: Guang-Zhi Zhang, Lei Li, Zhang-Bin Luo, Cang-Yu Zhang, Yong-Gang Wang, Xue-Wen Kang
• Journal: Bone & joint research (Bone Joint Res) Vol. 12 Issue 9 Pg. 522-535 (Sep 04 2023) ISSN: 2046-3758 [Print] England
• PMID: 37661086 (Publication Type: Journal Article)
• Copyright: © 2023 Author(s) et al.