软骨细胞外基质代谢障碍是大骨节病重要的病理损伤之一。针对大骨节病软骨细胞外基质代谢功能障碍及T-2毒素/和低硒引发大骨节病软骨细胞外基质代谢障碍作用机制与途径未明的关键科学问题，结合国际最新研究Zinc-ZIPs/ZNTs-MTFs轴可调控软骨细胞外基质代谢异常及课题组前期研究与预实验发现大骨节病软骨细胞ZIPs/ZNTs转运蛋白及其基因表达异常。本项目拟采用基因干扰、动物模型及现代生物学技术，集中研究：（1）大骨节病患者软骨细胞ZIPs/ZNTs转运蛋白及相关基因表达特点；（2）Zinc-ZIPs/ZNTs-MTFs轴调控大骨节病软骨细胞外基质代谢障碍的作用效应及其分子机制；（3）T-2毒素/和低硒通过Zinc-ZIPs/ZNTs-MTFs轴作用调控软骨细胞外基质代谢障碍与功能的机制，预期结果将从“环境因素-基因-信号途径-细胞效应”多层面阐明大骨节病软骨细胞外基质代谢障碍生物学机制。

The metabolic disorder of the extracellular matrix in chondrocyte is one of the important pathological injuries of Kashin-Beck disease (KBD). Based on the metabolic disturbance of chondrocyte extracellular matrix and the abnormality of synthesis and catabolism in chondrocyte extracellular matrix induced by T-2 toxin and selenium deficiency, the key scientific issues of pathogenesis of KBD is unknown. With the International latest research on Zinc-ZIPs/ZNTs-MTFs axis regulating the metabolic disorder of the extracellular matrix in chondrocyte, previous studies and the results of pre-experiment that the ZIPs/ZNTs transporter proteins and its genes abnormal expression in KBD. This project intends to adopt gene interference, animal model and modern biology to focus on the studying (1) Expression of ZIPs/ZNTs transporter and related genes in chondrocytes of KBD; (2) the effects and molecular mechanism of the metabolic disturbance of extracellular matrix in chondrocyte in KBD regulated by Zinc-ZIPs/ZNTs-MTFs axis; (3) the mechanism of Zinc-ZIPs/ZNTs-MTFs axis damaging chondrocyte via T-2 toxin and Selenium deficiency. The expected results will clarify the biological mechanism of the metabolic disorders of extracellular matrix in chondrocyte of KBD from the "environmental factors-gene-cell effect" level.