Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Int J Mol Sci. 2023 Jan 25;24(3):2365. doi: 10.3390/ijms24032365.
Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and cartilage degradation. Dendrobine (DEN) is reported to inhibit inflammation and oxidative stress in some diseases, but its role in chondrocyte senescence and OA progress has not yet been elucidated. Our study aimed to explore the protective effects of DEN on OA both in vitro and in vivo. We found that DEN inhibited extracellular matrix (ECM) degradation and promoted ECM synthesis. Meanwhile, DEN inhibited senescence-associated secretory phenotype (SASP) factors expression and senescence phenotype in IL-1β-treated chondrocytes. Furthermore, DEN improved mitochondrial function and reduced the production of intracellular reactive oxygen species (ROS). Also, DEN suppressed IL-1β-induced activation of the NF-κB pathway. Further, using NAC (ROS inhibitor), we found that DEN might inhibit NF-κB cascades by reducing ROS. Additionally, X-ray, micro-CT, and histological analyses in vivo demonstrated that DEN significantly alleviated cartilage inflammation, ECM degradation, and subchondral alterations in OA progression. In conclusion, DEN inhibits SASP factors expression and senescence phenotype in chondrocytes and alleviated the progression of OA via the ROS/NF-κB axis, which provides innovative strategies for the treatment of OA.
骨关节炎(OA)是一种退行性关节疾病,其特征为低度炎症和软骨降解。研究报道,石斛碱(DEN)可抑制某些疾病中的炎症和氧化应激,但它在软骨细胞衰老和 OA 进展中的作用尚未阐明。我们的研究旨在探讨 DEN 在体内和体外对 OA 的保护作用。我们发现 DEN 可抑制细胞外基质(ECM)降解并促进 ECM 合成。同时,DEN 抑制了 IL-1β 处理的软骨细胞中衰老相关分泌表型(SASP)因子的表达和衰老表型。此外,DEN 改善了线粒体功能并减少了细胞内活性氧物种(ROS)的产生。而且,DEN 抑制了 IL-1β 诱导的 NF-κB 通路的激活。此外,通过使用 NAC(ROS 抑制剂),我们发现 DEN 可能通过减少 ROS 来抑制 NF-κB 级联反应。此外,体内的 X 射线、微 CT 和组织学分析表明,DEN 可通过 ROS/NF-κB 轴显著减轻 OA 进展中的软骨炎症、ECM 降解和软骨下改变。总之,DEN 通过抑制 ROS/NF-κB 轴可抑制软骨细胞中 SASP 因子的表达和衰老表型,从而缓解 OA 的进展,为 OA 的治疗提供了创新策略。