Xu Yangkai, Chen Rongsheng, Zhuang Yan, Xu Weihong
Department of Spine Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
Int J Immunopathol Pharmacol. 2025 Jan-Dec;39:3946320251343365. doi: 10.1177/03946320251343365. Epub 2025 Jun 6.
The aim of this study was to investigate the role of glutathione peroxidase 7 (GPX7) in mitigating oxidative stress-induced cellular ageing and its contribution to intervertebral disc degeneration (IVDD).
Human nucleus pulposus (NP) cells in degenerated intervertebral discs (IVDs) show signs of ageing, such as telomere shortening, DNA damage, and mitochondrial dysfunction. GPX7, known for its ability to protect against ageing in cancer cells, may also play a role in NP cell ageing.
Two datasets (GSE34095 and GSE147383) were analysed to compare GPX7 expression in normal and degenerated IVDs and used KEGG analysis to identify related pathways. An HO-induced cell model and a natural ageing model were used to simulate ageing. GPX7 was transfected into and overexpressed in NP cells, and its protective effects were examined. Molecular docking identified GNF-5837 as a potential compound to prevent GPX7 cleavage, which was tested in an IVDD rat model.
The expression of GPX7 was increased in degenerated IVDs and HO-induced models. GPX7 overexpression reduced ageing in NP cells. GNF-5837 alleviated IVDD in rats by upregulating GPX7.
Our study demonstrates that GNF-5837 reduced the expression of ageing markers by upregulating GPX7, suggesting it could serve as a potential treatment for IVDD.
本研究旨在探讨谷胱甘肽过氧化物酶7（GPX7）在减轻氧化应激诱导的细胞衰老中的作用及其对椎间盘退变（IVDD）的影响。
退变椎间盘中的人髓核（NP）细胞表现出衰老迹象，如端粒缩短、DNA损伤和线粒体功能障碍。GPX7以其在癌细胞中抗衰老的能力而闻名，可能在NP细胞衰老中也发挥作用。
分析两个数据集（GSE34095和GSE147383）以比较正常和退变椎间盘中GPX7的表达，并使用KEGG分析确定相关途径。使用过氧化氢（HO）诱导的细胞模型和自然衰老模型来模拟衰老。将GPX7转染到NP细胞中并使其过表达，检测其保护作用。分子对接确定GNF-5837为防止GPX7裂解的潜在化合物，并在IVDD大鼠模型中进行测试。
GPX7在退变椎间盘和HO诱导模型中的表达增加。GPX7过表达减少了NP细胞的衰老。GNF-5837通过上调GPX7减轻了大鼠的IVDD。
我们的研究表明，GNF-5837通过上调GPX7降低了衰老标志物的表达，表明它可能是IVDD的一种潜在治疗方法。
