Integrin‐based focal adhesion is one of the major mechanosensory in osteocytes. The aim of this study was to mine the hub genes associated with focal adhesion and investigate their roles in osteoporosis based on the data of single‐cell RNA sequencing and RNA‐sequencing. Two hub genes (FAM129A and RNF24) with the same expression trend and AUC values greater than 0.7 in both GSE56815 and GSE56116 cohorts were uncovered. The nomogram was created to predict the risk of OP based on two hub genes. Subsequently, the competing endogenous RNA network was established based on two hub genes, 14 microRNAs and five long noncoding RNAs. Meanwhile, transcription factors‐hub gene network was established based on two hub genes and 14 TFs. Finally, 73 drugs were predicted, of which there were 13 drugs targeting FAM129A and 66 drugs targeting RNF24. In both mouse and human blood samples, FAM129A expression was decreased in granulocytes and RNF24 expression was increased in monocytes. In the mouse experiment, FAM129A and anti‐RNF24 were found to partially alleviate the progression of osteoporosis. In conclusion, two hub genes related to focal adhesion were identified by combined scRNA‐seq and RNA‐seq analyses, which might supply a new insight for the treatment and evaluation of OP.

中文翻译：

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整合单细胞和RNA-seq数据探索粘着斑相关基因在骨质疏松症中的作用

基于整合素的粘着斑是骨细胞中主要的机械感觉之一。本研究的目的是挖掘与粘着斑相关的中枢基因，并根据单细胞 RNA 测序和 RNA 测序数据研究它们在骨质疏松症中的作用。在 GSE56815 和 GSE56116 队列中发现了两个具有相同表达趋势且 AUC 值大于 0.7 的中心基因（FAM129A 和 RNF24）。创建列线图是为了根据两个中心基因预测 OP 的风险。随后，基于两个中心基因、14个microRNA和5个长非编码RNA建立了竞争性内源RNA网络。同时，基于2个hub基因和14个TF建立了转录因子-hub基因网络。最终预测出73种药物，其中针对FAM129A的药物有13种，针对RNF24的药物有66种。在小鼠和人类血液样本中，粒细胞中的 FAM129A 表达减少，单核细胞中的 RNF24 表达增加。在小鼠实验中，发现 FAM129A 和抗 RNF24 可以部分缓解骨质疏松症的进展。总之，通过结合 scRNA-seq 和 RNA-seq 分析，鉴定了两个与粘着斑相关的中心基因，这可能为 OP 的治疗和评估提供新的见解。