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紫苏醇通过体外抑制骨关节炎软骨细胞中的PI3K-AKT-mTOR信号通路来促进自噬。

Perillyl alcohol promotes autophagy by suppressing the PI3K-AKT-mTOR signalling pathway in osteoarthritic chondrocytes in vitro.

作者信息

Zhao Duo, Nong Jiean, Li Xiaofeng, Tan Jianshi, Liao Rongbo, Chen Qianfen, Qiu Minqi

机构信息

Department of Spine and Osteopathy Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, Guangxi, China.

Department of Joint Surgery, The Second Nanning People's Hospital, Nanning, 530031, Guangxi, China.

出版信息

Sci Rep. 2025 Jul 22;15(1):26549. doi: 10.1038/s41598-025-12274-2.

DOI:10.1038/s41598-025-12274-2
PMID:40695916
Abstract

Osteoarthritis (OA) is a common degenerative disease characterized by chondrocyte death and extracellular matrix (ECM) degradation, but the present OA treatments are only symptomatic and not aetiologic. Autophagy is a key protective mechanism for OA through the inhibition of chondrocyte apoptosis and degeneration. Perillyl alcohol (POH) is a monomer derived from Chinese herbal medicines that can regulate autophagy and has anti-inflammatory effects. In this study, cell viability, chondrocyte phenotype and the expression of molecules involved in autophagy and the PI3K-AKT-mTOR signalling pathway were detected to explore the hypothesis that POH may decrease the progression of OA by regulating autophagy. We found that POH significantly inhibited the expression of inflammatory cytokines, maintained the chondrocyte phenotype, and protected against ECM degeneration. We also provide evidence that the anti-inflammatory effect of POH works by regulating autophagy via the PI3K-AKT-mTOR signalling pathway. This study demonstrates for the first time that POH has a therapeutic effect on arthritis, which suggests that POH may be a promising candidate for OA therapy.

摘要

骨关节炎(OA)是一种常见的退行性疾病,其特征在于软骨细胞死亡和细胞外基质(ECM)降解,但目前的OA治疗仅为对症治疗而非病因治疗。自噬是通过抑制软骨细胞凋亡和退变对OA起关键保护作用的机制。紫苏醇(POH)是一种源自中药的单体,可调节自噬并具有抗炎作用。在本研究中,检测了细胞活力、软骨细胞表型以及自噬和PI3K-AKT-mTOR信号通路相关分子的表达,以探讨POH可能通过调节自噬来减缓OA进展这一假说。我们发现POH显著抑制炎性细胞因子的表达,维持软骨细胞表型,并防止ECM退变。我们还提供证据表明POH的抗炎作用是通过PI3K-AKT-mTOR信号通路调节自噬来实现的。本研究首次证明POH对关节炎具有治疗作用,这表明POH可能是OA治疗的一个有前景的候选药物。

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本文引用的文献

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Aptamer-Modified Tetrahedral Framework Nucleic Acid Synergized with TGF-β3 to Promote Cartilage Protection in Osteoarthritis by Enhancing Chondrogenic Differentiation of MSCs.适配体修饰的四面体框架核酸与转化生长因子-β3协同作用,通过增强间充质干细胞的软骨形成分化促进骨关节炎中的软骨保护。
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Molecular pharmacology and therapeutic advances of monoterpene perillyl alcohol.单萜化合物紫苏醇的分子药理学和治疗学进展。
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MiR-653-5p drives osteoarthritis pathogenesis by modulating chondrocyte senescence.
miR-653-5p 通过调控软骨细胞衰老驱动骨关节炎发病机制。
Arthritis Res Ther. 2024 May 29;26(1):111. doi: 10.1186/s13075-024-03334-5.
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PPARγ regulates osteoarthritis chondrocytes apoptosis through caspase-3 dependent mitochondrial pathway.过氧化物酶体增殖物激活受体γ 通过 caspase-3 依赖的线粒体途径调节骨关节炎软骨细胞凋亡。
Sci Rep. 2024 May 16;14(1):11237. doi: 10.1038/s41598-024-62116-w.
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The role of targeting glucose metabolism in chondrocytes in the pathogenesis and therapeutic mechanisms of osteoarthritis: a narrative review.靶向软骨细胞糖代谢在骨关节炎发病机制和治疗机制中的作用:叙述性综述。
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The role of inflammatory mediators and matrix metalloproteinases (MMPs) in the progression of osteoarthritis.炎症介质和基质金属蛋白酶(MMPs)在骨关节炎进展中的作用。
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The Role of Extracellular Vesicles in the Pathogenesis and Treatment of Rheumatoid Arthritis and Osteoarthritis.细胞外囊泡在类风湿关节炎和骨关节炎发病机制和治疗中的作用。
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