数字农科院2.0

The role of the TARDBP gene in osteonecrosis of the femoral head: Bioinformatics analysis and mechanistic exploration

文献类型： 外文期刊

作者： Sheng Sun;Jingjing Wang;Guangxu Ren;Jian Qi;Rongqiang Bu;Yi Zhang;Lei Zang

作者机构：

关键词： bioinformatics;differentially expressed genes;immune infiltration;osteonecrosis of the femoral head;TARDBP

期刊名称： Medicine (United States)

ISSN： 0025-7974

年卷期： 2025 年 104 卷 17 期

页码：

收录情况： SCIE（2025版）

摘要： Osteonecrosis of the femoral head (ONFH) is a condition caused by venous stasis, impaired arterial blood flow, or destruction of the femoral head, often resulting in the localized death of bone cells and bone marrow components, leading to joint collapse. Although the pathogenesis of ONFH is complex, recent attention has focused on the role of the TAR DNA-binding protein (TARDBP) gene and its encoded protein, TDP-43, in the disease process. TDP-43, which plays a role in neurodegenerative diseases, may also regulate apoptosis, oxidative stress, and immune responses in ONFH. This study utilized the GSE74089 and GSE123568 datasets from the gene expression omnibus database to analyze differentially expressed genes between ONFH and normal samples. Through batch effect correction, gene enrichment analysis (gene ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis), protein-protein interaction network construction, and weighted gene co-expression network analysis, key genes in ONFH were identified. Additionally, immune infiltration was analyzed using CIBERSORT, and a neural network model was developed to assess the importance of these genes in ONFH. The analysis revealed that TARDBP expression was significantly elevated in ONFH samples and correlated with the infiltration of monocytes and M1 macrophages. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses suggested that TARDBP may regulate bone metabolism and repair via the Wnt/β-catenin signaling pathway. Protein-protein interaction network analysis identified 9 core genes, with TARDBP scoring the highest in the neural network model, indicating its pivotal role in ONFH regulation. TARDBP is highly expressed in ONFH, and its possible role by regulating apoptosis, oxidative stress, and immune response provide new ideas for the study of the molecular mechanism of ONFH.

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