Li Yuguo, Wu Jiang, Zhuo Naiqiang
School of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.
School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China.
Exp Ther Med. 2023 Jul 10;26(2):406. doi: 10.3892/etm.2023.12105. eCollection 2023 Aug.
Ginsenoside compound K (GCK) has been previously reported to be a potent antiarthritic and bone-protective agent. Therefore, the present study aimed to explore the potential effects of GCK on osteoarthritis and its regulatory effects on the pyroptosis of chondrocytes. Primary mouse chondrocytes (PMCs) were used for analysis. ELISA assays revealed that compared with the untreated cells, TNF-α induced a significant increase in IL-6, MMP13, A disintegrin and metalloproteinase with thrombospondin motifs 5 and MMP3 expression but induced a significant decrease in aggrecan and collagen II expression. By contrast, GCK reversed the aforementioned alterations in a dose-dependent manner. Experimental osteoarthritis was subsequently induced in mice through transection of the medial meniscotibial ligament and medial collateral ligament in the right knee [destabilization of the medial meniscus (DMM) mice]. GCK was found to reduce cartilage degradation in DMM mice, which was assessed using the Osteoarthritis Research Society International (OARSI) score, collagen II and MMP13 expression. Cartilage degradation is associated with higher OARSI score, decreased collagen II and increased MMP13 expression. In PMCs, TNF-α treatment stimulated an increase in the expression of NLR family pyrin domain containing 3 (NLRP3), Gasdermin D-N terminal (GSDMD-NT), cleaved caspase-1 and mature IL-1β, markers that indicate the occurrence of pyroptosis. However, GCK treatment suppressed the increase of the aforementioned proteins in a dose-dependent manner. Immunohistochemistry staining of the knee joint tissue sections from the DMM mice confirmed that GCK attenuated the NLRP3 and GSDMD-NT expression that was induced by DMM surgery. In conclusion, the present study revealed that GCK can reduce cartilage degradation in an osteoarthritis model by inhibiting the NLRP3-inflammasome activation and subsequent pyroptosis.
人参皂苷Compound K（GCK）此前已被报道为一种有效的抗关节炎和骨保护剂。因此，本研究旨在探讨GCK对骨关节炎的潜在影响及其对软骨细胞焦亡的调节作用。使用原代小鼠软骨细胞（PMCs）进行分析。ELISA检测显示，与未处理的细胞相比，TNF-α诱导IL-6、MMP13、含血小板反应蛋白基序的解聚素和金属蛋白酶5以及MMP3表达显著增加，但诱导聚集蛋白聚糖和胶原蛋白II表达显著降低。相比之下，GCK以剂量依赖的方式逆转了上述变化。随后通过切断右膝内侧半月板胫骨韧带和内侧副韧带（内侧半月板失稳（DMM）小鼠）在小鼠中诱导实验性骨关节炎。发现GCK可减少DMM小鼠的软骨降解，这通过国际骨关节炎研究学会（OARSI）评分、胶原蛋白II和MMP13表达进行评估。软骨降解与较高的OARSI评分、胶原蛋白II减少和MMP13表达增加有关。在PMCs中，TNF-α处理刺激含NLR家族吡啶结构域3（NLRP3）、Gasdermin D-N端（GSDMD-NT）、裂解的半胱天冬酶-1和成熟IL-1β表达增加，这些标志物表明焦亡的发生。然而，GCK处理以剂量依赖的方式抑制了上述蛋白的增加。DMM小鼠膝关节组织切片的免疫组织化学染色证实，GCK减弱了DMM手术诱导的NLRP3和GSDMD-NT表达。总之，本研究表明，GCK可通过抑制NLRP3炎性小体激活及随后的焦亡来减少骨关节炎模型中的软骨降解。
