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

Inadequate vascularization is a major challenge in tissue engineering and can lead to the failure of tissue defect repair. Currently, the use of nanomaterials has emerged as a critical strategy for tissue engineering. Nanoparticles can be utilized as additives in composite materials to enhance the development of bone tissue engineering. Niobium (Nb), a transition metal element with notable biocompatibility, has potential in angiogenesis. However, the effect of Nb nanoparticles (a form of niobium in the nanoparticle state) on endothelial cell behavior remains unclear. This study focused on the effect of Nb nanoparticles on the differentiation of tip cells and its in-depth regulatory mechanism. Our results revealed that Nb nanoparticles promoted angiogenesis at an early stage and increased bone regeneration in calvarial bone defects. In addition, Nb nanoparticles activated tip cell differentiation and thereby promoted cell migration and tube formation. Furthermore, we verified that Nb nanoparticles promoted endothelial tip cell formation by activating YAP. Nb nanoparticles regulates YAP through the newly identified upstream regulatory molecules FOXA1 and PAK4. When FOXA1 or PAK4 was inhibited, YAP expression and tip cell activation were inhibited. Thus, Nb nanoparticles promoted angiogenesis by activating endothelial tip cells, and the FOXA1-PAK4-YAP signaling cascade regulated this process. The insights garnered from this study suggest a strategy for tissue engineering and lay a theoretical foundation for the expanded application of Nb nanoparticles in this field.