CD19, ALDH18A1, and CACNA1G as Significant Hub Genes in End-Stage Osteoarthritis

Mahshid  Malakootian; Akram  Gholipour; Maziar  Oveisee

doi:10.18502/ijph.v52i12.14326

Mahshid Malakootian Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Akram Gholipour Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Maziar Oveisee Orthopedics Department, School of Medicine, Bam University of Medical Sciences, Bam, Iran

DOI: https://doi.org/10.18502/ijph.v52i12.14326

Keywords: Osteoarthritis; IL-1B Protein; CD19; CACNA1G; Hub genes

Abstract

Background: Osteoarthritis is one of the principal causes of chronic joint disease and may progressively engender disability in elderly individuals. The present study aimed to identify differentially expressed genes and associated signaling pathways in end-stage osteoarthritis.

Methods: Differentially expressed messenger RNAs in the early and end stages of osteoarthritis were examined through gene expression omnibus 2R (GEO2R) in the GSE32317 dataset. Subsequently, gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analyses were conducted. Furthermore, microRNAs targeting hub genes were investigated using the miRcode database. This study was conducted jointly at Bam University of Medical Sciences and Rajaie Cardiovascular, Medical and Research Center on October 2022.

Results: Differentially expressed data demonstrated downregulation in 134 genes and upregulation in 189 genes in end-stage knee osteoarthritis. The results of the enrichment and PPI analyses determined 4 end-stage knee osteoarthritis-related hub genes: IL-1B, CD19, CACNA1G, and ALDH18A1. The knee osteoarthritis-related key genes were involved in the Wnt signaling, B cell receptor signaling, calcium signaling, circadian entrainment, arginine and proline metabolism, axon guidance, and cytokine-cytokine receptor pathways. Additionally, the microRNAs targeting the 4 aforementioned genes were predicted.

Conclusion: The present study is the first to provide fresh insights into the potential therapeutic targets of key genes, namely CD19, CACNA1G, and ALDH18A1, differentially expressed in end-stage osteoarthritis and their relevant signaling pathways and interactive microRNAs.