针对我国大骨节病可疑致病因素粮食T-2毒素中毒和低硒特异性损害儿童软骨细胞机制未明及缺乏有效治疗靶点的关键科学问题，基于国际上膳食外泌体miRNA调控软骨细胞凋亡、细胞外基质相关基因及蛋白表达而控制软骨细胞损伤性疾病的最新研究进展，本课题拟采用外泌体软骨细胞共培养、基因干扰技术和动物实验，重点研究膳食外泌体miR-23b对大骨节病软骨细胞损伤的保护作用及其分子机制，主要研究内容有1）确定外泌体与大骨节病软骨细胞损伤的关系；2）明确miR-23b介导PKA通路在大骨节病软骨细胞损伤中的作用机制；3）明确膳食外泌体miR-23b对T-2毒素和低硒所致大骨节病软骨细胞损伤的保护作用。预期结果将明确膳食外泌体miR-23b对大骨节病软骨细胞损伤的保护作用途径，从组织、细胞和分子不同水平上确定大骨节病致病因素和损伤靶向干预作用，以推进大骨节病发病机制研究，为发现新的生物标志物和治疗手段提供科学依据。

Previous studies have identified T-2 toxin and low selenium as suspected pathological factors of Kashin-Beck disease (KBD), however, the mechanism of cartilage injury of juvenile KBD caused by T-2 toxin and low selenium is still a conundrum. The most advanced international researches have established the protective or therapeutic role of dietary exosome miRNAs in repairing chondrocyte lesions by regulating the expression of genes and proteins which are associated with cellular apoptosis and extracellular matrix. Therefore, co-culture chondrocyte with exosome, gene interference and animal experiment would be applied in this study to explore and to establish the protective role of dietary exosome-miR-23b through PKA signaling pathway. The main contents are as follows: 1) to identify the relationship between the exosome and cartilage damage of KBD patients; 2) to identify the mechanism of miR-23b in cartilage damage through regulating PKA pathway; 3) to establish the therapeutic role of dietary exosome-miR-23b in repairing chondrocyte lesions induced by T-2 toxin and low selenium. To summarize, this study would establish the therapeutic role and mechanism of dietary exosome-miR-23b in repairing chondrocyte lesions on molecular, cellular and organic levels, which would promote the pathogenesis study and provide evidence to discover new biomarker and therapeutic means for KBD simultaneously.