miRNA-340 inhibits osteoclast differentiation via repression of MITF.

Abstract:

:Many miRNAs play critical roles in modulating various biological processes of osteoclast differentiation and function. Microphthalmia-associated transcription factor (MITF), a target of miR-340, served as pivotal transcription factor involved in osteoclast differentiation. However, the role of miR-340 and MITF during osteoclast differentiation has not yet been clearly established. Tartrate-resistant acid phosphatase (TRAP) staining assay was performed to identify osteoclasts differentiated from bone marrow-derived macrophages (BMMs). Quantitative reverse transcription PCR (qRT-PCR) or Western blotting was undertaken to examine the mRNA or protein expression respectively. Luciferase reporter assay was performed to investigate the interaction between miR-340 and MITF. MITF was knocked down and miR-340 was overexpressed and transfected into BMMs to detect their effects on osteoclast differentiation. Firstly, qRT-PCR analysis showed that miR-340 was down-regulated during osteoclast differentiation stimulated by macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)-κB (RANK) ligand (RANKL). Besides, we found that overexpression of miRNA-340 inhibited osteoclast differentiation and suppressed both the mRNA and protein level of MITF. Finally, Western blot and qRT-PCR analysis revealed that silencing MITF inhibited TRAP, calcitonin receptor, V-ATPase d2, and cathepsin K. miR-340 suppresses osteoclast differentiation by inhibiting MITF. Our findings may provide promising therapeutic targets for osteoclast-associated diseases.

journal_name

Biosci Rep

journal_title

Bioscience reports

authors

Zhao H,Zhang J,Shao H,Liu J,Jin M,Chen J,Huang Y

doi

10.1042/BSR20170302

subject

Has Abstract

pub_date

2017-07-20 00:00:00

issue

4

eissn

0144-8463

issn

1573-4935

pii

BSR20170302

journal_volume

37

pub_type

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