Analysis of altered microRNA expression profile in the reparative interface of the femoral head with osteonecrosis

Abstract

The reparative reaction is considered to be important during the occurrence of collapse in the femoral head with osteonecrosis (ONFH), but little is known about the long-term reparative process. The aim of this study was to determine and analyze the altered microRNA expression profile in the reparative interface of ONFH, and further validate the expression of the involved genes in the predicted pathways. Microarray analysis was performed comparing the reparative interface of patients with ONFH and normal tissue of patients with fresh femoral neck fracture (FNF) and partly validated by real-time PCR. Potential target genes of differentially expressed miRNAs were predicted by TargetScan and miRanda, and the target genes were used for further bioinformatics analysis such as Gene Ontology and Pathway assay. The filtered miRNAs and genes in the predict pathways were further examined by real-time PCR in another 6 independent ONFH patients. Among the 2578 miRNAs identified, 17 were consistently differentially expressed, 12 of which are up-regulated and 5 down-regulated. GO classification showed that the predicted target genes of these miRNAs are involved in signal transduction, cell differentiation, methylation, cell growth and apoptosis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) classification indicated that these genes play a role in angiogenesis and Wnt signaling pathways. The expression of miR-34a and miR-146a and genes in the predict pathways were significantly up-regulated. This study presented a global view of miRNA expression in the reparative interface of osteonecrosis. In addition, our data provided novel and robust information for further researches in the pathogenesis and molecular events of ONFH.