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

Abstract

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.