针对严重危害我国人口健康的大骨节病（KBD）研究中缺乏疾病模型和靶向干预的关键问题，基于长期与Lammi教授合作研究KBD软骨差异基因、蛋白表达和关节功能障碍治疗的进展，利用我方在KBD研究和合作方在干细胞研究的优势互补，应用生物医学和高通量组学技术，集中研究：(1)建立KBD诱导多能干细胞(iPSCs)和骨髓间充质干细胞(MSCs)疾病模型；(2)鉴定KBD-iPSCs/MSCs-软骨细胞基因型、关键靶点及重要信号通路；(3)确定T-2毒素和/或低硒致KBD-iPSCs/MSCs-软骨细胞损伤的病因学作用；(4)确定KBD-iPSCs/MSCs-软骨细胞的损伤靶点及其干预作用。预期在国内外率先获得KBD自体iPSC/MSCs-软骨细胞及其构建的三维立体软骨组织疾病模型，从组织、细胞和分子不同水平上确定KBD致病因素和损伤靶向干预作用，对提高早期诊断和预防水平具有重要的科学价值和应用前景。

It is a key scientific issue that Kashin-Beck disease (KBD), a harmful endemic osteoarthritis, lack the disease model and molecular targets in the study of etiology and prevention. With the long-term collaboration with Prof. Lammi’s research group on KBD, there was an improvement on the joint dysfunction treatment and the expression differences of genes and proteins had been identified. This project proposed to take full advantages of the etiology and pathogenesis researches of cartilage damages in KBD in our group and the stem cells and tissue engineering researches of cartilage in Sweden partner. Using the modern biotechnology and high-throughput omics, we focus on the following areas: (1) The establishment of the disease cell model by using mesenchymal stem cells (MSCs) and the induced pluripotent stem cells (iPSCs) generated from KBD patient's cells; (2) The identification of the phenotype and genotype, the key targets and important signaling pathways of KBD cell model; (3) The determination of the etiological role of T-2 toxin and/or low selenium in the damage of iPSCs-chondrocytes of KBD; (4) The confirmation of the damage target of iPSCs-chondrocytes of KBD and its prevention effects. Prospectively, the chondrocytes and the three-dimensional cartilage disease model differentiated from KBD autologous iPSCs/MSCs could been established firstly at home and abroad. The etiological factors of KBD and targeted intervention effects of damage will be identified and confirmed from organizations, cellular and molecular levels. This project has important scientific value and application prospect in the improvement of prevention, early diagnosis and clinical treatment of KBD.