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

Zhou,Long; Song,Han‑Yi; Gao,Lin‑Lin; Yang,Li‑Yu; Mu,Shuai; Fu,Qin

doi:10.3892/ijmm.2018.4017

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

Authors:
- Long Zhou
- Han‑Yi Song
- Lin‑Lin Gao
- Li‑Yu Yang
- Shuai Mu
- Qin Fu
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Affiliations: Department of Orthopedic Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of Animal Laboratory of Experimental Research Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: December 6, 2018 https://doi.org/10.3892/ijmm.2018.4017
Pages: 727-738
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNAs (miRNAs/miRs) are post‑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.

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