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Abstract：
Osteoarthritis (OA) is the most common joint disease, causing symptoms such as joint pain, swelling, and deformity, which severely affect patients\' quality of life. Despite advances in medical treatment, OA management remains challenging, necessitating the development of safe and effective drugs. Quercetin (QUE), a natural flavonoid widely found in fruits and vegetables, shows promise due to its broad range of pharmacological effects, particularly in various degenerative diseases. However, its role in preventing OA progression and its underlying mechanisms remain unclear. In this study, we demonstrated that QUE has a protective effect against OA development both in vivo and in vitro, and we elucidated the underlying molecular mechanisms. In vitro, QUE inhibited the expression of IL-1β-induced chondrocyte matrix metalloproteinases (MMP3 and MMP13) and inflammatory mediators such as INOS and COX-2. It also promoted the expression of collagen II, thereby preventing the extracellular matrix (ECM). Mechanistically, QUE exerts its protective effect on chondrocytes by activating the SIRT1/Nrf-2/HO-1 and inhibiting chondrocyte ferroptosis. Similarly, in an OA rat model induced by anterior cruciate ligament transection (ACLT), QUE treatment improved articular cartilage damage, reduced joint pain, and normalized abnormal subchondral bone remodeling. QUE also reduced serum IL-1β, TNF-α, MMP3, CTX-II, and COMP, thereby slowing the progression of OA. QUE exerts chondroprotective effects by inhibiting chondrocyte oxidative damage and ferroptosis through the SIRT1/Nrf-2/HO-1 pathway, effectively alleviating OA progression in rats.
摘要：
骨关节炎（OA）是最常见的关节疾病，引起关节疼痛等症状，肿胀,和畸形，严重影响患者的生活质量。尽管在医疗方面取得了进展,OA管理仍然具有挑战性，需要开发安全有效的药物。槲皮素（QUE），一种广泛存在于水果和蔬菜中的天然类黄酮，由于其广泛的药理作用而显示出希望，特别是在各种退行性疾病中。然而,其在预防OA进展中的作用及其潜在机制尚不清楚.在这项研究中,我们证明了QUE在体内和体外对OA的发展都有保护作用，我们阐明了潜在的分子机制。体外，QUE抑制IL-1β诱导的软骨细胞基质金属蛋白酶（MMP3和MMP13）和炎症介质如INOS和COX-2的表达。它还促进胶原蛋白II的表达，从而防止细胞外基质（ECM）。机械上,QUE通过激活SIRT1/Nrf-2/HO-1和抑制软骨细胞的铁凋亡来发挥其对软骨细胞的保护作用。同样，在前交叉韧带横断（ACLT）诱导的OA大鼠模型中，QUE医治改良关节软骨毁伤，减少关节疼痛，和异常软骨下骨重塑正常化。QUE还降低了血清IL-1β，TNF-α,MMP3CTX-II,和COMP,从而减缓OA的进展。QUE通过SIRT1/Nrf-2/HO-1通路抑制软骨细胞氧化损伤和铁凋亡发挥软骨保护作用,有效缓解大鼠OA进展。
