Assessment of bone vascularization and its role in bone remodeling (original) (raw)
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Role of vascular endothelial cells in bone biology
Journal of Cellular Biochemistry, 1994
Bone development and remodeling depend on complex interactions between bone-forming osteoblasts, bone-degrading osteoclasts, and other cells present within the bone microenvironment. Balanced control of bone formative and degradative processes is normally carefully maintained in the adult skeleton but becomes uncoupled in the course of aging or in various pathological disease states. Systemic regulators of bone metabolism and local mediators, including matrix molecules, cytokines, prostaglandins, leukotrienes, and other autocrine or paracrine factors, regulate the recruitment, differentiation, and function of cells participating in bone formation and turnover. Although some of these interactions are now understood, many yet remain to be elucidated. Recent studies have begun exploring in detail how vascular endothelial cells and their products function in bone physiology. The findings are revealing that bone vascular endothelial cells may be members of a complex communication network in bone which operates between endothelial cells, osteoblasts, osteoclasts, macrophages, stromal cells, and perhaps other cell types found in bone as well. Therefore, multiple systemic and locally produced signals may be received, transduced, and integrated by individual cells and then propagated by the release from these cells of further signals targeted to other members of the bone cell network. In this manner, bone cell activities may be continuously coordinated to afford concerted actions and rapid responses to physiological changes. The bone microvasculature may play a pivotal role in these processes, both in linking circulatory and local signals with cells of the bone microenvironment and in actively contributing itself to the regulation of bone cell physiology. Thus, skeletal homeostasis and the coupling observed between bone resorption and bone formation during normal bone remodeling may be manifestations of this dynamic interactive communication network, operating via diverse signals not only between osteoblasts and osteoclasts but between many cell types residing within bone.
The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology, 2010
The objective of this study was to develop and validate a technique for both 3D imaging and quantification of the vascular network of bone tissue in the rat. Five month-old male Wistar rats were divided into tailsuspension (21 days) and control groups. Sixty percent barium sulfate solution was infused into the vena cava. The tibiae were evaluated in 2D and 3D before and after decalcification, using conventional microcomputerized tomography (lCT) at 10 and 5 lm resolution and synchrotron radiation (SR) lCT. The perfusion technique and tomography exhibited excellent bone vasculature imaging. Significant positive correlations were observed between 2D histomorphometric and 3D lCT vascular parameters (P < 0.05). 3DlCT discriminated significant changes of vessel structures in unloading condition: vessel number decreased by 25%, (P < 0.005), vessel separation increased by 27%, P < 0.01. SRlCT could image sinusoid clusters in bone. lCT is an accurate and reproducible technique for 3D quantitative evaluation of long bone vascularisation in the rat.
In Vitro Model of Vascularized Bone: Synergizing Vascular Development and Osteogenesis
PLOS One, 2011
Tissue engineering provides unique opportunities for regenerating diseased or damaged tissues using cells obtained from tissue biopsies. Tissue engineered grafts can also be used as high fidelity models to probe cellular and molecular interactions underlying developmental processes. In this study, we co-cultured human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (MSCs) under various environmental conditions to elicit synergistic interactions leading to the colocalized development of capillary-like and bone-like tissues. Cells were encapsulated at the 1:1 ratio in fibrin gel to screen compositions of endothelial growth medium (EGM) and osteogenic medium (OM). It was determined that, to form both tissues, co-cultures should first be supplied with EGM followed by a 1:1 cocktail of the two media types containing bone morphogenetic protein-2. Subsequent studies of HUVECs and MSCs cultured in decellularized, trabecular bone scaffolds for 6 weeks assessed the effects on tissue construct of both temporal variations in growth-factor availability and addition of fresh cells. The resulting grafts were implanted subcutaneously into nude mice to determine the phenotype stability and functionality of engineered vessels. Two important findings resulted from these studies: (i) vascular development needs to be induced prior to osteogenesis, and (ii) the addition of additional hMSCs at the osteogenic induction stage improves both tissue outcomes, as shown by increased bone volume fraction, osteoid deposition, close proximity of bone proteins to vascular networks, and anastomosis of vascular networks with the host vasculature. Interestingly, these observations compare well with what has been described for native development. We propose that our cultivation system can mimic various aspects of endothelial cell -osteogenic precursor interactions in vivo, and could find utility as a model for studies of heterotypic cellular interactions that couple blood vessel formation with osteogenesis.
2009 IEEE Nuclear Science Symposium Conference Record (NSS/MIC), 2009
A method for simultaneous 3D imaging and analysis of microvascularization and bone microstructure in rat bone is presented. The method is based on the use of quantitative synchrotron micro-computed tomography (SRμ μ μ μCT) coupled to an automatic image analysis procedure. Previously, analysis of bone microvascularization has generally been performed from 2D histology. The proposed method enables for the first time to simultaneously analyze in 3D the microvascularization and bone microstructure in a rat model. We also propose a new parameter, utilizing the availablilty of both microstructures to relate the two, which we dub the vascular-trabecular interdistance (VTI). The proposed method was applied to investigate the effect of intermittent parathyroid hormone (PTH) administration on angiogenesis and osteogenesis in rats. It was possible to extract 3D quantitative parameters both on bone microstructure and microvascularization. Due to the short acquisition times of SR-μ μ μ μCT and the efficiency of the image analysis algorithm, a large data set was analyzed, which permitted statistical analysis of the measured parameters. Statistical analysis showed that treatment with PTH significantly modulated several bone and vessel parameters, including the VTI.
Human type H vessels are a sensitive biomarker of bone mass
Cell death & disease, 2017
Vascularization is fundamental for bone formation and bone tissue homeostasis. However, in human subjects, a direct molecular relationship has not been identified between angiogenesis and agents that promote bone disease or factors related to age. Osteopenia is a condition in which bone mineral density is lower than normal, and it represents a sign of normal aging. Here we tested whether the type H vessel, which was recently identified as strongly positive for CD31 and Endomucin (CD31(hi)Emcn(hi)) in mice, is an important indicator of aging and osteopenia in human subjects. We found that age-dependent losses of type H vessels in human bone sections conform to the observations in aged mice. The abundance of human type H vessels and osteoprogenitors may be relevant to changes in the skeletal microarchitecture and advanced osteopenia. Furthermore, ovariectomized mice, a widely used model for postmenopausal osteoporosis, exhibited significantly reduced type H vessels accompanied by redu...
Angiogenesis is uncoupled from osteogenesis during calvarial bone regeneration
Nature communications, 2024
Bone regeneration requires a well-orchestrated cellular and molecular response including robust vascularization and recruitment of mesenchymal and osteogenic cells. In femoral fractures, angiogenesis and osteogenesis are closely coupled during the complex healing process. Here, we show with advanced longitudinal intravital multiphoton microscopy that early vascular sprouting is not directly coupled to osteoprogenitor invasion during calvarial bone regeneration. Early osteoprogenitors emerging from the periosteum give rise to bone-forming osteoblasts at the injured calvarial bone edge. Microvessels growing inside the lesions are not associated with osteoprogenitors. Subsequently, osteogenic cells collectively invade the vascularized and perfused lesion as a multicellular layer, thereby advancing regenerative ossification. Vascular sprouting and remodeling result in dynamic blood flow alterations to accommodate the growing bone. Single cell profiling of injured calvarial bones demonstrates mesenchymal stromal cell heterogeneity comparable to femoral fractures with increase in cell types promoting bone regeneration. Expression of angiogenesis and hypoxia-related genes are slightly elevated reflecting ossification of a vascularized lesion site. Endothelial Notch and VEGF signaling alter vascular growth in calvarial bone repair without affecting the ossification progress. Our findings may have clinical implications for bone regeneration and bioengineering approaches. Despite substantial advancements in our understanding of the mechanisms underlying bone regeneration, major challenges in orthopedic surgery remain due to failing or delayed fracture healing and complications during bone repair 1,2. Segmental bone defects caused by trauma, infections and tumors associated with insufficient osteogenesis often result in significant disabilities in patients 3-5. The reasons for failed bone regeneration and non-union fractures often remain unclear 6,7. Bone repair is achieved through a highly complex and interconnected series of cellular and molecular events orchestrated by various mediators and signaling factors. In long bone, fracture healing involves several distinct stages starting with early hematoma formation, followed by a reparative and remodeling
Development, 2016
In recent years, blood vessels have been shown to be involved in morphogenesis of various organs. The vasculature is also known to be essential for endochondral bone development; yet, the underlying mechanism has remained elusive. Here, we show that a unique composition of blood vessels facilitates a role of the endothelium in bone mineralization and morphogenesis. Immunostaining and electron microscopy showed that the endothelium in developing bones lacks basement membrane, which normally isolates the vessel from its surroundings. Further analysis revealed the presence of collagen type I, secreted by osteoblasts, on the endothelial wall of these vessels. Because collagen type I is the main component of the osteoid, which serves as a template for mineral deposition during endochondral ossification, we hypothesized that the bone vasculature guides the formation of the collagenous template and consequently of the mature bone. Indeed, analysis showed that some of the bone vessels under...