Liu Nian, Deng Qian, Peng Zining, Mao Danning, Huang Yuanbo, Meng Fanyu, Zhang Xiaoyu, Shen Jiayan, Li Zhaofu, Yan Weitian, Peng Jiangyun
First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, PR China.
Department of Rheumatology, The No.1 Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, Yunnan, PR China.
PLoS One. 2025 Feb 7;20(2):e0316708. doi: 10.1371/journal.pone.0316708. eCollection 2025.
Alzheimer's disease (AD) and Osteoarthritis (OA) have been shown to have a close association in previous studies, but the pathogenesis of both diseases are unclear. This study explores the potential common molecular mechanisms between AD and OA through bioinformatics analysis, providing new insights for clinical treatment strategies.
The AD and OA-related datasets were downloaded from the gene expression database GEO. The datasets were analyzed to obtain differentially expressed gene (DEG) datasets for OA and AD, respectively. The intersection of these DEGs was analyzed to identify common DEGs (Co-DEGs). Subsequently, the Co-DEGs were enriched, and a protein-protein interaction network was constructed to identify core genes. The expression of these genes was validated in a separate dataset, and their diagnostic value for the diseases was analyzed. In addition, the core genes were analyzed using gene set enrichment analysis and single-gene genome variation analysis.
Analysis of DEGs on gene chips from OA and AD patients revealed significant changes in gene expression patterns. Notably, EFEMP2 and TSPO, genes associated with inflammatory responses, showed lower expression levels in both AD and OA patients, suggesting a downregulation in the pathological backgrounds of these diseases. Additionally, GABARAPL1, which is crucial for the maturation of autophagosomes, was found to be upregulated in both conditions. These findings suggest the potential of these genes as diagnostic biomarkers and potential therapeutic targets. However, to confirm the effectiveness of these genes as therapeutic targets, more in-depth mechanistic studies are needed in the future, particularly to explore the feasibility and specific mechanisms of combating disease progression by regulating the expression of these genes.
This study suggests that AD and OA shares common molecular mechanisms. The identification of EFEMP2, GABARAPL1, and TSPO as key target genes highlights potential common factors in both diseases. Further investigation into these findings could lead to new candidate targets and treatment directions for AD and OA, offering promising avenues for developing more effective and targeted therapeutic interventions.
先前的研究表明,阿尔茨海默病(AD)与骨关节炎(OA)存在密切关联,但两种疾病的发病机制尚不清楚。本研究通过生物信息学分析探索AD和OA之间潜在的共同分子机制,为临床治疗策略提供新的见解。
从基因表达数据库GEO下载与AD和OA相关的数据集。对这些数据集进行分析,分别获得OA和AD的差异表达基因(DEG)数据集。分析这些DEG的交集以鉴定共同的DEG(Co-DEG)。随后,对Co-DEG进行富集,并构建蛋白质-蛋白质相互作用网络以鉴定核心基因。在一个单独的数据集中验证这些基因的表达,并分析它们对疾病的诊断价值。此外,使用基因集富集分析和单基因基因组变异分析对核心基因进行分析。
对OA和AD患者基因芯片上的DEG分析显示基因表达模式有显著变化。值得注意的是,与炎症反应相关的基因EFEMP2和TSPO在AD和OA患者中均显示较低的表达水平,表明在这些疾病的病理背景中表达下调。此外,发现对自噬体成熟至关重要的GABARAPL1在两种情况下均上调。这些发现表明这些基因作为诊断生物标志物和潜在治疗靶点的潜力。然而,为了证实这些基因作为治疗靶点的有效性,未来需要更深入的机制研究,特别是探索通过调节这些基因的表达来对抗疾病进展的可行性和具体机制。
本研究表明AD和OA具有共同的分子机制。将EFEMP2、GABARAPL1和TSPO鉴定为关键靶基因突出了两种疾病中潜在的共同因素。对这些发现的进一步研究可能会为AD和OA带来新的候选靶点和治疗方向,为开发更有效和有针对性的治疗干预措施提供有希望的途径。