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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
NASA NTRS1993

Post-translational control of collagen fibrillogenesis in mineralizing cultures of chick osteoblasts

Cultured osteoblasts from chick embryo calvaria were used as a model system to investigate the post-translational extracellular mechanisms controlling the macroassembly of collagen fibrils. The results of these studies demonstrated that cultured osteoblasts secreted a collagenous extracellular matrix that assembled and mineralized in a defined temporal and spatial sequence. The assembly of collagen occurred in a polarized fashion, such that successive orthogonal arrays of fibrils formed between successive cell layers proceeding from the culture surface toward the media. Mineralization followed in the same manner, being observed first in the deepest and oldest fibril layers. Collagen fibrillogenesis, the kinetics of cross-link formation, and collagen stability in the extracellular matrix of the cultures were examined over a 30 day culture period. Between days 8 and 12 in culture, collagen fibril diameters increased from < 30 nm to an average of 30-45 nm. Thereafter, diameters ranged in size from 20 to 200 nm. Quantitation of the collagen cross-linking residues, hydroxylysyl pyridinoline (HP) and lysyl pyridinoline (LP), showed that these mature cross-links increased from undetectable levels to concentrations found in normal chick bone. Analysis of the kinetics of their formation by pulse-chase labeling the cultures with [3H]lysine showed a doubling time of approximately 5 days. The relationships between cross-link formation, fibrillogenesis, and collagen stability were examined in cultures treated with beta-aminopropionitrile (beta-APN), a potent inhibitor of lysyl oxidase and cross-link formation. In beta-APN-treated cultures, total collagen synthesis was increased twofold, with no change in mRNA levels for type I collagen, whereas the amount of collagen accumulated in the cell layer was decreased by 50% and mineral deposition was reduced. The rate of collagen retention in the matrix was assessed by pulse-chase analysis of [3H]proline over a 16 day period in control and beta-APN-treated cultures. In control cultures, about 20% of the labeled collagen was lost from the cell layers over a 16 day period compared with > 80% in the presence of beta-APN. The beta-APN-treated cultures also showed a wider diversity of fibril diameters with a median in the > 45-60 nm range. In summary, these data suggest that cross-linking and assembly of collagen fibrils secreted by osteoblasts in vitro occur in a fashion similar to that found in vivo. The rate of cross-link formation is relatively constant and may be correlated with increasing collagen mass.(ABSTRACT TRUNCATED AT 400 WORDS).

NASA Discipline Musculoskeletal↗
NASA NTRS1993

Skeletal unloading decreases production of 1,25-dihydroxyvitamin D

The plasma concentration of 1,25-dihydroxyvitamin D [1,25(OH)2D] decreases during skeletal unloading and increases when normal weight bearing is restored. To determine whether these changes in plasma 1,25(OH)2D reflect changes in production, metabolic clearance, or both we measured the kinetics of 1,25(OH)2D metabolism in rats whose skeletons were normally loaded, unloaded, or reloaded after a period of nonweight bearing. Skeletal unloading produced a transient but striking fall in the production (-73%) and plasma concentration (-72%) of 1,25(OH)2D without having a significant effect (< 20%) on metabolic clearance. Skeletal reloading returned production to normal. Bone formation predictably decreased during unloading and returned to normal after return to weight bearing. No consistent changes in blood ionized calcium, plasma immunoreactive parathyroid hormone (irPTH), or plasma phosphorus occurred. These data suggest that the changes in plasma 1,25-(OH)2D associated with changes in skeletal weight bearing primarily reflect changes in 1,25(OH)2D production. The data provide no evidence that the changes in 1,25(OH)2D production are a consequence of changes in blood ionized calcium, plasma irPTH, or phosphorus.

Non-NASA Center↗
NASA NTRS1989

Myoneural necrosis following high-frequency electrical stimulation of the cast-immobilized rabbit hindlimb

The morphological and physiological effects of 4 weeks of high-frequency electrical stimulation (1 h/day, 5 days/week) on cast-immobilized rabbit hindlimbs were investigated in the tibialis anterior muscle and peroneal nerve. In 2 out of 6 animals, high-frequency stimulation with immobilization caused muscle fiber death, internalization of muscle fiber nuclei, connective tissue proliferation, inflammatory response, altered fiber size distribution and variable staining intensities. The fast-twitch fibers were predominantly affected. Two of six peripheral nerves subjected to immobilization and stimulation showed severe damage. Tetanic forces were significantly reduced in the affected muscles. Therefore, the immobilization and high-frequency stimulation may be detrimental to myoneural structure and function and, thus, this combination of therapies should be applied conservatively.

Non-NASA Center↗
NASA NTRS1997

Contractile properties of rat, rhesus monkey, and human type I muscle fibers

It is well known that skeletal muscle intrinsic maximal shortening velocity is inversely related to species body mass. However, there is uncertainty regarding the relationship between the contractile properties of muscle fibers obtained from commonly studied laboratory animals and those obtained from humans. In this study we determined the contractile properties of single chemically skinned fibers prepared from rat, rhesus monkey, and human soleus and gastrocnemius muscle samples under identical experimental conditions. All fibers used for analysis expressed type I myosin heavy chain as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Allometric coefficients for type I fibers from each muscle indicated that there was little change in peak tension (force/fiber cross-sectional area) across species. In contrast, both soleus and gastrocnemius type I fiber maximal unloaded shortening velocity (Vo), the y-intercept of the force-velocity relationship (Vmax), peak power per unit fiber length, and peak power normalized for fiber length and cross-sectional area were all inversely related to species body mass. The present allometric coefficients for soleus fiber Vo (-0.18) and Vmax (-0.11) are in good agreement with published values for soleus fibers obtained from common laboratory and domesticated mammals. Taken together, these observations suggest that the Vo of slow fibers from quadrupeds and humans scale similarly and can be described by the same quantitative relationships. These findings have implications in the design and interpretation of experiments, especially those that use small laboratory mammals as a model of human muscle function.

NASA Discipline Musculoskeletal↗
NASA NTRS1990

Preosteoblast production 55 hours after a 12.5-day spaceflight on Cosmos 1887

The influence of 12.5 days of spaceflight and a 55 h stressful recovery period (at 1 g) on fibroblastlike osteoblast precursor cells was assessed in the periodontal ligament (PDL) of rats that were 91 days old at launch. Nuclear morphometry was used as a marker for precursor cell differentiation in 3 microns sections cut in the midsagittal plane from the maxillary first molar. According to nuclear volume, cells were classified as preosteoblasts (C + D cells, greater than or equal to 120 microns 3) and less differentiated progenitor cells (A + A' cells, 40-79 microns 3). Compared with synchronous controls (simulated flight conditions), the 55 h postflight recovery period at 1 g resulted in a 40% decrease in the A + A' cell population, a 42% increase in the C + D cells, and a 39% increase in the number of PDL fibroblastlike cells near the bone surface. These results are consistent with a postflight osteogenic response in PDL. This recovery response occurred despite physiological stress in the flight animals that resulted in a highly significant (P less than or equal to 0.001) increase in adrenal weight. The data suggest that after spaceflight there is a strong and rapid recovery mechanism for osteoblast differentiation that is not suppressed by physiological stress.

Cosmos 1887 Project↗
NASA NTRS1995

Application of high-performance computing to numerical simulation of human movement

We have examined the feasibility of using massively-parallel and vector-processing supercomputers to solve large-scale optimization problems for human movement. Specifically, we compared the computational expense of determining the optimal controls for the single support phase of gait using a conventional serial machine (SGI Iris 4D25), a MIMD parallel machine (Intel iPSC/860), and a parallel-vector-processing machine (Cray Y-MP 8/864). With the human body modeled as a 14 degree-of-freedom linkage actuated by 46 musculotendinous units, computation of the optimal controls for gait could take up to 3 months of CPU time on the Iris. Both the Cray and the Intel are able to reduce this time to practical levels. The optimal solution for gait can be found with about 77 hours of CPU on the Cray and with about 88 hours of CPU on the Intel. Although the overall speeds of the Cray and the Intel were found to be similar, the unique capabilities of each machine are better suited to different portions of the computational algorithm used. The Intel was best suited to computing the derivatives of the performance criterion and the constraints whereas the Cray was best suited to parameter optimization of the controls. These results suggest that the ideal computer architecture for solving very large-scale optimal control problems is a hybrid system in which a vector-processing machine is integrated into the communication network of a MIMD parallel machine.

NASA Discipline Musculoskeletal↗
NASA NTRS1996

Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non-human primate model.

NASA Discipline Musculoskeletal↗
NASA NTRS1996

Musculoskeletal adaptations to weightlessness and development of effective countermeasures

A Research Roundtable, organized by the American College of Sports Medicine with sponsorship from the National Aeronautics and Space Administration, met in November 1995 to define research strategies for effective exercise countermeasures to weightlessness. Exercise was considered both independently of, and in conjunction with, other therapeutic modalities (e.g., pharmacological nutritional, hormonal, and growth-related factors) that could prevent or minimize the structural and functional deficits involving skeletal muscle and bone in response to chronic exposure to weightlessness, as well as return to Earth baseline function if a degree of loss is inevitable. Musculoskeletal deficits and countermeasures are described with respect to: 1) muscle and connective tissue atrophy and localized bone loss, 2) reductions in motor performance, 3) potential proneness to injury of hard and soft tissues, and 4) probable interaction between muscle atrophy and cardiovascular alterations that contribute to the postural hypotension observed immediately upon return from space flight. In spite of a variety of countermeasure protocols utilized previously involving largely endurance types of exercise, there is presently no activity-specific countermeasure(s) that adequately prevent or reduce musculoskeletal deficiencies. It seems apparent that countermeasure exercises that have a greater resistance element, as compared to endurance activities, may prove beneficial to the musculoskeletal system. Many questions remain for scientific investigation to identify efficacious countermeasure protocols, which will be imperative with the emerging era of long-term space flight.

Non-NASA Center↗
NASA NTRS2003

Flexor bias of joint position in humans during spaceflight

The ability to estimate ankle and elbow joint position was tested before, during, and after a 17-day spaceflight. Subjects estimated targeted joint angles during isovelocity (IsoV) joint movements with agonist muscle groups either active or relaxed. These movements included elbow extension (EE) and elbow flexion (EF), and plantarflexion (PF) and dorsiflexion (DF) of the ankle. Subjects also estimated these joint positions while moving the dynamometer at their chosen (variable) velocity (VarV) during EE and PF. For IsoV tests, no differences were observed between active and passive movements for either the ankle or elbow. Compared with those of pre-flight test days, estimates of targeted elbow joint angles were approximately 5 degrees to 15 degrees more flexed in-flight, and returned toward the pre-flight values during recovery. The spaceflight effects for the ankle were inconsistent and less prevalent than those for the elbow. The VarV PF test condition for the 120 degrees target angle at the ankle exhibited approximately 5 degrees to 7 degrees more DF target angle estimates in-flight compared with those pre- or post-flight. In contrast, during IsoV PF there was a tendency for ankle estimates to be approximately 2 degrees to 3 degrees more PF after 2-3 days exposure to spaceflight. These data indicate that during spaceflight the perception of elbow extension is greater than actuality, and are consistent with the interpretation that microgravity induced a flexor bias in the estimation of the actual elbow joint position. Moreover, these effects in joint proprioception during spaceflight were observed in individual isolated single-joint movements during tasks in which vestibular function in maintaining posture were minimal.

STS-78 Shuttle Project↗
NASA NTRS2003

Hindlimb unloading increases oxidative stress and disrupts antioxidant capacity in skeletal muscle

Skeletal muscle disuse with space-flight and ground-based models (e.g., hindlimb unloading) results in dramatic skeletal muscle atrophy and weakness. Pathological conditions that cause muscle wasting (i.e., heart failure, muscular dystrophy, sepsis, COPD, cancer) are characterized by elevated "oxidative stress," where antioxidant defenses are overwhelmed by oxidant production. However, the existence, cellular mechanisms, and ramifications of oxidative stress in skeletal muscle subjected to hindlimb unloading are poorly understood. Thus we examined the effects of hindlimb unloading on hindlimb muscle antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase), nonenzymatic antioxidant scavenging capacity (ASC), total hydroperoxides, and dichlorohydrofluorescein diacetate (DCFH-DA) oxidation, a direct indicator of oxidative stress. Twelve 6 month old Sprague Dawley rats were divided into two groups: 28 d of hindlimb unloading (n = 6) and controls (n = 6). Hindlimb unloading resulted in a small decrease in Mn-superoxide dismutase activity (10.1%) in the soleus muscle, while Cu,Zn-superoxide dismutase increased 71.2%. In contrast, catalase and glutathione peroxidase, antioxidant enzymes that remove hydroperoxides, were significantly reduced in the soleus with hindlimb unloading by 54.5 and 16.1%, respectively. Hindlimb unloading also significantly reduced ASC. Hindlimb unloading increased soleus lipid hydroperoxide levels by 21.6% and hindlimb muscle DCFH-DA oxidation by 162.1%. These results indicate that hindlimb unloading results in a disruption of antioxidant status, elevation of hydroperoxides, and an increase in oxidative stress.

NASA Discipline Musculoskeletal↗
NASA NTRS2003

Administration of the non-steroidal anti-inflammatory drug ibuprofen increases macrophage concentrations but reduces necrosis during modified muscle use

OBJECTIVE: To test the hypothesis that ibuprofen administration during modified muscle use reduces muscle necrosis and invasion by select myeloid cell populations. METHODS: Rats were subjected to hindlimb unloading for 10 days, after which they experienced muscle reloading by normal weight-bearing to induce muscle inflammation and necrosis. Some animals received ibuprofen by intraperitoneal injection 8 h prior to the onset of muscle reloading, and then again at 8 and 16 h following the onset of reloading. Other animals received buffer injection at 8 h prior to reloading and then ibuprofen at 8 and 16 h following the onset of reloading. Control animals received buffer only at each time point. Quantitative immunohistochemical analysis was used to assess the presence of necrotic muscle fibers, total inflammatory infiltrate, neutrophils, ED1+ macrophages and ED2+ macrophages at 24 h following the onset of reloading. RESULT: Administration of ibuprofen beginning 8 h prior to reloading caused significant reduction in the concentration of necrotic fibers, but increased the concentration of inflammatory cells in muscle. The increase in inflammatory cells was attributable to a 2.6-fold increase in the concentration of ED2+ macrophages. Animals treated with ibuprofen 8 h following the onset of reloading showed no decrease in muscle necrosis or increase in ED2+ macrophage concentrations. CONCLUSION: Administration of ibuprofen prior to increased muscle loading reduces muscle damage, but increases the concentration of macrophages that express the ED2 antigen. The increase in ED2+ macrophage concentration and decrease in necrosis may be mechanistically related because ED2+ macrophages have been associated with muscle regeneration and repair.

Non-NASA Center↗
NASA NTRS2003

Evidence for altered alpha-adrenoreceptor responsiveness after a single bout of maximal exercise

We studied hemodynamic responses to alpha- and beta-receptor agonists in eight men to test the hypothesis that adrenoreceptor responsiveness is altered within 24 h of the performance of maximal exercise. Adrenoreceptor responsiveness was tested under two experimental conditions (with and without maximal exercise). Adrenoreceptor tests were performed 24 h after each subject performed graded upright cycle ergometry to volitional exhaustion. The 2 test days (experimental conditions) were separated by at least 1 wk, and the order of exercise and no-exercise conditions was counterbalanced. Steady-state graded infusions of phenylephrine (PE) and isoproterenol (Iso) were used to assess alpha- and beta-adrenoreceptor responsiveness, respectively. Slopes calculated from linear regressions between Iso and PE doses and changes in heart rate, blood pressure, and leg vascular resistance for each subject were used as an index of alpha- and beta-adrenoreceptor responsiveness. The slope of the relationship between heart rate and Iso with maximal exercise was 1773 +/- 164 beats x microm-1x kg-1x min-1 compared with 1987 +/- 142 beats x microg-1x kg-1x min-1 without exercise (P = 0.158), whereas the slopes of the relationship between vascular resistance to Iso were -438 +/- 123 peripheral resistance units (PRU) x microg-1x kg-1x min-1 with maximal exercise and -429 +/- 105 x microg-1x kg-1 x min-1 without exercise (P = 0.904). Maximal exercise was associated with greater (P < 0.05) vascular resistance (15.1 +/- 2.8 PRU x microg-1 kg-1x min-1) and mean arterial blood pressure (15.8 +/- 2.1 mmHg. microg-1x kg-1x min-1) responses to PE infusion compared with no exercise (9.0 +/- 2.0 PRU x microg-1 kg-1 x min-1 and 10.9 +/- 2.0 mmHg. microg-1x kg-1x min-1, respectively). These results provide evidence that a single bout of maximal exercise increases alpha1-adrenoreceptor responsiveness within 24 h without affecting beta-cardiac and vascular adrenoreceptor responses.

Non-NASA Center↗
NASA NTRS2002

The X-ray attenuation characteristics and density of human calcaneal marrow do not change significantly during adulthood

Changes in the material characteristics of bone marrow with aging can be a significant source of error in measurements of bone density when using X-ray and ultrasound imaging modalities. In the context of computed tomography, dual-energy computed techniques have been used to correct for changes in marrow composition. However, dual-energy quantitative computed tomography (DE-QCT) protocols, while increasing the accuracy of the measurement, reduce the precision and increase the radiation dose to the patient in comparison to single-energy quantitative computed tomography (SE-QCT) protocols. If the attenuation properties of the marrow for a particular bone can be shown to be relatively constant with age, it should be possible to use single-energy techniques without experiencing errors caused by unknown marrow composition. Marrow was extracted by centrifugation from 10 mm thick frontal sections of 34 adult cadaver calcanei (28 males, 6 females, ages 17-65 years). The density and energy-dependent linear X-ray attenuation coefficient of each marrow sample were determined. For purposes of comparing our results, we then computed an effective CT number at two GE CT/i scan voltages (80 and 120 kVp) for each specimen. The coefficients of variation for the density, CT number at 80 kVp and CT number at 120 kVp were each less than 1%, and the parameters did not change significantly with age (p > 0.2, r2 < 0.02, power > 0.8 where the minimum acceptable r2 = 0.216). We could demonstrate no significant gender-associated differences in these relationships. These data suggest that calcaneal bone marrow X-ray attenuation properties and marrow density are essentially constant from the third through sixth decades of life.

NASA Discipline Musculoskeletal↗
NASA NTRS2001

No effect of hypergravity on adult rat ventral horn neuron size or SDH activity

BACKGROUND: Spaceflights of short duration (approximately 2 wk) result in adaptations in the size and/or metabolic properties of a select population of motoneurons located in the lumbosacral region of the rat spinal cord. A decrease in succinate dehydrogenase (SDH, an oxidative marker enzyme) activity of moderately sized (500-800 microm2) motoneurons in the retrodorsolateral region of the spinal cord (L6) has been observed after a 14-d flight. HYPOTHESIS: Our hypothesis was that exposure to short-term hypergravity would result in adaptations in the opposite direction, reflecting a continuum of morphological and biochemical responses in the spinal motoneurons from zero gravity to hypergravity. METHODS: Young, male rats were centrifuged at either 1.5 or 2.0 G for 2 wk. The size and SDH activity of a population of motoneurons in the retrodorsolateral region of the spinal cord (L5) were determined and compared with age-matched rats maintained at 1.0 G. The absolute and relative (to body weight) masses of the soleus, gastrocnemius, adductor longus and tibialis anterior muscles were compared among the three groups. RESULTS: There were no effects of either hypergravity intervention on the motoneuron properties. Rats maintained under hypergravity conditions gained less body mass than rats kept at 1.0 G. For the 1.5 and 2.0 G groups, the muscle absolute mass was smaller and relative mass similar to that observed in the 1.0 G rats, except for the adductor longus. The adductor longus absolute mass was similar to and the relative mass larger in both hypergravity groups than in the 1.0 G group. CONCLUSIONS: Our hypothesis was rejected. The findings suggest that rat motoneurons are more responsive to short-term chronic exposure to spaceflight than to hypergravity conditions.

NASA Discipline Musculoskeletal↗
NASA NTRS2001

Depression, mood state, and back pain during microgravity simulated by bed rest

OBJECTIVE: The objective of this study was to develop a ground-based model for spinal adaptation to microgravity and to study the effects of spinal adaptation on depression, mood state, and pain intensity. METHODS: We investigated back pain, mood state, and depression in six subjects, all of whom were exposed to microgravity, simulated by two forms of bed rest, for 3 days. One form consisted of bed rest with 6 degrees of head-down tilt and balanced traction, and the other consisted of horizontal bed rest. Subjects had a 2-week period of recovery between the studies. The effects of bed rest on pain intensity in the lower back, depression, and mood state were investigated. RESULTS: Subjects experienced significantly more intense lower back pain, lower hemisphere abdominal pain, headache, and leg pain during head-down tilt bed rest. They had higher scores on the Beck Depression Inventory (ie, were more depressed) and significantly lower scores on the activity scale of the Bond-Lader questionnaire. CONCLUSIONS: Bed rest with 6 degrees of head-down tilt may be a better experimental model than horizontal bed rest for inducing the pain and psychosomatic reactions experienced in microgravity. Head-down tilt with balanced traction may be a useful method to induce low back pain, mood changes, and altered self-rated activity level in bed rest studies.

NASA Discipline Musculoskeletal↗
NASA NTRS2000

Effect of spaceflight on the maximal shortening velocity, morphology, and enzyme profile of fast- and slow-twitch skeletal muscle fibers in rhesus monkeys

Weightlessness has been shown to cause limb muscle wasting and a reduced peak force and power in the antigravity soleus muscle. Despite a reduced peak power, Caiozzo et al. observed an increased maximal shortening velocity in the rat soleus muscle following a 14-day space flight. The major purpose of the present investigation was to determine if weightlessness induced an elevated velocity in the antigravity slow type I fibers of the rhesus monkey (Macaca mulatta), as well as to establish a cellular mechanism for the effect. Spaceflight or models of weightlessness have been shown to increase glucose uptake, elevate muscle glycogen content, and increase fatigability of the soleus muscle. The latter appears to be in part caused by a reduced ability of the slow oxidative fibers to oxidize fats. A second goal of this study was to establish the extent to which weightlessness altered the substrate profile and glycolytic and oxidative enzyme capacity of individual slow- and fast-twitch fibers.

Bion 11 Project↗
NASA NTRS1995

Integrin-extracellular matrix interactions in connective tissue remodeling and osteoblast differentiation

The differentiaton of bone cells is a complex multistep process. Bone is somewhat unusual in that it is very actively and continually remodeled in the adult and that maintenance of its mass in the mature organism is exquisitely sensitive to mechanical as well as chemical signals. Bone is also unique because it consists of a very large amount of extracellular matrix (ECM) that is mineralized. The integrin family of ECM receptors has been shown to play an important role in tissue morphogenesis in several systems. Our studies on the regulation of matrix remodeling enzymes by integrins in rabbit synovial fibroblasts show that two b1 integrin fibronectin (FN) receptor complexes (alpha 5 beta 1 and alpha 4 beta 1) cooperate in detecting subtle changes in the composition of the ECM. As a result of signal transduction by these integrins, the levels of mRNA and protein for several members of the metalloproteinase family are regulated in these cells. We have also used antibody and RGD peptide perturbation studies to determine the significance of cell/ECM interactions to normal osteogenesis. We found that interactions between the cell binding domain of FN and integrins are required for both normal morphogenesis and gene expression in cultured osteoblasts that differentiate to form bone-like tissue in culture. These data lead us to propose that beta 1 integrins play an important role in osteoblast differentiation as well as in bone remodeling.

NASA Discipline Number 26-10↗
NASA NTRS2001

Comparison of a space shuttle flight (STS-78) and bed rest on human muscle function

The purpose of this investigation was to assess muscle fiber size, composition, and in vivo contractile characteristics of the calf muscle of four male crew members during a 17-day spaceflight (SF; Life and Microgravity Sciences Spacelab Shuttle Transport System-78 mission) and eight men during a 17-day bed rest (BR). The protocols and timelines of these two investigations were identical, therefore allowing for direct comparisons between SF and the BR. The subjects' age, height, and weight were 43 +/- 2 yr, 183 +/- 4 cm, and 86 +/- 3 kg for SF and 43 +/- 2 yr, 182 +/- 3 cm, and 82 +/- 4 kg for BR, respectively. Calf muscle strength was examined before SF and BR; on days 2, 8, and 12 during SF and BR; and on days 2 and 8 of recovery. Muscle biopsies were obtained before and within 3 h after SF (gastrocnemius and soleus) and BR (soleus) before reloading. Maximal isometric calf strength and the force-velocity characteristics were unchanged with SF or BR. Additionally, neither SF nor BR had any effect on fiber composition or fiber size of the calf muscles studied. In summary, no changes in calf muscle strength and morphology were observed after the 17-day SF and BR. Because muscle strength is lost during unloading, both during spaceflight and on the ground, these data suggest that the testing sequence employed during the SF and BR may have served as a resistance training countermeasure to attenuate whole muscle strength loss.

Non-NASA Center↗