过度压缩会通过Piezo1/NAT10/mTOR信号轴诱导软骨末板退化
Hongzhou Sun1, Zhongxuan Wu1, Yu Zhang2
1Department of Spine Surgery, Yijishan Hospital of Wannan Medical College, No. 2 Zheshan West Road, Wuhu, Anhui 241001, China.
Osteoarthritis and cartilage
|November 1, 2025
概括
过度的脊柱压缩会触发N-乙转移酶10 (NAT10) 来修改RNA,从而增加mTOR. 这会破坏自,导致软骨末板细胞 (CEP) 退化和磁盘问题.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 脊柱生物力学 脊柱生物力学
背景情况:
- 软骨端板 (CEP) 完整性对脊柱功能至关重要,对机械压缩敏感.
- N4-乙基丁 (ac4C) 修饰是一种新兴的RNA调节机制,与各种疾病有关.
研究的目的:
- 调查ac4C修饰在过度压缩下CEP退化中的作用和机制.
- 探索N-乙转移酶10 (NAT10) 在这个过程中的参与.
主要方法:
- 实验室细胞压缩和大鼠腰部不稳定模型被用于研究NAT10的影响.
- 包括acRIP-seq,RNA-seq和RT-qPCR在内的技术阐明了NAT10-ac4C-mTOR通路.
- 使用电子显微镜和mRFP-GFP-LC3进行了自的评估;Piezo1的作用通过光酶试验进行了检查.
主要成果:
- 过度压缩诱导了NAT10介导的ac4C修饰,上调了哺乳动物目标的拉巴胺素 (mTOR) 表达.
- 这导致了抑制自,增加了软骨末板细胞 (CEPC) 亡,细胞外基质退化和椎间盘退化.
- 发现Piezo1在压缩下通过P65增强NAT10促进体活性.
结论:
- 由NAT10介导的ac4C修饰驱动CEPC亡和在机械应力下代谢失衡.
- 这一途径突出了一个新的机制,有助于椎间盘变性.
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