In the vertebrate body, endothelial cells and supporting mesenchymal cells, namely pericytes and vascular smooth muscle cells, form a complex and adaptable network that is essential for the circulation of gases, nutrients, waste products, signaling molecules, and blood cells. In addition to this traditional transport role, there is increasing evidence that endothelial cells control tissue growth, homeostasis and regeneration through the release of growth factors or by controlling the metabolic properties of the surrounding tissue. In the skeletal system, blood vessels provide specialized niche microenvironments for mesenchymal and hematopoietic stem cells, which are essential for bone formation, the self-renewal of stem cells and the lifelong production of blood cells. We use state-of-the-art mouse genetics, immunohistochemistry, confocal and two-photon microscopy, cell/organoid culture, single-cell RNA sequencing, bioinformatics, and molecular biology methods to study the pathways controlling endothelial cell behavior, artery formation, and functional specialization of blood vessels in bone with a focus on aging, regeneration and osteoporosis.