Gossypol Acetic Acid Alleviates the Ferroptosis of Chondrocytes in Osteoarthritis by Inhibiting GPX4 Methylation.

IF 3.5 4区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current medicinal chemistry Pub Date : 2025-01-01 DOI:10.2174/0109298673280730231211092905

Jingjing Shang, Chenwei Xiong, Wei Jiang, Zhentang Yu, Junjie Zhang, Yi Zhang, Long Han, Kaisong Miao, Changlin Yu, Yong Huang, Xindie Zhou

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引用次数: 0

Abstract

Background: Osteoarthritis (OA) is a chronic joint disease, usually accompanied by degeneration of the articular cartilage, fibrosis, bone hyperplasia around the joint, and damage to the entire articular surface. Gossypol is a natural phenolic compound isolated from the seed of cotton plants, and gossypol acetic acid (GAA) is a medicinal form of Gossypol. Recently, various biological activities of GAA, including anti-inflammatory and anti-tumor effects, have been widely reported. However, its effect on chondrocytes in OA has yet to be determined.

Methods: In this study, we investigated the effect of GAA on ferroptosis in OA chondrocytes. The effect of GAA on the cell viability and cytotoxicity of chondrocytes in rat cells was investigated using CCK8. Western blotting, Reverse-transcription PCR (RT-PCR), and immunofluorescence staining were used to elucidate the molecular mechanisms and signaling pathways of GAA inhibition of ferroptosis in OA chondrocytes. The effect of GAA on reactive oxygen species (ROS) production and lipid peroxidation levels in chondrocytes was examined using dihydroethidium (DHE) staining and fluorescent dye BODIPY581/591 C11. In vivo, micro-CT imaging, hematoxylin and eosin staining, Safranin O-Fast staining, and immunohistochemistry were performed to evaluate the effects of GAA on OA cartilage.

Results: The results showed that GAA treatment regulated the expression of chondrocyte extracellular matrix (ECM) related factors, including ADAMTS5, MMP13, SOX9, Aggrecan, and COL1A2 and reduced the ROS and lipid peroxidation levels. Besides, Erastin could reverse the effects of GAA on chondrocytes. Similar to GAA, 5-AZA caused the reduction of ROS and lipid peroxidation levels and reversed the effect of IL-1β on the expression of ECM-related factors in OA chondrocytes. The above results clarified that GAA alleviated the ferroptosis of chondrocytes in OA by inhibiting GPX4 methylation.

Conclusion: Our findings revealed that GAA might be developed as a drug for treating OA clinically.

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棉酚乙酸通过抑制 GPX4 甲基化减轻骨关节炎软骨细胞的铁沉积。

背景：骨关节炎（OA）是一种慢性关节疾病，通常伴有关节软骨退化、纤维化、关节周围骨质增生以及整个关节表面的损伤。棉酚是从棉花种子中分离出来的一种天然酚类化合物，棉酚乙酸（GAA）是棉酚的一种药用形式。最近，GAA 的各种生物活性，包括抗炎和抗肿瘤作用已被广泛报道。然而，它对 OA 中软骨细胞的影响尚未确定：本研究探讨了 GAA 对 OA 软骨细胞铁突变的影响。使用 CCK8 研究了 GAA 对大鼠软骨细胞的细胞活力和细胞毒性的影响。采用Western印迹、逆转录PCR（RT-PCR）和免疫荧光染色等方法阐明了GAA抑制OA软骨细胞铁突变的分子机制和信号通路。在体内，通过显微CT成像、苏木精和伊红染色、Safranin O-Fast染色和免疫组化来评估GAA对OA软骨的影响：结果表明：GAA能调节软骨细胞细胞外基质（ECM）相关因子（包括ADAMTS5、MMP13、SOX9、Aggrecan和COL1A2）的表达，降低ROS和脂质过氧化水平。此外，Erastin 还能逆转 GAA 对软骨细胞的影响。与 GAA 相似，5-AZA 也能降低 ROS 和脂质过氧化水平，并逆转 IL-1β 对 OA 软骨细胞中 ECM 相关因子表达的影响。上述结果说明，GAA通过抑制GPX4甲基化减轻了OA软骨细胞的铁变态反应：我们的研究结果表明，GAA 可作为一种药物用于临床治疗 OA。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current medicinal chemistry 医学-生化与分子生物学

CiteScore

8.60

自引率

2.40%

发文量

468

审稿时长

3 months

期刊介绍： Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.