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Results for “NASA Discipline Musculoskeletal”

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At least 127 records · Page 7Linked to original sources

PubMed1995

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.

Alkaline Phosphatase↗

PubMed1995

Transduction of mechanical strain in bone.

One physiologic consequence of extended periods of weightlessness is the rapid loss of bone mass associated with skeletal unloading. Conversely, mechanical loading has been shown to increase bone formation and stimulate osteoblastic function. The mechanisms underlying mechanotransduction, or how the osteoblast senses and converts biophysical stimuli into cellular responses has yet to be determined. For non-innervated mechanosensitive cells like the osteoblast, mechanotransduction can be divided into four distinct phases: 1) mechanocoupling, or the characteristics of the mechanical force applied to the osteoblast, 2) biochemical coupling, or the mechanism through which mechanical strain is transduced into a cellular biochemical signal, 3) transmission of signal from sensor to effector cell and 4) the effector cell response. This review examines the characteristics of the mechanical strain encountered by osteoblasts, possible biochemical coupling mechanisms, and how the osteoblast responds to mechanical strain. Differences in osteoblastic responses to mechanical strain are discussed in relation to the types of strain encountered and the possible transduction pathways involved.

Animals↗

PubMed1995

Impact of weightlessness on muscle function.

The most studied skeletal muscles which depend on gravity, "antigravity" muscles, are located in the posterior portion of the legs. Antigravity muscles are characterized generally by a different fiber type composition than those which are considered nonpostural. The gravity-dependent function of the antigravity muscles makes them particularly sensitive to weightlessness (unweighting) resulting in a substantial loss of muscle protein, with a relatively greater loss of myofibrillar (structural) proteins. Accordingly alpha-actin mRNA decreases in muscle of rats exposed to microgravity. In the legs, the soleus seems particularly responsive to the lack of weight-bearing associated with space flight. The loss of muscle protein leads to a decreased cross-sectional area of muscle fibers, particularly of the slow-twitch, oxidative (SO) ones compared to fast-twitch glycolytic (FG) or oxidative-glycolytic (FOG) fibers. In some muscles, a shift in fiber composition from SO to FOG has been reported in the adaptation to spaceflight. Changes in muscle composition with spaceflight have been associated with decreased maximal isometric tension (Po) and increased maximal shortening velocity. In terms of fuel metabolism, results varied depending on the pathway considered. Glucose uptake, in the presence of insulin, and activities of glycolytic enzymes are increased by space flight. In contrast, oxidation of fatty acids may be diminished. Oxidation of pyruvate, activity of the citric acid cycle, and ketone metabolism in muscle seem to be unaffected by microgravity.

Actins↗

PubMed1994

Effects of 5 weeks of lower limb suspension on muscle size and strength.

Lack of weight-bearing, as occurs in space, appears to be associated with reductions in strength and mass of skeletal muscle. Very limited data, however, is at hand describing changes in skeletal muscle size and function following manned space missions. Our current knowledge therefore is mainly based on studies of space flown rats. It is obvious though that this information, only in part can be extrapolated to humans. A few bed rest studies have demonstrated that decreases in strength and muscle size are substantial. At this time, however, the magnitude or time course of such changes either in response to space flight or simulations of microgravity have not been defined. In the last few years we have employed a human model to simulate unloading of lower limb skeletal muscles that occurs in microgravity. This model was essentially adopted from the rat hindlimb suspension technique. The purpose of this study was to assess the magnitude of decreases in muscle strength and size as a result of five weeks of unilateral lower limb suspension.

Adaptation, Physiological↗

PubMed1994

Hormonal and metabolic responses of hypophysectomized rats with head-down suspension.

The primary purpose of this investigation was to secure select anatomical and physiological measurements from hypophysectomized rats and their sham-operated control to determine how various endocrine influences could be modified by conditions of simulated microgravity. The focal point of the study was the exercise responses after head-down suspension; however, we were also interested in obtaining insights on nonexercise-related mechanisms. Since more details and information concerning this study will be published elsewhere, we will highlight those findings which warrant further research.

Animals↗

PubMed1994

The effects of space flight on the contractile apparatus of antigravity muscles: implications for aging and deconditioning.

Previous studies have shown that the unloading of skeletal muscle, as occurring during exposure to space flight, exerts a profound effect on both the mass (cross sectional area) of skeletal muscle fibers and the relative expression of protein isoforms comprising the contractile system. Available information suggests that slow (type I) fibers, comprising chiefly the antigravity muscles of experimental animals, in addition to atrophying, undergo alterations in the type of myosin heavy chain (MHC) expressed such that faster isoforms become concomitantly expressed in a sub-population of slow fibers when insufficient force-bearing activity is maintained on the muscle. Consequently, these transformations in both mass and myosin heavy chain phenotype could exert a significant impact on the functional properties of skeletal muscle as manifest in the strength, contractile speed, and endurance scope of the muscle. To further explore these issues, a study was performed in which young adult male rats were exposed to zero gravity for six days, following which, the antigravity soleus muscle was examined for a) contractile properties, determined in situ and b) isomyosin expression, as studied using biochemical, molecular biology, and histochemical/immunohistochemical techniques.

Aging↗

PubMed1995

Mineral distribution in rat skeletons after exposure to a microgravity model.

Exposure to space flight models induces changes in the distribution of bone mineral in the human skeleton that has the features of a gravitational gradient. Regional bone mineral measurements with dual energy x-ray absorptiometry (DEXA) in male adults exposed to head-down tilt bed rest for 30 days show non-significant decrements in the pelvis and legs with 10% increases in the head region. Horizontal bed rest for 17 weeks reveals losses of bone mineral ranging from 2.2 to 10.4% from the lumbar spine to the calcaneus and an increase of 3.4% in the skull. Investigation of this phenomena would be most definitively carried out in an animal model. One candidate is the flight simulation model in the rat which removes body weight from the hind limbs and induces a cephalad fluid shift by suspending the animal by the tail. Weanling rats exposed to this model showed bone mineral to be lower in the hind limbs and higher in the skull after 3 weeks. These findings are similar in older 200 g animals after 2 weeks tail suspension. The purpose of this study was to determine the effect of age on the distribution of skeletal mineral in this model.

Aging↗

PubMed1995

Developmental testing of the Advanced Animal Habitat to determine compatibility with rats and mice.

The Research Animal Holding Facility (RAHF) and the Animal Enclosure Module (AEM) have housed rats during Space Shuttle flights since the 1980s, but the operational constraints of the hardware have limited the scientific return from these Shuttle flights. The RAHF provides environmental control and monitoring for 24 rats with in-flight animal access, but it must be flown in the Spacelab. Due to the infrequent availability of Spacelab flights, rodent experiments rely heavily on the AEM. Unfortunately, the AEM supports only six rats, has no environmental control and provides no animal access in flight. The Advanced Animal Habitat (AAH) is being developed to support up to 12 adult rats or 30 adult mice for up to 30 days, provide active temperature control, animal telemetry and on-orbit video, record environmental parameters in the animal cage, and provide in-flight animal access in the Middeck, the Spacelab or the Space Station. To ensure the AAH can meet these requirements, animal testing is being conducted with rats and mice in every step of development. Testing began with the cage configuration.

Animals↗

PubMed1995

Functional and cellular adaptations of rodent skeletal muscle to weightlessness.

Microgravity perturbs a wide variety of physiological systems. Specifically, skeletal muscle has been shown to undergo dramatic changes even during spaceflights of short durations. Despite a growing body of knowledge, many critical issues related to sarcomeric gene expression and the translation of this information into muscle function remain relatively unexplored. Ultimately, the types and quantities of contractile proteins present in skeletal muscle fibers determine muscle function. As shown in Figure 1, the pool of contractile proteins is determined by 4 important processes: i) transcription of sarcomeric genes; ii) translation of sarcomeric mRNA transcripts; iii) myofibrillar assembly; and iv) myofibrillar disassembly (i.e., protein degradation). Any factor(s) affecting one or more of these systems will ultimately impact skeletal muscle function. With respect to Figure 1, the objective of this paper is to provide a focused summary of the affects of short duration spaceflights on myosin composition of the soleus (SOL) muscle. This will be achieved by describing the affects of spaceflight upon: i) mechanical properties of skeletal muscle that are determined by the types and quantity of myosin; ii) myosin heavy chain (MHC) protein isoform composition; and ii) MHC mRNA isoform content. Data reported in this paper are from spaceflight missions having durations of 6 (PARE-02;2) and 14 days (SLS-2).

Animals↗

PubMed1995

Functional and cellular adaptation to weightlessness in primates.

Considerable data has been collected on the response of hindlimb muscles to unloading due to both spaceflight and hindlimb suspension. One generalized response to a reduction in load is muscle fiber atrophy, although not all muscles respond the same. For example, predominantly slow extensor muscles like the Sol exhibit a large reduction in fiber size to unloading, while fast extensors like the plantaris and fast flexors like the tibialis anterior show little, if any, atrophy. Our understanding of how muscles respond to microgravity, however, has come primarily from the examination of hindlimb muscles in the unrestrained rat in space. The non-human primate spaceflight paradigm differs considerably from the rodent paradigm in that the monkeys are restrained, usually in a sitting position, while in space. Recently, we examined the effects of microgravity on muscles of the Rhesus monkey by taking biopsies of selected hindlimb muscles prior to and following spaceflights of 14 and 12 day durations (Cosmos 2044 and 2229). Our results revealed that the monkey's response to microgravity differs from that of the rat. The apparent differences in the atrophic response of the hindlimb muscles of the monkey and rat to spaceflight may be attributed to 1) a species difference, 2) a difference in the manner in which the animals were maintained during the flight (i.e., chair restraint or "free-floating"), and/or 3) an ability of the monkeys to counteract the effects of spaceflight with resistive exercise.

Animals↗

PubMed1995

Adaptations of human skeletal muscle fibers to spaceflight.

Human skeletal muscle fibers seem to share most of the same interrelationships among myosin ATPase activity, myosin heavy chain (MHC) phenotype, mitochondrial enzyme activities, glycolytic enzyme activities and cross-sectional area (CSA) as found in rat, cat and other species. One difference seems to be that fast fibers with high mitochondrial content occur less frequently in humans than in the rat or cat. Recently we have reported that the type of MHC expressed and the size of the muscle fibers in humans that have spent 11 days in space change significantly. Specifically, about 8% more fibers express fast MHCs and all phenotypes atrophy in the vastus lateralis (VL) post compared to preflight. In the present paper we examine the relationships among the population of myonuclei, MHC type and CSA of single human muscle fibers before and after spaceflight. These are the first data that define the relationship among the types of MHC expressed, myonuclei number and myonuclei domain of single fibers in human muscle. We then compare these data to similar measures in the cat. In addition, the maximal torque that can be generated by the knee extensors and their fatigability before and after spaceflight are examined. These data provide some indication of the potential physiological consequences of the muscle adaptations that occur in humans in response to spaceflight.

Adaptation, Physiological↗

PubMed1995

Future research directions in seeking countermeasures to weightlessness.

The goal of this paper is to briefly review the state of knowledge concerning the adaptive properties of mammalian skeletal muscle in response to varying duration in weightlessness, to identify voids in the understanding of this adaptive process, and to provide some insight for undertaking future research on this important topic.

Animals↗

PubMed1995

Effect of spaceflight on oxidative and antioxidant enzyme activity in rat diaphragm and intercostal muscles.

There are limited data regarding changes in oxidative and antioxidant enzymes induced by simulated or actual weightlessness, and any additional information would provide insight into potential mechanisms involving other changes observed in muscles from animals previously flown in space. Thus, the NASA Biospecimen Sharing Program was an opportunity to collect valuable information. Oxidative and antioxidant enzyme levels, as well as lipid perioxidation, were measured in respiratory muscles from rats flown on board Space Shuttle mission STS-54. The results indicated that there was an increasing trend in citrate synthase activity in the flight diaphragm when compared to ground based controls, and there were no significant changes observed in the intercostal muscles for any of the parameters. However, lipid peroxidation was significantly (p<0.05) decreased in the flight diaphragm. These results indicate that 6 day exposure to microgravity may have a different effect on oxidative and antioxidant activity in rat respiratory muscles when compared to data from previous 14 day hindlimb suspension studies.

Animals↗

PubMed1995

Electrical impedance measurements in the arm and the leg during a thirty day bed rest study.

The need to detect, follow and understand the effects of gravity on body fluid distribution is a constant stimulus to the quest for new techniques in this area of research. One of these techniques is electrical bioimpedance spectroscopy (BIS). Although not new, this is a technique whose applications to biomedical research are fairly recent. What is new is the development of instrumentation that has made practical the use of impedance spectroscopy in the biomedical setting, particularly in studies involving human subjects. The purpose of this paper is to report impedance spectroscopy observations made on a subject who was submitted to bed rest for a period of thirty days. These observations were made as part of a study on muscle atrophy during a thirty day head down bed rest. Since bed rest studies are very costly in human and financial terms, and technically difficult to realize, we felt that even though the present study deals only with a single case it was worthy of reporting because it illustrates kinds of questions impedance spectroscopy may help to answer in microgravity research.

Adult↗

PubMed1995

Neuromuscular adaptations during 30 days of cast-immobilization and head-down bedrest.

Prolonged skeletal muscle disuse, during space flights and on Earth, produces distinct adaptive changes in the neuromuscular system of human subjects. There is a significant decline in muscle mass and strength, exercise capacity, fatigue resistance, integrated EMG (IEMG) output and time-dependent alterations in the behavior of Hoffman (H) and deep tendon reflexes. The objective of this study was to examine the changes in excitability of segmental motoneuronal network and its influence upon gastrocnemius-soleus (G-S) function in healthy male and female subjects, who underwent either 6 degrees head-down bedrest (HDB) or unilateral cast-immobilization (CIM) for a period of 30 days.

Adult↗

PubMed1984

Muscularity as a function of species, sex and age in small mammals.

The size of individual skeletal muscles in mammals is well known to change with the degree of mechanical loading imposed on the muscle. Less clear has been the effect of changes in loading of the whole organism on size of the total skeletal musculature. Pitts and coworkers have provided valuable insights by dissection and weighing of the skeletal musculature of animals subjected to various chronic centrifugation, exercise and dietary regimens, and their recent findings are reported at this meeting. However, questions remain. Independently, our laboratory several years ago embarked on a systematic definition of body composition and energy metabolism changes as a function of sex and age in 5 species of small laboratory mammals, the mouse, hamster, rat, guinea pig and rabbit. Six animals of each sex were examined in 8 age cohorts ranging from 1 to 24 months for each of the 5 species.

Aging↗

PubMed1984

Activity of calcium activated protease in skeletal muscles and its changes in atrophy and stretch.

The reduction of protein content in skeletal muscle undergoing disuse-induced atrophy is correlated with accelerated rates of protein degradation and reduced rates of protein synthesis. It is not known in what manner myofibers are partially disassembled during disuse atrophy to fibers of smaller diameter; nor is it known which proteases are responsible for this morphological change in contractile protein mass. Dayton and colleagues have suggested that the Ca(2+)-activated protease (CaP) may initiate myofibril degradation. The discovery of a form of CaP that is activatable by nanomolar concentrations of Ca2+ indicates that CaP activity may be regulated by physiological concentrations of Ca2+. The enhancement of proteolysis by the Ca2+ ionophore A23187, reported by Etlinger, is consistent with a significant role for CaP in protein degradation. It was of interest, therefore, to measure the levels of CaP activity and the CaP inhibitor in extracts obtained from skeletal muscles of rat and chicken limbs undergoing disuse atrophy or stretch hypertrophy, respectively.

Animals↗

PubMed1984

Alterations in bone forming cells due to reduced weight bearing.

A reduction in new bone formation occurred as a result of space flight (Cosmos 1129) and in the suspended animal model of Morey-Holton. Our results indicate that alkaline phosphatase activity of the bone forming cells is also reduced under these conditions, and the cells in the diaphysis are more affected than those in the metaphyseal region. In addition, these cells show (1) reduced proline incorporation into bone matrix, and (2) increased intracellular lysosomal activity. A change in the cytoskeleton could be the common factor in explaining these results. This suggestion is further supported by our previous observations that colchicine injections result in decreased osteoblastic function.

Alkaline Phosphatase↗