Qi Baochuang, Li Chuan, Cai Xingbo, Pu Luqiao, Guo Minzheng, Tang Zhifang, Bu Pengfei, Xu Yongqing
Graduate School, Kunming Medical University, No.1168, Chunrong West Road, Yuhua Street, Chenggong District, Kunming 650500, China.
Department of Orthopaedics, 920th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Kunming 650032, China.
Biomedicines. 2023 Mar 13;11(3):873. doi: 10.3390/biomedicines11030873.
Osteonecrosis of the femoral head (ONFH) is a common disabling disease. Copper has positive effects on cells that regulate bone metabolism. However, the relationship between copper metabolism (CM) and steroid-induced ONFH (SONFH) remains unclear. The GSE123568 dataset was downloaded from the Gene Expression Omnibus. The differentially expressed CM-related SONFH genes (DE-CMR-SONFHGs) were identified via differential analysis and weighted gene coexpression network analysis (WGCNA). Receiver operating characteristic (ROC) analysis was performed for the predictive accuracy of key genes. Targeting drugs and the copper death-related genes (CDRGs) relevant to key genes were investigated. The bioinformatics results were confirmed via quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analysis. Two out of 106 DE-CMR-SONFHGs were identified as key genes (PNP and SLC2A1), which had diagnostic value in distinguishing SONFH from control samples and were related to various immune cell infiltrations. Eleven PMP-targeting drugs and five SLC2A1-targeting drugs were identified. The qRT-PCR, as well as WB, results confirmed the downregulation PNP and SLC2A1 and high expression of the CDRGs DLD, PDHB, and MTF1, which are closely related to these two key genes. In conclusion, PNP and SLC2A1 were identified as key genes related to SONFH and may provide insights for SONFH treatment.
股骨头坏死（ONFH）是一种常见的致残性疾病。铜对调节骨代谢的细胞具有积极作用。然而，铜代谢（CM）与类固醇诱导的股骨头坏死（SONFH）之间的关系仍不清楚。从基因表达综合数据库下载了GSE123568数据集。通过差异分析和加权基因共表达网络分析（WGCNA）鉴定差异表达的CM相关SONFH基因（DE-CMR-SONFHGs）。对关键基因的预测准确性进行了受试者工作特征（ROC）分析。研究了与关键基因相关的靶向药物和铜死亡相关基因（CDRGs）。通过定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹（WB）分析证实了生物信息学结果。106个DE-CMR-SONFHGs中有2个被鉴定为关键基因（PNP和SLC2A1），它们在区分SONFH与对照样本方面具有诊断价值，并且与各种免疫细胞浸润有关。鉴定出11种靶向PNP的药物和5种靶向SLC2A1的药物。qRT-PCR以及WB结果证实了PNP和SLC2A1的下调以及与这两个关键基因密切相关的CDRGs DLD、PDHB和MTF1的高表达。总之，PNP和SLC2A1被鉴定为与SONFH相关的关键基因，可能为SONFH治疗提供思路。
