Exosomal miR-590-3p derived from bone marrow mesenchymal stem cells promotes osteoblast differentiation and osteogenesis by targeting TGFBR1.

Abstract

Bone marrow mesenchymal stem cells (BMSCs) have been verified to be essential factors regulating osteogenic functions, which is mainly attributed to their secretion of extracellular vesicles. Exosomes derived from BMSCs (BMSCs-Exo) contribute to osteoblast functions that are critical for improving bone defect. Our current study aims to investigate the molecular mechanism dominated by BMSCs-Exo that affects osteoblast differentiation and osteogenesis. The first step this study validated that BMSCs co-culture enhanced the differentiation ability of osteoblast and promoted bone mineralization, while these tendencies were abolished after GW4869 treatment. Next, the BMSCs-Exo was isolated and identified by TEM observation, insight detection, and western blot analysis. Furthermore, BMSCs-Exo treatment could efficiently promote the differentiation ability and the bone mineralization of osteoblasts, decrease the mRNA levels of Collagen I and Collagen III, and increase the levels of osteogenic proteins, including alkaline phosphatase (ALP), Turning Bone Morphogenetic Protein 2 (BMP2), Bone sialoprofein (BSP), osteocalcin (OCN), and osterix (OSX). However, the abovementioned effects of BMSCs-Exo could be abolished by miR-590-3p silencing. Mechanistic analysis unmasked the negative regulation of miR-590-3p on its downstream target TGFBR1. Finally, the effects of miR-590-3p/TGFBR1 axis on the differentiation and osteogenesis of osteoblasts were validated by rescue assays. In conclusion, the present study demonstrates that exosomal miR-590-3p secreted by BMSCs can induce osteoblast differentiation and osteogenesis.