Abstract:
PIEZO1 is a mechano-sensitive ion channel that can sense various forms of mechanical stimuli and convert them into biological signals, affecting bone-related diseases. The present study aimed to identify key genes and signaling pathways in Piezo1-regulated bone-related diseases and to explain the potential mechanisms using bioinformatic analysis. The differentially expressed genes (DEGs) in tendon, femur, and humerus bone tissue; cortical bone; and bone-marrow-derived macrophages were identified with the criteria of |log2FC| > 1 and adjusted p-value < 0.05 analysis based on a dataset from GSE169261, GSE139121, GSE135282, and GSE133069, respectively, and visualized in a volcano plot. Venn diagram analyses were performed to identify the overlapping DEGs expressed in the above-mentioned tissues. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, protein−protein interaction (PPI) analysis, and module analysis were also conducted. Furthermore, qRT-PCR was performed to validate the above results using primary chondrocytes. As a result, a total of 222 overlapping DEGs and 12 mostly overlapping DEGs were identified. Key Piezo1-related genes, such as Lcn2, Dkk3, Obscn, and Tnnt1, were identified, and pathways, such as Wnt/β-catenin and PI3k-Akt, were also identified. The present informatic study provides insight, for the first time, into the potential therapeutic targets of Piezo1-regulated bone-related diseases
摘要:
PIEZO1是一种机械敏感离子通道,可以感知各种形式的机械刺激并将其转换为生物信号,影响骨相关疾病。本研究旨在确定Piezo1调节骨相关疾病的关键基因和信号通路,并使用生物信息学分析解释潜在的机制。肌腱中差异表达基因(DEGs),股骨,和肱骨骨组织;皮质骨;和骨髓来源的巨噬细胞分别根据来自GSE169261,GSE139121,GSE135282和GSE133069的数据集以|log2FC|>1的标准和调整的p值<0.05分析进行鉴定,并在火山地块中可视化。进行维恩图分析以鉴定在上述组织中表达的重叠DEGs。基因本体论(GO)富集分析,京都基因和基因组百科全书(KEGG)分析,蛋白质-蛋白质相互作用(PPI)分析,并进行了模块分析。此外,使用原代软骨细胞进行qRT-PCR以验证上述结果。因此,共识别出222个重叠DEG和12个大部分重叠DEG.关键的Piezo1相关基因,如Lcn2,Dkk3,Obscn,和Tnnt1被识别,和路径,如Wnt/β-catenin和PI3K-Akt,也被确认了。当前的信息学研究提供了见解,第一次,进入Piezo1调节骨相关疾病的潜在治疗靶点