Abstract
BackgroundSteroid-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.MethodsMicroarray 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.ResultsA 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.ConclusionsThe 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.
Highlights
Osteonecrosis of the femoral head (ONFH) is a common disease of the hip with a higher incidence in elderly patients, and the most common clinical symptom is severe pain [1]
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
Summary
Osteonecrosis of the femoral head (ONFH) is a common disease of the hip with a higher incidence in elderly patients, and the most common clinical symptom is severe pain [1]. The pathogenesis and molecular mechanism of steroid-induced ONFH remain unclear, and there are few effective prevention and early treatment methods. During the development of steroid-induced ONFH, the cartilage on the surface of the femoral head and the labrum of the acetabulum are significantly damaged. Degeneration of cartilage on the surface of the femoral head and tearing of the labrum enhance the instability of the hip joint and accelerate the development of steroid-induced ONFH [13]. Prevention and early treatment of hip cartilage damage may slow the development of steroid-induced ONFH and relieve hip dysfunction. There are few studies on the molecular mechanism of steroidinduced ONFH hip cartilage damage. Steroid-induced osteonecrosis of the femoral head (ONFH) is a common hip joint disease and is difficult to be diagnosed early. The present study aimed to identify potentially important genes and signaling pathways involved in steroid-induced ONFH and investigate their molecular mechanisms
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