Comprehensive analysis of pivotal biomarkers, immune cell infiltration and therapeutic drugs for steroid-induced osteonecrosis of the femoral head

Abstract

Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive disease that leads to an increased disability rate. This study aimed to ascertain biomarkers, infiltrating immune cells, and therapeutic drugs for SONFH. The gene expression profile of the GSE123568 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using the NetworkAnalyst platform. Functional enrichment, proteinprotein interaction network (PPI), and module analyses were performed using Metascape tools. An immune cell abundance identifier was used to explore immune cell infiltration. Furthermore, hub genes were identified based on maximal clique centrality (MCC) evaluation using cytoHubba application and confirmed by qRT-PCR using clinical samples. Finally, the L1000 platform was used to determine potential drugs for SONFH treatment. The SONFH mouse model was used to determine the therapeutic effects of aspirin. In total, 429 DEGs were identified in SONFH samples. Functional enrichment analysis showed that these DEGs were enriched in myeloid leukocyte activation and osteoclast differentiation processes. A set of nine immune cell types was confirmed to be markedly different between the SONFH and control samples. All 10 hub genes were significantly highly expressed in the serum of SONFH patients, as shown by qRT-PCR. Finally, the therapeutic effect of aspirin on SONFH was examined in animal experiments. Taken together, our data revealed the hub genes and infiltrating immune cells in SONFH, and we also screened potential drugs for use in SONFH treatment.

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

“…However, these studies also present some defects, such as inability to accurately interpret high-throughput sequence data to ensure that a certain deviation exists between PCR verification data and the data significance. [ 9 , 10 ] In the present study, we explored the signaling pathways regulating development of early SONFH and predicted diagnostic biomarkers in peripheral blood from this group of patients.…”

Polarization Behavior of Bone Macrophage as Well as Associated Osteoimmunity in Glucocorticoid-Induced Osteonecrosis of the Femoral Head

“…64 During the progression of GIONFH, large numbers of chronic inflammatory cells may infiltrate into the peripheral blood and necrotic zone. 65 Multiple studies [66][67][68] evaluated immune infiltration in serum by analyzing GSE123568 which enrolled thirty patients with GIONFH and ten healthy controls, and found decreased infiltration of memory B cells and activated dendritic cells. It could be noticed that macrophages (M0, M1 and M2) were not significantly enriched in the GIONFH group.…”

The role of immune cells in modulating chronic inflammation and osteonecrosis

“…IL-9 secreted by Th2, Th9 and Th17 cells upregulates inflammatory factors and enzymes related to cartilage degradation, promoting ONFH progression ( 42 , 81 ). High numbers of CTLs infiltrate areas of osteonecrosis and contribute to it ( 24 ). They promote interactions between T cells and osteoclasts and enhance the activity of osteoclasts by secreting cytotoxic T lymphocyte-associated protein 4 (CTLA-4) ( 79 ).…”

“…In the past, osteonecrosis was considered to result from the death of osteoblasts and osteocytes as well as abnormal activation of osteoclasts. However, studies have found a close link between abnormal immune responses and immune cell infiltration in osteonecrotic tissues, which show signs of uncontrolled inflammation (23)(24)(25)(26)(27)(28). How various immune cells regulate inflammation in osteonecrosis has not been fully elucidated.…”