Oleocanthal Inhibits Catabolic and Inflammatory Mediators in LPS-Activated Human Primary Osteoarthritis (OA) Chondrocytes Through MAPKs/NF-κB Pathways
Oleocanthal Inhibits Catabolic and Inflammatory Mediators in LPS-Activated Human Primary Osteoarthritis (OA) Chondrocytes Through MAPKs/NF-κB Pathways
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DOI：
10.1159/000493840
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Gualillo, Oreste
中科院分区：
文献类型：
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作者：
Scotece, Morena;Conde, Javier;Gualillo, Oreste
背景/目的：油橄榄醛 (OC) 是一种存在于特级初榨橄榄油 (EVOO) 中的酚类化合物，自从发现其在包括炎症在内的不同致病过程中的相关药理学特性以来，引起了人们的关注。在这里，我们研究了 OC 在 LPS 激活的骨关节炎 (OA) 人原代软骨细胞中的作用。方法：从 OA 患者的关节软骨样本中采集人原代软骨细胞。通过MTT法检测OC对软骨细胞活力的影响。分别通过 RT-qPCR 和蛋白质印迹测量 OC 治疗后几种分解代谢因子和促炎因子的蛋白质和 mRNA 表达。此外，我们还分析了格里斯反应产生的NO。 Finally, several pathways mediators were analysed by western blot.结果：我们证明 OC 没有任何细胞毒性作用。在 LPS 激活的人原代 OA 软骨细胞中，Oleocanthal 抑制 NO 产生并强烈降低 NOS2 和 COX-2 蛋白及 mRNA 表达。有趣的是，OC 还抑制 MMP-13 和 ADAMTS-5。此外，OC 还能下调人原代 OA 软骨细胞中由 LPS 诱导的多种促炎因子，例如 IL-6、IL-8、CCL3、LCN2 和 TNF-α。最后，我们证明了 OC 通过 MAPK/P38/NF kappa B 途径发挥其作用。结论：这些数据表明，OC 能够通过 MAPKs/NF kappa B 途径阻断 LPS 介导的炎症反应以及人原代 OA 软骨细胞中 MMP-13 和 ADAMTS-5 的诱导，表明 OC 可能是治疗软骨炎症的有前途的药物，也是通过抑制金属蛋白酶和蛋白聚糖酶来预防疾病进展的潜在分子。 (C) 2018 作者由巴塞尔 S. Karger AG 出版
Background/Aims: Oleocanthal (OC), a phenolic compound present in extra virgin olive oil (EVOO), has attracted attention since its discovery for its relevant pharmacological properties in different pathogenic processes, including inflammation. Here, we investigated the involvement of OC in LPS-activated osteoarthritis (OA) human primary chondrocytes. Methods: Human primary chondrocytes were harvested from articular cartilage samples obtained from OA patients. The effects of OC on the viability of chondrocytes were tested by MTT assay. Protein and mRNA expression of several catabolic and pro-inflammatory factors after OC treatment were measured by RT-qPCR and western blot respectively. Moreover, we analysed the NO production by Griess reaction. Finally, several pathways mediators were analysed by western blot. Results: We demonstrated that OC did not have any cytotoxic effect. Oleocanthal inhibited NO production and strongly decreased NOS2 and COX-2 protein and mRNA expression in LPS-activated human primary OA chondrocytes. Interestingly, OC also inhibits MMP-13 and ADAMTS-5. In addition, OC downregulates several pro-inflammatory factors, such as IL-6, IL-8, CCL3, LCN2 and TNF-alpha induced by LPS in human primary OA chondrocytes. Finally, we demonstrated that OC exerts its effects through the MAPK/P38/NF kappa B pathways. Conclusion: These data show that OC is able to block LPS-mediated inflammatory response and MMP-13 and ADAMTS-5 induction in human primary OA chondrocytes via MAPKs/NF kappa B pathways, suggesting that OC may be a promising agent for the treatment of inflammation in cartilage and a potential molecule to prevent disease progression by inhibiting metalloproteases and aggrecanases. (C) 2018 The Author(s) Published by S. Karger AG, Basel