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

Hongling Li; Tangping Li; Shihua Wang; Jianfeng Wei; Junfen Fan; Jing Li; Qin Han; Lianming Liao; Changshun Shao; Robert Chunhua Zhao

doi:10.1016/j.scr.2012.11.007

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

Stem Cell Res. 2013 May;10(3):313-24. doi: 10.1016/j.scr.2012.11.007. Epub 2012 Dec 3.

Authors

Hongling Li¹, Tangping Li, Shihua Wang, Jianfeng Wei, Junfen Fan, Jing Li, Qin Han, Lianming Liao, Changshun Shao, Robert Chunhua Zhao

Affiliation

¹ Center of Excellence in Tissue Engineering, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 5# Dongdansantiao, Beijing, People's Republic of China.

PMID: 23399447
DOI: 10.1016/j.scr.2012.11.007

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes / cytology
Adipocytes / metabolism
Adipogenesis
Adipose Tissue / cytology*
Bone Morphogenetic Protein 2 / antagonists & inhibitors
Bone Morphogenetic Protein 2 / genetics
Bone Morphogenetic Protein 2 / metabolism
CCAAT-Enhancer-Binding Protein-alpha / metabolism
Cell Differentiation*
Cell Lineage
Cells, Cultured
Core Binding Factor Alpha 1 Subunit / metabolism
Down-Regulation
Homeodomain Proteins / metabolism
Humans
Intracellular Signaling Peptides and Proteins / metabolism
Mesenchymal Stem Cells / cytology*
MicroRNAs / antagonists & inhibitors
MicroRNAs / genetics
MicroRNAs / metabolism*
Osteoblasts / cytology
Osteoblasts / metabolism
Osteogenesis
PPAR gamma / metabolism
RNA Interference
RNA, Small Interfering / metabolism
Trans-Activators
Transcription Factors
Transcriptional Coactivator with PDZ-Binding Motif Proteins
Up-Regulation

Substances

Bone Morphogenetic Protein 2
CCAAT-Enhancer-Binding Protein-alpha
Core Binding Factor Alpha 1 Subunit
Homeodomain Proteins
Intracellular Signaling Peptides and Proteins
MIRN106 microRNA, human
MIRN17 microRNA, human
MSX2 protein
MicroRNAs
PPAR gamma
RNA, Small Interfering
Trans-Activators
Transcription Factors
Transcriptional Coactivator with PDZ-Binding Motif Proteins
WWTR1 protein, human