针对大骨节病环境危险因素损伤软骨的分子途径未明，缺乏有效阻断方法的科学难题，采用分子流行病学、细胞生物学和动物实验技术，研究miRNA介导的基因、蛋白表达调控在T-2毒素、低硒诱导软骨损伤中的作用及干预靶点，探索miRNA干预防治大骨节病新方法。内容包括：（1）采用miRNA表达芯片和多组学数据整合分析鉴定大骨节病软骨损伤相关miRNA及其调控基因、蛋白；（2）采用软骨细胞培养和动物实验技术确定大骨节病相关miRNA在低硒、T-2毒素诱导软骨损伤中的作用及干预靶点；（3）采用miRNA干预技术阐明低硒、T-2毒素通过miRNA诱导软骨细胞损伤的关键分子途径及其调控机制。本项目集中研究新的"T-2毒素、低硒-miRNA-软骨损伤相关基因、蛋白表达异常"的分子致病途径假说，为明确miRNA在大骨节病软骨损伤中的作用，阐明T-2毒素、低硒诱导软骨损伤的分子途径提供科学依据，为研发大骨节病防治新方法提供靶点。

For the scientific issues on the unknown molecular damage pathways and lack of effectively blocking approaches of environmental risk factors of Kashin-Beck disease(KBD), using molecular epidemiology, cell biology and animal experiment technologies, this project will study the role and intervention targets of miRNA-mediated gene and protein expression regulation in T-2 toxin/low selenium-induced cartilage lesions, and explore new miRNA intervention-based approach for preventing and treating KBD. The main contents include:(1) identifying KBD cartilage lesions related miRNAs and their regulatory genes and proteins using miRNA expression chip and integrated analysis of multi-omics; (2) clarifying the roles and intervention targets of KBD related miRNAs in T-2 toxin/low selenium-induced cartilage lesions using chondrocyte culture and miRNA intervention; (3) evaluating the efficacy and safety of miRNA intervention for blocking T-2 toxin/low selenium-induced articular cartilage lesions using animal experiment. This project aims to study the novel hypothesis of "T-2 toxin/low selenium-miRNA-abnormal expression of cartilage lesions related genes and proteins" pathogenic pathway, to provide scientific basis for clarifying the role of miRNA in KBD cartilage lesions,and revealing the molecular pathways of T-2 toxin/low selenium-induced cartilage lesions, to provide targets for developing novel miRNA intervention-based approaches for preventing and treating KBD.