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

Delong Chen; Gangyu Zhang; Ying Li; Meng Zhang; Qi He; Junzheng Yang; Longfei Wen; Xuting Zou; Ziqi Li; Haibin Wang; Peng Chen

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

Am J Transl Res. 2021 Jul 15;13(7):7574-7590. eCollection 2021.

Authors

Delong Chen¹, Gangyu Zhang², Ying Li³, Meng Zhang⁴, Qi He², Junzheng Yang², Longfei Wen¹, Xuting Zou⁵, Ziqi Li⁶, Haibin Wang⁷, Peng Chen⁷

Affiliations

¹ Department of Orthopaedic Surgery, Clifford Hospital, Jinan University Guangzhou 510006, China.
² The First School of Clinical Medicine, Guangzhou University of Chinese Medicine Guangzhou 510405, China.
³ Department of Orthopaedic Surgery, Third Affiliated Hospital, Guangzhou University of Chinese Medicine Guangzhou 510360, China.
⁴ Department of Orthopedics, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University Zhengzhou 450003, China.
⁵ Orthopedics Department, Quanzhou Orthopedic-Traumatological Hospital, Fujian University of Chinese Medicine 61, Citong Road, Fengze Area, Quanzhou 362000, China.
⁶ Department of Joint Diseases, Third Affiliated Hospital, Guangzhou University of Chinese Medicine Guangzhou 510405, China.
⁷ Department of Orthopaedic Surgery, First Affiliated Hospital, Guangzhou University of Chinese Medicine Guangzhou 510405, China.

PMID: 34377236
PMCID: PMC8340157

Abstract

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-β 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.

Keywords: Steroid-induced osteonecrosis of femoral head; bioinformatics analysis; microRNAs; urinary exosomes.