T-2 toxin exacerbates chondrocyte extracellular matrix degradation potentially through YAP/NLRP3/GSDMD-mediated pyroptosis.

Kashin-Beck disease (KBD) is an endemic osteoarthropathy, with T-2 toxin recognized as a major pathogenic factor. This study investigates the role of the YAP/NLRP3/GSDMD signaling pathway in T-2 toxin-induced cartilage injury. Differentially expressed genes associated with KBD were retrieved from PubMed and subjected to KEGG pathway enrichment analysis, revealing significant enrichment of the Hippo signaling pathway. Elevated serum levels of IL-1β, IL-18, and LDH were observed in KBD patients. In both in vivo and in vitro models, T-2 toxin inhibited Hippo/YAP signaling and promoted the nuclear translocation of YAP while activating NLRP3/GSDMD-mediated pyroptosis and extracellular matrix (ECM) degradation. Inhibition of YAP by verteporfin effectively suppressed NLRP3/GSDMD pathway activation and alleviated ECM degradation, whereas YAP overexpression further exacerbated pyroptosis and ECM damage. These findings indicate that YAP activation mediates chondrocyte pyroptosis and exacerbates ECM degradation, potentially through the NLRP3/GSDMD pathway, representing a key mechanism underlying T-2 toxin-induced cartilage injury and a potential therapeutic target.