Gao Qingxia, Yao Dawei, Yin Zuozhen, Yu Gongchang, Shi Bin, Wang Jiaying
Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University, Shandong First Medical University (Shandong Academy of Medical Sciences), No. 18877, Jing 10 Road, Jinan 250000, Shandong, China.
Endocrine and Metabolic Disease Hospital of Shandong First Medical University, No. 18877, Jing 10 Road, Jinan 250000, Shandong, China.
Postgrad Med J. 2025 Apr 22;101(1195):464-474. doi: 10.1093/postmj/qgae176.
The mechanisms underlying osteoarthritis (OA) remain unclear, and effective treatments are lacking. This study aims to identify OA-related genes and explore their potential in drug repositioning for OA treatment.
Transcriptome-wide association studies (TWAS) were performed using genome-wide association studies summary data and expression quantitative trait loci data from the Genotype-Tissue Expression project. Differentially expressed genes between OA patients and healthy controls were identified using four datasets from the Gene Expression Omnibus database. Gene ontology and pathway enrichment analyses identified potential hub genes associated with OA. A network-based drug repositioning approach was applied to discover potential therapeutic drugs for OA.
Through TWAS and mRNA expression profiling, 7 and 167 OA-related genes were identified, respectively. From these, 128 OA-related genes were selected based on common biological processes. Using the maximal clique centrality algorithm, 10 core-related genes (JUN, VEGFA, FN1, CD44, PTGS2, STAT1, MAP 2K7, GRB2, EP300, and PXN) were identified for network-based drug repositioning. Consequently, 24 drugs were identified based on 128 OA-related genes and 23 drugs based on 10 core OA-related genes. Some identified drugs, such as dexamethasone, menadione, and hyaluronic acid, have been previously reported for OA and/or rheumatoid arthritis treatment. Network analysis also indicated that spironolactone, lovastatin, and atorvastatin may have potential in OA treatment.
This study identified potential OA-related genes and explored their roles in drug repositioning, suggesting the repurposing of existing drugs and the development of new therapeutic options for OA patients. Key message What is already known on this topic The exact pathogenesis of osteoarthritis (OA) remains unclear, and currently, there are no approved drugs that can prevent, halt, or inhibit the progression of OA. What this study adds We identified 128 OA-related genes and 10 core-related genes based on common biological processes revealed by TWAS and mRNA expression profiling. Using these genes, we discovered potential drugs for OA through the Network-based drug repositioning method. How this study might affect research, practice, or policy This study provides recommendations for repositioning existing drugs and developing new treatment options for patients with OA.
骨关节炎（OA）的潜在机制尚不清楚，且缺乏有效的治疗方法。本研究旨在识别与OA相关的基因，并探索其在OA治疗药物重新定位中的潜力。
使用全基因组关联研究汇总数据和来自基因型-组织表达项目的表达定量性状位点数据进行全转录组关联研究（TWAS）。使用来自基因表达综合数据库的四个数据集识别OA患者和健康对照之间的差异表达基因。基因本体和通路富集分析确定了与OA相关的潜在枢纽基因。应用基于网络的药物重新定位方法来发现OA的潜在治疗药物。
通过TWAS和mRNA表达谱分析，分别鉴定出7个和167个与OA相关的基因。从中，基于共同的生物学过程选择了128个与OA相关的基因。使用最大团中心性算法，确定了10个核心相关基因（JUN、VEGFA、FN1、CD44、PTGS2、STAT1、MAP 2K7、GRB2、EP300和PXN）用于基于网络的药物重新定位。因此，基于128个与OA相关的基因鉴定出24种药物，基于10个核心OA相关基因鉴定出23种药物。一些已鉴定出的药物，如地塞米松、甲萘醌和透明质酸，先前已报道可用于OA和/或类风湿性关节炎的治疗。网络分析还表明螺内酯、洛伐他汀和阿托伐他汀可能在OA治疗中具有潜力。
本研究确定了潜在的与OA相关的基因，并探索了它们在药物重新定位中的作用，提示现有药物的重新利用以及为OA患者开发新的治疗选择。关键信息 关于该主题已知的信息 骨关节炎（OA）的确切发病机制尚不清楚，目前尚无批准的药物可预防、阻止或抑制OA的进展。本研究的补充内容 我们基于TWAS和mRNA表达谱分析揭示的共同生物学过程，确定了128个与OA相关的基因和10个核心相关基因。利用这些基因，我们通过基于网络的药物重新定位方法发现了OA的潜在药物。本研究可能对研究、实践或政策产生的影响 本研究为现有药物的重新定位和为OA患者开发新的治疗选择提供了建议。
