Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China.
Oxid Med Cell Longev. 2021 Nov 3;2021:3137066. doi: 10.1155/2021/3137066. eCollection 2021.
Osteoarthritis (OA) is a progressive illness that destroys cartilage. Oxidative stress is a major contributor of OA, while endoplasmic reticulum (ER) stress is the key cellular damage under oxidative stress in chondrocytes. Echinacoside (ECH) is the main extract and active substance of , with potent antioxidative stress (OS) properties, and currently under clinical trials in China. However, its function in OA is yet to be determined.
We aimed to explore the specific role of ECH in the occurrence and development of OA and its underlying mechanism and .
After the mice were anesthetized, the bilateral medial knee joint meniscus resection was performed to establish the DMM model. TBHP was used to induce oxidative stress to establish the OA model in chondrocytes . Western blot and RT-PCR were used to evaluate the level of ER stress-related biomarkers such as p-PERK/PERK, GRP78, ATF4, p-eIF2/eIF2, and CHOP and apoptosis-related proteins such as BAX, Bcl-2, and cleaved caspase-3. Meanwhile, we used SO staining, immunofluorescence, and immunohistochemical staining to evaluate the pharmacological effects of ECH in mice .
We demonstrated the effectiveness of ECH in suppressing ER stress and restoring ECM metabolism . In particular, ECH was shown to suppress tert-Butyl hydroperoxide- (TBHP-) induced OS and subsequently lower the levels of p-PERK/PERK, GRP78, ATF4, p-eIF2/eIF2, and CHOP . Simultaneously, ECH reduced MMP13 and ADAMTS5 levels and promoted Aggrecan and Collagen II levels, suggesting ECM degradation suppression. Moreover, we showed that ECH mediates its cellular effects via upregulation of Sirt1. Lastly, we confirmed that ECH can protect against OA in mouse OA models.
In summary, our findings indicate that ECH can inhibit ER stress and ECM degradation by upregulating Sirt1 in mouse chondrocytes treated with TBHP. It can also prevent OA development .
骨关节炎（OA）是一种渐进性疾病，会破坏软骨。氧化应激是 OA 的主要致病因素，而内质网（ER）应激是软骨细胞氧化应激下的关键细胞损伤。松果菊苷（ECH）是 的主要提取物和活性物质，具有强大的抗氧化应激（OS）特性，目前正在中国进行临床试验。然而，其在 OA 中的作用尚待确定。
我们旨在探讨 ECH 在 OA 发生发展中的具体作用及其潜在机制。
将小鼠麻醉后，双侧膝关节内侧半月板切除术建立 DMM 模型。TBHP 诱导氧化应激建立软骨细胞 OA 模型。Western blot 和 RT-PCR 用于评估 ER 应激相关生物标志物如 p-PERK/PERK、GRP78、ATF4、p-eIF2/eIF2 和 CHOP 以及凋亡相关蛋白如 BAX、Bcl-2 和 cleaved caspase-3 的水平。同时，我们使用 SO 染色、免疫荧光和免疫组化染色评估 ECH 在小鼠中的药效。
我们证明了 ECH 抑制 ER 应激和恢复 ECM 代谢的有效性。特别是，ECH 抑制 tert-Butyl hydroperoxide-（TBHP-）诱导的 OS，随后降低 p-PERK/PERK、GRP78、ATF4、p-eIF2/eIF2 和 CHOP 的水平。同时，ECH 降低了 MMP13 和 ADAMTS5 的水平，促进了 Aggrecan 和 Collagen II 的水平，提示 ECM 降解抑制。此外，我们表明 ECH 通过上调 Sirt1 介导其细胞作用。最后，我们证实 ECH 可以保护小鼠 OA 模型免受 OA 的影响。
总之，我们的研究结果表明，ECH 可以通过上调 TBHP 处理的小鼠软骨细胞中的 Sirt1 来抑制 ER 应激和 ECM 降解。它还可以预防 OA 的发展。
