Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.
Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan.
Aging (Albany NY). 2024 Sep 5;16(18):12559-12573. doi: 10.18632/aging.206101.
Osteoarthritis (OA) is a chronic inflammatory disease accompanied by joint pain, bone degradation, and synovial inflammation. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β play key roles in chronic inflammation, and matrix metalloproteinase (MMP)3 is the first enzyme released by chondrocytes and synovial cells that promotes MMPs' degrading cartilage matrix (including collage II and aggrecan) function. Using an anterior cruciate ligament transection (ACLT) rat model, GKD7 has shown anti-inflammatory and analgesic properties. The present investigation examined the chondroprotective effects of several dosages and formulas of GKD7 on rats in an ACLT-induced OA model. The findings indicate that oral treatment with both live-GKD7 (GKD7-L) and dead-GKD7 (GKD7-D), along with celecoxib (positive control), all reduce post-ACLT pain and inflammation in OA joints. Subsequently, the immunohistochemical staining results demonstrate that following GKD7-L and GKD7-D treatment, there was a reversal of the degradation of collagen II and aggrecan, as well as a decrease in the expression of IL-1β and TNF-α on the synovial tissue and MMP3 on the cartilage. Accordingly, our findings imply that the treatment of both GKD7-L and GKD7-D has chondroprotective and analgesic effects on the OA rat model, and that celecoxib and GKD7-L at dosages (100 mg/kg) have comparable therapeutic benefits. As a result, we propose that both GKD7-L and GKD7-D are helpful supplements for OA management.
骨关节炎（OA）是一种慢性炎症性疾病，伴有关节疼痛、骨降解和滑膜炎症。肿瘤坏死因子（TNF）-α 和白细胞介素（IL）-1β 在慢性炎症中发挥关键作用，基质金属蛋白酶（MMP）3 是软骨细胞和滑膜细胞释放的第一种促进 MMP 降解软骨基质（包括胶原 II 和聚集蛋白聚糖）的酶。使用前交叉韧带切断（ACLT）大鼠模型，GKD7 表现出抗炎和镇痛作用。本研究检查了几种剂量和配方的 GKD7 对 ACLT 诱导的 OA 模型大鼠的软骨保护作用。研究结果表明，口服活 GKD7（GKD7-L）和死 GKD7（GKD7-D）以及塞来昔布（阳性对照）均可减轻 OA 关节的术后疼痛和炎症。随后，免疫组织化学染色结果表明，在 GKD7-L 和 GKD7-D 治疗后，胶原 II 和聚集蛋白聚糖的降解得到逆转，滑膜组织中 IL-1β 和 TNF-α 的表达以及软骨上的 MMP3 表达减少。因此，我们的研究结果表明，GKD7-L 和 GKD7-D 的治疗对 OA 大鼠模型具有软骨保护和镇痛作用，塞来昔布和 GKD7-L（100mg/kg）的剂量具有相当的治疗益处。因此，我们建议 GKD7-L 和 GKD7-D 都是 OA 管理的有益补充。
