Bioinformatics proved the existence of potential hub genes activating autophagy to participate in cartilage degeneration in osteonecrosis of the femoral head

IF 2.9 4区生物学 Q3 CELL BIOLOGY

Journal of Molecular Histology Pub Date : 2024-05-17 DOI:10.1007/s10735-024-10200-w

Yingkang Zhu, Xianxuan Wang, Ruiyu Liu

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Abstract

The obvious degeneration of articular cartilage occurs in the late stage of osteonecrosis of the femoral head (ONFH), which aggravates the condition of ONFH. This study aimed to demonstrate aberrant activation of autophagy processes in ONFH chondrocytes through bioinformatics and to predict and identify relevant hub genes and pathways. Differentially expressed genes (DEGs) were identified using R software in the GSE74089 dataset from the GEO database. DEGs were crossed with the Human Autophagy Database (HADb) autophagy genes to screen out autophagy-related differential genes (AT-DEGs). GSEA, GSVA, GO, and KEGG pathway enrichment analyses of AT-DEGs were performed. The STRING database was used to analyze the protein-protein interaction (PPI) of the AT-DEGs network, and the MCODE and CytoHubba plugin in the Cytoscape software was used to analyze the key gene cluster module and screen the hub genes. The PPI network of hub genes was constructed using the GeneMANIA database, and functional enrichment and gene connectivity categories were analyzed. The expression levels of hub genes of related genes in the ONFH patients were verified in the dataset GSE123568, and the protein expression was verified by immunohistochemistry in tissues. The analysis of DEGs revealed abnormal autophagy in ONFH cartilage. AT-DEGs in ONFH have special enrichment in macroautophagy, autophagosome membrane, and phosphatidylinositol-3-phosphate binding. In the GSE123568 dataset, it was also found that ATG2B, ATG4B, and UVRAG were all significantly upregulated in ONFH patients. By immunohistochemistry, it was verified that ATG2B, ATG4B, and UVRAG were significantly overexpressed. These three genes regulate the occurrence and extension of autophagosomes through the PI3KC3C pathway. Finally, we determined that chondrocytes in ONFH undergo positive regulation of autophagy through the corresponding pathways involved in three genes: ATG2B, ATG4B, and UVRAG.

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生物信息学证明，股骨头坏死中存在激活自噬的潜在枢纽基因，参与软骨变性。

股骨头坏死（ONFH）晚期出现明显的关节软骨变性，加重了ONFH的病情。本研究旨在通过生物信息学方法证明ONFH软骨细胞自噬过程的异常激活，并预测和识别相关的枢纽基因和通路。研究人员使用 R 软件从 GEO 数据库的 GSE74089 数据集中识别了差异表达基因（DEGs）。将 DEGs 与人类自噬数据库（HADb）中的自噬基因交叉，筛选出与自噬相关的差异基因（AT-DEGs）。对 AT-DEGs 进行了 GSEA、GSVA、GO 和 KEGG 通路富集分析。利用STRING数据库分析AT-DEGs网络的蛋白-蛋白相互作用（PPI），并利用Cytoscape软件中的MCODE和CytoHubba插件分析关键基因簇模块和筛选枢纽基因。利用GeneMANIA数据库构建了枢纽基因的PPI网络，并分析了功能富集和基因连接类别。在数据集GSE123568中验证了ONFH患者中相关基因的枢纽基因表达水平，并通过免疫组化验证了组织中的蛋白表达。DEGs分析显示ONFH软骨中存在异常的自噬现象。ONFH中的AT-DEGs在大自噬、自噬体膜和3-磷酸肌醇结合方面特别富集。在 GSE123568 数据集中还发现，ATG2B、ATG4B 和 UVRAG 在 ONFH 患者中均显著上调。通过免疫组化，可以证实 ATG2B、ATG4B 和 UVRAG 明显过表达。这三个基因通过 PI3KC3C 通路调控自噬体的发生和扩展。最后，我们确定 ONFH 中的软骨细胞通过三个基因参与的相应途径对自噬进行正向调节：ATG2B、ATG4B 和 UVRAG。

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来源期刊

Journal of Molecular Histology 生物-细胞生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.