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Results for “Bone and Bones/physiology”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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16 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS1995

Mechanotransduction and the functional response of bone to mechanical strain

Mechanotransduction plays a crucial role in the physiology of many tissues including bone. Mechanical loading can inhibit bone resorption and increase bone formation in vivo. In bone, the process of mechanotransduction can be divided into four distinct steps: (1) mechanocoupling, (2) biochemical coupling, (3) transmission of signal, and (4) effector cell response. In mechanocoupling, mechanical loads in vivo cause deformations in bone that stretch bone cells within and lining the bone matrix and create fluid movement within the canaliculae of bone. Dynamic loading, which is associated with extracellular fluid flow and the creation of streaming potentials within bone, is most effective for stimulating new bone formation in vivo. Bone cells in vitro are stimulated to produce second messengers when exposed to fluid flow or mechanical stretch. In biochemical coupling, the possible mechanisms for the coupling of cell-level mechanical signals into intracellular biochemical signals include force transduction through the integrin-cytoskeleton-nuclear matrix structure, stretch-activated cation channels within the cell membrane, G protein-dependent pathways, and linkage between the cytoskeleton and the phospholipase C or phospholipase A pathways. The tight interaction of each of these pathways would suggest that the entire cell is a mechanosensor and there are many different pathways available for the transduction of a mechanical signal. In the transmission of signal, osteoblasts, osteocytes, and bone lining cells may act as sensors of mechanical signals and may communicate the signal through cell processes connected by gap junctions. These cells also produce paracrine factors that may signal osteoprogenitors to differentiate into osteoblasts and attach to the bone surface. Insulin-like growth factors and prostaglandins are possible candidates for intermediaries in signal transduction. In the effector cell response, the effects of mechanical loading are dependent upon the magnitude, duration, and rate of the applied load. Longer duration, lower amplitude loading has the same effect on bone formation as loads with short duration and high amplitude. Loading must be cyclic to stimulate new bone formation. Aging greatly reduces the osteogenic effects of mechanical loading in vivo. Also, some hormones may interact with local mechanical signals to change the sensitivity of the sensor or effector cells to mechanical load.

Non-NASA Center↗
NASA NTRS2001

Biomaterials and bone mechanotransduction

Bone is an extremely complex tissue that provides many essential functions in the body. Bone tissue engineering holds great promise in providing strategies that will result in complete regeneration of bone and restoration of its function. Currently, such strategies include the transplantation of highly porous scaffolds seeded with cells. Prior to transplantation the seeded cells are cultured in vitro in order for the cells to proliferate, differentiate and generate extracellular matrix. Factors that can affect cellular function include the cell-biomaterial interaction, as well as the biochemical and the mechanical environment. To optimize culture conditions, good understanding of these parameters is necessary. The new developments in bone biology, bone cell mechanotransduction, and cell-surface interactions are reviewed here to demonstrate that bone mechanotransduction is strongly influenced by the biomaterial properties.

Review↗
NASA NTRS2001

Cellular and molecular mechanisms for the bone response to mechanical loading

To define the cellular and molecular mechanisms for the osteogenic response of bone to increased loading, several key steps must be defined: sensing of the mechanical signal by cells in bone, transduction of the mechanical signal to a biochemical one, and transmission of that biochemical signal to effector cells. Osteocytes are likely to serve as sensors of loading, probably via interstitial fluid flow produced during loading. Evidence is presented for the role of integrins, the cell's actin cytoskeleton, G proteins, and various intracellular signaling pathways in transducing that mechanical signal to a biochemical one. Nitric oxide, prostaglandins, and insulin-like growth factors all play important roles in these pathways. There is growing evidence for modulation of these mechanotransduction steps by endocrine factors, particularly parathyroid hormone and estrogen. The efficiency of this process is also impaired in the aged animal, yet what remains undefined is at what step mechanotransduction is affected.

Review↗
NASA NTRS1998

The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects

This study was undertaken to examine the effects of 12 weeks of skeletal unloading on parameters of calcium homeostasis, calcitropic hormones, bone histology, and biochemical markers of bone turnover in 11 normal subjects (9 men, 2 women; 34 +/- 11 years of age). Following an ambulatory control evaluation, all subjects underwent 12 weeks of bed rest. An additional metabolic evaluation was performed after 12 days of reambulation. Bone mineral density declined at the spine (-2.9%, p = 0.092) and at the hip (-3.8%, p = 0.002 for the trochanter). Bed rest prompted a rapid, sustained, significant increase in urinary calcium and phosphorus as well as a significant increase in serum calcium. Urinary calcium increased from a pre-bed rest value of 5.3 mmol/day to values as high as 73 mmol/day during bed rest. Immunoreactive parathyroid hormone and serum 1,25-dihydroxyvitamin D declined significantly during bed rest, although the mean values remained within normal limits. Significant changes in bone histology included a suppression of osteoblastic surface for cancellous bone (3.1 +/- 1.3% to 1.9 +/- 1.5%, p = 0.0142) and increased bone resorption for both cancellous and cortical bone. Cortical eroded surface increased from 3.5 +/- 1.1% to 7.3 +/- 4.0% (p = 0.018) as did active osteoclastic surface (0.2 +/- 0.3% to 0.7 +/- 0.7%, p = 0.021). Cancellous eroded surface increased from 2.1 +/- 1.1% to 4.7 +/- 2.2% (p = 0.002), while mean active osteoclastic surface doubled (0.2 +/- 0.2% to 0.4 +/- 0.3%, p = 0.020). Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, and type I procollagen extension peptide) did not change significantly during bed rest. Urinary biochemical markers of bone resorption (hydroxyproline, deoxypyridinoline, and N-telopeptide of type I collagen) as well as a serum marker of bone resorption (type I collagen carboxytelopeptide) all demonstrated significant increases during bed rest which declined toward normal during reambulation. Thus, under the conditions of this study, the human skeleton appears to respond to unloading by a rapid and sustained increase in bone resorption and a more subtle decrease in bone formation.

NASA Discipline Musculoskeletal↗
NASA NTRS2003

Physiology, medicine, long-duration space flight and the NSBRI

The hazards of long-duration space flight are real and unacceptable. In order for humans to participate effectively in long-duration orbital missions or continue the exploration of space, we must first secure the health of the astronaut and the success of such missions by assessing in detail the biomedical risks of space flight and developing countermeasures to these hazards. Acquiring the understanding necessary for building a sound foundation for countermeasure development requires an integrated approach to research in physiology and medicine and a level of cooperative action uncommon in the biomedical sciences. The research program of the National Space Biomedical Research Institute (NSBRI) was designed to accomplish just such an integrated research goal, ameliorating or eliminating the biomedical risks of long-duration space flight and enabling safe and productive exploration of space. The fruits of these labors are not limited to the space program. We can also use the gained understanding of the effects and mechanisms of the physiological changes engendered in space and the applied preventive and rehabilitative methods developed to combat these changes to the benefit of those on Earth who are facing similar physiological and psychological difficulties. This paper will discuss the innovative approach the NSBRI has taken to integrated research management and will present some of the successes of this approach. c2003 International Astronautical Federation. Published by Elsevier Science Ltd. All rights reserved.

NASA Discipline General Space Life Sciences↗
NASA NTRS2001

An extensometer for global measurement of bone strain suitable for use in vivo in humans

An axial extensometer able to measure global bone strain magnitudes and rates encountered during physiological activity, and suitable for use in vivo in human subjects, is described. The extensometer uses paired capacitive sensors mounted to intraosseus pins and allows measurement of strain due to bending in the plane of the extensometer as well as uniaxial compression or tension. Data are presented for validation of the device against a surface-mounted strain gage in an acrylic specimen under dynamic four-point bending, with square wave and sinusoidal loading inputs up to 1500 mu epsilon and 20 Hz, representative of physiological strain magnitudes and frequencies. Pearson's correlation coefficient (r) between extensometer and strain gage ranged from 0.960 to 0.999. Mean differences between extensometer and strain gage ranged up to 15.3 mu epsilon. Errors in the extensometer output were directly proportional to the degree of bending that occurs in the specimen, however, these errors were predictable and less than 1 mu epsilon for the loading regime studied. The device is capable of tracking strain rates in excess of 90,000 mu epsilon/s.

Non-NASA Center↗
NASA NTRS1999

Mechanical signaling in the development of postmenopausal osteoporosis

Estrogen deficiency results in increased bone turnover and net bone loss in rats as well as humans. The respective roles of bone turnover and mechanical strain in mediating estrogen deficiency-induced cancellous bone loss were investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in long bones. However, cancellous bone was preferentially lost in the metaphysis, a site that experiences low strain energy during normal physical activity. No bone loss was observed in the epiphysis, a site experiencing higher strain energy, despite a similar increase in bone turnover. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased or decreased in long bones of ovariectomized rats by treadmill exercise or functional unloading, respectively. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing weight bearing accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in unloaded limbs and prevented bone loss in the loaded limbs. These results suggest that estrogen alters the mechanosensory (mechanostat) set point for skeletal adaptation, effectively reducing the minimum strain energy levels at which bone is added. Additionally, these studies suggest that physical activity as well as endocrine status play an important role in maintenance of the female skeleton during aging.

Non-NASA Center↗
NASA NTRS1998

The bearable lightness of being: bones, muscles, and spaceflight

Bones and muscles support and move the body. Tendons link the two tissues and serve as a mechanism for transfer of forces from muscle to bone. These three tissues interact and respond to periods of activity or inactivity with appropriate alterations in structure and strength. There is substantial evidence that an environment devoid of mechanical stress on the skeleton (such as reduced gravitational forces during spaceflight, a "microgravity environment") produces direct effects on bone structure and function. There is little agreement concerning the biologic mechanisms for these atrophic changes. Changes in fluid balance and distribution coincident to spaceflight also affect muscles and bones by an unknown mechanism. Tendon-bone junctions are presumed to be spared from the effects of spaceflight. However, recent evidence from rodents suggests that spaceflight profoundly effects both the skeleton and the tendon-bone junctions. These effects include cortical bone resorption, which undermines the Sharpey's fibers that anchor the tendon to the bone matrix. The challenge to biomedical scientists is to devise methods for protecting spaceflight crews from these atrophic changes; such protection would allow for longer and more extensive spaceflights.

manned↗
NASA NTRS1996

Human physiology in space

The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

NASA Center HQS↗
NASA NTRS1996

Effect of a hypergravity environment on cortical bone elasticity in rats

There is considerable interest in determining whether hypergravity can be used as a countermeasure for microgravity-induced bone loss. This study was conducted on 20 immature male rats in order to investigate possible elastic adaptations of cortical bone in rapidly growing rats exposed to chronic hypergravity. Ten rats were continuously centrifuged for 14 days at twice gravitational acceleration (2G) on a 12.75 foot radius centrifuge and 10 rats concurrently acted as stationary controls. The effect of hypergravity on the elastic characteristics of cortical bone was quantified via ultrasonic wave propagation. Propagation velocities of longitudinal and shear waves were measured through cubic cortical specimens from the posterior femoral diaphyses. Density was measured with an Archimedes' technique. The orthotropic elastic properties were calculated and used to compare the difference between groups. Results showed an average increase in both the Young's moduli (Eii, + 2.2%) and shear moduli (Gij, + 4.3%) with a statistically significant increase only in G12 (+15.7%, P = 0.046). The ratio of transverse to axial strain (Poisson's ratio, nuij) demonstrated statistically significant changes in nu12, nu21, nu13, and nu31 (P < 0.05). These findings suggest that although slight elastic changes were incurred via a hypergravity environment, the treatment level or duration in this study do not dramatically perturb the normal elastic behavior of cortical bone and that dramatic biomechanical differences noted in previous studies were due more to structural changes than material elasticity changes. Hypergravity applied post facto to a microgravity environment would offer further illucidation of this method as treatment for a degenerative spaceflight experience.

Non-NASA Center↗
NASA NTRS1995

Hologic QDR 2000 whole-body scans: a comparison of three combinations of scan modes and analysis software

This study reports on the short-term in vivo precision and absolute measurements of three combinations of whole-body scan modes and analysis software using a Hologic QDR 2000 dual-energy X-ray densitometer. A group of 21 normal, healthy volunteers (11 male and 10 female) were scanned six times, receiving one pencil-beam and one array whole-body scan on three occasions approximately 1 week apart. The following combinations of scan modes and analysis software were used: pencil-beam scans analyzed with Hologic's standard whole-body software (PB scans); the same pencil-beam analyzed with Hologic's newer "enhanced" software (EPB scans); and array scans analyzed with the enhanced software (EA scans). Precision values (% coefficient of variation, %CV) were calculated for whole-body and regional bone mineral content (BMC), bone mineral density (BMD), fat mass, lean mass, %fat and total mass. In general, there was no significant difference among the three scan types with respect to short-term precision of BMD and only slight differences in the precision of BMC. Precision of BMC and BMD for all three scan types was excellent: < 1% CV for whole-body values, with most regional values in the 1%-2% range. Pencil-beam scans demonstrated significantly better soft tissue precision than did array scans. Precision errors for whole-body lean mass were: 0.9% (PB), 1.1% (EPB) and 1.9% (EA). Precision errors for whole-body fat mass were: 1.7% (PB), 2.4% (EPB) and 5.6% (EA). EPB precision errors were slightly higher than PB precision errors for lean, fat and %fat measurements of all regions except the head, although these differences were significant only for the fat and % fat of the arms and legs. In addition EPB precision values exhibited greater individual variability than PB precision values. Finally, absolute values of bone and soft tissue were compared among the three combinations of scan and analysis modes. BMC, BMD, fat mass, %fat and lean mass were significantly different between PB scans and either of the EPB or EA scans. Differences were as large as 20%-25% for certain regional fat and BMD measurements. Additional work may be needed to examine the relative accuracy of the scan mode/software combinations and to identify reasons for the differences in soft tissue precision with the array whole-body scan mode.

NASA Discipline Musculoskeletal↗
NASA NTRS1988

Effects of a 1-wk spaceflight on morphological and mechanical properties of growing bone

The morphological and mechanical responses of tibia and humerus were assessed in growing male rats after a 1-wk spaceflight aboard NASA Spacelab 3. In contrast to flights of longer duration, changes in middiaphysial cross-sectional morphology were minimal. Inhibition of longitudinal growth was not found in the tibia but was apparent in the humerus. The normal age-related increase in tibial middiaphysial density was not observed in the flight animals. Three-point bending tests indicated that a 1-wk spaceflight impeded the maturation of bone strength and stiffness, with the effects more pronounced in the tibia than in the humerus. Material property alterations in bone thus overshadowed morphological factors in determining the bone's mechanical response. It is likely that deprivation of normal weight-bearing loads was a major factor contributing to the observed changes, but endocrine and other local factors must also be considered.

short duration↗
NASA NTRS2005

Responses across the gravity continuum: hypergravity to microgravity

In response to hypergravity, it appears that the larger the animal, the greater the response, if present. Therefore, the response of a rat exceeds that of a mouse in the same hypergravity environment. When investigated in the microgravity environment of space flight, this appears to hold true. The lack of definitive data obtained in space for either species makes the extrapolation of the continuum to levels below Earth-gravity problematic. However, in systems where responses are detected for both space flight and acceleration by centrifugation, a gravitational continuum is present supporting the "principle of continuity". For those and similar systems, it appears that the use of hypergravity could be used to predict responses to space flight.

Review, Tutorial↗