Transport mechanism operating between blood supply and osteocytes in long bones

Piekarski, K.; Munro, M.

doi:10.1038/269080a0

Cited by 405 publications

(284 citation statements)

References 6 publications

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“…Motion of this fluid is driven through two distinct sources. The first source of interstitial fluid flow is the pressure differential of the circulatory system (Dillaman et al, 1991;Keanini et al, 1995) and the second source is the externally applied mechanical loading (Piekarski and Munro, 1977). When bone is loaded, fluid is forced out of regions of high compressive strains, returning when the load is removed.…”

Section: What Mechanical Factors Are Generated By Loading?mentioning

confidence: 99%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

403

303

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Bone tissue has the capacity to adapt to its functional environment such that its morphology is "optimized" for the mechanical demand. The adaptive nature of the skeleton poses an interesting set of biological questions (e.g., how does bone sense mechanical signals, what cells are the sensing system, what are the mechanical signals that drive the system, what receptors are responsible for transducing the mechanical signal, what are the molecular responses to the mechanical stimuli). Studies of the characteristics of the mechanical environment at the cellular level, the forces that bone cells recognize, and the integrated cellular responses are providing new information at an accelerating speed. This review first considers the mechanical factors that are generated by loading in the skeleton, including strain, stress and pressure. Mechanosensitive cells placed to recognize these forces in the skeleton, osteoblasts, osteoclasts, osteocytes and cells of the vasculature are reviewed. The identity of the mechanoreceptor(s) is approached, with consideration of ion channels, integrins, connexins, the lipid membrane including caveolar and noncaveolar lipid rafts and the possibility that altering cell shape at the membrane or cytoskeleton alters integral signaling protein associations. The distal intracellular signaling systems on-line after the mechanoreceptor is activated are reviewed, including those emanating from G-proteins (e.g., intracellular calcium shifts), MAPKs, and nitric oxide. The ability to harness mechanical signals to improve bone health through devices and exercise is broached. Increased appreciation of the importance of the mechanical environment in regulating and determining the structural efficacy of the skeleton makes this an exciting time for further exploration of this area.

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Section: What Mechanical Factors Are Generated By Loading?mentioning

confidence: 99%

Molecular pathways mediating mechanical signaling in bone

Rubin

Jacobs

2006

Gene

403

303

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“…Osteocytes, the most numerous cells in adult bone, lie buried within the mineralized matrix and do not directly contact the tissue's vascular supply; consequently, they depend on solute transport through the tissue to obtain nutrients, dispose of metabolic wastes (1)(2)(3)(4), and transmit chemical signals (e.g., nitric oxide and prostaglandins) to nearby cells (5,6). These transport processes are thought to be crucial for osteocytes to carry out their physiological functions in sensing mechanical stimuli and targeting damaged bone areas for osteoclastic resorption (5,(7)(8)(9)(10).…”

mentioning

confidence: 99%

In situ measurement of solute transport in the bone lacunar-canalicular system

Wang

Han

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

184

212

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Solute transport through the bone lacunar-canalicular system is believed to be essential for osteocyte survival and function but has proved difficult to measure. We report an approach that permits direct measurement of real-time solute movement in intact bones. By using fluorescence recovery after photobleaching, the movement of a vitally injected fluorescent dye (sodium fluorescein) among individual osteocytic lacunae was visualized in situ beneath the periosteal surface of mouse cortical bone at depths up to 50 m with laser scanning confocal microscopy. Transport was analyzed by using a two-compartment mathematical model of solute diffusion that accounted for the characteristic anatomical features of the lacunar-canalicular system. The diffusion coefficient of fluorescein (376 Da) was determined to be 3.3 ؎ 0.6 ؋ 10 ؊6 cm 2 ͞sec, which is 62% of its diffusion coefficient in water and is similar to diffusion coefficients measured for comparably sized molecules in cartilage. The diffusion of fluorescein in bone is also consistent with the presence of an osteocyte pericellular matrix whose structure resembles that proposed for the endothelial glycocalyx diffusion coefficient ͉ fiber matrix theory ͉ fluorescence recovery after photobleaching ͉ osteocyte ͉ confocal microscopy

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“…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%

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

Ciani¹,

Doty²,

Fritton³

2005

Bone

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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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Transport mechanism operating between blood supply and osteocytes in long bones

Cited by 405 publications

References 6 publications

Molecular pathways mediating mechanical signaling in bone

Molecular pathways mediating mechanical signaling in bone

In situ measurement of solute transport in the bone lacunar-canalicular system

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

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