Bidirectional regulation between bone and vasculature: Mechanisms of osteogenesis and angiogenesis

• Bone-vascular bidirectional regulation is fundamental to maintaining skeletal physiological homeostasis and mediating the pathological progression of bone-related disorders. • The core regulatory mechanisms of bone-vascular crosstalk, including cellular interactions, molecular mediators, and signaling pathways, are systematically clarified in this review. • This work summarizes the translational significance of targeting bone-vascular interactions, as well as current research limitations and future exploration directions in the field. Background: The skeletal and vascular systems exhibit critical bidirectional regulation essential for skeletal homeostasis, with distinct mechanisms in intramembranous and endochondral ossification. Disruption of this balance triggers bone diseases like osteoporosis, osteoarthritis, and rheumatoid arthritis. Aim of Review: This review aims to dissect the molecular networks of bone-vascular crosstalk, clarify its physiological/pathological regulatory mechanisms, emphasize the therapeutic value of targeting the vascular microenvironment, and provide perspectives for bone disease translational research. Key Scientific Concepts of Review: This work discusses bone-vascular interactions in normal and diseased states, highlighting that osteogenic cells regulate angiogenesis via VEGF/PDGF/miRNAs, while vascular endothelial cells modulate osteogenesis through BMP-SMAD/Notch/HIF pathways. Targeting this crosstalk can intervene in bone pathologies, laying a foundation for precision therapies for bone diseases.