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MiR-140 is involved in T-2 toxin-induced matrix degradation of articular cartilage.
T-2 toxin is one of the most toxic mycotoxins contaminating various grains. It is considered an environmental risk factor for Kashin-Beck disease (KBD), an endemic degenerative osteochondrosis. Currently, the underlying molecular mechanisms of articular cartilage damage caused by T-2 toxin have not been elucidated. Studies have shown that miR-140 is essential for cartilage formation, and extracellular matrix (EMC) synthesis and degradation. The objective of this study was to investigate the mechanism of miR-140 involvement in T-2 toxin-induced articular cartilage damage. Two treatment groups, each containing wild-type mice and miR-140 knockout mice were administered with T-2 toxin (200 ng/g BW/day) or a normal diet for 1 month, 3 months, and 6 months. Results showed that T-2 toxin caused articular cartilage and growth plate damage in mice. The expression of miR-140 decreased in articular cartilage of wild-type mice treated with T-2 toxin, and miR-140 deficiency aggravated T-2 toxin-induced knee cartilage damage. T-2 toxin-caused the reduction of miR-140 expression was consistent with collagen type II (COL2A1), aggrecan (ACAN), and SRY-box containing gene 9 (SOX9) and opposite to matrix metalloproteinase 13 (MMP13), a disintegrin and metalloproteinase with thrombospondin motif 5 (ADAMTS-5), and v-ral simian leukemia viral oncogene homolog A (RALA). In addition, we collected finger joints cartilage and knee joints cartilage from KBD patients and controls for paraffin embedding and sectioning. Results found that the expression of miR-140 in the articular cartilage of the KBD group was lower than that of the control group. The expression of COL2A1, ACAN, and SOX9 decreased, whereas ADAMTS-5, MMP13, and RALA increased in the articular cartilage of the KBD group. These results revealed that miR-140 might be involved in T-2 toxin-induced degradation of the ECM of articular cartilage. Moreover, the occurrence of KBD might be related to the decreased expression of miR-140 in articular cartilage.
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