Department of Knee Surgery, Luoyang Orthopedic-Traumatological Hospital of Henan Province, Zhengzhou, China.
Lab of Molecular Biology, Luoyang Orthopedic-Traumatological Hospital of Henan Province, Zhengzhou, China.
Bioengineered. 2022 Jan;13(1):1802-1813. doi: 10.1080/21655979.2021.1997090.
Osteoarthritis (OA) is a cartilage degenerative disease commonly observed in the elderly population and is pathologically characterized by the degradation of the cartilage extracellular matrix (ECM). Matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) are critical enzymes involved in the degradation of ECM. Olmesartan is an inhibitor of the angiotensin II receptor developed for the treatment of hypertension, and recent studies show that it exerts anti-inflammatory effects in arthritis. The present study aimed to investigate the mechanism of the protective effect of Olmesartan on cartilage ECM degradation. Interleukin-29 (IL-29) is a novel inflammatory mediator involved in the inflammation and degradation of cartilage in OA, and human T/C-28a2 cells treated with it were the inflammatory model . We found that the degradation of type 2 collagens and aggrecans was induced by IL-29, accompanied by the upregulation of MMPs and ADAMTSs, but the presence of Olmesartan significantly ameliorated these increases. In addition, Olmesartan abolished IL-29- induced oxidative stress and elevated the expression level of TNF receptor-associated factor 6 (TRAF-6). Mechanistically, we showed that Olmesartan suppressed IL-29- caused inhibitor kappa B α (IκBα) expression and nuclear translocation of nuclear factor kappa-B (NF-κB) p65, indicating it suppressed the activation of the NF-κB pathway. Collectively, our data reveal that Olmesartan exerted a protective function on IL-29- induced type 2 collagen degradation in human chondrocytes.
骨关节炎（OA）是一种常见于老年人群的软骨退行性疾病，其病理特征为软骨细胞外基质（ECM）降解。基质金属蛋白酶（MMPs）和含有解整合素金属蛋白酶与凝血酶敏感蛋白基元（ADAMTSs）是参与 ECM 降解的关键酶。奥美沙坦是一种用于治疗高血压的血管紧张素 II 受体抑制剂，最近的研究表明它在关节炎中具有抗炎作用。本研究旨在探讨奥美沙坦对软骨 ECM 降解的保护作用机制。白细胞介素-29（IL-29）是一种新型炎症介质，参与 OA 中软骨的炎症和降解，用其处理的人 T/C-28a2 细胞是炎症模型。我们发现 IL-29 诱导 2 型胶原和聚集素降解，同时 MMPs 和 ADAMTSs 表达上调，但奥美沙坦的存在显著改善了这些增加。此外，奥美沙坦消除了 IL-29 诱导的氧化应激并提高了肿瘤坏死因子受体相关因子 6（TRAF-6）的表达水平。从机制上讲，我们表明奥美沙坦抑制了 IL-29 引起的抑制剂 kappa B α（IκBα）表达和核因子 kappa-B（NF-κB）p65 的核转位，表明它抑制了 NF-κB 通路的激活。总之，我们的数据表明奥美沙坦对人软骨细胞中 IL-29 诱导的 2 型胶原降解具有保护作用。
