MicroRNA-543 promotes ovariectomy-induced osteoporosis through inhibition of AKT/p38 MAPK signaling pathway by targeting YAF2.

Abstract:

:The present study aimed to determine the roles of miRNA-543 in osteoporosis in rats induced by ovariectomy. The osteoporosis rat model was established by ovariectomy induction. MiRNA-543 expression in osteoblasts was measured by quantitative real-time polymerase chain reaction. The cell proliferation and apoptosis were measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assays, respectively. Western blot analysis was conducted to examine the expression of YAF-2 and AKT signaling. TargetScan analysis and dual-luciferase reporter assay were performed to determine the target gene of miRNA-543. MiRNA-543 was significantly upregulated in osteoporosis rat model. Overexpression of miRNA-543 significantly suppressed cell growth and promoted apoptosis in osteoblasts, whereas downregulation of miRNA-543 significantly enhanced cell growth and inhibited apoptosis. MiRNA-543 upregulation significantly inhibited YAF-2 expression and suppressed the phosphorylation and expression of AKT and p38 mitogen-activated protein kinases (MAPK) in osteoblasts. Furthermore, YAF-2 knockdown enhanced the effects of miRNA-543 on apoptosis in osteoblasts. AKT inhibitor MK2206 and p38 MAPK inhibitor SB203580 also enhanced the effects of miRNA-543 on apoptosis in osteoblasts. Our findings revealed that inhibition of miRNA-543 could protect osteoblasts against ovariectomy-induced osteoporosis through AKT/p38 MAPK signaling pathway by targeting YAF2.

journal_name

J Cell Biochem

authors

Li X,Ning L,Zhao X,Wan S

doi

10.1002/jcb.28143

subject

Has Abstract

pub_date

2018-12-02 00:00:00

eissn

0730-2312

issn

1097-4644

pub_type

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