Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
Int Immunopharmacol. 2024 Oct 25;140:112741. doi: 10.1016/j.intimp.2024.112741. Epub 2024 Aug 1.
Osteoarthritis (OA) is a chronic degenerative disease characterized by cartilage degeneration, involving inflammation, pyroptosis, and degeneration of the extracellular matrix (ECM). Pectolinarigenin (PEC) is a natural flavonoid with antioxidant, anti-inflammatory and anti-tumor properties. This study aims to explore the potential of PEC in ameliorating OA progression and its underlying mechanisms.
Chondrocytes were exposed to 10 ng/mL IL-1β to simulate OA-like changes. The effect of PEC on IL-1β-treated chondrocytes was assessed using ELISA, western blot, and immunofluorescence. The mRNA sequencing (mRNA-seq) was employed to explore the possible targets of PEC in delaying OA progression. The OA mouse model was induced through anterior cruciate ligament transection (ACLT) and divided into sham, ACLT, ACLT+5 mg/kg PEC, and ACLT+10 mg/kg PEC groups. Micro-computed tomography and histological analysis were conducted to confirm the beneficial effects of PEC on OA in vivo.
PEC mitigated chondrocyte pyroptosis, as evidenced by reduced levels of pyroptosis-related proteins. Additionally, PEC attenuated IL-1β-mediated chondrocyte ECM degradation and inflammation. Mechanistically, mRNA-seq showed that FGFR3 was a downstream target of PEC. FGFR3 silencing reversed the beneficial effects of PEC on IL-1β-exposed chondrocytes. PEC exerted anti-pyroptotic, anti-ECM degradative, and anti-inflammatory effects through upregulating FGFR3 to inhibit the NF-κB/NLRP3 pyroptosis-related pathway. Consistently, in vivo experiments demonstrated the chondroprotective effects of PEC in OA mice.
PEC alleviate OA progression by FGFR3/NF-κB/NLRP3 pathway mediated chondrocyte pyroptosis, ECM degradation and inflammation, suggesting the potential of PEC as a therapeutic agent for OA.
骨关节炎（OA）是一种以软骨退化为特征的慢性退行性疾病，涉及炎症、细胞焦亡和细胞外基质（ECM）的退化。红厚壳素（PEC）是一种具有抗氧化、抗炎和抗肿瘤特性的天然类黄酮。本研究旨在探讨 PEC 改善 OA 进展的潜力及其潜在机制。
用 10ng/mL IL-1β 处理软骨细胞模拟 OA 样变化。用 ELISA、western blot 和免疫荧光法评估 PEC 对 IL-1β 处理的软骨细胞的作用。采用 mRNA 测序（mRNA-seq）探讨 PEC 延缓 OA 进展的可能靶点。通过前交叉韧带切断术（ACLT）诱导 OA 小鼠模型，并分为假手术组、ACLT 组、ACLT+5mg/kgPEC 组和 ACLT+10mg/kgPEC 组。通过微计算机断层扫描和组织学分析确认 PEC 对体内 OA 的有益作用。
PEC 减轻了软骨细胞的细胞焦亡，表现为细胞焦亡相关蛋白水平降低。此外，PEC 减弱了 IL-1β 介导的软骨细胞 ECM 降解和炎症。机制上，mRNA-seq 显示 FGFR3 是 PEC 的下游靶点。沉默 FGFR3 逆转了 PEC 对 IL-1β 暴露的软骨细胞的有益作用。PEC 通过上调 FGFR3 抑制 NF-κB/NLRP3 细胞焦亡相关通路发挥抗细胞焦亡、抗 ECM 降解和抗炎作用。同样，体内实验证明了 PEC 在 OA 小鼠中的软骨保护作用。
PEC 通过 FGFR3/NF-κB/NLRP3 通路介导的软骨细胞细胞焦亡、ECM 降解和炎症减轻 OA 进展，提示 PEC 作为 OA 治疗药物的潜力。
