MicroRNA profile and its regulatory network in the subchondral bone between Kashin-Beck disease and knee osteoarthritis / 西安交通大学学报(医学版)

ABSTRACT

【Objective】 To compare the MicroRNA (miRNA) expression profiles in the subchondral bone between patients with Kashin-Beck disease and knee osteoarthritis and to conduct target gene prediction and biological function and signal pathway analysis so as to construct the regulatory network of miRNAs and target genes. 【Methods】 The subchondral bone samples were collected from four pairs of patients with Kashin-Beck disease and osteoarthritis. The total RNA was extracted and the miRNA array profiling was performed using Affymetrix miRNA 4.0 Array. The target gene prediction was performed using six different prediction programs including miRWalk. Cytoscape software was used to construct the regulatory network of significantly different miRNAs and predicted target genes; GO biological function and KEGG pathway enrichment analysis were performed based on target genes. 【Results】 A total of 124 miRNAs were significantly downregulated in the subchondral bone of patients with Kashin-Beck disease than that in patients with osteoarthritis. Target genes were predicted for eight miRNAs with a fold change more than 5, and 542 target genes and 1094 miRNA-mRNA regulatory relationships were obtained. Enrichment analysis of target genes in the regulatory relationship showed that these target genes were mainly involved in protein digestion and absorption, focal adhesion, PI3K-Akt signaling pathway and ECM-receptor interaction, and other signaling pathways. 【Conclusion】 Differentially expressed miRNAs in the subchondral bone of patients with Kashin-Beck disease and osteoarthritis may be used as the differential diagnostic markers between the two diseases. In addition, we preliminarily explored the potential molecular mechanism of changes in the subchondral bone of Kashin-Beck disease by bioinformatics analysis.