Endothelial diversity in bone vasculature coordinates osteogenesis and hematopoiesis.

Abstract

Bone is a highly vascularized organ, and the vasculature in bone not only delivers oxygen and nutrients but also helps determine when and where bone forms, how the marrow is organized, and how hematopoietic stem cells (HSCs) are maintained. Over the past decade, research has shifted from a single, uniform view of bone vessels to site- and stage-specific endothelial programs along the metaphysis-diaphysis-epiphysis axis of long bones. Local endothelial identity and hemodynamic signals coordinate angiogenesis with osteogenesis and shape the marrow niche. These programs also shift with aging. This review summarizes the recent advances in these endothelial programs and their roles in bone growth and hematopoiesis. Considering the vasculature as an active driver of skeletal integrity and hematopoietic function suggests strategies to strengthen bone, reduce skeletal fragility, and sustain hematopoiesis. This framework provides a roadmap for future studies and clinical translation.