The impact of Benzophenone-3 on osteoarthritis pathogenesis: a network toxicology approach.

Li, Yongji; Wang, Geqiang; Liu, Peiran; Zhang, Lin; Hu, Hai; Yang, Xiangjun; Liu, Hongpeng

Background Arthritis is a degenerative joint disease influenced by various environmental factors, including exposure to Benzophenone-3 (BP3), a common UV filter. This study aims to elucidate the toxicological impact of BP3 on arthritis pathogenesis using network toxicology approaches. Method We integrated data from the Comparative Toxicogenomics Database (CTD) and Gene Expression Omnibus (GEO) to identify differentially expressed BP3-related toxicological targets in osteoarthritis (OA). Enrichment analyses were conducted to determine the implicated biological processes, cellular components, and molecular functions. Further, the involvement of the PI3K-Akt signaling pathway was investigated, along with correlations with immune cell infiltration and immune-related pathways. Molecular docking analysis was performed to examine BP3 interactions with key PI3K-Akt pathway proteins. Results A total of 74 differentially expressed BP3-related targets were identified. Enrichment analysis revealed significant pathways, including PI3K-Akt, MAPK, and HIF-1 signaling. The PI3K-Akt pathway showed notable dysregulation in OA, with reduced activity and differential expression of key genes such as ANGPT1, ITGA4, and PIK3R1. Correlation analysis indicated significant associations between PI3K-Akt pathway activity and various immune cell types and immune pathways. Molecular docking highlighted strong interactions between BP3 and proteins like AREG, suggesting potential disruptions in signaling processes. Conclusions BP3 exposure significantly alters the expression of toxicological targets and disrupts the PI3KAkt signaling pathway, contributing to OA pathogenesis. These findings provide insights into the molecular mechanisms of BP3-induced OA and identify potential therapeutic targets for mitigating its effects.

OSTEOARTHRITIS; MOLECULAR docking; CELL anatomy; CELLULAR signal transduction; TOXICOGENOMICS

Toxicology Research, 2024, Vol 13, Issue 6, p1

2045-452X

Academic Journal

10.1093/toxres/tfae199