Transcriptomics and Metabolomics Insights into the Dysregulation of Chondrocyte Differentiation Induced by T-2 Toxin

T-2 toxin, a potent mycotoxin produced by Fusarium species, is recognized for its neurotoxic, hepatotoxic, and reproductive toxic effects. However, its impact on chondrocyte differentiation and cartilage development is not well understood. This study combines transcriptomic and metabolomic analyses to investigate the impact of T-2 toxin on ATDC5 cells during differentiation at days 3, 7, 14, and 21, following 48 h of exposure. Additionally, real-time quantitative PCR (RT-qPCR) was used to evaluate the expression levels of key chondrocyte differentiation-related genes (e.g., Fn1, Sox9, Runx2, Acan, Col1a1, Col2a1, and Col10a1) under T-2 toxin exposure alone or in combination with recombinant Mouse BMP2, BMP4, or both. Our results show that T-2 toxin disrupts several genes and signaling pathways crucial for chondrogenesis, including the BMP signaling pathway, extracellular matrix organization, and arachidonic acid metabolism. Significant temporal alterations in Bmp2, Bmp4, and other key genes were observed, disrupting chondrocyte differentiation. Notably, these changes were mitigated by BMP2 and BMP4 co-treatment, highlighting their protective effects. These findings provide insights into the molecular mechanisms underlying T-2 toxin-induced disruptions in chondrocyte differentiation and support the potential use of BMP signaling pathways as the therapeutic strategies to counteract the detrimental effect of T-2 toxin exposure.