The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.
Department of Orthopedic Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
PLoS One. 2021 Dec 2;16(12):e0259130. doi: 10.1371/journal.pone.0259130. eCollection 2021.
The green-lipped mussel (GLM) contains novel omega-3 polyunsaturated fatty acids, which exhibit anti-inflammatory and joint-protecting properties. Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage; oxidative stress plays a role in the pathogenesis of OA. The objectives of this study were to investigate the in vivo effects of the GLM on pain severity and cartilage degeneration using an experimental rat OA model, and to explore the mode of action of GLM. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) into the knee. Oral GLM was initiated on the day after 3dyas of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed both macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-1β (IL-1β), IL-6, nitrotyrosine, and inducible nitric oxide synthase (iNOS) in knee joints. Also, the GLM was applied to OA chondrocyte, and the expression on catabolic marker and necroptosis factor were evaluated by real-time polymerase chain reaction. Administration of the GLM improved pain levels by preventing cartilage damage and inflammation. GLM significantly attenuated the expression levels of mRNAs encoding matrix metalloproteinase-3 (MMP-3), MMP-13, and ADAMTS5 in IL-1β-stimulated human OA chondrocytes. GLM decreased the expression levels of the necroptosis mediators RIPK1, RIPK3, and the mixed lineage kinase domain-like protein (MLKL) in IL-1β-stimulated human OA chondrocytes. Thus, GLM reduced pain and cartilage degeneration in rats with experimentally induced OA. The chondroprotective properties of GLM included suppression of oxidative damage and inhibition of catabolic factors implicated in the pathogenesis of OA cartilage damage. We suggest that GLM may usefully treat human OA.
绿唇贻贝（GLM）含有新型的ω-3 多不饱和脂肪酸，具有抗炎和保护关节的特性。骨关节炎（OA）是一种退行性关节疾病，其特征是软骨逐渐丧失；氧化应激在 OA 的发病机制中起作用。本研究的目的是通过实验性大鼠 OA 模型研究 GLM 对疼痛严重程度和软骨退化的体内作用，并探讨 GLM 的作用方式。通过向膝关节内注射单碘乙酸钠（MIA）诱导大鼠 OA。在 MIA 注射后的第 3 天开始口服 GLM。通过测量足底退缩潜伏期和阈值来评估肢体痛觉。对样本进行宏观和组织学分析。免疫组织化学用于检测膝关节中白细胞介素-1β（IL-1β）、IL-6、硝基酪氨酸和诱导型一氧化氮合酶（iNOS）的表达。此外，将 GLM 应用于 OA 软骨细胞，并通过实时聚合酶链反应评估分解代谢标志物和坏死性凋亡因子的表达。GLM 通过防止软骨损伤和炎症来改善疼痛水平。GLM 显著降低了 IL-1β 刺激的人 OA 软骨细胞中编码基质金属蛋白酶-3（MMP-3）、MMP-13 和 ADAMTS5 的 mRNA 的表达水平。GLM 降低了 IL-1β 刺激的人 OA 软骨细胞中坏死性凋亡介质 RIPK1、RIPK3 和混合谱系激酶结构域样蛋白（MLKL）的表达水平。因此，GLM 减轻了实验诱导的 OA 大鼠的疼痛和软骨退化。GLM 的软骨保护特性包括抑制氧化损伤和抑制与 OA 软骨损伤发病机制相关的分解代谢因子。我们建议 GLM 可有效治疗人类 OA。
