MicroRNA-21a-5p-modified macrophage exosomes as natural nanocarriers promote bone regeneration by targeting GATA2

Bone immune responses based on macrophages are critical in the osteogenesis of bone abnormalities. In general, M2 macrophage facilitate the promotion of osteogenesis, as well, M1 macrophage play an important role in early bone healing, as confirmed by previous studies. However, it is not clear how M1 macrophage are involved in the bone immune response. MiR-21a-5p is a highly expressed microRNA in M1 macrophage in contrast to M2. Therefore, the current work sought to ascertain the influence of M1 macrophage on bone healing via exosomal miR-21a-5p and the probable mechanism. We discovered that injecting M1 macrophage exosomes overexpressing miR-21a-5p into bone defect locations enhanced bone regeneration in vivo. Furthermore, by directly targeting GATA2, miR-21a-5p accelerated MC3T3-E1 osteogenic differentiation. Our findings showed that exosomal miR-21a-5p from M1 macrophage may be transported to osteoblasts and target GATA2 to enhance bone defect healing. Graphical Abstract

Automated summary

Bone immune responses mediated by macrophages are crucial for bone abnormalities. While M2 macrophages promote osteogenesis, previous studies indicated that M1 macrophages play a significant role in early bone healing. However, the involvement of M1 macrophages in bone immune response remains unclear. This study focuses on the role of M1 macrophages and their miR-21a-5p exosomes in bone healing, demonstrating their potential to enhance bone regeneration and osteoblast differentiation by targeting GATA2.