Electrochemically derived nanographene oxide activates endothelial tip cells and promotes angiogenesis by binding endogenous lysophosphatidic acid.
Electrochemically derived nanographene oxide activates endothelial tip cells and promotes angiogenesis by binding endogenous lysophosphatidic acid.
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DOI：
10.1016/j.bioactmat.2021.07.007
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发表时间：
2022-03
影响因子：
18.9
通讯作者：
Shao L
中科院分区：
文献类型：
--
作者：
Liu W;Luo H;Wei Q;Liu J;Wu J;Zhang Y;Chen L;Ren W;Shao L
氧化石墨烯（GO）表现出良好的机械和物理化学特性，在骨组织工程中具有广泛的应用前景。然而，其对血管生成的影响尚不清楚，其潜在的毒性作用也存在很大争议。在此，我们发现通过一步水电解氧化合成的纳米氧化石墨烯（NGO）更小并且表现出优异的生物相容性。此外，NGO显着增强了体内颅骨骨缺损区域的血管生成，为骨再生提供了良好的微环境。内皮尖端细胞分化是血管生成启动的重要步骤。我们验证了NGO通过强氢键相互作用与血清中的溶血磷脂酸（LPA）偶联来激活内皮尖细胞，这一点尚未见报道。此外，还系统研究了NGO促进血管生成的机制。 NGO 偶联的 LPA 激活 LPAR6，并通过 Hippo/Yes 相关蛋白 (YAP) 促进迁移尖端细胞的形成，不受活性氧 (ROS) 刺激或其他复杂修饰的影响。这些结果为电化学衍生的 NGO 的应用提供了有效的策略，并更深入地了解 NGO 介导的血管生成。 NGO 促进骨缺损部位早期血管生成的机制示意图。 NGO结合的内源性LPA激活LPAR6并诱导YAP的核转位，从而诱导尖端细胞特化并促进血管生成。电化学衍生的纳米氧化石墨烯（NGO）具有良好的细胞相容性，且不会上调活性氧。 NGO表现出更好的分散性，并与体液中的内源性溶血磷脂酸（LPA）结合。 NGO 通过募集内源性 LPA 和促进内皮尖端细胞形成来增强血管生成。
Graphene oxide (GO) exhibits good mechanical and physicochemical characteristics and has extensive application prospects in bone tissue engineering. However, its effect on angiogenesis is unclear, and its potential toxic effects are heavily disputed. Herein, we found that nanographene oxide (NGO) synthesized by one-step water electrolytic oxidation is smaller and shows superior biocompatibility. Moreover, NGO significantly enhanced angiogenesis in calvarial bone defect areas in vivo, providing a good microenvironment for bone regeneration. Endothelial tip cell differentiation is an important step in the initiation of angiogenesis. We verified that NGO activates endothelial tip cells by coupling with lysophosphatidic acid (LPA) in serum via strong hydrogen bonding interactions, which has not been reported. In addition, the mechanism by which NGO promotes angiogenesis was systematically studied. NGO-coupled LPA activates LPAR6 and facilitates the formation of migratory tip cells via Hippo/Yes-associated protein (YAP) independent of reactive oxygen species (ROS) stimulation or additional complex modifications. These results provide an effective strategy for the application of electrochemically derived NGO and more insight into NGO-mediated angiogenesis. Schematic representation of the mechanisms by which NGO promotes early angiogenesis at the bone defect site. NGO-bound endogenous LPA activates LPAR6 and induces the nuclear translocation of YAP, thereby inducing tip cell specialization and promoting angiogenesis. Electrochemically derived nanographene oxide (NGO) has good cytocompatibility without upregulating reactive oxygen species. NGO exhibits better dispersibility and couples with endogenous lysophosphatidic acid (LPA) in body fluid. NGO enhances the angiogenesis by recruiting endogenous LPA and promoting endothelial tip cell formation.
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影响因子：
9.8
作者：
Dallinga MG;Yetkin-Arik B;Kayser RP;Vogels IMC;Nowak-Sliwinska P;Griffioen AW;van Noorden CJF;Klaassen I;Schlingemann RO
通讯作者：
Schlingemann RO
具有骨诱导和抗纤维化作用的生物相容性血管化氧化石墨烯（GO）胶原室可促进体内骨再生
影响因子：
12.4
作者：
Fang, Huimin;Luo, Chao;Wang, Zhenxing
通讯作者：
Wang, Zhenxing
影响因子：
3.1
作者：
Chen, Yiliang;Ramakrishnan, Devi Prasadh;Ren, Bin
通讯作者：
Ren, Bin
影响因子：
9.5
作者：
Frahs, Stephanie M.;Reeck, Jonathon C.;Oxford, Julia Thom
通讯作者：
Oxford, Julia Thom
影响因子：
7.4
作者：
Liu, Si-Jia;Wen, Qian;Jiang, Jian-Hui
通讯作者：
Jiang, Jian-Hui