Spine Center, Sanbo Brain Hospital, Capital Medical University, Beijing, China.
Graduate Department, Jinzhou Medical University, Jinzhou, China.
Immun Inflamm Dis. 2024 Nov;12(11):e70072. doi: 10.1002/iid3.70072.
Intervertebral disc degeneration (IDD) is a major cause for low back pain. Studies showed the association between senescence and degenerative diseases. Cell senescence can promote the occurrence and development of degenerative diseases through multiple mechanisms including inflammatory stress, oxidative stress and nutritional deprivation. The roles of senescence and senescence-associated genes (SAGs) remains unknown in IDD.
Four differently expressed SAGs were identified as hub SAGs using "limma" package in R. We then calculated the immune infiltration of IDD patients, and investigated the relation between hub SAGs and immune infiltration. Enrichment analysis was performed to explore the functions of hub SAGs in IDD. Nomogram and LASSO model based on hub SAGs was constructed to predict the risk of severe degeneration (SD) for IDD patients. Subsequently, single cell analysis was conducted to describe the expression pattern of hub SAGs in intervertebral disc tissue.
We identified ASPH, CCND1, IGFBP3 and SGK1 as hub SAGs. Further analysis demonstrated that the hub SAGs might mediate the development of IDD by regulating immune infiltration and multiple pathways. The LASSO model based on the four hub SAGs showed good performance in predicting the risk of SD. Single cell analysis revealed that ASPH, CCND1 and SGK1 mainly expressed in nucleus pulposus cells, while IGFBP3 mainly expressed in epithelial cells. Eleven candidate drugs targeting hub SAGS were predicted for IDD patients through Comparative Toxicogenomics Database (CDT). PCR and immunohistochemical analysis showed that the levels of four hub SAGs were higher in SD than MD (mild degeneration) patients.
We performed a comprehensive analysis of SAGs in IDD, which revealed their functions and expression pattern in intervertebral disc tissue. Based on hub SAGs, we established a predictive model and explored the potential drugs. These findings provide new understandings of SAG mechanism and promising therapeutic strategies for IDD.
椎间盘退行性变（IDD）是腰痛的主要原因。研究表明衰老与退行性疾病之间存在关联。细胞衰老可通过炎症应激、氧化应激和营养剥夺等多种机制促进退行性疾病的发生和发展。衰老和衰老相关基因（SAGs）在 IDD 中的作用尚不清楚。
使用 R 中的“limma”包鉴定了 4 个差异表达的 SAGs 作为核心 SAGs。然后，我们计算了 IDD 患者的免疫浸润情况，并研究了核心 SAGs 与免疫浸润之间的关系。进行富集分析以探索核心 SAGs 在 IDD 中的功能。基于核心 SAGs 构建了列线图和 LASSO 模型，以预测 IDD 患者严重退变（SD）的风险。随后，进行单细胞分析以描述核心 SAGs 在椎间盘组织中的表达模式。
我们鉴定了 ASPH、CCND1、IGFBP3 和 SGK1 作为核心 SAGs。进一步的分析表明，核心 SAGs 可能通过调节免疫浸润和多种途径来介导 IDD 的发生发展。基于四个核心 SAGs 的 LASSO 模型在预测 SD 风险方面表现良好。单细胞分析表明，ASPH、CCND1 和 SGK1 主要在髓核细胞中表达，而 IGFBP3 主要在上皮细胞中表达。通过比较毒理学基因组数据库（CDT）预测了 11 种针对核心 SAGS 的候选药物用于 IDD 患者。PCR 和免疫组化分析显示，SD 患者的四个核心 SAGs 水平高于 MD（轻度退变）患者。
我们对 IDD 中的 SAG 进行了全面分析，揭示了它们在椎间盘组织中的功能和表达模式。基于核心 SAGs，我们建立了预测模型并探索了潜在的药物。这些发现为 SAG 机制提供了新的认识，并为 IDD 提供了有前途的治疗策略。
