Introduction: Disruptions of extracellular matrix (ECM) degradation homeostasis play a significant role in the pathogenesis of osteoarthritis (OA). Matrix metalloproteinase 13 (MMP13) and collagen Ⅱ are important components of ECM. Earlier we found that quercitrin could significantly decrease MMP13 gene expression and increase collagen Ⅱ gene expression in IL-1β-induced rat chondrocytes and human chondrosarcoma (SW1353) cells.

Objectives: The effects and mechanism of quercitrin on OA were explored.

Methods: Molecular mechanisms of quercitrin on OA were studied in vitro in primary chondrocytes and SW1353 cells. An anterior cruciate ligament transection (ACLT) rat model of OA was used to investigate the effect of quercitrin in vivo. Micro-CT analysis and Safranin O-Fast Green Staining of knee joint samples were performed to observe the damage degree of tibial subchondral bone. Immunohistochemistry of knee joint samples were conducted to observe the protein level of MMP13, collagen Ⅱ and p110α in articular cartilage.

Results: In vitro, quercitrin promoted cell proliferation and delayed ECM degradation by regulating MMP13 and collagen II gene and protein expressions. Moreover, quercitrin activated the Phosphatidylinositol 3-kinase p110α (p110α)/AKT/mTOR signaling pathway by targeting p110α. We also firstly showed that the gene expression level of p110α was remarkably decreased in cartilage of OA patients. The results showed that intra-articular injection of quercitrin increased bone volume/tissue volume of tibial subchondral bone and cartilage thickness and reduced the Osteoarthritis Research Society International scores in OA rats. Meanwhile, immunohistochemical results showed that quercitrin exerted anti-OA effect by delaying ECM degradation.

Conclusion: These findings suggested that quercitrin may be a prospective disease-modifying OA drug for prevention and treatment of early stage OA.

简介：细胞外基质（ECM）降解稳态的破坏在骨关节炎（OA）的发病机理中起着重要作用。基质金属蛋白酶13（MMP13）和Ⅱ型胶原是ECM的重要组成部分。早先我们发现槲皮素可以显着降低IL-1β诱导的大鼠软骨细胞和人软骨肉瘤（SW1353）细胞中MMP13基因表达并增加Ⅱ型胶原蛋白表达。

目的：探讨槲皮素对OA的作用及其机制。

方法：在体外研究了槲皮素在OA和SW1353细胞中的作用机理。OA的前十字韧带横断（ACLT）大鼠模型用于研究槲皮素在体内的作用。进行膝关节标本的显微CT分析和番红O型-快速绿染色，观察胫骨软骨下骨的损伤程度。进行膝关节标本的免疫组织化学检查，观察关节软骨中MMP13，Ⅱ型胶原和p110α的蛋白水平。

结果：在体外，槲皮素通过调节MMP13和胶原II基因和蛋白质表达来促进细胞增殖并延迟ECM降解。此外，槲皮素通过靶向p110α激活了磷脂酰肌醇3-激酶p110α（p110α）/ AKT / mTOR信号通路。我们还首先表明，OA患者软骨中p110α的基因表达水平显着降低。结果表明，关节腔内注射槲皮素可增加OA大鼠的胫骨软骨下骨的骨体积/组织体积和软骨厚度，并降低国际骨关节炎研究协会的评分。同时，免疫组织化学结果显示槲皮素通过延迟ECM降解发挥抗OA作用。

结论：这些发现表明槲皮素可能是预防和治疗早期OA的前瞻性疾病改良OA药物。