Aims

The development of osteoarthritis (OA), the most common form of arthritis, is commonly associated with oxidative stress. Indeed, the lack of antioxidant responses largely increases OA incidence. OA is a leading cause of disability in the elderly, which reduces the quality of life and places high socioeconomic burdens on them. Several polyphenolic compounds, including chlorogenic acid (CGA), have shown cytoprotective effects via their antioxidant activity, but the exact mechanism (s) remain elusive. In this study, we demonstrated how CGA protects human chondrocytes against H₂O₂-induced apoptosis.

Materials and methods

The cytoprotective effect by CGA in 500 μM hydrogen peroxide-treated C28/I2 cells was evaluated by cell viability, TUNEL assay, and Western blotting analyses, and autophagy assessment was further performed by AO and MDC staining and tandem mRFP-GFP fluorescence analyses.

Key findings

Treatment of CGA to the human chondrocytes under oxidative stress significantly decreased apoptosis markers, such as cleaved caspase 3 and cleaved PARP, and increased anti-apoptotic marker Bcl-xL and the antioxidant response proteins NRF2 and NF-κB. Furthermore, CGA-dependent activation of antioxidant response proteins NRF2 and NF-κB and its protective effects in chondrocytes depended on autophagy. Indeed, CGA treatment and autophagy induction significantly decreased reactive oxygen species (ROS)–induced apoptosis.

Significance

CGA exhibited the protective effect to human chondrocyte C28/I2 cells against oxidative stress-induced cell death by activating autophagy. These findings indicate that CGA is a potential therapeutic agent for the development of OA drugs.

中文翻译：

---

绿原酸通过激活自噬保护人类软骨细胞 C28/I2 细胞免受氧化应激诱导的细胞死亡

宗旨

骨关节炎 (OA) 是最常见的关节炎形式，通常与氧化应激有关。事实上，缺乏抗氧化反应在很大程度上增加了 OA 的发生率。OA 是老年人残疾的主要原因，它降低了生活质量并给他们带来了沉重的社会经济负担。包括绿原酸 (CGA) 在内的几种多酚化合物已通过其抗氧化活性显示出细胞保护作用，但确切的机制仍然难以捉摸。在这项研究中，我们展示了 CGA 如何保护人类软骨细胞免受 H ₂ O ₂诱导的细胞凋亡。

材料和方法

通过细胞活力、TUNEL 测定和蛋白质印迹分析评估 CGA 在 500 μM 过氧化氢处理的 C28/I2 细胞中的细胞保护作用，并通过 AO 和 MDC 染色和串联 mRFP-GFP 荧光分析进一步进行自噬评估。

主要发现

在氧化应激下对人软骨细胞进行 CGA 处理可显着降低细胞凋亡标志物，例如裂解的半胱天冬酶 3 和裂解的 PARP，并增加抗凋亡标志物 Bcl-xL 和抗氧化反应蛋白 NRF2 和 NF-κB。此外，抗氧化反应蛋白 NRF2 和 NF-κB 的 CGA 依赖性激活及其对软骨细胞的保护作用取决于自噬。事实上，CGA 处理和自噬诱导显着降低了活性氧 (ROS) 诱导的细胞凋亡。

意义

CGA 通过激活自噬对人软骨细胞 C28/I2 细胞具有抗氧化应激诱导的细胞死亡的保护作用。这些发现表明 CGA 是开发 OA 药物的潜在治疗剂。