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.

let-7Enhances Osteogenesis and Bone Formation While Repressing Adipogenesis of Human Stromal/Mesenchymal Stem Cells by Regulating HMGA2

“…hADSCs in the third passage were used for the following experiments. Adipogenic and osteogenic differentiation of hADSCs was performed as described earlier [23,24]. hADSCs from three different individuals were used as biological replicates.…”

“…Recently, several miRNAs have also been identified to be responsible for the balance of adipogenesis and osteogenesis. Overexpression of miR-204, miR-17-5p, and miR-106a suppresses osteoblast differentiation and promotes adipocyte differentiation [23,24]. In contrast, miR-637 has an opposite effect, suggesting that adipocyte and osteoblast differentiation are tightly regulated by specific miRNAs in hMSCs [25].…”

MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation

“…Recently, several miRNAs were found to be involved in either osteogenesis or adipogenesis (8)(9)(10)(11)(12). However, most of these miRNAs have only been investigated in vitro, and their functional roles in the pathophysiological mechanisms responsible for age-related bone loss and accumulation of fat in bone marrow remain to be established.…”

miR-148a and miR-17–5p synergistically regulate milk TAG synthesis via PPARGC1A and PPARA in goat mammary epithelial cells

“…45 Although previous studies have shown that miR-148a and miR-17-5p also influence adipocyte differentiation 37 and regeneration, the function of miR-148a and miR-17-5p in the goat mammary gland is unknown. Therefore, the main purpose of the present work was to investigate the synergistic role that miR-148a and miR-17-5p play in the control of mammary cell lipid metabolism using primary goat mammary epithelial cells (GMEC).…”