Mi Bobin, Wang Junqing, Liu Yi, Liu Jing, Hu Liangcong, Panayi Adriana C, Liu Guohui, Zhou Wu
Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, China.
Front Pharmacol. 2018 Jun 6;9:605. doi: 10.3389/fphar.2018.00605. eCollection 2018.
Osteoarthritis (OA) is a common chronic and degenerative joint condition that is mainly characterized by cartilage degradation, osteophyte formation, and joint stiffness. The NF-κB signaling pathway in inflammation, autophagy, and apoptosis plays a prominent role in the progression of OA. Icariin, a prenylated flavonol glycoside extracted from Epimedium, have been proven to exert anti-osteoporotic and anti-inflammatory effects in OA. However, the action mechanisms of its effect on chondrocytes have yet to be elucidated. In the present study, we demonstrated that the therapeutic effects of icariin on rat chondrocytes in a dose-dependent manner. We found that TNF-α induced the production of IL-1, IL-6, IL-12, reactive oxygen species (ROS), nitric oxide (NO), Caspase-3, and Caspase-9 in chondrocytes. We also provided evidence that TNF-α inhibited autophagy markers (Atg 5, Atg 7) and prevented LC3 I translate to LC3 II. Furthermore, TNF-α induced matrix metalloproteinase (MMP)3 and MMP9 expression. The negative effects of TNF-α on chondrocytes can be partially blocked by treating with icariin or ammonium pyrrolidinedithiocarbamate (PDTC, an NF-κB inhibitor). The present study data also suggested that icariin suppressed both TNF-α-stimulated p65 nuclear translocation and IκBα protein degradation. These results indicated that icariin protected against OA by suppressing inflammatory cytokines and apoptosis, through activation of autophagy via NF-κB inhibition. In conclusion, icariin appears to favorably modulate autophagy and apoptosis in chondrocytes making it a promising compound for cartilage tissue engineering in the treatment of OA.
骨关节炎（OA）是一种常见的慢性退行性关节疾病，主要特征为软骨降解、骨赘形成和关节僵硬。炎症、自噬和凋亡中的核因子κB（NF-κB）信号通路在OA进展中起重要作用。淫羊藿苷是从淫羊藿中提取的一种异戊烯基黄酮醇苷，已被证明在OA中具有抗骨质疏松和抗炎作用。然而，其对软骨细胞作用的机制尚待阐明。在本研究中，我们证明淫羊藿苷对大鼠软骨细胞具有剂量依赖性治疗作用。我们发现肿瘤坏死因子-α（TNF-α）诱导软骨细胞产生白细胞介素-1（IL-1）、白细胞介素-6（IL-6）、白细胞介素-12、活性氧（ROS）、一氧化氮（NO）、半胱天冬酶-3（Caspase-3）和半胱天冬酶-9。我们还提供证据表明TNF-α抑制自噬标志物（自噬相关蛋白5（Atg 5）、自噬相关蛋白7（Atg 7）），并阻止微管相关蛋白1轻链3（LC3）I转化为LC3 II。此外，TNF-α诱导基质金属蛋白酶（MMP）3和MMP9表达。淫羊藿苷或吡咯烷二硫代氨基甲酸铵（PDTC，一种NF-κB抑制剂）处理可部分阻断TNF-α对软骨细胞的负面影响。本研究数据还表明淫羊藿苷抑制TNF-α刺激的p65核转位和IκBα蛋白降解。这些结果表明淫羊藿苷通过抑制炎症细胞因子和凋亡，通过抑制NF-κB激活自噬来预防OA。总之，淫羊藿苷似乎能有利地调节软骨细胞中的自噬和凋亡，使其成为治疗OA的软骨组织工程中有前景的化合物。
