Delineating bone's interstitial fluid pathway in vivo

Wang, Liyun; Ciani, Cesare; Doty, Stephen B.; Fritton, Susannah P.

doi:10.1016/j.bone.2003.11.022

Cited by 118 publications

(109 citation statements)

References 28 publications

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“…Two key features of osteocytes as mechanosensors are their ability to detect mechanical stimuli and to send signals to other effector cells that regulate bone formation and resorption (5,6,56,58,59). Dynamic fluid flow is one of the mechanical stimuli that osteocytes experience in vivo with habitual loading (24,25,54). Previous studies have established that this loading-induced dynamic fluid flow is a potent physical signal in the regulation of bone cell metabolism (7,16,37,57), yet it is unclear what role it might play in osteocyte mediated regulation of bone resorption.…”

Section: Introductionmentioning

confidence: 99%

Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading

You

Temiyasathit

Lee

et al. 2008

Bone

291

156

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Bone has the ability to adjust its structure to meet its mechanical environment. The prevailing view of bone mechanobiology is that osteocytes are responsible for detecting and responding to mechanical loading and initiating the bone adaptation process. However, how osteocytes signal effector cells and initiate bone turnover is not well understood. Recent in vitro studies have shown that osteocytes support osteoclast formation and activation when co-cultured with osteoclast precursors. In this study, we examined the osteocytes' role in the mechanical regulation of osteoclast formation and activation.We demonstrated here that 1) Mechanical stimulation of MLO-Y4 osteocyte-like cells decreases their osteoclastogenic-support potential when co-cultured with RAW264.7 monocyte osteoclast precursors, 2) Soluble factors released by these mechanically stimulated MLO-Y4 cells inhibit osteoclastogenesis induced by ST2 bone marrow stromal cells or MLO-Y4 cells, and 3) Soluble RANKL and OPG were released by MLO-Y4 cells, and the expressions of both were found to be mechanically regulated.Our data suggests that mechanical loading decreases the osteocyte's potential to induce osteoclast formation by direct cell-cell contact. However, it is not clear that osteocytes in vivo are able to form contacts with osteoclast precursors. Our data also demonstrates that mechanically stimulated osteocytes release soluble factors that can inhibit osteoclastogenesis induced by other supporting

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Section: Introductionmentioning

confidence: 99%

Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading

You

Temiyasathit

Lee

et al. 2008

Bone

291

156

View full text Add to dashboard Cite

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“…The left jugular vein was then exposed surgically and a 25G5/8 needle attached to a 3-ml syringe was inserted into the vein to inject a bolus of tracer solution. Our previous experiments showed that ferritin was best detected if injected at a dosage of at least 150 mg/100 g of body weight [24]. We concentrated the ferritin solution using Amicon Ultra-4 centrifugal filter devices (100,000 molecular weight cutoff, Millipore, Billerica, MA), from 85 mg/ ml to a final solution of 309 mg/ml.…”

Section: Methodsmentioning

confidence: 99%

“…Our previous tracer studies indicate that ferritin injected into rats is confined to the bone blood vessels and does not pass into the mineralized matrix [24]. However, other investigators have shown that ferritin forms halo-shaped labeling that appears to enter the mineralized matrix around blood vessels, along with appositional fronts along the bone surfaces [5,15,16,19].…”

Section: Introductionmentioning

confidence: 95%

“…Bone interstitial fluid flow is also believed to aid in delivering nutrients and transporting metabolic waste products from the bone cells [17]. To better understand interstitial fluid movement in bone, techniques using markers or tracers such as procion red (300-400 Da, diameter <1 nm), reactive red (1470 Da, diameter ~1 nm), microperoxidase (1860 Da, diameter ~2 nm), horseradish peroxidase (40 kDa, diameter ~6 nm), ferritin (440 kDa, diameter ~12 nm [20]), and different-sized dextrans (range 300 Da-2000 kDa, diameter ~1 nm-60 nm) have been used to map how different sized molecules travel through the various porosities in bone [1,5,8,[13][14][15][16]19,[22][23][24].…”

Section: Introductionmentioning

confidence: 99%

“…Lastly, the smallest bone porosity is the collagen-apatite porosity associated with the space between the collagen fibers and the crystallites of mineral apatite. The dimensions of this porosity have not been well characterized, and there is contradictory evidence from tracer studies as to whether molecules <10 nm can pass into the mineralized matrix [22,24].…”

Section: Introductionmentioning

confidence: 99%

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Mapping bone interstitial fluid movement: Displacement of ferritin tracer during histological processing

Ciani¹,

Doty²,

Fritton³

2005

Bone

Self Cite

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Bone interstitial fluid flow is thought to play a fundamental role in the mechanical stimulation of bone cells, either via shear stresses or cytoskeletal deformations. Recent evidence indicates that osteocytes are surrounded by a fiber matrix that may be involved in the mechanotransduction of external stimuli as well as in nutrient exchange. In our previous tracer studies designed to map how different-sized molecules travel through the bone porosities, we found that injected ferritin was confined to blood vessels and did not pass into the mineralized matrix. However, other investigators have shown that ferritin forms halo-shaped labeling that enters the mineralized matrix around blood vessels. This labeling is widely used to explain normal interstitial fluid movement in bone; in particular, it is said to demonstrate bulk centrifugal interstitial fluid movement away from a highly pressurized vascular porosity. In addition, appositional ferritin fronts are said to demonstrate centrifugal interstitial fluid movement from the medullary canal to the periosteal surface. The purpose of this study was to investigate the conflicting ferritin labeling results by evaluating the role of different histological processes in the formation of ferritin "halos." Ferritin was injected into the rat vasculature and allowed to circulate for 5 min. Samples obtained from tibiae were reacted for different times with Perl's reagent and then were either paraffin-embedded or sectioned with a cryostat. Halo-like labeling surrounding vascular pores was found in all groups, ranging from 1.2-3.9% for the samples treated with the shortest histological processes (unembedded, frozen sections) to 5.6-15% for the samples treated with the longest histological processes (paraffin-embedded sections). These results indicate that different histological processing methods are able to create ferritin "halos," with some processing methods allowing more redistribution of the ferritin tracer than others. Based on these results and the fact that "halo" labeling has not been found with any other tracer, as we seek to further delineate the movement of interstitial fluid and the role it plays in bone mechanotransduction, we believe that ferritin "halo" labeling should not be used to demonstrate physiological bone interstitial fluid flow.

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Interstitial Fluid Movement in Cortical Bone Tissue

Cowin

2010

Biomechanics of Hard Tissues

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Blood and interstitial fluid have many functions in a bone. They transport nutrients to, and carry waste from, the bone cells (osteocytes) buried in the bony matrix. They are involved in the transport of minerals to the bone tissue for storage and the retrieval of those minerals when the body needs them. Interstitial flow is considered to have a role in bone's mechanosensory system. Bone deformation causes the interstitial flow over the cell processes of the osteocyte creating a drag on the fibers that connect the cell; the drag force created by the flowing interstitial fluid is sensed by the cell [1][2][3][4]. A full physiological understanding of this mechanosensory system will provide insight into the following three important clinical problems: (i) how to maintain the long-term stability of bone implants, (ii) the physiological mechanism underlying osteoporosis, and (iii) how to maintain bones in long-duration space flights and long-term bed rest.Since one purpose of this work is to describe how these fluid systems work, consideration is limited to cortical bone in the mid-diaphysis of a long bone.Although most of what is described is also applicable to the bone tissue at other anatomical sites, the discussion is more concise and direct if this limitation is stipulated.The majority of the motive force for the blood flow is from the heart, but the contraction of muscles attached to the bone and the mechanical loading of bone also contribute to this motive force. The majority of the motive force for the interstitial fluid flow is due to the mechanical loading of bone, but the contraction of muscles attached to bone and the heart also supply some of its motive force. The influence of the mechanical loading of a whole bone on the fluid system's maintenance of the bone tissue is critical. The fluid flow resulting from the mechanical loading is modeled by the theory of poroelasticity. This theory models the interaction of deformation and fluid flow in a fluid-saturated porous medium. The theory was proposed by Biot [5, 6] as a theoretical extension of soil consolidation models developed to calculate the settlement of structures placed on fluid-saturated porous soils. The theory has been widely applied to geotechnical problems beyond soil

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Delineating bone's interstitial fluid pathway in vivo

Cited by 118 publications

References 28 publications

Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading

Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading

Mapping bone interstitial fluid movement: Displacement of ferritin tracer during histological processing

Interstitial Fluid Movement in Cortical Bone Tissue

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