Abstract
BackgroundOsteoblast differentiation is a vital process for fracture healing, and exosomes are nanosized membrane vesicles that can deliver therapeutic drugs easily and safely. Macrophages participate in the regulation of various biological processes in vivo, and macrophage-derived exosomes (MD-Exos) have recently been a topic of increasing research interest. However, few study has explored the link between MD-Exos and osteoblast differentiation. Herein, we sought to identify miRNAs differentially expressed between M1 and M2 macrophage-derived exosomes, and to evaluate their roles in the context of osteoblast differentiation.ResultsWe found that microRNA-5106 (miR-5106) was significantly overexpressed in M2 macrophage-derived exosomes (M2D-Exos), while its expression was decreased in M1 macrophage-derived exosomes (M1D-Exos), and we found that this exosomal miRNA can induce bone mesenchymal stem cell (BMSC) osteogenic differentiation via directly targeting the Salt-inducible kinase 2 and 3 (SIK2 and SIK3) genes. In addition, the local injection of both a miR-5106 agonist or M2D-Exos to fracture sites was sufficient to accelerate healing in vivo.ConclusionsOur study demonstrates that miR-5106 is highly enriched in M2D-Exos, and that it can be transferred to BMSCs wherein it targets SIK2 and SIK3 genes to promote osteoblast differentiation.
Highlights
Osteoblast differentiation is a vital process for fracture healing, and exosomes are nanosized membrane vesicles that can deliver therapeutic drugs and safely
We demonstrate that miR-5106 is highly enriched in M2D-Exos, and that it can be transferred to bone mesenchymal stem cell (BMSC) wherein it targets the SIK2 and SIK3 genes to induce osteoblastic differentiation in vitro and in vivo
M1 and M2 macrophages secrete exosomal miRNAs We first assessed the expression of phenotypic markers associated with bone marrow-derived macrophages (BMDMs) by flow cytometry (Additional file 1: Figure S1A)
Summary
Osteoblast differentiation is a vital process for fracture healing, and exosomes are nanosized membrane vesicles that can deliver therapeutic drugs and safely. We sought to identify miRNAs differentially expressed between M1 and M2 macrophage-derived exosomes, and to evaluate their roles in the context of osteoblast differentiation. Xiong et al J Nanobiotechnol (2020) 18:66 healing [5] They are among the earliest cells to migrate to fracture sites, stimulated by the tissue injury and the associated acute inflammatory phase [6]. Macrophages are necessary for osteoblast differentiation in vitro, and have been shown to be important during both early and late stages of fracture healing [7, 8]. The mechanisms governing the beneficial role of M2 macrophages in the context of osteoblasts differentiation remain elusive
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