M2 Macrophagy-derived exosomal miRNA-5106 induces bone mesenchymal stem cells towards osteoblastic fate by targeting salt-inducible kinase 2 and 3

• Published in: Journal of nanobiotechnology 2020-04, Vol.18 (1), p.66-66
• Main Authors: Xiong, Yuan, Chen, Lang, Yan, Chenchen, Zhou, Wu, Yu, Tao, Sun, Yun, Cao, Faqi, Xue, Hang, Hu, Yiqiang, Chen, Dong, Mi, Bobin, Liu, Guohui
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Animals; Antagomirs - metabolism; Biological activity; Biomedical materials; Bone healing; Cell Differentiation; Coculture Techniques; Differentiation (biology); Drug delivery systems; Exosome; Exosomes; Exosomes - metabolism; Exosomes - transplantation; Femoral Fractures - pathology; Femoral Fractures - therapy; Flow cytometry; Fracture; Fractures; Genes; Healing; Health aspects; In vivo methods and tests; Kinases; Macrophages; Macrophages - cytology; Macrophages - metabolism; Male; Membrane vesicles; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mice; Mice, Inbred C57BL; MicroRNA; MicroRNAs; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; MiR-5106; miRNA; Nanomaterials; Osteoblast; Osteoblastogenesis; Osteoblasts; Osteoblasts - cytology; Osteoblasts - metabolism; Osteocalcin - genetics; Osteocalcin - metabolism; Osteogenesis; Protein Serine-Threonine Kinases - antagonists & inhibitors; Protein Serine-Threonine Kinases - chemistry; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Ribonucleic acid; RNA; RNA Interference; RNA, Small Interfering - metabolism; Salt-inducible kinase; SIK2; SIK3; Stem cells; Transcription factors
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-020-00622-5

Osteoblast 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. We 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. Our 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.