School of Physical Education and Health, Guangzhou University of Chinese Medicine, Guangzhou, China.
The Department of Orthopedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Mol Pain. 2024 Jan-Dec;20:17448069241289961. doi: 10.1177/17448069241289961.
Pain sensitivity is a significant factor in knee osteoarthritis (KOA), influencing patient outcomes and complicating treatment. Genetic differences, particularly in pain-sensing genes (PSRGs), are known to contribute to the variability in pain experiences among KOA patients. This study aims to systematically analyze PSRGs in KOA to better understand their role and potential as therapeutic targets. We utilized bulk RNA-seq data from the GSE114007 and GSE169077 datasets to identify differentially expressed genes, with 20 genes found to be significantly altered. Key PSRGs, including PENK, NGF, HOXD1, and TRPA1, were identified using LASSO, SVM, and random forest algorithms. Further, KEGG and GO enrichment analyses revealed pathways such as "Neuroactive ligand-receptor interaction" and "ECM-receptor interaction," which were validated through external datasets. Single-cell RNA-seq analysis from GSE152805, GSE133449, and GSE104782 datasets demonstrated the heterogeneity and dynamic expression of PSRGs across different cell subpopulations in synovium, meniscus, and cartilage samples. UMAP and pseudotime analyses were used to visualize spatial distribution and developmental trajectories of these genes. The findings emphasize the critical roles of PSRGs in KOA, highlighting their potential as therapeutic targets and suggesting that integrating genetic information into clinical practice could significantly improve pain management and treatment strategies for KOA.
疼痛敏感性是膝骨关节炎（KOA）的一个重要因素，影响患者的预后并使治疗复杂化。已知遗传差异，特别是疼痛感应基因（PSRGs），导致 KOA 患者的疼痛体验存在差异。本研究旨在系统分析 KOA 中的 PSRGs，以更好地了解它们作为治疗靶点的作用和潜力。我们利用 GSE114007 和 GSE169077 数据集的批量 RNA-seq 数据来识别差异表达的基因，发现有 20 个基因发生了显著改变。使用 LASSO、SVM 和随机森林算法鉴定了关键 PSRGs，包括 PENK、NGF、HOXD1 和 TRPA1。此外，KEGG 和 GO 富集分析揭示了“神经活性配体-受体相互作用”和“ECM-受体相互作用”等途径，这些途径通过外部数据集得到了验证。来自 GSE152805、GSE133449 和 GSE104782 数据集的单细胞 RNA-seq 分析表明，PSRGs 在滑膜、半月板和软骨样本中不同细胞亚群中的表达具有异质性和动态性。UMAP 和伪时间分析用于可视化这些基因的空间分布和发育轨迹。研究结果强调了 PSRGs 在 KOA 中的关键作用，突出了它们作为治疗靶点的潜力，并表明将遗传信息纳入临床实践可以显著改善 KOA 的疼痛管理和治疗策略。
