In the bone immune microenvironment,immune cells can regulate osteoblasts through a complex communication network.Macrophages play a central role in mediating immune osteogenesis,exosomes derived from them have osteog...In the bone immune microenvironment,immune cells can regulate osteoblasts through a complex communication network.Macrophages play a central role in mediating immune osteogenesis,exosomes derived from them have osteogenic regulation and can be used as cariers in bone tissue engineering.However,there are problems with exosomal therapy alone,such as poor targeting,and the content of loaded molecules cannot reach the therapeutic concentration.In this study,macrophage-derived exosomes modified with miR-365-2-5p were developed to accelerate bone healing.MC3T3-E1 cells were incubated with the culture supermatants of Mo,M1 and M2 macrophages,and it was found that the culture medium of M2 macrophages had the most significant effects in contributing to osteogenesis.High-throughput sequencing identified that miR-365-2-5p was significantly expressed in exosomes derived from M2 macrophages.We incubated MC3T3-E1 with exosomes overexpressing or kmocking down miR-365-2-5p to examine the biological function of exosome miR-365-2-5p on MC3T3-E1 differentiation.These findings suggested that miR-365-2-5p secreted by exosomes increased the osteogenesis of MC3T3-E1.Moreover,miR-365-2-5p had a direct influence over osteogenesis for MC3T3-Ei.Sequencing analysis combined with dual luciferase detection indicated that miR-365-2-5p binded to the 3'-UTR of OLFML1.In summary,exosomes secreted by M2 macrophages targeted OLFML1 through miR-365-2-5p to facilitate osteogenesis.展开更多
基金the Science Foundation of Shandong Province of China(Grant Nos ZR2021MH026,ZR2022MH075,ZR2020MH100)Shandong Province Medical and Health Science and Technology Development Plan(2018WS426)Liaocheng Key Research and Development Plan of Shandong Province of China(Grant Nos 2022YDSF16,2022YDSF21,2023YD28,2023YD34).
文摘In the bone immune microenvironment,immune cells can regulate osteoblasts through a complex communication network.Macrophages play a central role in mediating immune osteogenesis,exosomes derived from them have osteogenic regulation and can be used as cariers in bone tissue engineering.However,there are problems with exosomal therapy alone,such as poor targeting,and the content of loaded molecules cannot reach the therapeutic concentration.In this study,macrophage-derived exosomes modified with miR-365-2-5p were developed to accelerate bone healing.MC3T3-E1 cells were incubated with the culture supermatants of Mo,M1 and M2 macrophages,and it was found that the culture medium of M2 macrophages had the most significant effects in contributing to osteogenesis.High-throughput sequencing identified that miR-365-2-5p was significantly expressed in exosomes derived from M2 macrophages.We incubated MC3T3-E1 with exosomes overexpressing or kmocking down miR-365-2-5p to examine the biological function of exosome miR-365-2-5p on MC3T3-E1 differentiation.These findings suggested that miR-365-2-5p secreted by exosomes increased the osteogenesis of MC3T3-E1.Moreover,miR-365-2-5p had a direct influence over osteogenesis for MC3T3-Ei.Sequencing analysis combined with dual luciferase detection indicated that miR-365-2-5p binded to the 3'-UTR of OLFML1.In summary,exosomes secreted by M2 macrophages targeted OLFML1 through miR-365-2-5p to facilitate osteogenesis.
