Kashin-Beck disease is a bone and cartilage disease found in Siberia, North Korea, and northeast China. Patients suffer from short stature, malformed joints, and pain. The cause of the disease is unclear, but it is thought to be an interaction between genes and environmental factors such as selenium deficiency and mycotoxins from grains grown in the region.
T2 toxin, a mycotoxin, has already been identified as a risk factor for Kashin-Beck disease. What of Ht-2 toxin, one of its metabolites? A team of researchers from the Xi’an School of Public Health, China, wanted to know if HT-2 toxin disrupts the development of cartilage.
They used HiPSCs (human induced pluripotent stem cells) to build a model of Kashin-Beck disease. HiPSC cells with a Kashin-Beck genetic background were differentiated into chondrocytes. HT-2 toxin was toxic to these cells: microscopy found that treatment caused microtubules, mitochondria, and endoplasmic reticulum to be disordered. The cell cycle regulation, including p53, p21, and CDK6, had disrupted expression.
This study confirms that HT-2 toxin is a direct risk factor for Kashin-Beck disease. The results also suggest a mechanism for how HT-2 toxin and T-2 toxin contribute to this disease. HT-2 toxin disrupted the cell cycle, which inhibited chondrocytes from differentiating into mature cartilage. This disruption in growth could cause cartilage malformation in people.
Zhang Y, Liu H, Lin X, et al. Dysregulation of cells cycle and apoptosis in human induced pluripotent stem cells chondrocytes through p53 pathway by HT-2 toxin: an in vitro study. Frontiers in Genetics. 2021 Aug 4;12:677723. PMID: 34421989. doi: 10.3389/fgene.2021.677723.