Osteoblast recruitment to sites of bone formation in skeletal development, homeostasis, and regeneration.
During endochondral bone development, bone-forming osteoblasts have to colonize the regions of cartilage that will be replaced by bone. In adulthood, bone remodeling and repair require osteogenic cells to reach the sites that need to be rebuilt, as a prerequisite for skeletal health. A failure of osteoblasts to reach the sites in need of bone formation may contribute to impaired fracture repair. Conversely, stimulation of osteogenic cell recruitment may be a promising osteo-anabolic strategy to improve bone formation in low bone mass disorders such as osteoporosis and in bone regeneration applications. Yet, still relatively little is known about the cellular and molecular mechanisms controlling osteogenic cell recruitment to sites of bone formation. In vitro, several secreted growth factors have been shown to induce osteogenic cell migration. Recent studies have started to shed light on the role of such chemotactic signals in the regulation of osteoblast recruitment during bone remodeling. Moreover, trafficking of osteogenic cells during endochondral bone development and repair was visualized in vivo by lineage tracing, revealing that the capacity of osteoblast lineage cells to move into new bone centers is largely confined to undifferentiated osteoprogenitors, and coupled to angiogenic invasion of the bone-modeling cartilage intermediate. It is well known that the presence of blood vessels is absolutely required for bone formation, and that a close spatial and temporal relationship exists between osteogenesis and angiogenesis. Studies using genetically modified mouse models have identified some of the molecular constituents of this osteogenic-angiogenic coupling. This article reviews the current knowledge on the process of osteoblast lineage cell recruitment to sites of active bone formation in skeletal development, remodeling, and repair, considering the role of chemo-attractants for osteogenic cells and the interplay between osteogenesis and angiogenesis in the control of bone formation.
are from the Laboratory of Skeletal Cell Biology and Physiology (SCEBP), Skeletal Biology and Engineering Research Center (SBE), Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
Naomi
N
Dirckx
Matthias
M
Van Hul
Christa
C
Maes
D000818:Animals; D001842:Bone and Bones / Q000502:physiology*; D002356:Cartilage; D002454:Cell Differentiation; D019070:Cell Lineage; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000235:genetics / Q000378:metabolism; D023421:Models, Animal; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D023822:Tissue Engineering; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A
angiogenesis; bone formation; bone repair; chemotaxis; osteoblast recruitment; osteoprogenitor