Exploring the pathogenesis of steroid-induced osteonecrosis of the femoral head co-regulated by mesenchymal stem cells and pyroptosis-related genes with the use of transcriptome.

Abstract

Purpose: Mesenchymal stem cells (MSCs) and pyroptosis play an important part in steroid-induced osteonecrosis of the femoral head (SONFH). The present study aimed at the identification and analysis of MSC and pyroptosis-related biomarkers for the treatment of SONFH, as well as the elucidation of their biological mechanisms.

Methods: The present study first use the outliers in GSE123568 data set were removed by principal component analysis (PCA). Next, differentially expressed genes (DEGs) in GSE123568 were identified using different expression analysis. Then, immune infiltration analysis and Wilcoxon test were performed. Later, acquires the DE_MSCs between DEGs and MSC, and DE_PRGs between DEGs and PRGs score. After, the top 20 intersected genes were selected by overlapping the two related genes. Afterward, select characteristic genes and diagnostic genes. Finally, the function enrichment analysis, drug prediction, molecular docking, molecular dynamic simulation. Then, reverse transcription quantitative PCR (RT qPCR), Western blot analysis, and immunohistochemical staining were performed on the femoral head specimens separately. (The model group specimens are from necrotic femoral heads, while the control group specimens are from femoral heads of patients with femoral neck fractures).

Results: The expression of FKBP8 and ANK1 was significantly lower in RT qPCR, western blot analysis, and immunohistochemical staining compared to the control samples. The expression of PTGS2 is actually higher.

Conclusions: In this study, FKBP8, PTGS2 and ANK1 were identified as the biomarkers of SONFH, providing a potential rationale for diagnosing and treating SONFH.