Integrating network toxicology, molecular modeling, and in vitro experiments to reveal potential targets and mechanism of BPS-induced osteoporosis.

Abstract

Bisphenol S (BPS) is an environmental pollutant widely detected in nature. Given the high global burden of osteoporosis and increased human exposure to BPS, studying its potential bone toxicity is of great significance, but its underlying mechanisms are still unclear. Here, we explored the potential mechanism of BPS-induced osteoporosis by combining network toxicology, molecular docking, normal mode analysis (NMA), and in vitro experimental verification. By overlapping BPS-related genes with genes associated with osteoporosis, we identified 14 overlapping targets, which were mainly enriched in IL-17/TNF signaling pathways. Four hub targets (SIRT1, MMP2, MMP3, JAK2) were identified based on four topological algorithms, and all exhibited strong binding affinity and stable interactions in molecular docking and NMA study. In vitro experiments showed that, in the BPS exposure model, calcium deposition in ARS staining was reduced, alkaline phosphatase (ALP) activity was inhibited, and the mRNA expression of osteogenic markers decreased in MC3T3-E1 cells. In addition, qRT-PCR analysis confirmed significant downregulation of SIRT1, MMP2, MMP3, and JAK2. Collectively, these findings provide experimental evidence for the bone toxicity of BPS and offer a scientific basis for understanding its potential role in osteoporosis.