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

Journal of Nanobiotechnology

Yun Sun¹  Lang Chen²  Yuan Xiong²  Guohui Liu²  Wu Zhou²  Dong Chen²  Bobin Mi²  Chenchen Yan²  Yiqiang Hu²  Faqi Cao²  Hang Xue²  Tao Yu³ 

[1] Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China;Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China;Department of Orthopedic Surgery, Tongji Hospital, Tongji University School of Medicine, 200065, Shanghai, China;

关键词: Exosome;    MiR-5106;    Osteoblast;    Fracture;    SIK2;    SIK3;   

DOI  :  10.1186/s12951-020-00622-5

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY