Comprehensive Summary
This study conducted by Liu et al. investigated the potential impact of a brominated flame retardant, BDE-47, on osteoarthritis progression. The researchers first identified target genes of BDE-47 and osteoarthritis across multiple databases, resulting in 30 overlapping genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to identify the roles of the identified target genes. Protein–protein interaction (PPI) analysis was also performed to investigate the interactions between the targets. Furthermore, a big range of machine learning models were constructed using the target gene data and a SHapley Additive exPlanations (SHAP) analysis was used to identify which genes had greater influence on the predicted osteoarthritis risk. Finally, molecular docking analysis and docking simulations were done to evaluate the binding affinity of the genes to BDE-47. The researchers concluded that the genes (MAFF, TLR7, RGS1, MXD1, RYR1, PTX3, MGAM, THBS4, CXCL3, and FKBP5) play a big role in BDE-47’s influence on osteoarthritis progression. Moreover, the result of SHAP analysis and molecular dynamics simulation points out that FKBP5 is a potential therapeutic target.
Outcomes and Implications
Brominated flame retardant, BDE-47, is a prevalent molecule in consumer products such as electronics, and building materials. Previous studies linked BDE-47 to various health hazards, including disruption in thyroid axis function and impairing mitochondrial function. Over the lifetime of these products, the chemical leaches out, becoming a health hazard. It is therefore important to investigate the health impacts of the molecule, especially in osteoarthritis, which lacks effective clinical therapies. The researchers believe that the genes they identified layout the foundation for target treatment strategies. However, they acknowledge the need of in vitro and in vivo experiments to confirm the roles of these genes.