Selenium deficiency and T-2 toxin trigger ferroptosis in cartilage from Kashin-Beck diseases

Abstract

Kashin-Beck disease (KBD) is a prevalent, endemic, and degenerative cartilage injury disorder, characterized by high rates of teratogenicity and disability. The etiology and pathogenesis of KBD are not fully understood, although research suggests that selenium deficiency and exposure to T-2 toxin are significant environmental risk factors. The initial pathological changes of KBD manifest as necrosis of deep chondrocytes, dedifferentiation of chondrocytes, excessive apoptosis of chondrocytes, and subsequent disruption of extracellular matrix metabolism. However, the precise pathogenic mechanisms of chondrocyte damage in KBD remain incompletely understood. Ferroptosis is a unique form of programmed cell death triggered by iron-dependent lipid peroxide accumulation. It has been shown to contribute to cartilage damage and chondrocyte death in various osteoarticular conditions, particularly osteoarthritis (OA). Notably, KBD not only exhibits clinical and pathological similarities with OA, but also indicates a potential association with ferroptosis in morphological and molecular similarities. Additionally, the environmental risk factors T-2 toxin exposure and selenium deficiency are also significant contributors to ferroptosis. Consequently, it is plausible to postulate that environmental risk factors may trigger ferroptosis, leading to the initiation of cartilage damage in KBD. Our hypothesis can be verified through both in vitro and in vivo experiments. Chondrocyte injury induced by ferroptosis may be a novel finding in KBD, which is important for clarifying its etiology and developing effective therapeutic strategies.