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  • Zhang, Yujue  (5)
  • 1
    In: Regenerative Biomaterials, Oxford University Press (OUP), Vol. 10 ( 2023-01-17)
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2056-3426
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2799042-4
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  • 2
    In: International Journal of Biological Macromolecules, Elsevier BV, ( 2024-4), p. 131800-
    Type of Medium: Online Resource
    ISSN: 0141-8130
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 1483284-7
    SSG: 12
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  • 3
    In: Regenerative Biomaterials, Oxford University Press (OUP), Vol. 10 ( 2023-01-17)
    Abstract: Immune response is an important factor in determining the fate of bone replacement materials, in which macrophages play an important role. It is a new idea to design biomaterials with immunomodulatory function to reduce inflammation and promote bone integration by regulating macrophages polarization. In this work, the immunomodulatory properties of CaP Zn-Mn-Li alloys and the specific mechanism of action were investigated. We found that the CaP Zn0.8Mn0.1Li alloy promoted the polarization of macrophages toward M2 and reduced inflammation, which could effectively upregulate osteogenesis-related factors and promote new bone formation, indicating the important role of macrophages polarization in biomaterial induction of osteogenesis. In vivo studies further demonstrated that CaP Zn0.8Mn0.1Li alloy could stimulate osteogenesis better than other Zn-Mn-Li alloys implantations by regulating macrophages polarization and reducing inflammation. In addition, transcriptome results showed that CaP Zn0.8Mn0.1Li played an important regulatory role in the life process of macrophages, activating Toll-like receptor signaling pathway, which participated in the activation and attenuation of inflammation, and accelerated bone integration. Thus, by preparing CaP coatings on the surface of Zn-Mn-Li alloys and combining the bioactive ingredient with controlled release, the biomaterial will be imbibed with beneficial immunomodulatory properties that promote bone integration.
    Type of Medium: Online Resource
    ISSN: 2056-3426
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2799042-4
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  • 4
    Online Resource
    Online Resource
    Wiley ; 2021
    In:  Journal of Biomedical Materials Research Part A Vol. 109, No. 8 ( 2021-08), p. 1328-1336
    In: Journal of Biomedical Materials Research Part A, Wiley, Vol. 109, No. 8 ( 2021-08), p. 1328-1336
    Abstract: Mineralized collagen (MC) is a biomaterial that is commonly used in the treatment of bone defects. However, the inflammatory response after biomaterial implantation is a recurrent problem that requires urgent attention. Our previous studies on MC‐macrophage interactions were descriptive but we did not perform an in‐depth analysis on a genetic level to investigate the underlying mechanisms. In this study, we cultured RAW264.7 cells on MC or collagen and examined the proliferation of the macrophages by Cell Counting Kit‐8 assay. We sequenced the RNA of the cultured cells to discover differential gene expression patterns and found that a total of 1183 genes were differentially expressed between the MC‐ and collagen‐cultured groups, of which 396 genes were upregulated and 787 were downregulated. Gene ontology analysis revealed that biological processes in MC‐cultured cells, such as inflammation and innate immunity, were downregulated; whereas nucleosome assembly, megakaryocyte differentiation, and chromatin assembly were upregulated. We identified several pathways associated with immunity that were significantly enriched using the Kyoto Encyclopedia of Genes and Genomes. Furthermore, we validated the differentially expressed genes from RNA sequencing by quantitative real‐time polymerase chain reaction. This study provides insight into the macrophage phenotype based on the microenvironment, which is the foundation for the clinical application of MC‐based interventions.
    Type of Medium: Online Resource
    ISSN: 1549-3296 , 1552-4965
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1477192-5
    SSG: 12
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  • 5
    In: Regenerative Biomaterials, Oxford University Press (OUP)
    Abstract: 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 carriers 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 supernatants of M0, 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 knocking down miR-365-2-5p to examine the biological function of exosome miR-365-2-5p on MC3T3-E1 differentiation. This 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-E1. 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.
    Type of Medium: Online Resource
    ISSN: 2056-3426
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2799042-4
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