Chen He, Xu Peng, Mao Leijing, Wang Yicong, Feng Zian, Wang Zhongxin, Shen Cailiang, Xu Yuanhong
Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
Department of Pathogen Biology and Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University, Hefei, Anhui Province, China.
Sci Rep. 2025 Apr 9;15(1):12146. doi: 10.1038/s41598-025-94989-w.
Intervertebral disc degeneration (IVDD) is a prevalent and debilitating condition associated with low back pain (LBP). Despite its significant impact, effective diagnostic markers for early-stage IVDD remain elusive. Recent research has implicated ferroptosis, a newly recognized form of programmed cell death, in the pathogenesis of IVDD, particularly involving disturbances in iron homeostasis. Additionally, the CC Chemokine Ligand 3 (CCL3) has been linked to macrophage migration and the progression of IVDD, yet its precise diagnostic and prognostic utility remains uncertain. This study aims to elucidate the underlying mechanisms of ferroptosis and the involvement of CCL3 in IVDD, with the objective of establishing their diagnostic and prognostic significance. By uncovering these mechanisms, novel biomarkers and therapeutic targets for the diagnosis and prognosis of IVDD may be identified. Single-cell sequencing data were acquired from the TCGA database, and a range of bioinformatics methods were employed for comprehensive analysis. Furthermore, validation experiments were conducted using in vitro techniques, including the analysis of human tissue samples, co-culture assays with neutralizing antibodies, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. Our findings suggest that CCL3 holds promise as a diagnostic and may was prognostic biomarker for IVDD. Validation experiments demonstrated that CCL3 functions via the pAMPK/AMPK pathway, thereby modulating apoptosis and impacting the progression of IVDD. Our study underscores the diagnostic and prognostic potential of CCL3 in patients with IVDD. Further investigations are warranted to explore therapeutic strategies targeting CCL3, ultimately enhancing the management of IVDD.
椎间盘退变(IVDD)是一种与腰痛(LBP)相关的常见且使人衰弱的病症。尽管其影响重大,但早期IVDD的有效诊断标志物仍然难以捉摸。最近的研究表明,铁死亡这种新认识的程序性细胞死亡形式在IVDD的发病机制中起作用,特别是涉及铁稳态的紊乱。此外,CC趋化因子配体3(CCL3)与巨噬细胞迁移和IVDD的进展有关,但其确切的诊断和预后效用仍不确定。本研究旨在阐明铁死亡的潜在机制以及CCL3在IVDD中的作用,目的是确定它们的诊断和预后意义。通过揭示这些机制,可能会确定IVDD诊断和预后的新型生物标志物和治疗靶点。从TCGA数据库获取单细胞测序数据,并采用一系列生物信息学方法进行综合分析。此外,使用体外技术进行验证实验,包括分析人体组织样本、用中和抗体进行共培养测定、定量实时聚合酶链反应(qRT-PCR)和蛋白质免疫印迹法。我们的研究结果表明,CCL3有望成为IVDD的诊断和预后生物标志物。验证实验表明,CCL3通过pAMPK/AMPK途径发挥作用,从而调节细胞凋亡并影响IVDD的进展。我们的研究强调了CCL3在IVDD患者中的诊断和预后潜力。有必要进一步研究探索针对CCL3的治疗策略,最终改善IVDD的管理。
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