Transcriptomic analysis reveals genetic factors regulating early steroid-induced osteonecrosis of the femoral head.

Abstract

The present study aimed to explore the signaling pathways involved in development of early steroid-induced osteonecrosis of the femoral head (SONFH) and identify diagnostic biomarkers regulating peripheral blood in SONFH patients. We downloaded transcriptome data and identified differentially expressed genes (DEGs) using the R software. We used ClusterProfiler to perform enrichment analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, and analyzed protein–protein interactions using the STRING database. Network X was used to visualize the networks in Python. A total of 584 DEGs were identified, of which 294 and 290 were upregulated and downregulated, respectively. Enrichment analysis showed that the DEGs were mainly involved in red blood cell differentiation, cell protein catabolism, gas transportation, activation of myeloid leukocytes, phagocytosis, and inflammatory response. Pathway analysis revealed that these DEGs were involved in regulation of mitophagy-animal, human T-cell leukemia virus-1 infection, Forkhead box O, phagocytosis, osteoclast differentiation, and cytokine–cytokine receptor interaction. Quantitative real-time polymerase chain reaction results were consistent with findings from protein–protein interaction network analysis. Several genes, including peroxiredoxin 2, haptoglobin, matrix metallopeptidase 8, formyl peptide receptor 2, and integrin subunit alpha X, promote SONFH occurrence by regulating the redox, inflammatory response, and osteoblast and osteoclast structure and function pathways. They may be important targets for designing approaches for early diagnosis and treatment of SONFH.