Role and Regulation of Vascularization Processes in Endochondral Bones
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REVIEW
Role and Regulation of Vascularization Processes in Endochondral Bones Christa Maes
Received: 11 May 2012 / Accepted: 2 December 2012 / Published online: 5 January 2013 Ó Springer Science+Business Media New York 2013
Abstract Adequate vascularization is an absolute requirement for bone development, growth, homeostasis, and repair. Endochondral ossification during fetal skeletogenesis is typified by the initial formation of a prefiguring cartilage template of the future bone, which itself is intrinsically avascular. When the chondrocytes reach terminal hypertrophic differentiation they become invaded by blood vessels. This neovascularization process triggers the progressive replacement of the growing cartilage by bone, in a complex multistep process that involves the coordinated activity of chondrocytes, osteoblasts, and osteoclasts, each standing in functional interaction with the vascular system. Studies using genetically modified mice have started to shed light on the molecular regulation of the cartilage neovascularization processes that drive endochondral bone development, growth, and repair, with a prime role being played by vascular endothelial growth factor and its isoforms. The vasculature of bone remains important throughout life as an intrinsic component of the bone and marrow environment. Bone remodeling, the continual renewal of bone by the balanced activities of osteoclasts resorbing packets of bone and osteoblasts building new bone, takes place in close spatial relationship with the vascular system and depends on signals, oxygen, and cellular delivery via the bloodstream. Conversely, the integrity and functionality of the vessel system, including the exchange of blood cells between the hematopoietic marrow and the circulation, rely on a delicate interplay with the cells of bone. Here, the The author has stated that there is no conflict of interest. C. Maes (&) Laboratory for Skeletal Cell Biology and Physiology, Department of Development and Regeneration, KU Leuven, Health Sciences Campus Gasthuisberg, O&N1, Herestraat 49, Box 813, 3000 Leuven, Belgium e-mail: [email protected]
current knowledge on the cellular relationships and molecular crosstalk that coordinate skeletal vascularization in bone development and homeostasis will be reviewed. Keywords Endochondral ossification Angiogenesis Vascular endothelial growth factor Cartilage Bone
Introduction During embryonic development, two distinct mechanisms are responsible for the establishment of the skeleton. The flat bones, such as those of the skull, develop via intramembranous ossification. The long bones, representing the majority of the bones of the vertebrate body including those of the axial and appendicular skeleton, develop through endochondral ossification [1, 2]. In intramembranous bone formation, mesenchymal cells aggregate at the site of the future bone and differentiate directly into osteoblasts, which deposit and mineralize the bone matrix. In contrast, endochondral ossification is typified by the initial form
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