Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 503, Issue 3, Pages 2186-2193Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.08.011
Keywords
ATF4; LGR4; miR-193a-3p; Osteoblast differentiation
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Funding
- Natural Science Foundation of China [81001225]
- Fundamental Research Funds for the Central Universities [xjj2016107]
- International Co-operative Plan of Shaanxi [S2016YFKW0013]
- International Co-operative Fund of Xian Jiaotong University [08143004]
- Integrative Medicine Research and Innovation Team of Degenerative Bone Disease Prevention of Shaanxi Traditional Chinese Medicine College [2013KCT-26]
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Emerging evidence indicates that microRNAs (miRNAs) are crucial regulators of osteoblast differentiation. A previous study has reported that miR-193a-3p expression is altered during the induction of osteoblast differentiation. However, the precise biological function and regulatory mechanism of miR193a-3p during osteoblast differentiation remains unclear. In this study, we aimed to investigate the precise role and underlying mechanism of miR-193a-3p in regulating osteoblast differentiation. The results showed that miR-193a-3p expression was significantly down-regulated during the induction of osteoblast differentiation. Functional experiments demonstrated that the overexpression of miR-193a-3p impeded osteoblast differentiation while miR-193a-3p inhibition promoted osteoblast differentiation. Bioinformatics analysis and a luciferase assay revealed that leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4), a critical regulator of osteoblast differentiation, was a target gene of miR-193a-3p. We showed that miR-193a-3p negatively regulated the expression of LGR4 and activating transcription factor 4 (ATF4). Moreover, the knockdown of LGR4 or ATF4 significantly reversed the promotion effect of miR-193a-3p inhibition on osteoblast differentiation. Overall, these findings demonstrate that miR-193a-3p regulates osteoblast differentiation by modulating LGR4/ATF4 signaling and suggests that the miR-193a-3p/LGR4/ATF4 regulation axis may play an important role in regulating bone remodeling. (C) 2018 Elsevier Inc. All rights reserved.
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