整合素β5作为骨关节炎的潜在诊断生物标志物

ITGB5 as a Potential Diagnostic Biomarker for Osteoarthritis.

作者信息

Hu Shouchao, Huang Jianxin, Wang Wenzhi

机构信息

Department of Orthopedics, Baodi Hospital of Tianjin Medical University, Tianjin, China.

出版信息

J Musculoskelet Neuronal Interact. 2025 Mar 1;25(1):86-100. doi: 10.22540/JMNI-25-086.

OBJECTIVE

Osteoarthritis (OA) is a prevalent degenerative joint disease, especially occur in the elderly. This study aimed to uncover a novel biomarker for early diagnosis and treatment of OA.

METHODS

WGCNA, differential expression analysis and PPI network were used for screening hub genes-related to OA, utilizing the GSE55235 and GSE57218 datasets from GEO database.

RESULTS

Based on the data in the GEO datasets, compared to normal tissues, ITGB5 was obviously elevated in OA cartilage and synovial samples. Additionally, ROC curve results validated the diagnostic value of ITGB5 in OA. Mechanistically, transcription factors KLF4 and KLF11 could modulate ITGB5 gene transcription via binding to its promoter region, thereby affecting ITGB5 gene expression in OA tissues. GSEA results showed that ITGB5 gene was closely related to p53, wnt, TNF and T cell receptor signaling pathways, suggesting that ITGB5 may play potential roles in affecting cell apoptosis and inflammation in OA. Moreover, ITGB5 levels in OA samples was positively correlated to T helper type 1 cells, natural killer T cells, macrophages, memory CD8 T cells, activated dendritic cells.

CONCLUSION

In this study, we found that ITGB5 was obviously elevated in OA samples. Moreover, ITGB5 may function as a diagnostic biomarker in OA.

目的

骨关节炎（OA）是一种常见的退行性关节疾病，尤其多见于老年人。本研究旨在发现一种用于OA早期诊断和治疗的新型生物标志物。

方法

利用来自基因表达综合数据库（GEO数据库）的GSE55235和GSE57218数据集，通过加权基因共表达网络分析（WGCNA）、差异表达分析和蛋白质-蛋白质相互作用（PPI）网络筛选与OA相关的枢纽基因。

结果

基于GEO数据集中的数据，与正常组织相比，整合素β5（ITGB5）在OA软骨和滑膜样本中明显升高。此外，受试者工作特征（ROC）曲线结果验证了ITGB5在OA中的诊断价值。机制上，转录因子KLF4和KLF11可通过结合其启动子区域来调节ITGB5基因转录，从而影响OA组织中ITGB5基因的表达。基因集富集分析（GSEA）结果表明，ITGB5基因与p53、Wnt、肿瘤坏死因子（TNF）和T细胞受体信号通路密切相关，提示ITGB5可能在影响OA中的细胞凋亡和炎症方面发挥潜在作用。此外，OA样本中ITGB5水平与1型辅助性T细胞、自然杀伤T细胞、巨噬细胞、记忆性CD8 T细胞、活化树突状细胞呈正相关。