Dysregulation of Cells Cycle and Apoptosis in Human Induced Pluripotent Stem Cells Chondrocytes Through p53 Pathway by HT-2 Toxin: An in vitro Study

• Published in: Frontiers in genetics Vol. 12; p. 677723
• Main Authors: Zhang, Yanan, Liu, Huan, Lin, Xialu, Zhang, Feng’e, Meng, Peilin, Tan, Sijia, Lammi, Mikko J., Guo, Xiong
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 04-08-2021
• Subjects: cell apoptosis; cell cycle; cell research; cellforskning; Genetics; HT-2 toxin; Kashin–Beck disease; Medical Cell Biology; medicinsk cellbiologi; Orthopaedics; ortopedi; p53
• ISSN: 1664-8021; 1664-8021
• DOI: 10.3389/fgene.2021.677723

Kashin–Beck disease (KBD) mainly damages growth plate of adolescents and is susceptible to both gene and gene–environmental risk factors. HT-2 toxin, which is a primary metabolite of T-2 toxin, was regarded as one of the environmental risk factors of KBD. We used successfully generated KBD human induced pluripotent stem cells (hiPSCs) and control hiPSCs, which carry different genetic information. They have potential significance in exploring the effects of HT-2 toxin on hiPSC chondrocytes and interactive genes with HT-2 toxin for the purpose of providing a cellular disease model for KBD. In this study, we gave HT-2 toxin treatment to differentiating hiPSC chondrocytes in order to investigate the different responses of KBD hiPSC chondrocytes and control hiPSC chondrocytes to HT-2 toxin. The morphology of HT-2 toxin-treated hiPSC chondrocytes investigated by transmission electron microscope clearly showed that the ultrastructure of organelles was damaged and type II collagen expression in hiPSC chondrocytes was downregulated by HT-2 treatment. Moreover, dysregulation of cell cycle was observed; and p53, p21, and CKD6 gene expressions were dysregulated in hiPSC chondrocytes after T-2 toxin treatment. Flow cytometry also demonstrated that there were significantly increased amounts of late apoptotic cells in KBD hiPSC chondrocytes and that the mRNA expression level of Fas was upregulated. In addition, KBD hiPSC chondrocytes presented stronger responses to HT-2 toxin than control hiPSC chondrocytes. These findings confirmed that HT-2 is an environmental risk factor of KBD and that p53 pathway interacted with HT-2 toxin, causing damaged ultrastructure of organelles, accelerating cell cycle in G1 phase, and increasing late apoptosis in KBD hiPSC chondrocytes.