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• W2802968757 abstract "The Masquelet’s induced membrane technique for repairing bone defects has been demonstrated to be a promising treatment strategy. Previous studies have shown that the vessel density of induced membrane is decreased in the late stage of membrane formation, which consequently disrupts the bone healing process. However, relatively little is known about certain mechanisms of vessel degeneration in the induced membrane tissue and whether promotion of angiogenesis in induced membranes can improve bone regeneration. Here, we showed that the Delta-like ligand 4/ Notch homolog 1 (Dll4/Notch1) pathway was relatively activated in the late stage of induced membrane, especially at the subcutaneous site. Then, DAPT, a classical γ-secretase inhibitor, was applied to specifically inhibit Notch1 activation, followed by up-regulation of vascular endothelial growth factor receptor 2 (VEGFR2) and CD31 expression. DAPT-modified induced membranes were further confirmed to contribute to bone regeneration after autogenous bone grafting. Finally, in vitro experiments revealed that knocking down Notch1 contributed to the functional improvement of endothelial progenitor cells (EPCs) and that DAPT-treated induced membrane tissue was more favorable for angiogenesis of EPCs compared with the vehicle group. In conclusion, the present findings demonstrate that Dll4/Notch1 signaling is negatively associated with the vessel density of induced membrane. Pharmacological inhibition of Notch1 attenuated the vessel degeneration of induced membrane both in vitro and in vivo, which consequently improved bone formation at the bone defect site and graft resorption at the subcutaneous site. Repairs to serious bone injuries may be improved by blocking a signaling pathway that causes newly forming membranes to fail. Masquelet’s technique involves placing acrylic spacers in areas of bone damage, inducing the formation of vascularised membranes which encourage the body to accept bone grafts. However, sometimes Masquelet’s membranes do not form correctly, leading to weaknesses in bone repairs and potential graft rejection. In experiments on rats, Qian Tang from Wenzhou Medical University, China, and coworkers found that a particular signaling pathway, D114/Notch1, was upregulated around 6 weeks post-operation, reducing blood vessel density and limiting new vessel growth, weakening the membranes. The team inhibited this pathway using an existing therapy that prevents blood clots. This treatment improved bone repairs by promoting the formation and function of blood vessels in membranes." @default.
• W2802968757 created "2018-05-17" @default.
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• W2802968757 date "2018-04-01" @default.
• W2802968757 modified "2023-10-16" @default.
• W2802968757 title "Inhibition of Dll4/Notch1 pathway promotes angiogenesis of Masquelet’s induced membrane in rats" @default.
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• W2802968757 doi "https://doi.org/10.1038/s12276-018-0062-9" @default.
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