Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Int Immunopharmacol. 2023 Jun;119:110261. doi: 10.1016/j.intimp.2023.110261. Epub 2023 May 9.
Osteoarthritis (OA) is a common, progressive, and chronic disorder of the joints that is characterized by the inflammation and degradation of articular cartilage and is known to significantly impair quality of daily life. Stevioside (SVS) is a natural diterpenoid glycoside that has anti-inflammatory benefits. Hence, in the current research, it was hypothesized that SVS might exert anti-inflammatory effects on articular chondrocytes and alleviate cartilage degradation in mice with OA. The expression of inflammatory cytokines, like inducible nitric oxide synthase (iNOS), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), and cyclooxygenase-2 (COX-2) in chondrocytes after interleukin-1β (IL-1β) exposure, was inhibited by the pretreatment of SVS. As well, SVS inhibited the reduction of collagen II and sry-box transcription factor 9 (SOX9) in chondrocytes stimulated by IL-1β and suppressed the expression of MMP3 and MMP13. Further, after treatment with SVS, cell cytometry, autophagy flux, and related protein expression showed diminished cell apoptosis and reduced autophagy impairment. Moreover, SVS blocked the activation of phosphoinositide-3-kinase/Akt/nuclear factor-kappa beta (PI3K/Akt/NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways stimulated by IL-1β. This resulted in decreased cellular inflammation. In vivo experiments with intra-articular injections of SVS in mice with the DMM mouse model demonstrated a decrease in cartilage degradation and an improvement in subchondral bone remodeling. After the integrin αVβ3-related knockdown using siRNA, a reversed effect was observed on the anti-inflammatory, anabolic promoting, catabolic blocking, and NF-κB and MAPK signaling pathway inhibition of SVS on chondrocytes treated with IL-1β. The above findings highlighted that SVS blocked IL-1β, triggered an inflammatory response in mice chondrocytes, and prevented cartilage degradation in vivo through integrin αVβ3. This suggested that SVS might serve as a novel therapeutic option for OA.
骨关节炎（OA）是一种常见的、进行性的、慢性关节疾病，其特征为关节软骨炎症和降解，已知会显著降低日常生活质量。甜菊苷（SVS）是一种天然的二萜糖苷，具有抗炎作用。因此，在当前的研究中，假设 SVS 可能对软骨细胞发挥抗炎作用，并减轻 OA 小鼠的软骨降解。SVS 预处理可抑制白细胞介素-1β（IL-1β）暴露后软骨细胞中炎症细胞因子（如诱导型一氧化氮合酶（iNOS）、核苷酸结合寡聚化结构域样受体含pyrin 结构域 3（NLRP3）和环氧化酶-2（COX-2）的表达。此外，SVS 抑制 IL-1β刺激的软骨细胞中胶原 II 和 sry-box 转录因子 9（SOX9）的减少，并抑制 MMP3 和 MMP13 的表达。进一步，用 SVS 处理后，细胞细胞术、自噬流和相关蛋白表达显示细胞凋亡减少和自噬损伤减轻。此外，SVS 阻断了 IL-1β刺激的磷酸肌醇 3-激酶/Akt/核因子-κB（PI3K/Akt/NF-κB）和丝裂原活化蛋白激酶（MAPK）信号通路的激活。这导致细胞炎症减少。用 SVS 进行关节内注射的体内实验显示，DMM 小鼠模型中软骨降解减少，软骨下骨重塑改善。用 siRNA 敲低整合素 αVβ3 后，观察到 SVS 对 IL-1β处理的软骨细胞的抗炎、促进合成、抑制分解代谢以及 NF-κB 和 MAPK 信号通路抑制作用的逆转。上述发现强调了 SVS 通过整合素 αVβ3 阻断 IL-1β，在小鼠软骨细胞中引发炎症反应，并在体内防止软骨降解，表明 SVS 可能成为 OA 的一种新的治疗选择。
