退行性骨关节炎(OA)是最常见的临床挑战，目前基本是“一视同仁”的对症性治疗。而我们首批开展的临床软骨细胞移植治疗研究（Stem cell Trans Med 2016）发现，同样质控的处理但病人的治疗结果差异很大。因此假说：OA可能有不同的病理亚型，建立更精准的OA治疗体系需要针对性阻断病理退变和启动软骨再生。我们前期临床样本筛查研究也发现，骨关节炎软骨组织和关节液中炎症因子表达谱有差异，如部分病人标本的EGFR或IL-17等高表达，这些结果更加支持了我们的假说。因此，本课题将采用表达谱、表观谱和炎症因子谱等手段解析OA的GO亚型和炎症亚型，并探寻相应的关键基因和分子病理机制；同时进行高通量筛选，寻找针对性阻断病理通路与维持软骨细胞表型的小分子药物组合；再结合生物材料改善理化微环境，实现阻断关节软骨退变和启动软骨修复。本项目的研究发现将有助于实现关节OA分型并建立更精确的OA治疗新体系。

Osteoarthritis （OA） is one of the most common degenerative joint disease and clinical challenge. It is caused by many factors, and its subtypes and pathological mechanism is unclear so far; Based on imaging diagnosis, its treatment is mainly to release pain and joint replacement without the differentiation of patients . Our clinical study of chondrocyte transplantation found that the outcome of patients are very variant (Stem Cell Trans Med 2016) So, we hypothesized that OA has different subtypes and precise pathological and regenerative treatments. Our previous screening of OA cartilage found that there are different inflammatory factor expression pattern in the joint fluid and cartilage, such as EGFR or IL-17 is activated in osteoarthritis cartilage from some patients, suggesting that EGFR or IL-17 maybe is the biomarker of some subpopulations of OA patients. In order to prove that, we will identify inflammation subtypes of degenerative osteoarthritis with inflammatory factor array and Go subtypes with second generation sequence technology, as well as illustrated the crucial pathological genes and pathway. Secondly, we will screen out small molecules to specifically inhibit the degeneration and initiate cartilage repair with high-throughput and high-content screening platforms. Thirdly, we will combine some biomaterials functionalized with specific groups for controlled release of small molecules, thus blocking cartilage degeneration and initiating its repair. We believe that the findings of this project will help us to classify OA subtypes and develop a more precise therapeutic system in which pathological process of OA will be precisely blocked and its regeneration will be better initiated as well.