Sirt1 mitigates HT-2 toxin-induced chondrocyte injury potentially via the Wnt/β-catenin signaling pathway

Sirt1 is crucial for cartilage homeostasis, and its dysregulation is implicated in Kashin-Beck disease (KBD), an osteochondropathy linked to HT-2 toxin exposure. This study investigated Sirt1's role in HT-2 toxin-induced chondrocyte injury. Human fetal chondrocytes treated with HT-2 toxin (0, 5, 10, 20 ng/mL) for 48 h showed dose-dependent viability reduction, extracellular matrix (ECM) degradation (↓Collagen II, ↓TIMP1, ↑MMP13), and senescence (↑P21, ↑β-galactosidase). HT-2 toxin suppressed Sirt1 while activating Wnt/β-catenin signaling (↑WNT3A, ↑β-catenin). Resveratrol (25 μM), a Sirt1 agonist, restored TIMP1 and Collagen II levels and reduced P21 without affecting MMP13, while inhibiting the WNT3A/β-catenin pathway. These results demonstrate that Sirt1 activation mitigates HT-2 toxin-induced chondrocyte damage by inhibiting Wnt/β-catenin signaling.