MicroRNA-100-5p inhibits osteoclastogenesis and bone resorption by regulating fibroblast growth factor 21

Abstract

MicroRNAs(miRNAs/miRs)arepost-transcriptional regulators that serve important roles in osteoclastogenesis and bone metabolism; however, the roles of miRNAs have not been completely clarified. The present study aimed to investigate the effects of miR-100-5p on the mechanism of liver-bone endocrine metabolism. A miRNA microarray analysis was conducted to evaluate the miRNA expression profile during receptor activator of nuclear factor-κB ligand-stimulated osteoclastogenesis. Hematoxylin and eosin and tartrate-resistant acid phosphatase staining were performed to analyze the trabecular bone microstructure and osteoclast differentiation. The mRNA and protein expression levels were assessed by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The results revealed that in vitro osteoclast differentiation and in vivo bone resorption were suppressed by miR-100-5p overexpression. In vivo, a decrease in miR-100-5p and an increase in FGF21 were simultaneously observed in mice following ovariectomy (OVX). Bioinformatics analysis and experimental data confirmed that FGF21 was a direct target of miR-100-5p. Conversely, augmentation of miR-100-5p using a specific agomir in OVX-operated mice decreased the levels of FGF21 in the serum and liver, and prevented osteoclastogenesis and bone loss. The present study revealed that FGF21 may be a signal molecule associated with the mechanism of liver-bone endocrine metabolism and may be targeted by miR-100-5p. In addition, miR-100-5p may serve an important role in protecting against OVX-induced osteoporosis.