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Research Paper|Volume 15, Issue 18|pp 9499—9520

M2 macrophage-derived exosomal miR-486-5p influences the differentiation potential of bone marrow mesenchymal stem cells and osteoporosis

Jincheng Liu1,2, Zhenqian Sun1,2, Yunhao You1,2, Lu Zhang1,2, Dehui Hou1,2, Guanghui Gu1,2, Yunzhen Chen1, Guangjun Jiao1
  • 1Department of Orthopaedics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
  • 2The First Clinical College of Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China
* Equal contribution and shared the first authors
Received: February 13, 2023Accepted: August 20, 2023Published: September 25, 2023
https://doi.org/10.18632/aging.205031

Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: An imbalance between osteogenesis and adipogenesis in bone marrow mesenchymal stem cells (BMMSCs) can cause osteoporosis. Macrophage-derived exosomes (MD-Exos) and microRNAs (miRNAs) enriched in exosomes participate in the differentiation of BMMSCs.

Methods: Bioinformatics methods were used to analyze differentially expressed miRNAs. We cocultured M2 macrophages and BMMSCs to examine the biological function of exosomal microRNA-486-5p (miR-486-5p) on BMMSCs differentiation. Gain-of-function experiments related to osteogenesis were designed to investigate the effects of exosomes carrying miR-486-5p on an ovariectomized (OVX) mice model and the direct impact of miR-486-5p on BMMSCs. A dual luciferase experiment was performed to demonstrate the target gene of miR-486-5p.

Results: Bioinformatics analysis identified high expression of miRNA-486 in M2 macrophage-derived exosomes (M2D-Exos). The in vitro results demonstrated that M2 macrophage-derived exosomal miR-486-5p enhanced osteogenic capacity but inhibited the adipogenesis of BMMSCs. The direct effect of miR-486-5p on BMMSCs showed the same effects. Animal experiments revealed that exosomal miR-486-5p rescued bone loss of OVX mice. SMAD2 was characterized as a target gene of miR-486-5p. Pathway analysis showed that M2 macrophage-derived exosomal miR-486-5p stimulated osteogenic differentiation via the TGF-β/SMAD2 signalling pathway.

Conclusions: Taken together, M2 macrophage-derived exosomal miR-486-5p influences the differentiation potential of BMMSCs through the miR-486-5p/SMAD2/TGF-β signalling pathway and osteoporosis.