Up-regulation of urinary exosomal hsa-microRNA-200b-3p and hsa-microRNA-206 in patients of steroid-induced osteonecrosis of femoral head.

The aim of this study was to determine the value of microRNAs (miRNAs) in urinary exosomes in the diagnosis of steroid-induced osteonecrosis of femoral head (SONFH). RNA was extracted from urinary exosomes from 9 SONFH patients and 9 hip osteoarthritis (HOA) patients with age and gender matched and then miRNAs were analyzed by next generation sequencing. Intriguingly, 15 miRNAs including hsa-miR-200b-3p and hsa-miR-206 were significantly upregulated in exosomes from SONFH patients. Furthermore, qRT-PCR and area under curve (AUC) analysis of an independent cohort of 30 SONFH patients, 10 HOA patients and 10 healthy donors confirmed that hsa-miR-200b-3p and hsa-miR-206 were upregulated in SONFH samples which AUC values were 0.938 (95% CI: 0.828-1) and 0.926 (95% CI: 0.806-1) respectively. GO function, KEGG pathway, miRNAs-mRNAs network and protein-protein interaction (PPI) network were also constructed to analyze potentially pathological mechanisms. The enriched functions and pathways included Hippo, PI3K-Akt, TGF-ß and Wnt signaling pathways. The top five hub genes (MAPK1, EP300, RHOA, PIK3CA, and CBL) were selected from PPI network, which consisted of 180 nodes and 518 edges. Collectively, our results showed that hsa-miR-200b-3p and hsa-miR-206 in urinary exosomes might serve as non-invasive biomarkers for SONFH.