Extracellular vesicle-encapsulated miR-22-3p from bone marrow mesenchymal stem cell promotes osteogenic differentiation via FTO inhibition.

Stem Cell Research & Therapy
Xueliang ZhangWenji Wang

Abstract

Bone marrow mesenchymal stem cells (BMSCs) exhibit the capacity to self-renew and differentiate into multi-lineage cell types, including osteoblasts, which are crucial regulators of fracture healing. Thus, this study aims to investigate the effect of microRNA (miR)-22-3p from BMSC-derived EVs on osteogenic differentiation and its underlying mechanism. Extracellular vesicles (EVs) were isolated from BMSCs and taken up with BMSCs. Dual-luciferase reporter gene assay was used to verify the binding relationship between miR-22-3p and FTO. Loss- and gain-of-function experiments were performed to determine the roles of EV-delivered miR-22-3p and FTO in osteogenic differentiation as well as their regulatory role in the MYC/PI3K/AKT axis. To determine the osteogenic differentiation, ALP and ARS stainings were conducted, and the levels of RUNX2, OCN, and OPN level were determined. In vivo experiment was conducted to determine the function of EV-delivered miR-22-3p and FTO in osteogenic differentiation, followed by ALP and ARS staining. miR-22-3p expression was repressed, while FTO expression was elevated in the ovariectomized mouse model. Overexpression of miR-22-3p, EV-delivered miR-22-3p, increased ALP activity and matrix mineralizatio...Continue Reading

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Citations

Apr 28, 2021·Molecular Medicine·Li-Rong RenKai-Shun Yang
Apr 20, 2021·Advanced Drug Delivery Reviews·Anika NagelkerkeMolly M Stevens
Jul 3, 2021·International Journal of Molecular Sciences·Marco Ponzetti, Nadia Rucci
Jul 27, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Soudeh Ghafouri-FardMohammad Samadian

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Methods Mentioned

BETA
transfection
PCR
Assay
Protein Assay
electrophoresis
Fluorescence
fluorescence microscopy

Software Mentioned

Image J
RNA22
Zetaview
DIANA TOOLS
SPSS
miRWalk
NTA
MEM
DIANA
TargetScan

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