小分子化合物BNTA通过上调SOD3促进软骨细胞外基质合成对骨关节炎的治疗作用机制研究

骨关节炎（Osteoarthritis，OA）是引起中老年人慢性残疾最常见的退行性关节疾患。软骨细胞外基质合成和降解失衡是OA渐进性发展的重要因素。目前临床上尚无有效药物能够改善与缓解OA病情进展。小分子化合物具有非免疫原性、方便制备、易保存等优点，已广泛用于其它重要疾病研究。本课题组前期研究从2320种天然和合成小分子化合物中进行筛选，发现BNTA为促进软骨细胞外基质合成代谢最明显的化合物。利用高通量转录组测序发现SOD3为BNTA潜在作用靶点。本项目拟通过临床标本、体内外实验等多角度、多层次来证实BNTA在软骨细胞外基质合成和降解代谢中的作用，综合评价BNTA对于OA进程的延缓和治疗效果；明确SOD3通过清除软骨组织内超氧阴离子来促进软骨细胞外基质合成代谢的作用机制，最终阐明BNTA通过上调SOD3促进软骨细胞外基质合成对OA的治疗作用机制，为OA临床治疗策略提供理论依据和转化基础。

Osteoarthritis (OA) is the most common degradative joint disease that would cause chronic disability in elder people. The imbalance between synthesis and degradation of extracelluar matrix (ECM) plays a vital role in the progression of OA. However, there is no existing drug that is effective on alleviating this condition. Small molecule compound has already been applied in the treatment of many disease because of its non-immunogenicity, conveniency and stability. Previously, we have screened 2320 natural or synthetic compound and have confirmed that BNTA is the most effective compound to facilitate the regeneration of cartilage ECM. High throughput transcriptome sequencing revealed that SOD3 was a potential target for BNTA. Our plan is to verify the function of BNTA in ECM metabolism and its efficacy as an alternative therapy by utilizing clinical samples and conducting in vitro and in vivo experiments. In addition，we will further clarify the mechanism of SOD3 as a new target to promote ECM metabolism by eliminating superoxide anion in cartilage. Eventually, to provide evidence and transformation basis for OA treatment strategy, we will explore the therapeutic effect of BNTA that promote ECM synthesis by up-regulating SOD3.