BMSC-Derived Exosomal miR-29a Promotes Angiogenesis and Osteogenesis.

Guo-Dong Lu,Ting Liu,Peng Cheng,Zhong Wang

doi:10.3389/fcell.2020.608521

Abstract

Angiogenesis and osteogenesis are tightly coupled during bone modeling and remodeling processes. Here we reported that bone marrow mesenchymal stem cell (BMSC)-derived exosomal miR-29a promotes angiogenesis and osteogenesis in vitro and in vivo. BMSC-derived exosomes (BMSCs-Exos) can be taken up by human umbilical vein endothelial cells (HUVECs) and promote the proliferation, migration, and tube formation of HUVECs. MiRNA-29a level was high in BMSCs-Exos and can be transported into HUVECs to regulate angiogenesis. VASH1 was identified as a direct target of miR-29a, mediating the effects of BMSC-derived exosomal miR-29a on angiogenesis. More interestingly, miR29a-loaded exosomes from engineered BMSCs (miR-29a-loaded BMSCs-Exos) showed a robust ability of promoting angiogenesis and osteogenesis in vivo. Taken together, these findings suggest that BMSC-derived exosomal miR-29a regulates angiogenesis and osteogenesis, and miR-29a-loaded BMSCs-Exos may serve as a potential therapeutic target for osteoporosis.

Highlights

Bone undergoes sustained modeling and remodeling processes throughout life to ensure the integrity and structure of the skeleton (Wu et al, 2010)
bone marrow mesenchymal stem cell (BMSC)-Exos and phosphate-buffered saline (PBS) control were added to the culture medium of human umbilical vein endothelial cells (HUVECs), respectively, for tube-like structure formation assay
We have shown that BMSCs-Exos promote angiogenesis and osteogenesis

Summary

Introduction

Bone undergoes sustained modeling and remodeling processes throughout life to ensure the integrity and structure of the skeleton (Wu et al, 2010). Angiogenesis is tightly coupled with bone formation and regeneration for proper bone homeostasis (Hui et al, 2014; Kusumbe et al, 2014; Yang et al, 2017). Mesenchymal stem cell (MSC)-derived exosomes have been reported to be involved in multiple physiology and pathology activities including osteogenesis, bone regeneration, osteoarthritis, cardiomyoblast hypoxia–reperfusion, cognitive impairment, inflammation, stroke, sepsis, and tumorigenesis (Zheng et al, 2018; Huang et al, 2020; Jin et al, 2020; Nakano et al, 2020; Tan et al, 2020; Venkat et al, 2020; Xu et al, 2020; Zou et al, 2020). Jia et al (2020) report that exosomes secreted by young MSCs promote osteogenesis and bone formation in older rats. Zuo et al (2019) report that bone marrow MSC (BMSC)-derived exosomes alleviate radiationinduced bone loss by activating Wnt/β-catenin signaling. The effects of BMSC-derived exosomes (BMSCs-Exos), especially the key microRNAs within the BMSCs-Exos, on angiogenesis and osteogenesis are not well studied

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Conclusion