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- W4320040612 abstract "Bone morphogenetic protein (BMP-2) has been approved by the FDA to promote bone regeneration, but uncertain osteogenic effect and dose-dependent side effects may occur. Osteoimmunomodulation plays an important role in growth factor-based osteogenesis. Here, we explored how proinflammatory signals affect the dose-dependent osteogenic potential of BMP-2. We observed that the expression level of local IL-1β did not increase with the dose of BMP-2 in the mouse osteogenesis model. A low dose of BMP-2 could not promote new bone formation, but trigger the release of IL-1β from M1 macrophages. As the dose of BMP-2 increased, the IL-1β expression and M1 infiltration in local microenvironment were inhibited by IL-1Ra from MSCs under osteogenic differentiation induced by BMP-2, and new bone tissues formed, even excessively. Anti-inflammatory drugs (Dexamethasone, Dex) promoted osteogenesis via inhibiting M1 polarization and enhancing BMP-2-induced MSC osteo-differentiation. Thus, we suggest that the osteogenic effect of BMP-2 involves macrophage-MSC interaction that is dependent on BMP-2 dose and based on IL-1R1 ligands, including IL-1β and IL-1Ra. The dose of BMP-2 could be reduced by introducing immunoregulatory strategies." @default.
- W4320040612 created "2023-02-12" @default.
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- W4320040612 date "2023-07-01" @default.
- W4320040612 modified "2023-09-29" @default.
- W4320040612 title "Regulating macrophage-MSC interaction to optimize BMP-2-induced osteogenesis in the local microenvironment" @default.
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- W4320040612 doi "https://doi.org/10.1016/j.bioactmat.2023.02.001" @default.
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