Study on the Molecular Mechanism amd Immune Cell Infiltration of Bushenhuoluo Decoction in Osteoarthritis Treatment Based on Network Pharmacology

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Abstract

Background Osteoarthritis (OA) is a common degenerative joint disorder marked by the deterioration of cartilage, joint discomfort, and inflammation. The Bushenhuoluo Decoction (BSHLD) is a traditional Chinese remedy utilized for the management of OA. The aim of this study is to examine and elucidate the mechanism of BSHLD and how the compound interacts with the target of OA. Methods We used a network pharmacology approach that integrates multiple bioinformatics techniques to study OA. First, we collected and analyzed OA datasets from the Gene Expression Omnibus with the R package GEOquery. To identify key differentially expressed genes (DEGs), we performed differential expression analysis using the limma package. We obtained target genes from the Online Mendelian Inheritance in Man (OMIM) and the Comparative Toxicogenomics Database (CTD). Additionally, we obtained components of traditional Chinese medicine and their targets from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). To enhance our understanding of the biological processes and pathways involved, we conducted enrichment analyses using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We constructed protein-protein interaction networks to pinpoint crucial genes, which we then validated using receiver operating characteristic curve analysis. Lastly, we assessed immune cell infiltration through the CIBERSORT algorithm. Results Differential expression analysis using the limma package identified key difference genes (KDGs) by intersecting DEGs with OA-RELAted genes, TCM target genes, and RBIRGs, resulting in 16 KDGs. GO and KEGG pathway enrichment analyses revealed significant biological processes and pathways, including muscle cell proliferation and PI3K-Akt signaling. Protein-protein interaction (PPI) networks were constructed using STRING, and hub genes were identified through CytoHubba algorithms, highlighting nine hub genes, including MYC and CDKN1A. Expression validation and ROC curve analysis demonstrated the diagnostic potential of hub genes, with HSP90AA1 , MYC , and CDKN1A showing high accuracy (AUC > 0.9). The immune infiltration analysis showed a significant positive corRELAtion between the hub gene MYC and activated mast cells. There was a significant negative corRELAtion between hub gene CDKN1A and immune cell Mast cells resting. Conclusion These findings provide valuable insights into the molecular interactions of BSHLD in OA treatment, potentially revealing therapeutic targets and pathways for future studies.

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