Mg<sup>2+</sup>‐mediated autophagy‐dependent polarization of macrophages mediates the osteogenesis of bone marrow stromal stem cells by interfering with macrophage‐derived exosomes containing miR‐381
Yong Zhu, Shushan Zhao, Liang Cheng, Zhangyuan Lin, Min Zeng, Zhe Ruan, Buhua Sun, Zhong‐Wei Luo, Yifu Tang, Haitao Long
Abstract
Abstract Magnesium ion (Mg 2+ ) has received increased attention due to the roles it plays in promoting osteogenesis and preventing inflammation. This study was designed to investigate the mechanism by which Mg 2+ influences the osteoblastic differentiation of bone marrow stromal stem cells (BMSCs). The polarization of Mø (macrophages) was measured after treatment with Mg 2+ . Meanwhile, autophagy in Mø was measured by detecting LC3B expression. Mø‐derived exosomes were isolated and cocultured with BMSCs; after which, osteogenic differentiation was evaluated by Alizarin Red staining and detection of alkaline phosphatase (ALP). Our results showed that Mg 2+ could induce autophagy in macrophages and modulate the M1/M2 polarization of macrophages. Mg 2+ ‐mediated macrophages could facilitate the osteogenic differentiation of BMSCs by regulating autophagy, and this facilitation by Mg 2+ ‐mediated macrophages was closely related to macrophage‐derived exosomes, and especially exosomes containing miR‐381. However, miR‐381 in macrophages did not influence autophagy or the polarization of Mg 2+ ‐mediated macrophages. Furthermore, macrophage‐derived exosomes containing miR‐381 mainly determined the osteogenic differentiation of BMSCs. Mg 2+ ‐mediated macrophages were shown to promote the osteogenic differentiation of BMSCs via autophagy through reducing miR‐381 in macrophage‐derived exosomes. In conclusion, our results suggest Mg 2+ ‐mediated macrophage‐derived exosomes containing miR‐381 as novel vehicles for promoting the osteogenic differentiation of BMSCs.