Identification of Hub Genes and Pathways Associated with Oxidative Stress of Cartilage in Osteonecrosis of Femoral Head Using Bioinformatics Analysis

Shi, Wei; Zhang, Xinglong; Xu, Chengcheng; Pang, Ran; Fan, Zhen-Qi; Wan, Xin; Jiang, Zhaohui; Li, Hui; Li, Zhijun; Zhang, Hua-feng

doi:10.1177/19476035221074000

Cited by 12 publications

(9 citation statements)

References 41 publications

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“…14 In addition, TFAP2A is discovered to be a transcription factor of the hub genes. 26 Zhang et al 27 found that RELA and TFAP2A are transcription factors connected to cerebral ischemia-reperfusion injury, which are mostly involved in pathways having to do with inflammation. Furthermore, Jiang et al 28 demonstrated that TFAP2A and RELA selectively modulate gene expression in glioma by physically binding to the promoter region of these genes that are mainly relevant to the regulation of the immune system and cell growth and proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…The study by Shi et al suggests that RELA is the hub gene of genes related to oxidative stress in cartilage for those suffering from osteonecrosis of the femoral head. In addition, TFAP2A is discovered to be a transcription factor of the hub genes 26 . Zhang et al 27 found that RELA and TFAP2A are transcription factors connected to cerebral ischemia–reperfusion injury, which are mostly involved in pathways having to do with inflammation.…”

Section: Discussionmentioning

confidence: 99%

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RELA promotes the progression of oral squamous cell carcinoma via TFAP2A‐Wnt/β‐catenin signaling

Yang

Zhao

Liu

et al. 2023

Molecular Carcinogenesis

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Oral squamous cell carcinoma (OSCC) has emerged as the most prevailing oral malignancy worldwide, characterized by cervical solid lymph node metastasis and strong local invasiveness. Overexpression of Transcription Factor AP-2 alpha (TFAP2A) is observed in a significant proportion of OSCC cases. In this study, we aimed to elucidate the function of TFAP2A in the progression of OSCC and the related molecular signaling pathways. The role of RELA was predicted using bioinformatics analysis. The mRNA abundances of RELA, TFAP2A, and β-catenin were assessed by Western blot and quantitative real-timePCR. The relationship between RELA, TFAP2A, and β-catenin and their correlation with clinicopathological characteristics of OSCC was evaluated. The target of RELA and TFAP2A was identified by the chromatin immunoprecipitation as well as luciferase reporter assay. The colony formation assay and MTS assay were performed to determine the proliferative level of OSCC cells. OSCC cell motility was determined by Transwell assay and wound-healing assay. The protein expressions of epithelial-mesenchymal transition-associated factors were evaluated by Western blot. The expressions of RELA and TFAP2A were elevated in OSCC, and their expressions displayed a positive correlation. The expression levels of RELA and TFAP2A were found to be associated with TNM staging and lymphatic metastasis of OSCC patients. RELA upregulation promoted OSCC progression, as manifested by increased levels of proliferation, invasion, and migration of OSCC cells. We also demonstrated that RELA was directly bound to the promoter of TFAP2A transcription, which activated multiple malignant and metastatic phenotypes.Furthermore, TFAP2A activated the Wnt/β-catenin signaling by targeting the promoter regions of β-catenin. The study found that RELA is critical for promoting the progression of OSCC via the RELA-TFAP2A-Wnt/β-catenin signaling pathway.The RELA-TFAP2A-Wnt/β-catenin signaling pathway is a potential target for reducing the aggressiveness of OSCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

RELA promotes the progression of oral squamous cell carcinoma via TFAP2A‐Wnt/β‐catenin signaling

Yang

Zhao

Liu

et al. 2023

Molecular Carcinogenesis

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“…Here, results of mRNA microarray analysis and RT-qPCR indicated that 6 genes were increased in DEX-treated MLO-Y4 cells, and SP1 mRNA was decreased with APS treatment. Shi et al reported that SP1 was a vital regulatory factor of hub genes in osteonecrosis of femoral head [ 32 ]. We demonstrated that SP1 reversed the effects of APS on osteocyte autophagy and apoptosis in DEX-treated MLO-Y4 cells, suggesting that APS promotes autophagy and inhibits apoptosis in SONFH cell model via reducing SP1 level.…”

Section: Discussionmentioning

confidence: 99%

Astragalus polysaccharide ameliorates steroid-induced osteonecrosis of the femoral head by regulating miR-200b-3p-mediated Wnt/β-catenin signaling pathway via inhibiting SP1 expression

Zhang

Ke-fang

Zeng

et al. 2023

BMC Musculoskelet Disord

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Background Steroid-induced osteonecrosis of the femoral head (SONFH) is the necrosis of the femur bone caused by prolonged and massive use of corticosteroids. The present study probed into the significance of Astragalus polysaccharide (APS) in SONFH progression. Methods SONFH cell model was constructed using murine long bone osteocyte Y4 (MLO-Y4) cells and then treated with APS. mRNA microarray analysis selected differentially expressed genes between control group and SONFH group. RT-qPCR determined SP1 and miR-200b-3p expression. Levels of SP1, β-catenin, autophagy-related proteins (LC3II/LC3I, Beclin1, p62) and apoptosis-related proteins (Bax, C-caspase3, C-caspase9, Bcl-2) were tested by Western blot. ChIP and luciferase reporter assays confirmed relationship between SP1 and miR-200b-3p. Fluorescence intensity of LC3 in cells was detected by immunofluorescence. Flow cytometry assessed cell apoptosis. Osteonecrosis tissues from SONFH mice were examined by HE and TRAP staining. Results APS induced autophagy and suppressed apoptosis in SONFH cell model. APS inhibited SP1 expression and SP1 overexpression reversed effects of APS on SONFH cell model. Mechanistically, SP1 targeted miR-200b-3p to inhibit Wnt/β-catenin pathway. MiR-200b-3p depletion rescued the promoting effect of SP1 on SONFH cell model by activating Wnt/β-catenin pathway. HE staining showed that APS treatment reduced the empty lacunae and alleviated inflammation in trabecular bone of SONFH mice. TRAP staining revealed decreased osteoclasts number in SONFH mice after APS treatment. Conclusion APS regulated osteocyte autophagy and apoptosis via SP1/miR-200b-3p axis and activated Wnt/β-catenin signaling, thereby alleviating SONFH, shedding new insights for therapy of SONFH.

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“…IL-17 signaling pathway can play a more auxiliary role in activating RA broblast-like synovial cell (FLS), which has a strong regulatory effect on osteoclast formation and provides a basis for targeting IL-17-related pathways in the therapeutic regulation of arthritis in ammation [39,52]. The MAPK signaling pathway modulates a variety of biological processes and cellular functions [53].Surprisingly, Schisandrin A has been reported to inhibit the expression of IL-1β through MAPK signaling and NF-κB signal pathways [54], improve the in ammatory microenvironment and reduce cartilage absorption [54,55].In addition, the MAPK-activated protein kinase 2 (MK2) inhibitor decreased the production of HGF,IL-12B,CXCR3, etc., It plays a role in the treatment of immune-mediated in ammatory arthritis such as RA [56]. Consequently, the MAPK signal pathway is crucial for the maintenance and treatment of RA-induced ONFH.…”

Section: Discussionmentioning

confidence: 99%

Drug discovery in Rheumatoid Arthritis-induced Osteonecrosis of the Femoral Head

Yang

Wang

Liu

et al. 2023

Preprint

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Background: Rheumatoid arthritis is a common inflammatory disease, with osteonecrosis of the femoral head being one of its common complications. However, the treatment of "osteonecrosis of the femoral head " is limited with insufficient drug development. The aim of this study is to explore molecular pathways and core genes associated with rheumatoid arthritis-induced osteonecrosis of the femoral head and investigate pharmacological targeting therapy for rheumatoid arthritis-induced osteonecrosis of the femoral head. Methods: In this analysis, intersection genes involved with both " rheumatoid arthritis " and "osteonecrosis of the femoral head " were identified using the Gene-Cards database, followed by functional analysis. The software programs STRING Online and Cytoscape were used to build protein-protein interaction (PPI) networks. Upon completion of the drug-gene interaction study, core genes and potential medicines were identified. Results: The Gene-Cards database discovered a total of 110 genes overlapped by "rheumatoid arthritis " and "osteonecrosis of the femoral head ". Following functional analysis, 108 important genes were selected. Subsequently, PPI analysis revealed 29 genes that may be targeted by 12 medicines and were candidates to treat rheumatoid arthritis-induced osteonecrosis of the femoral head. Conclusions: We used the Gene-Cards database and pathway analysis to identify highly related genes between " rheumatoid arthritis " and "osteonecrosis of the femoral head " and to explore potential therapeutic drugs. The following genes were investigated: HGF, MMP9, IL-1, EP300, SERPINC1, PLG, F5, and APOA1 are all involved in rheumatoid arthritis-induced osteonecrosis of the femoral head. It was found that fondaparinux, garcinol, canakinumab, and andecaliximab could be used as promising medications to treat rheumatoid arthritis-induced osteonecrosis of the femoral head.

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Identification of Hub Genes and Pathways Associated with Oxidative Stress of Cartilage in Osteonecrosis of Femoral Head Using Bioinformatics Analysis

Cited by 12 publications

References 41 publications

RELA promotes the progression of oral squamous cell carcinoma via TFAP2A‐Wnt/β‐catenin signaling

RELA promotes the progression of oral squamous cell carcinoma via TFAP2A‐Wnt/β‐catenin signaling

Astragalus polysaccharide ameliorates steroid-induced osteonecrosis of the femoral head by regulating miR-200b-3p-mediated Wnt/β-catenin signaling pathway via inhibiting SP1 expression

Drug discovery in Rheumatoid Arthritis-induced Osteonecrosis of the Femoral Head

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