Bioinformatics analysis and identification of genes and molecular pathways in steroid-induced osteonecrosis of the femoral head
Abstract Background Steroid-induced osteonecrosis of the femoral head (ONFH) is a common hip joint disease and is difficult to be diagnosed early. At present, the pathogenesis of steroid-induced ONFH remains unclear, and recognized and effective diagnostic biomarkers are deficient. The present study...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-05-01
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| Series: | Journal of Orthopaedic Surgery and Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13018-021-02464-9 |
| _version_ | 1817997411525591040 |
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| author | Tianye Lin Weijian Chen Peng Yang Ziqi Li Qiushi Wei Du Liang Haibin Wang Wei He Qingwen Zhang |
| author_facet | Tianye Lin Weijian Chen Peng Yang Ziqi Li Qiushi Wei Du Liang Haibin Wang Wei He Qingwen Zhang |
| author_sort | Tianye Lin |
| collection | DOAJ |
| description | Abstract Background Steroid-induced osteonecrosis of the femoral head (ONFH) is a common hip joint disease and is difficult to be diagnosed early. At present, the pathogenesis of steroid-induced ONFH remains unclear, and recognized and effective diagnostic biomarkers are deficient. The present study aimed to identify potentially important genes and signaling pathways involved in steroid-induced ONFH and investigate their molecular mechanisms. Methods Microarray data sets GSE123568 (peripheral blood) and GSE74089 (cartilage) were obtained from the Gene Expression Omnibus database, including 34 ONFH samples and 14 control samples. Morpheus software and Venn diagram were used to identify DEGs and co-expressed DEGs, respectively. Besides, we conducted Kyoto Encyclopedia of Genome (KEGG) and gene ontology (GO) pathway enrichment analysis. We construct a protein-protein interaction (PPI) network through GEO2R and used cytoHubba to divide the PPI network into multiple sub-networks. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the bioinformatics analysis results. Results A total of 118 intersecting DEGs were obtained between the peripheral blood and cartilage samples, including 40 upregulated genes and 78 downregulated genes. Then, GO and KEGG pathway enrichment analysis revealed that upregulated DEGs focused on the signaling pathways related to staphylococcus aureus infection, leishmaniasis, antigen processing, and presentation, as well as asthma and graft-versus-host disease. Downregulated genes were concentrated in the FoxO signaling pathway, AMPK signaling pathway, signaling pathway regulating stem cell pluripotency, and mTOR signaling pathway. Some hub genes with high interactions such as CXCR1, FPR1, MAPK1, FOXO3, FPR2, CXCR2, and TYROBP were identified in the PPI network. The results of qRT-PCR demonstrated that CXCR1, FPR1, and TYROBP were upregulated while MAPK1 was downregulated in peripheral blood of steroid-induced ONFH patients. This was consistent with the bioinformatics analysis. Conclusions The present study would provide novel insight into the genes and associated pathways involved in steroid-induced ONFH. CXCR1, FPR1, TYROBP, and MAPK1 may be used as potential drug targets and biomarkers for the diagnosis and prognosis of steroid-induced ONFH. |
| first_indexed | 2024-04-14T02:37:48Z |
| format | Article |
| id | doaj.art-6c21c0555977470f9769977ba56671de |
| institution | Directory Open Access Journal |
| issn | 1749-799X |
| language | English |
| last_indexed | 2024-04-14T02:37:48Z |
| publishDate | 2021-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Orthopaedic Surgery and Research |
| spelling | doaj.art-6c21c0555977470f9769977ba56671de2022-12-22T02:17:19ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2021-05-0116111410.1186/s13018-021-02464-9Bioinformatics analysis and identification of genes and molecular pathways in steroid-induced osteonecrosis of the femoral headTianye Lin0Weijian Chen1Peng Yang2Ziqi Li3Qiushi Wei4Du Liang5Haibin Wang6Wei He7Qingwen Zhang8The First Clinical Medical College, Guangzhou University of Chinese MedicineGuangzhou University of Chinese MedicineThe First Clinical Medical College, Guangzhou University of Chinese MedicineDepartment of Joint Orthopaedic, the Third Affiliated Hospital, Guangzhou University of Chinese MedicineDepartment of Joint Orthopaedic, the Third Affiliated Hospital, Guangzhou University of Chinese MedicineGuangzhou Orthopedic Hospital, Guangzhou University of Chinese MedicineGuangzhou University of Chinese MedicineDepartment of Joint Orthopaedic, the Third Affiliated Hospital, Guangzhou University of Chinese MedicineDepartment of Joint Orthopaedic, the Third Affiliated Hospital, Guangzhou University of Chinese MedicineAbstract Background Steroid-induced osteonecrosis of the femoral head (ONFH) is a common hip joint disease and is difficult to be diagnosed early. At present, the pathogenesis of steroid-induced ONFH remains unclear, and recognized and effective diagnostic biomarkers are deficient. The present study aimed to identify potentially important genes and signaling pathways involved in steroid-induced ONFH and investigate their molecular mechanisms. Methods Microarray data sets GSE123568 (peripheral blood) and GSE74089 (cartilage) were obtained from the Gene Expression Omnibus database, including 34 ONFH samples and 14 control samples. Morpheus software and Venn diagram were used to identify DEGs and co-expressed DEGs, respectively. Besides, we conducted Kyoto Encyclopedia of Genome (KEGG) and gene ontology (GO) pathway enrichment analysis. We construct a protein-protein interaction (PPI) network through GEO2R and used cytoHubba to divide the PPI network into multiple sub-networks. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the bioinformatics analysis results. Results A total of 118 intersecting DEGs were obtained between the peripheral blood and cartilage samples, including 40 upregulated genes and 78 downregulated genes. Then, GO and KEGG pathway enrichment analysis revealed that upregulated DEGs focused on the signaling pathways related to staphylococcus aureus infection, leishmaniasis, antigen processing, and presentation, as well as asthma and graft-versus-host disease. Downregulated genes were concentrated in the FoxO signaling pathway, AMPK signaling pathway, signaling pathway regulating stem cell pluripotency, and mTOR signaling pathway. Some hub genes with high interactions such as CXCR1, FPR1, MAPK1, FOXO3, FPR2, CXCR2, and TYROBP were identified in the PPI network. The results of qRT-PCR demonstrated that CXCR1, FPR1, and TYROBP were upregulated while MAPK1 was downregulated in peripheral blood of steroid-induced ONFH patients. This was consistent with the bioinformatics analysis. Conclusions The present study would provide novel insight into the genes and associated pathways involved in steroid-induced ONFH. CXCR1, FPR1, TYROBP, and MAPK1 may be used as potential drug targets and biomarkers for the diagnosis and prognosis of steroid-induced ONFH.https://doi.org/10.1186/s13018-021-02464-9Osteonecrosis of the femoral headDifferentially expressed geneEnrichment analysisPeripheral bloodCartilage |
| spellingShingle | Tianye Lin Weijian Chen Peng Yang Ziqi Li Qiushi Wei Du Liang Haibin Wang Wei He Qingwen Zhang Bioinformatics analysis and identification of genes and molecular pathways in steroid-induced osteonecrosis of the femoral head Journal of Orthopaedic Surgery and Research Osteonecrosis of the femoral head Differentially expressed gene Enrichment analysis Peripheral blood Cartilage |
| title | Bioinformatics analysis and identification of genes and molecular pathways in steroid-induced osteonecrosis of the femoral head |
| title_full | Bioinformatics analysis and identification of genes and molecular pathways in steroid-induced osteonecrosis of the femoral head |
| title_fullStr | Bioinformatics analysis and identification of genes and molecular pathways in steroid-induced osteonecrosis of the femoral head |
| title_full_unstemmed | Bioinformatics analysis and identification of genes and molecular pathways in steroid-induced osteonecrosis of the femoral head |
| title_short | Bioinformatics analysis and identification of genes and molecular pathways in steroid-induced osteonecrosis of the femoral head |
| title_sort | bioinformatics analysis and identification of genes and molecular pathways in steroid induced osteonecrosis of the femoral head |
| topic | Osteonecrosis of the femoral head Differentially expressed gene Enrichment analysis Peripheral blood Cartilage |
| url | https://doi.org/10.1186/s13018-021-02464-9 |
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