PDF(Pubmed)
Abstract：
BACKGROUND: Early angiogenesis provides nutrient supply for bone tissue repair, and insufficient angiogenesis will lead tissue engineering failure. Lanthanide metal nanoparticles (LM NPs) are the preferred materials for tissue engineering and can effectively promote angiogenesis. Holmium oxide nanoparticles (HNPs) are LM NPs with the function of bone tissue \"tracking\" labelling. Preliminary studies have shown that HNPs has potential of promote angiogenesis, but the specific role and mechanism remain unclear. This limits the biological application of HNPs.
RESULTS: In this study, we confirmed that HNPs promoted early vessel formation, especially that of H-type vessels in vivo, thereby accelerating bone tissue repair. Moreover, HNPs promoted angiogenesis by increasing cell migration, which was mediated by filopodia extension in vitro. At the molecular level, HNPs interact with the membrane protein EphrinB2 in human umbilical vein endothelial cells (HUVECs), and phosphorylated EphrinB2 can bind and activate VAV2, which is an activator of the filopodia regulatory protein CDC42. When these three molecules were inhibited separately, angiogenesis was reduced.
CONCLUSIONS: Overall, our study confirmed that HNPs increased cell migration to promote angiogenesis for the first time, which is beneficial for bone repair. The EphrinB2/VAV2/CDC42 signalling pathway regulates cell migration, which is an important target of angiogenesis. Thus, HNPs are a new candidate biomaterial for tissue engineering, providing new insights into their biological application.
RESULTS: In this study, we confirmed that HNPs promoted early vessel formation, especially that of H-type vessels in vivo, thereby accelerating bone tissue repair. Moreover, HNPs promoted angiogenesis by increasing cell migration, which was mediated by filopodia extension in vitro. At the molecular level, HNPs interact with the membrane protein EphrinB2 in human umbilical vein endothelial cells (HUVECs), and phosphorylated EphrinB2 can bind and activate VAV2, which is an activator of the filopodia regulatory protein CDC42. When these three molecules were inhibited separately, angiogenesis was reduced.
CONCLUSIONS: Overall, our study confirmed that HNPs increased cell migration to promote angiogenesis for the first time, which is beneficial for bone repair. The EphrinB2/VAV2/CDC42 signalling pathway regulates cell migration, which is an important target of angiogenesis. Thus, HNPs are a new candidate biomaterial for tissue engineering, providing new insights into their biological application.
摘要：
背景：早期血管生成为骨组织修复提供营养供应，血管生成不足会导致组织工程失败。镧系元素金属纳米粒子(LMNPs)是组织工程的首选材料,能有效促进血管生成。氧化钬纳米粒子（HNPs）是具有骨组织“跟踪”标记功能的LMNPs。初步研究表明，HNPs具有促进血管生成的潜力，但具体作用和机制尚不清楚。这限制了HNPs的生物学运用。
结果：在这项研究中，我们证实HNP促进了早期血管形成，特别是体内的H型血管，从而加速骨组织修复。此外，HNP通过增加细胞迁移促进血管生成，这是由丝足虫在体外延伸介导的。在分子水平上,在人脐静脉内皮细胞（HUVECs）中，HNPs与膜蛋白EphrinB2相互作用，和磷酸化的EphrinB2可以结合并激活VAV2，VAV2是丝状足调节蛋白CDC42的激活剂。当这三个分子分别被抑制时，血管生成减少。
结论：总体而言，我们的研究首次证实HNPs增加细胞迁移以促进血管生成,有利于骨修复。EphrinB2/VAV2/CDC42信号通路调节细胞迁移，是血管生成的重要靶点。因此，HNP是一种新的组织工程候选生物材料，提供对其生物学应用的新见解。
结果：在这项研究中，我们证实HNP促进了早期血管形成，特别是体内的H型血管，从而加速骨组织修复。此外，HNP通过增加细胞迁移促进血管生成，这是由丝足虫在体外延伸介导的。在分子水平上,在人脐静脉内皮细胞（HUVECs）中，HNPs与膜蛋白EphrinB2相互作用，和磷酸化的EphrinB2可以结合并激活VAV2，VAV2是丝状足调节蛋白CDC42的激活剂。当这三个分子分别被抑制时，血管生成减少。
结论：总体而言，我们的研究首次证实HNPs增加细胞迁移以促进血管生成,有利于骨修复。EphrinB2/VAV2/CDC42信号通路调节细胞迁移，是血管生成的重要靶点。因此，HNP是一种新的组织工程候选生物材料，提供对其生物学应用的新见解。
