The role of vasculature in bone development, regeneration and proper systemic functioning

Abstract

Bone is a richly vascularized connective tissue. As the main source of oxygen, nutrients, hormones, neurotransmitters and growth factors delivered to the bone cells, vasculature is indispensable for appropriate bone development, regeneration and remodeling. Bone vasculature also orchestrates the process of hematopoiesis. Blood supply to the skeletal system is provided by the networks of arteries and arterioles, having distinct molecular characteristics and localizations within the bone structures. Blood vessels of the bone develop through the process of angiogenesis, taking place through different, bone-specific mechanisms. Impaired functioning of the bone blood vessels may be associated with the occurrence of some skeletal and systemic diseases, i.e., osteonecrosis, osteoporosis, atherosclerosis or diabetes mellitus. When a disease or trauma-related large bone defects appear, bone grafting or bone tissue engineering-based strategies are required. However, a successful bone regeneration in both approaches largely depends on a proper blood supply. In this paper, we review the most recent data on the functions, molecular characteristics and significance of the bone blood vessels, with a particular emphasis on the role of angiogenesis and blood vessel functioning in bone development and regeneration, as well as the consequences of its impairment in the course of different skeletal and systemic diseases.

Keywords: Angiogenesis and osteogenesis; Bone development and regeneration; Bone vasculature; Bone vasculature impairment; Skeletal and systemic diseases; Type H and L endothelial cells.

Fig. 1

The stages of blood vessel invasion during endochondral a and intramembraneous b ossification. VEGF vascular endothelial growth factor, POC Primary Ossification Center, SOC Secondary Ossification Center. Based on [12, 20]

Fig. 2

Vascular system supplying the long bones. Based on [30]. Arteries/arterioles are marked in red and veins/venules in blue

Fig. 3

Molecular crosstalk between type H endothelial cells (Type H EC) and mesenchymal stem cells, leading to osteoblast maturation and final bone formation. Based on [51]

Fig. 4

Effects of the intrinsic/extrinsic (a) and intrinsic (b) vascularization modes on in vivo bone formation and remodeling by the bone substitutes composed of Teflon^® chambers. Based on [82]