Elsevier

Stem Cell Research

Volume 10, Issue 3, May 2013, Pages 313-324
Stem Cell Research

miR-17-5p and miR-106a are involved in the balance between osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells

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Abstract

Mesenchymal stem cells (MSCs) can differentiate into several distinct cell types, including osteoblasts and adipocytes. The balance between osteogenic and adipogenic differentiation is disrupted in several osteogenic-related disorders, such as osteoporosis. So far, little is known about the molecular mechanisms that drive final lineage commitment of MSCs. In this study, we revealed that miR-17-5p and miR-106a have dual functions in the modulation of human adipose-derived mesenchymal stem cells (hADSCs) commitment by gain- and loss-of-function assays. They could promote adipogenesis and inhibit osteogenesis. Luciferase reporter assay, western blot and ELISA suggested BMP2 was a direct target of miR-17-5p and miR-106a. Downregulation of endogeneous BMP2 by RNA interference suppressed osteogenesis and increased adipogenesis, similar to the effect of miR-17-5p and miR-106a upregulation. Moreover, the inhibitory effects of miR-17-5p on osteogenic and adipogenic differentiation of hADSCs could be reversed by BMP2 RNA interference. In conclusion, miR-17-5p and miR-106a regulate osteogenic and adipogenic lineage commitment of hADSCs by directly targeting BMP2, and subsequently decreased osteogenic TAZ, MSX2 and Runx2, and increased adipogenic C/EBPα and PPARγ.

Highlights

► miR-17-5p and miR-106a significantly inhibit osteogenesis and promote adipogenesis. ► BMP2 is a novel target of miR-17-5p and miR-106a. ► siBMP2 can mimic the effect of those miRNAs on osteogenesis and adipogenesis. ► The effect of miR-17-5p and miR-106a downregulation can be reversed by siBMP2. ► Overexpression of those miRNAs suppressed BMP2 and its downstream targets.

Abbreviations

ELISA
enzyme-linked immunosorbent assay
MSCs
mesenchymal stem cells
hADSCs
human adipose-derived mesenchymal stem cells
BMP2
bone morphogenetic protein 2
TAZ
transcriptional co-activator with PDZ-binding motif
MSX2
msh homeobox 2
Runx2
runt-related transcription factor 2
OSX
Osterix
ALP
alkaline phosphatase
OPN
osteopontin
OCN
osteocalcin
C/EBPα
CCAAT/enhancer binding proteins alpha
PPARγ
peroxisome proliferator-activated receptor gamma
LPL
lipoprotein lipase
AP2 (FABP4)
fatty acid binding protein 4, adipocytes
ID1
helix-loop-helix proteins1

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