抗氧化剂牛磺酸通过上调OGT/Gpx4信号抑制前交叉韧带横断引起的骨关节炎软骨细胞铁下垂

IF 11.4 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Journal of Advanced Research Pub Date : 2025-01-06 DOI:10.1016/j.jare.2025.01.010
Xuchang Zhou, Yajing Yang, Xu Qiu, Huili Deng, Hong Cao, Tao Liao, Xier Chen, Caihua Huang, Donghai Lin, Guoxin Ni
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引用次数: 0

摘要

目的探讨牛磺酸对软骨退行性变的潜在分子机制。方法采用前交叉韧带横断术(ACLT)建立骨关节炎(OA)动物模型。代谢组学用于鉴定骨关节炎软骨细胞的特征性代谢物。转录组学和代谢组学被用于探索小分子代谢物牛磺酸防止炎症性软骨细胞损伤的潜在机制。细胞转染和小分子抑制剂/激动剂被用来验证牛磺酸在体外保护炎性软骨细胞的分子机制。最后,使用腺相关病毒和小分子抑制剂/激动剂来验证牛磺酸在体内保护软骨变性的分子机制。结果代谢组学分析确定牛磺酸可能是OA进展中的关键代谢分子。转录组学和代谢组学显示,O-GlcNAc转移酶(OGT)依赖的o - glcn酰化和gpx4依赖的铁凋亡可能介导牛磺酸对软骨细胞的炎症保护作用,这一点在体外功能的获得和丧失中得到进一步证实。随后,进一步的实验表明Gpx4和OGT蛋白可能存在直接结合位点,这为Gpx4蛋白存在O-GlcNAc修饰提供了证据。最后,我们证明了gpx4依赖性铁下垂和ogt依赖性o - glcn酰化可能是牛磺酸在体内保护软骨变性的潜在机制。结论抗氧化牛磺酸通过上调OGT/Gpx4信号通路抑制软骨细胞铁下垂。补充牛磺酸,一种安全的非必需氨基酸,可能是OA的潜在治疗策略。
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Antioxidant taurine inhibits chondrocyte ferroptosis through upregulation of OGT/Gpx4 signaling in osteoarthritis induced by anterior cruciate ligament transection

Objective

The aim of this study was to investigate the potential molecular mechanisms by which taurine protects against cartilage degeneration.

Methods

The anterior cruciate ligament transection (ACLT) surgery was used to construct an animal model of osteoarthritis (OA). Metabolomics was used to identify characteristic metabolites in osteoarthritic chondrocytes. Transcriptomics and metabolomics were used to explore potential mechanisms by which the small molecule metabolite taurine protects against inflammatory chondrocyte damage. Cell transfection and small molecule inhibitors/agonists were used to validate the molecular mechanisms by which taurine protects inflammatory chondrocytes in vitro. Finally, adeno-associated virus and small molecule inhibitors/agonists were used to validate the molecular mechanisms by which taurine protects against cartilage degeneration in vivo.

Results

Metabolomic assays identified taurine as a possible key metabolic molecule in the progression of OA. Transcriptomics and metabolomics revealed that O-GlcNAc transferase (OGT)-dependent O-GlcNAcylation and Gpx4-dependent ferroptosis may mediate the inflammatory protective effects of taurine on chondrocytes, which was further confirmed by gain and loss of function in vitro. Subsequently, further experiments indicated that the possible existence of a direct binding site for Gpx4 and OGT proteins, which provides evidence for the presence of O-GlcNAc modification of Gpx4 protein. Finnaly, we demonstrated that Gpx4-dependent ferroptosis and OGT-dependent O-GlcNAcylation may be potential mechanisms by which taurine protects against cartilage degeneration in vivo.

Conclusion

Antioxidant taurine inhibits chondrocyte ferroptosis through upregulation of OGT/Gpx4 signaling. Supplementation with taurine, a safe nonessential amino acid, may be a potential therapeutic strategy for OA.
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来源期刊
Journal of Advanced Research
Journal of Advanced Research Multidisciplinary-Multidisciplinary
CiteScore
21.60
自引率
0.90%
发文量
280
审稿时长
12 weeks
期刊介绍: Journal of Advanced Research (J. Adv. Res.) is an applied/natural sciences, peer-reviewed journal that focuses on interdisciplinary research. The journal aims to contribute to applied research and knowledge worldwide through the publication of original and high-quality research articles in the fields of Medicine, Pharmaceutical Sciences, Dentistry, Physical Therapy, Veterinary Medicine, and Basic and Biological Sciences. The following abstracting and indexing services cover the Journal of Advanced Research: PubMed/Medline, Essential Science Indicators, Web of Science, Scopus, PubMed Central, PubMed, Science Citation Index Expanded, Directory of Open Access Journals (DOAJ), and INSPEC.
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