Journal Article

High expression of transcription factor EGR1 is associated with postoperative muscle atrophy in patients with knee osteoarthritis undergoing total knee arthroplasty

Guo, Si-qin, Yu, Qiu-ping, Chen, Xu-ming, Zeng, Wei-Nan, Liu, Xiao-yang, Zhou, Zong-Ke

2024

Overview

Background Muscle atrophy is a typical affliction in patients affected by knee Osteoarthritis (KOA). This study aimed to examine the potential pathogenesis and biomarkers that coalesce to induce muscle atrophy, primarily through the utilization of bioinformatics analysis. Methods Two distinct public datasets of osteoarthritis and muscle atrophy (GSE82107 and GSE205431) were subjected to differential gene expression analysis and gene set enrichment analysis (GSEA) to probe for common differentially expressed genes (DEGs) and conduct transcription factor (TF) enrichment analysis from such genes. Venn diagrams were used to identify the target TF, followed by the construction of a protein-protein interaction (PPI) network of the common DEGs governed by the target TF. Hub genes were determined through the CytoHubba plug-in whilst their biological functions were assessed using GSEA analysis in the GTEx database. To validate the study, reverse transcriptase real-time quantitative polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Flow Cytometry techniques were employed. Results A total of 138 common DEGs of osteoarthritis and muscle atrophy were identified, with 16 TFs exhibiting notable expression patterns in both datasets. Venn diagram analysis identified early growth response gene-1 (EGR1) as the target TF, enriched in critical pathways such as epithelial mesenchymal transition, tumor necrosis factor-alpha signaling NF-κB, and inflammatory response. PPI analysis revealed five hub genes, including EGR1, FOS, FOSB, KLF2, and JUNB. The reliability of EGR1 was confirmed by validation testing, corroborating bioinformatics analysis trends. Conclusions EGR1, FOS, FOSB, KLF2, and JUNB are intricately involved in muscle atrophy development. High EGR1 expression directly regulated these hub genes, significantly influencing postoperative muscle atrophy progression in KOA patients.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Arthroplasty, Replacement, Knee - adverse effects / Bioinformatic analysis / Biomarkers - metabolism / Computational Biology - methods / DNA polymerases / Early Growth Response Protein 1 - genetics / Early Growth Response Protein 1 - metabolism / EGR1 / Enzyme-linked immunosorbent assay / Enzymes / Female / Gene expression / Gene Expression - genetics / Genes / Genetic aspects / Humans / Knee osteoarthritis / Male / Medicine / Medicine & Public Health / Muscle atrophy / Muscular Atrophy - etiology / Muscular Atrophy - genetics / Muscular Atrophy - metabolism / Muscular Atrophy - pathology / Orthopedics / Osteoarthritis / Osteoarthritis, Knee - genetics / Osteoarthritis, Knee - metabolism / Osteoarthritis, Knee - pathology / Osteoarthritis, Knee - surgery / Postoperative Complications - etiology / Postoperative Complications - genetics / Postoperative Complications - metabolism / Protein Interaction Maps - genetics / Protein-protein interactions / Research Article / Stem cells / Surgical Orthopedics / Total knee arthroplasty