骨关节炎（OA）中常出现软骨下骨（SB）重塑和硬化等特征性病理改变，其发生机制及与软骨病变相互联系不明。本团队前期研究发现OA软骨细胞（AC）可诱导软骨下骨祖细胞（SBPC）异变（成骨能力增加、矿化能力降低），外泌体（EXO）与Wnt/β-catenin可能分别是其中关键信使和调控通路，提出OA中关节软骨介导EXO下调Wnt/β-catenin诱导SPBC表型异变及SB特征性病理改变的假说。拟体外研究明确OA-AC诱导SBPC异变并通过EXO介导完成的现象；动物研究验证EXO是否诱发SB组织形态异变；体外研究探索EXO诱导SBPC异变的逐级调控机制：验证EXO诱导SBPC异变通过Wnt/β-catenin下调实现，筛选下调Wnt/β-catenin的关键因子，探索EXO中发挥关键作用的miRNAs；通过临床标本检测验证上述机制；以阐明OA发生过程中关节软骨对软骨下骨病变的调控作用及机制。

Characteristic pathological changes such as remodeling and sclerosis of subchondral bone (SB) are usually observed in osteoarthritis (OA). The mechanism of these changes and their relationship with cartilage lesions are not clear. Our previous study found that OA articular chondrocytes (AC) can change the phenotype of subchondral bone progenitor cells (SBPC) (increase osteogenic capacity and decrease mineralizing ability). Exosome (EXO) and Wnt/β-catenin may be the key messenger and pathway respectively. Base on this, we put forward the hypothesis that Articular cartilage can induce phenotypic changes of SPBC and characteristic pathological changes of SB via down-regulation of Wnt/β-catenin by chondrocyte-mediated EXO in OA. We plan to demonstrate the hypothesis through ways below. In vitro study to prove the phenomenon that OA-AC induce SBPC phenotypic changes by mediating EXO. In vivo study to examine whether EXO can induce SB tissue abnormalities. In vitro research on the stepwise regulation mechanism of EXO-induced SBPC abnormalities in vitro: Verification of EXO-induced SBPC phenotypic changes via Wnt/β-catenin down-regulation, screening key factors of Wnt/β-catenin down-regulation in SBPC, exploring the key miRNAs, which play the key role in EXO to induce SBPC phenotypic changes. Verify the mechanism by clinical specimen detection. Finally clarify the role and mechanism of chondrocyte-mediated exosomes in regulating subchondral bone progenitor cells Wnt/β-catenin pathway in osteoarthritis.