Vascular Biology and the Skeleton

Brandi, Maria Luisa; Collin‐Osdoby, Patricia

doi:10.1359/jbmr.050917

Cited by 284 publications

(247 citation statements)

References 178 publications

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“…In addition to the classical bone marrow stromal cells [2], it is possible that bone marrow non-adherent cells, as previously identified by Long et al [3,4] access the BRC via this mechanism, or that circulating osteoblastic cells contribute to the pool of osteoblastic cells entering the BRC. On the other hand, given the potential overlap between osteoblastic and endothelial cells noted in the present and previous work [21,22,25], and the evidence that vascular pericytes can differentiate into osteoblasts [26], as well as recent work demonstrating the pericytes, themselves, may arise from a CD34 pos progenitor in the vessel wall [27], it is also possible that precursor cells in the vasculature (i.e., within the capillary wall penetrating the BRC) give rise to osteoblastic progenitors. Clearly, additional studies are needed to test these hypotheses and to further identify the source of the circulating OCN and AP expressing cells as well as their possible role in bone remodeling.…”

Section: Discussionsupporting

confidence: 54%

Characterization of circulating osteoblast lineage cells in humans

Eghbali‐Fatourechi

Mödder

Charatcharoenwitthaya

et al. 2007

Bone

123

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We recently identified circulating osteoblastic cells using antibodies to osteocalcin (OCN) or alkaline phosphatase (AP). We now provide a more detailed characterization of these cells. Specifically, we demonstrate that 46% of OCN positive (OCN pos ) cells express AP, and 37% also express the hematopoietic/endothelial marker, CD34. Using two different anti-OCN antibodies and forward/side light scatter characteristics by flow cytometry, we find that OCN pos cells consist of two distinct populations: one population exhibits low forward/side scatter, consistent with a small cell phenotype with low granularity, and a second population has higher forward/side scatter (larger and more granular cell). The smaller, low granularity population also co-expresses CD34, whereas the larger, more granular cells are CD34 negative. Using samples from 26 male subjects aged 28 to 68 years, we demonstrate that the concentration of circulating OCN pos cells increases as a function of age (R = 0.59, P = 0.002). By contrast, CD34 pos cells tend to decrease with age (R = −0.31, P = 0.18); as a consequence, the ratio of OCN pos :CD34 pos cells also increases significantly with age (R = 0.54, P = 0.022). These findings suggest significant overlap between circulating cells expressing OCN and those expressing the hematopoietic/endothelial marker, CD34. Further studies are needed to define the precise role of circulating OCN pos cells not only in bone remodeling but rather also potentially in the response to vascular injury.

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Section: Discussionsupporting

confidence: 54%

Characterization of circulating osteoblast lineage cells in humans

Eghbali‐Fatourechi

Mödder

Charatcharoenwitthaya

et al. 2007

Bone

123

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“…Vasculature development is one of the first steps in embryonic development, resulting in a complex network of arteries, capillaries, and veins. New blood vessels are formed de novo from angioblastic stem cells (a process called vasculognesis) and via expansion of existing vessels through pruning and vessel enlargement (angiogenesis) 33. Endothelial cell growth is regulated by vascular endothelial growth factor (VEGF), which also acts as an essential mediator during endochondrial ossification and intramembranous ossification.…”

Section: Discussionmentioning

confidence: 99%

Bone Mineral Density Is Positively Related to Carotid Intima-Media Thickness: Findings From a Population-Based Study in Adolescents and Premenopausal Women

Frysz

Deere

Lawlor

et al. 2016

Journal of Bone and Mineral Research

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Osteoporosis and cardiovascular disease (CVD) are both common causes of morbidity and mortality. Previous studies, mainly of people older than 60 years, suggest a relationship between these conditions. Our aim was to determine the association between bone characteristics and CVD markers in younger and middle‐aged individuals. Women (n = 3366) and their adolescent offspring (n = 4368) from the UK population‐based cohort study, Avon Longitudinal Study of Parents and Children (ALSPAC), were investigated. We measured total body (TB) and hip bone mineral density (BMD), TB bone area (BA) and bone mineral content (BMC) by dual‐energy X‐ray absorptiometry (DXA), and carotid intima‐media thickness (cIMT) by high‐resolution ultrasound. Arterial distensibility was calculated as the difference between systolic and diastolic arterial diameters. Linear regression determined associations between bone exposures and cIMT (in adolescents) and both cIMT and arterial distensibility (in women), generating partial correlation coefficients. Mean (SD) age of women was 48 (4.2) years, body mass index (BMI) was 26.2 (5.0) kg/m2, and 71% were premenopausal. In confounder‐adjusted analyses (age, height, lean mass, fat mass, menopause, smoking, estrogen replacement, calcium/vitamin D supplementation, and education) TB and hip BMD were both positively associated with cIMT (0.071 [0.030, 0.112], p = 0.001; 0.063 [0.025, 0.101], p = 0.001, respectively). Femoral neck BMD and TB BMD, BMC, and BA were positively associated with arterial distensibility. Mean (SD) age of adolescents was 17 (0.4) years, BMI was 23 (4.1) kg/m2, and 44.5% were male. Total hip and TB measurements were positively associated with cIMT, with similar magnitudes of association to those found in their mothers. In contrast to most published findings, we identified weak positive associations between BMD and cIMT in predominantly premenopausal women and their adolescent offspring. We found greater femoral neck BMD and TB DXA measurements to be associated with reduced arterial stiffness. Rather than a relationship with preclinical atherosclerosis, in these relatively young populations, we speculate our associations between BMD, cIMT, and arterial distensibility may reflect a shared relationship between bone and vascular growth and development. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…Finally, other rodent models of rapidly induced osteopenia, such as paraplegia (117) and orchidectomy (118), have increased bone blood flow in the face of rapid bone loss. Determining the relationship between bone blood flow and formation/resorption is highly desirable, but the signaling that regulates these mechanisms is not well understood (1). Additional work on the interaction and regulation of the bone and vascular compartments, particularly during acute and chronic bone loss, is necessary.…”

Section: Blood Flow For Maintenance Of Bonementioning

confidence: 99%

“…However, a frequently overlooked feature of bone is its extensive vascular network. Many studies have demonstrated that the blood vessels in bone are necessary for nearly all skeletal functions, including development, homeostasis, and repair (1). In addition, blood vessels lost due to trauma are regenerated, and new bone tissue formed in response to injury is vascularized.…”

Section: Introductionmentioning

confidence: 99%

Skeletal Blood Flow in Bone Repair and Maintenance

2013

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Bone is a highly vascularized tissue, although this aspect of bone is often overlooked. In this article, the importance of blood flow in bone repair and regeneration will be reviewed. First, the skeletal vascular anatomy, with an emphasis on long bones, the distinct mechanisms for vascularizing bone tissue, and methods for remodeling existing vasculature are discussed. Next, techniques for quantifying bone blood flow are briefly summarized. Finally, the body of experimental work that demonstrates the role of bone blood flow in fracture healing, distraction osteogenesis, osteoporosis, disuse osteopenia, and bone grafting is examined. These results illustrate that adequate bone blood flow is an important clinical consideration, particularly during bone regeneration and in at-risk patient groups. IntroductionThe rate at which blood vessels deliver oxygen, nutrients, growth factors, and circulating cells to boneis tightly regulated as a function of blood pressure and vascularizaAll biological tissues, including bone, require vascular support to survive. However, a frequently overlooked feature of bone is its extensive vascular network. Many studies have demonstrated that the blood vessels in bone are necessary for nearly all skeletal functions, including development, homeostasis, and repair (1). In addition, blood vessels lost due to trauma are regenerated, and new bone tissue formed in response to injury is vascularized. As a consequence of this environment, the blood vessels in bone are highly active, not simply a passive source for the delivery of nutrients (2). Readers are referred to recent publications for more information about the active processes of the vasculature not covered in this review, including the vascular niche and hypoxia-driven signaling pathways (3-4). tion. Given that blood pressure is generally maintained, the number and size of blood vessels determines the local blood flow rate. These two factors are regulated through the processes of angiogenesis and vasomotor function, respectively. Although a variety of skeletal disorders are associated with general vascular dysfunction (5-7), this review will focus on the regulation of bone blood flow, through the number and size of vessels, during bone repair and regeneration. To introduce this topic, the skeletal vascular anatomy and techniques for measuring bone blood flow are briefly discussed. Blood supply in boneA dense vascular network delivers oxygen and nutrients to all 206 bones in the human body. In general, this requires a substantial portion of the total cardiac output. Experimental work in various animal species has demonstrated that a significant portion of the resting cardiac output is directed to the skeleton, likely between 10% and 15% (8-12).For some time, the blood flow pattern in bones has been described as primarily centrifugal: blood is supplied to the cortical bone through the nutrient arteries in the (Figure 1), and returned by the periosteal veins (13). Particularly in long bones, the vascular anatomy is well characterized, wi...

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Vascular Biology and the Skeleton

Cited by 284 publications

References 178 publications

Characterization of circulating osteoblast lineage cells in humans

Characterization of circulating osteoblast lineage cells in humans

Bone Mineral Density Is Positively Related to Carotid Intima-Media Thickness: Findings From a Population-Based Study in Adolescents and Premenopausal Women

Skeletal Blood Flow in Bone Repair and Maintenance

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