School of Sport Science, Beijing Sport University, Beijing, 100084, China.
Key Laboratory of Physical Fitness and Exercise, Ministry of Education, Beijing Sport University, Beijing, 10084, China.
Sci Rep. 2023 Oct 18;13(1):17757. doi: 10.1038/s41598-023-44724-0.
Osteoarthritis (OA), a degenerative disease of the joints, has one of the highest disability rates worldwide. This study investigates the role of pyroptosis-related genes in osteoarthritis and their expression in different chondrocyte subtypes at the individual cell level. Using OA-related datasets for single-cell RNA sequencing and RNA-seq, the study identified PRDEGs and DEGs and conducted Cox regression analysis to identify independent prognostic factors for OA. CASP6, NOD1, and PYCARD were found to be prognostic factors. Combined Weighted Gene Correlation Network Analysis with PPI network, a total of 15 hub genes related to pyroptosis were involved in the notch and oxidative phosphorylation pathways, which could serve as biomarkers for the diagnosis and prognosis of OA patients. The study also explored the heterogeneity of chondrocytes between OA and normal samples, identifying 19 single-cell subpopulation marker genes that were significantly different among 7 chondrocyte cell clusters. AGT, CTSD, CYBC, and THYS1 were expressed differentially among different cell subpopulations, which were associated with cartilage development and metabolism. These findings provide valuable insights into the molecular mechanisms underlying OA and could facilitate the development of new therapeutic strategies for this debilitating disease.
骨关节炎（OA）是一种关节退行性疾病，其致残率在全球范围内位居前列。本研究旨在探讨与细胞焦亡相关的基因在骨关节炎中的作用及其在不同软骨细胞亚群中的个体细胞水平上的表达。本研究通过单细胞 RNA 测序和 RNA-seq 分析 OA 相关数据集，鉴定了 PRDEGs 和 DEGs，并进行 Cox 回归分析以确定 OA 的独立预后因素。结果发现 CASP6、NOD1 和 PYCARD 是预后因素。通过加权基因共相关网络分析（WGCNA）与蛋白质-蛋白质相互作用网络（PPI）的联合分析，共涉及 15 个与细胞焦亡相关的枢纽基因，这些基因参与了 Notch 和氧化磷酸化途径，可作为 OA 患者诊断和预后的生物标志物。此外，本研究还探索了 OA 和正常样本之间软骨细胞的异质性，鉴定出 7 个软骨细胞簇中存在 19 个显著不同的单细胞亚群标记基因。AGT、CTSD、CYBC 和 THYS1 在不同细胞亚群中的表达存在差异，这些基因与软骨发育和代谢有关。这些发现为 OA 的分子机制提供了有价值的见解，并可能为这种致残性疾病的治疗策略的发展提供新的思路。
