Gujiansan Ameliorates Avascular Necrosis of the Femoral Head by Regulating Autophagy via the HIF-1α/BNIP3 Pathway

Han, Jing; Chai, Yuan; Zhang, Xiaoyun; Chen, Feng; Xu, Zhiwei; Feng, Zhe Chuan; Qian, Yan; Wen, Shuaibo; Wu, Yukun

doi:10.1155/2021/6683007

Cited by 4 publications

(3 citation statements)

References 30 publications

(35 reference statements)

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“…Some scholars have also confirmed the involvement of the HIF-1 signaling pathway in the pathogenesis of hormonal osteonecrosis. Animal experiments have confirmed that bone health supplements can expedite the formation of new bone, promote the resorption of damaged bone, inhibit the inflammatory response, and ultimately ameliorate SONFH through the HIF-1α/BNIP3 pathway [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics-Based Analysis of Key Genes in Steroid-Induced Osteonecrosis of the Femoral Head That Are Associated with Copper Metabolism

Cai

et al. 2023

Biomedicines

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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.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics-Based Analysis of Key Genes in Steroid-Induced Osteonecrosis of the Femoral Head That Are Associated with Copper Metabolism

Cai

et al. 2023

Biomedicines

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“…Some scholars have also con rmed the involvement of the HIF-1 signaling pathway in the pathogenesis of hormonal osteonecrosis. Animal experiments have con rmed that bone health supplements can expedite the formation of new bone, promote the resorption of damaged bone, inhibit the in ammatory response and ultimately ameliorate SONFH through the HIF-1α/BNIP3 pathway [37].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics-based analysis of key genes in steroid-induced osteonecrosis of the femoral head that are associated with copper metabolism

Cai

et al. 2022

Preprint

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Background: The copper metabolism may play a role in angiogenesis and osteogenesis. However, the relationship between copper metabolism and steroid-induced osteonecrosis of the femoral head (SONFH) still remains unclear.Methods: The GSE123568 dataset and 2062 copper metabolism-related genes (CMRGs) were downloaded from the Gene Expression Omnibus (GEO) and GeneCards databases, respectively. The differentially expressed copper metabolism-related SONFH genes (DE-CMR-SONFHGs) were identified by differential analysis and weighted gene coexpression network analysis (WGCNA). The Least-Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine (SVM) algorithms were employed to screen key DE-CMR-SONFHGs. Receiver operating characteristic (ROC) analysis and functional enrichment analysis were performed on the key genes. Targeting drugs were predicted with The Drug Gene Interaction Database (DGIdb). The correlation between key SONFH genes and copper death-related genes was calculated by Pearson method. The result of bioinformatics analysis were confirmed by quantitative real-time polymerase chain reaction (qRT‒PCR).Results: A total of 106 DE-CMR-SONFHGs were identified. Then, 2 key genes (PNP and SLC2A1) were identified by LASSO and SVM algorithms. The ROC curves of PNP and SLC2A1 indicated that they had diagnostic value in distinguishing SONFH from control samples. Additionally, 20 immune cell populations had notably different abundances between the SONFH and control samples. PNP showed the most significant correlations with plasmacytoid dendritic cells and CD56bright natural killer cells, and SLC2A1 expression showed the most significant correlations with T follicular helper cells and T helper 17 cells. Moreover, 11 drugs that target PNP and 5 drugs that target SLC2A1 were identified. Four copper death-related genes (LIPT1, DLD, PDHB, and MTF1) were upregulated in the disease samples. The qRT‒PCR results showed that PNP and SLC2A1 expression was downregulated and that the copper death-related genes DLD, PDHB and MTF1, which are closely related to these two key genes, were notably highly expressed in the peripheral blood of SONFH patients. These findings were consistent with the bioinformatics analysis results.Conclusions: Copper homeostatic imbalance may be involved in the process of SONFH. PNP and SLC2A1 were confirmed to be key genes related to SONFH, and these genes may provide insights for the treatment of SONFH.

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“…Gujiansan consists of Radix Panacis Quinquefolii, Heterophylly Falsestarwort Root, Radix Astragali, Cornu Cervi Pantotrichum, Notoginseng, Rhizoma Drynariae, Ganoderma, Radix Salviae Miltiorrhizae, Moghania, Litsea, Endothelium Corneum Gigeriae Galli, Herba Asari, and Saffron. Previous studies by the team indicate that Gujiansan acts as a vascular and bone protector by promoting the levels of HIF-1 α , autophagy-associated factors (including BNIP3, LC3, and Beclin-1), and bone formation markers (including osteocalcin (OC), bone-specific alkaline phosphatase (BAP)) and decreasing the levels of proinflammatory cytokines (including TNF- α , IL-6, and CRP) [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Network-Based Pharmacology and Bioinformatics Study on the Mechanism of Action of Gujiansan in the Treatment of Steroid-Induced Avascular Necrosis of the Femoral Head

Ren

Wen

Han

et al. 2022

BioMed Research International

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Objective. To investigate the main pharmacological basis and mechanism of action of Gujiansan in the treatment of steroid-induced avascular necrosis of the femoral head (SANFH). Methods. The active constituents and targets of Gujiansan were screened by using TCMSP and other databases, and relevant disease targets were obtained by analyzing the microarray of SANFH in the GEO database. The intersection of the two was taken to obtain the potential targets of Gujiansan for the treatment of SANFH, and key active constituents were screened with the “active constituent-target” network constructed by the Cytoscape software; then, the STRING database was used to construct the protein interaction network to screen the key targets. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses of key targets were performed by the DAVID database, and the relationship between the “key active constituent-key target-key signaling pathway” was explored. Finally, the molecular docking between key active constituents and key targets was verified. In addition, qPCR detection technology was used to evaluate the preventive and therapeutic effects of key active constituents of Gujiansan in a rat osteoblast model of SANFH to verify the possible mechanism of the effect of Gujiansan in the treatment of SANFH. Results. (1) 106 active constituents and 55 targets were obtained for the treatment of SANFH. (2) Quercetin, luteolin, kaempferol, cryptotanshinone, and naringenin were the key active constituents for the treatment of SANFH. (3) IL1B, STAT3, CAT, PTGS2, and MAPK3 were the key targets for the treatment of SANFH. (4) IL1B, STAT3, CAT, PTGS2, MAPK3, and HMOX1 are key targets in the protein interaction network. (5) DAVID enrichment analysis mainly covers the regulation of DNA-binding transcription factor activity, positive regulation of cytokine production, and response to oxidative stress and other biological processes, involving IL-17, AGE-RAGE, C-type lectin receptor, and other signaling pathways. (6) Gujiansan is a multitarget and multisignaling pathway for the treatment of SANFH. (7) Good binding activity exists between key active constituents and key targets. Conclusion. This study analyzes the potential mechanism of action of Gujiansan in the treatment of SANFH with network pharmacology, which can provide a reference for the further study of its pharmacological basis and targets.

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Gujiansan Ameliorates Avascular Necrosis of the Femoral Head by Regulating Autophagy via the HIF-1α/BNIP3 Pathway

Cited by 4 publications

References 30 publications

Bioinformatics-Based Analysis of Key Genes in Steroid-Induced Osteonecrosis of the Femoral Head That Are Associated with Copper Metabolism

Bioinformatics-Based Analysis of Key Genes in Steroid-Induced Osteonecrosis of the Femoral Head That Are Associated with Copper Metabolism

Bioinformatics-based analysis of key genes in steroid-induced osteonecrosis of the femoral head that are associated with copper metabolism

Network-Based Pharmacology and Bioinformatics Study on the Mechanism of Action of Gujiansan in the Treatment of Steroid-Induced Avascular Necrosis of the Femoral Head

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