Niobium Nanoparticles Activates Endothelial Tip Cells\nand Promotes Angiogenesis by FOXA1-PAK4-YAP Signaling Pathway

Inadequate\nvascularization is a major challenge in tissue engineering\nand can lead to the failure of tissue defect repair. Currently, the\nuse of nanomaterials has emerged as a critical strategy for tissue\nengineering. Nanoparticles can be utilized as additives in composite\nmaterials to enhance the development of bone tissue engineering. Niobium\n(Nb), a transition metal element with notable biocompatibility, has\npotential in angiogenesis. However, the effect of Nb nanoparticles\n(a form of niobium in the nanoparticle state) on endothelial cell\nbehavior remains unclear. This study focused on the effect of Nb nanoparticles\non the differentiation of tip cells and its in-depth regulatory mechanism.\nOur results revealed that Nb nanoparticles promoted angiogenesis at\nan early stage and increased bone regeneration in calvarial bone defects.\nIn addition, Nb nanoparticles activated tip cell differentiation and\nthereby promoted cell migration and tube formation. Furthermore, we\nverified that Nb nanoparticles promoted endothelial tip cell formation\nby activating YAP. Nb nanoparticles regulates YAP through the newly\nidentified upstream regulatory molecules FOXA1 and PAK4. When FOXA1\nor PAK4 was inhibited, YAP expression and tip cell activation were\ninhibited. Thus, Nb nanoparticles promoted angiogenesis by activating\nendothelial tip cells, and the FOXA1-PAK4-YAP signaling cascade regulated\nthis process. The insights garnered from this study suggest a strategy\nfor tissue engineering and lay a theoretical foundation for the expanded\napplication of Nb nanoparticles in this field.