ABSTRACT
BACKGROUND:In addition to a conduit system for oxygen,nutrients and waste products,blood vessels in bones manipulate multiple aspects of bone formation and provide niches for bone marrow hematopoietic stem cells.Coupling of osteogenesis and angiogenesis plays a crucial role in bone development,maturation,ageing and diseases.OBJECTIVE:To review the architecture of bone vasculature and process of angiogenesis,and then discuss the factors regulating coupling of osteogenesis and angiogenesis.METHODS:CBM and PubMed databases were retrieved using the keywords of "osteogenesis,blood vasculature,angiogenesis" in Chinese and English,respectively.High-quality articles related to the blood vasculature and angiogenesis in bones were included,and the repetitive studies were excluded.Finally 65 eligible articles were included to explore the coupling of osteogenesis and angiogenesis.RESULTS AND CONCLUSION:The formation and stabilization of the skeletal system rely on the coordination of several different types of cellular activities,especially endothelial cells as an important source of signals that regulate chondrocytes and osteogenesis-related cells,thus allowing the coupling of angiogenesis and osteogenesis during development and regeneration.Like other organs,the vascular system in the bones exhibits a typical hierarchy;the arterial trunk branches flow into the capillary network and then converge into the large veins in the center of the bone.Vascular endothelial growth factor,fibroblast growth factor 2,platelet-derived growth factor,matrix metalloproteinases,hypoxia,and Notch signaling pathway are involved in the angiogenesis in bones.The signaling pathways and related cytokines regulating the coupling of osteogenesis and angiogenesis will provide a new treatment strategy to battle bone diseases such as osteoporosis,bone tumor,bone fracture and bone repair.