Zhao Xuan, Wang Qijun, Wang Wei, Chen Xiaolong, Lu Shibao
Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, China.
National Clinical Research Center for Geriatric Diseases, Beijing, China.
Noncoding RNA Res. 2024 Sep 2;10:177-191. doi: 10.1016/j.ncrna.2024.09.003. eCollection 2025 Feb.
Intervertebral disc degeneration (IVDD) is one of the important causes of lower back pain, seriously affecting people's health and quality of life. This research employs single-cell analysis to identify the specific cellular subtypes and key regulatory genes associated with IVDD.
We analyzed the single-cell data and screened cells that closely associated with the development of IVDD. The differential expression of feature genes between IVDD and control groups was analyzed. Additionally, drugs and regulatory transcription factors that interact with feature genes were predicted and clinically validated by reverse transcription quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA).
Our study identified the Chond2 cell subtype associated with IVDD and selected four feature genes influencing the development of IVDD, namely IGFBP3, ACAN, VAPA and TMEM45A, through the high-dimensional weighted gene co-expression network analysis (hdWGCNA) analysis, least absolute shrinkage and selection operator (LASSO), and random forest (RF). Besides, compared to the MDD group, IGFBP3 and TMEM45A were significantly upregulated in the SDD group, while ACAN and VAPA showed no significant difference between the two groups. ELISA testing revealed a positive correlation between IGFBP3 concentration and the grading of IVDD. Furthermore, Celecoxib may be used to treat IVDD by inhibiting IGFBP3.
Our study identified the Chond2 cell subtype associated with IVDD and selected four feature genes influencing the development of IVDD, namely IGFBP3, ACAN, VAPA and TMEM45A. Our findings establish a robust theoretical foundation for the clinical diagnosis and treatment of IVDD patients.
椎间盘退变（IVDD）是下腰痛的重要原因之一，严重影响人们的健康和生活质量。本研究采用单细胞分析来鉴定与IVDD相关的特定细胞亚群和关键调控基因。
我们分析了单细胞数据并筛选出与IVDD发展密切相关的细胞。分析了IVDD组和对照组之间特征基因的差异表达。此外，通过逆转录定量实时PCR（RT-qPCR）、免疫组织化学（IHC）和酶联免疫吸附测定（ELISA）对与特征基因相互作用的药物和调控转录因子进行了预测和临床验证。
我们的研究鉴定出与IVDD相关的Chond2细胞亚群，并通过高维加权基因共表达网络分析（hdWGCNA）、最小绝对收缩和选择算子（LASSO）以及随机森林（RF）选择了四个影响IVDD发展的特征基因，即IGFBP3、ACAN、VAPA和TMEM45A。此外，与MDD组相比，SDD组中IGFBP3和TMEM45A显著上调，而ACAN和VAPA在两组之间无显著差异。ELISA检测显示IGFBP3浓度与IVDD分级呈正相关。此外，塞来昔布可能通过抑制IGFBP3来治疗IVDD。
我们的研究鉴定出与IVDD相关的Chond2细胞亚群，并选择了四个影响IVDD发展的特征基因，即IGFBP3、ACAN、VAPA和TMEM45A。我们的研究结果为IVDD患者的临床诊断和治疗奠定了坚实的理论基础。
