title: miR-17-5p and miR-106a are involved in the balance between osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells.
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.
authors: 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.
authors: Hongling
authors: H
authors: Li
authors: Tangping
authors: T
authors: Li
authors: Shihua
authors: S
authors: Wang
authors: Jianfeng
authors: J
authors: Wei
authors: Junfen
authors: J
authors: Fan
authors: Jing
authors: J
authors: Li
authors: Qin
authors: Q
authors: Han
authors: Lianming
authors: L
authors: Liao
authors: Changshun
authors: C
authors: Shao
authors: Robert Chunhua
authors: RC
authors: Zhao
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis; D000273:Adipose Tissue / Q000166:cytology*; D055396:Bone Morphogenetic Protein 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D015536:Down-Regulation; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D047495:PPAR gamma / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D015854:Up-Regulation
chemical_list: D055396:Bone Morphogenetic Protein 2; D022763:CCAAT-Enhancer-Binding Protein-alpha; D050659:Core Binding Factor Alpha 1 Subunit; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; C542541:MIRN106 microRNA, human; C524941:MIRN17 microRNA, human; C084119:MSX2 protein; D035683:MicroRNAs; D047495:PPAR gamma; D034741:RNA, Small Interfering; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; C551991:WWTR1 protein, human