Stigmasterol alleviates endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis.

IF 1.7 4区生物学 Q3 BIOLOGY

Open Life Sciences Pub Date : 2025-04-08 eCollection Date: 2025-01-01 DOI:10.1515/biol-2022-0913

Hao Li, Xiaofeng Chen, Baoci Huang, Junjie He, Junxian Xie, Weijun Guo, Jinjun Liang, Jiajian Ruan, Jincheng Liu, Zhen Xiang, Lixin Zhu

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Abstract

Intervertebral disc degeneration (IVDD) is a core factor in spinal degeneration. To date, there is no effective treatment for IVDD. It is urgent to identify the pathogenesis of IVDD to develop effective strategies for IVDD treatment. Alleviating endplate chondrocyte degeneration is a promising strategy for IVDD treatment, while mitophagy prevents degeneration of endplate chondrocytes. Stigmasterol (STM) protects neurons from injuries by triggering mitophagy, yet the effect of STM on the mitophagy of endplate chondrocytes in IVDD has not been reported. In this study, endplate chondrocyte degeneration was induced by interleukin-1β, and the ribonucleic acid (RNA) acetylation level was identified by acetylated RNA immunoprecipitation. Herein, results indicated that STM alleviated endplate chondrocyte degeneration. Besides, STM induced PTEN-induced kinase 1 (PINK1)-mediated mitophagy in degenerated endplate chondrocytes. Moreover, N-acetyltransferase 10 (NAT10) increased PINK1 expression by improving PINK1 mRNA acetylation in endplate chondrocytes. In addition, STM regulated NAT10 expression by estrogen receptor 1 (ESR1) in degenerated endplate chondrocytes. In summary, the present study revealed that STM attenuated endplate chondrocyte degeneration through inducing mitophagy by enhancing PINK1 mRNA acetylation via the ESR1/NAT10 axis. These findings would provide novel strategies for the treatment of IVDD.

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豆甾醇通过ESR1/NAT10轴增强PINK1 mRNA乙酰化，诱导线粒体自噬，从而减轻终板软骨细胞变性。

椎间盘退变（IVDD）是脊柱退变的核心因素。迄今为止，IVDD还没有有效的治疗方法。迫切需要明确IVDD的发病机制，制定有效的IVDD治疗策略。缓解终板软骨细胞变性是治疗IVDD的一种很有前景的策略，而线粒体自噬可防止终板软骨细胞变性。豆甾醇（STM）通过触发线粒体自噬来保护神经元免受损伤，但其对IVDD终板软骨细胞线粒体自噬的影响尚未见报道。本研究采用白细胞介素-1β诱导终板软骨细胞变性，采用乙酰化RNA免疫沉淀法鉴定RNA乙酰化水平。本研究结果表明STM可减轻终板软骨细胞变性。此外，STM诱导pten诱导的激酶1 （PINK1）介导的变性终板软骨细胞有丝分裂。此外，n -乙酰基转移酶10 （NAT10）通过改善终板软骨细胞中PINK1 mRNA乙酰化而增加PINK1的表达。此外，STM通过雌激素受体1 （ESR1）调节变性终板软骨细胞中NAT10的表达。综上所述，本研究表明STM通过ESR1/NAT10轴增强PINK1 mRNA乙酰化，从而诱导线粒体自噬，从而减弱终板软骨细胞变性。这些发现将为IVDD的治疗提供新的策略。

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

Open Life Sciences BIOLOGY-

CiteScore

2.50

自引率

4.50%

发文量

131

审稿时长

43 weeks

期刊介绍： Open Life Sciences (previously Central European Journal of Biology) is a fast growing peer-reviewed journal, devoted to scholarly research in all areas of life sciences, such as molecular biology, plant science, biotechnology, cell biology, biochemistry, biophysics, microbiology and virology, ecology, differentiation and development, genetics and many others. Open Life Sciences assures top quality of published data through critical peer review and editorial involvement throughout the whole publication process. Thanks to the Open Access model of publishing, it also offers unrestricted access to published articles for all users.