Bioinformatics analysis and identification of genes and molecular pathways in steroid-induced osteonecrosis of the femoral head.
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.
['Lin|Tianye|T|', 'Chen|Weijian|W|', 'Yang|Peng|P|', 'Li|Ziqi|Z|', 'Wei|Qiushi|Q|', 'Liang|Du|D|', 'Wang|Haibin|H|', 'He|Wei|W|', 'Zhang|Qingwen|Q|']
D048868:Adaptor Proteins, Signal Transducing D000328:Adult D019295:Computational Biology D030541:Databases, Genetic D066264:Datasets as Topic D005260:Female D005270:Femur Head D000071316:Forkhead Box Protein O3 D056726:Genetic Association Studies D005938:Glucocorticoids D006801:Humans D008297:Male D008565:Membrane Proteins D008875:Middle Aged D019950:Mitogen-Activated Protein Kinase 1 D010020:Osteonecrosis D044042:Receptors, Formyl Peptide D023062:Receptors, Interleukin-8A D023063:Receptors, Interleukin-8B D015398:Signal Transduction D055815:Young Adult
Osteonecrosis of the femoral head Peripheral blood Cartilage Enrichment analysis Differentially expressed gene