Alterations in skeletal perfusion with simulated microgravity: a possible mechanism for bone remodeling

Colleran, Patrick N.; Wilkerson, M. Keith; Bloomfield, Susan A.; Suva, Larry J.; Turner, Russell T.; Delp, Michael D.

doi:10.1152/jappl.2000.89.3.1046

Cited by 186 publications

(174 citation statements)

References 47 publications

(60 reference statements)

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“…In addition, OPN may have a role in alterations of blood flow in hind limbs of unloaded animals, because OPN is reported to be involved in vasculogenesis (Asou et al 2001, Yumoto et al 2002, Pritzker et al 2004, Cheriyath & Hussein, 2005. Blood perfusion is reduced in the bones of the hind limbs of tail-suspended animals (Colleran et al 2000). The loss of alkaline phosphatase activity after unloading is closely associated with the suppression of platelet endothelial cell adhesion molecule-1 (CD31) signaling on the bone marrow cell surface (Sakuma-Zenke et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Osteopontin is required for mechanical stress-dependent signals to bone marrow cells

Ishijima¹,

Tsuji²,

Rittling³

et al. 2007

Journal of Endocrinology

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Mechanical stress to bone plays a crucial role in the maintenance of bone homeostasis. It causes the deformation of bone matrix and generates strain force, which could initiate the mechanotransduction pathway. The presence of osteopontin (OPN), which is one of the abundant proteins in bone matrix, is required for the effects of mechanical stress on bone, as we have reported that OPN-null (OPNK/K) mice showed resistance to unloading-induced bone loss. However, cellular mechanisms underlying the phenomenon have not been completely elucidated. To obtain further insight into the role of OPN in mediating mechanical stress effect on bone, we examined in vitro mineralization and osteoclast-like cell formation in bone marrow cells obtained from hind limb bones of OPNK/K mice after tail suspension. The levels of mineralized nodule formation of bone marrow cells derived from the femora subjected to unloading were decreased compared with that from loaded control in wild-type mice. However, these were not decreased in cells from OPNK/K mice after tail suspension compared with that from loaded OPNK/K mice. Moreover, while spreading of osteoclast-like cells derived from bone marrow cells of the femora subjected to unloading was enhanced compared with that from loaded control in wild-type mice, this enhancement of spreading of these cells derived from the femora subjected to unloading was not recognized compared with those from loaded control in OPNK/K mice. These data provided cellular bases for the effect of the OPN deficiency on in vitro reduced mineralized nodule formation by osteoblasts and on enhancement of osteoclast spreading in vitro induced by the absence of mechanical stress. These in vitro results correlate well with the resistance to unloading-induced bone loss in OPNK/K mice in vivo, suggesting that OPN has an important role in the effects of unloading-induced alterations of differentiation of bone marrow into osteoblasts and osteoclasts.

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Section: Discussionmentioning

confidence: 99%

Osteopontin is required for mechanical stress-dependent signals to bone marrow cells

Ishijima¹,

Tsuji²,

Rittling³

et al. 2007

Journal of Endocrinology

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“…Importantly, even a short period of skeletal unloading has been associated with significant decreases in bone blood flow (109). In a recent study, rats were subjected to 7 or 14 days of hindlimb unloading, then blood flow and vascular resistance were quantified following reloading (35).…”

Section: Blood Flow For Maintenance Of Bonementioning

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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“…For instance, in the rat, an hindlimb unloading experiment which simulates microgravity, the blood perfusion in femur, tibia and bone marrow were significantly decreased. This blood supply change corresponded to the unloading-induced bone loss (Colleran et al, 2000). This suggested that bone vascularization might be implicated in the unloading-induced bone loss.…”

Section: Introductionmentioning

confidence: 70%

Imaging and Quantitative Assessment of Long Bone Vascularization in the Adult Rat Using Microcomputed Tomography

Jia¹,

Peyrin²,

Malaval³

et al. 2010

The Anatomical Record

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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. Anat Rec,

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Alterations in skeletal perfusion with simulated microgravity: a possible mechanism for bone remodeling

Cited by 186 publications

References 47 publications

Osteopontin is required for mechanical stress-dependent signals to bone marrow cells

Osteopontin is required for mechanical stress-dependent signals to bone marrow cells

Skeletal Blood Flow in Bone Repair and Maintenance

Imaging and Quantitative Assessment of Long Bone Vascularization in the Adult Rat Using Microcomputed Tomography

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