Reduced expression of α2 integrin is involved in T-2 toxin-induced matrix degradation in C28/I2 cells and cartilages from rats administrated with T-2 toxin

Abstract

T-2 toxin is a mycotoxin demonstrating several harmful effects on chondrocyte and cartilage functions. In the present study, we investigated the toxic effects of T-2 toxin on cartilage matrix degradation and evaluated the involvement of α2 integrin in T-2 toxin-induced matrix damage. In C28/I2 cells, T-2 toxin decreased cell viability in a dose-dependent manner. Regarding matrix degradation, T-2 toxin decreased type II collagen and increased matrix metalloproteinase 13 (MMP-13) expression. Moreover, T-2 toxin significantly decreased the expression of α2 integrin in C28/I2 cells, indicating impaired chondrocyte-matrix interaction. Additionally, cartilage matrix degradation with decreased type II collagen expression was observed in the animal model, established using rats treated with T-2 toxin, with or without a selenium-deficient diet, presenting chondrocytes with necrosis in the deep zone. Simultaneously, rats administered T-2 toxin demonstrated overtly decreased α2 integrin expression in the articular cartilage. In the T-2 toxin plus selenium-deficient diet group, α2 integrin expression was further decreased in the deep zone of the cartilage. Furthermore, inhibition of α2β1 integrin in C28/I2 cells could induce MMP-13 activation and type II collagen reduction, contributing to matrix degradation. These results indicate that the cytotoxic effects of T-2 toxin on chondrocyte damage and cartilage matrix degradation are associated with α2 integrin downregulation, by reducing type II collagen and MMP-13 activation.