Jiang Chen, Song Chao, Chen Chaoqi, Shen Baoxin, Yang Lei, Zhang Chi, Liu Fei, Wu Xiaofei, Chen Feng
Medical Insurance Section RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine Nanning Guangxi China.
Department of Orthopedics RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine Nanning Guangxi China.
JOR Spine. 2025 Mar 31;8(2):e70055. doi: 10.1002/jsp2.70055. eCollection 2025 Jun.
Through the use of network toxicology, the research sought to determine whether cellular senescence and associated molecular mechanisms in nicotine-induced intervertebral disc degeneration (IVDD) were potentially harmful.
The primary chemical structure and 105 targets of action of nicotine were determined by using the Swiss Target Prediction, Cell Age, and PubChem databases. 855 IVDD senescence genes were found using the GEO and Cell Age datasets.
After additional screening and Cytoscape development, 9 key targets were identified. Additionally, these targets' co-expression pattern analysis and protein interactions were confirmed to be identical. The core targets of nicotine-induced IVDD cellular senescence were found to be primarily enriched in the positive regulation of cell proliferation, telomere shortening, histone acetylation, and cellular senescence-related processes, according to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The KEGG signaling pathway also made it clear that the Apelin signaling route, nicotinate and nicotinamide metabolism, cell cycle, and apoptosis are all strongly linked to nicotine-induced IVDD cellular senescence. We chose four genes associated with the cellular senescence pathway-HDAC1, HDAC4, and NAMPT, MYLK-for molecular docking with the toxic substance nicotine. The findings validated nicotine's strong affinity for the primary targets.
All things considered, the current research indicates that nicotine may contribute to cellular senescence in IVDD via controlling the histone deacetylation process, telomere shortening, the Apelin signaling pathway, and pathways linked to the metabolism of nicotinate and nicotinamide. The theoretical foundation for investigating the molecular mechanisms of nicotine-induced senescence in IVDD is established.
通过网络毒理学研究，确定尼古丁诱导的椎间盘退变（IVDD）中的细胞衰老及相关分子机制是否具有潜在危害。
利用瑞士靶点预测数据库、细胞衰老数据库和PubChem数据库确定尼古丁的主要化学结构和105个作用靶点。使用GEO和细胞衰老数据集发现855个IVDD衰老基因。
经过进一步筛选和Cytoscape平台分析，确定了9个关键靶点。此外，证实了这些靶点的共表达模式分析和蛋白质相互作用是一致的。根据基因本体论（GO）和京都基因与基因组百科全书（KEGG），发现尼古丁诱导的IVDD细胞衰老的核心靶点主要富集于细胞增殖的正调控、端粒缩短、组蛋白乙酰化以及细胞衰老相关过程。KEGG信号通路还表明，阿片肽信号通路、烟酸和烟酰胺代谢、细胞周期和细胞凋亡均与尼古丁诱导的IVDD细胞衰老密切相关。我们选择了四个与细胞衰老途径相关的基因——HDAC1、HDAC4、NAMPT、MYLK——与有毒物质尼古丁进行分子对接。研究结果验证了尼古丁对主要靶点具有很强的亲和力。
综合考虑，当前研究表明尼古丁可能通过控制组蛋白去乙酰化过程、端粒缩短、阿片肽信号通路以及与烟酸和烟酰胺代谢相关的途径，导致IVDD中的细胞衰老。本研究为探讨尼古丁诱导IVDD衰老的分子机制奠定了理论基础。
