Formation of ectopic osteogenesis in weightlessness

NASA Technical Reports Server (NTRS)

1977-01-01

An ectopic osteogenesis experiment aboard the Cosmos-936 biosatellite is described. Decalcified, lyophilized femur and tibia were implanted under the fascia or in the anterior wall of the abdomen in rats. Bone formation before and after the tests is described and illustrated. The extent of formation of ectopic bone in weightlessness did not differ significantly from that in the ground controls, but the bone marrow of the ectopic bone of the flight rats consisted exclusively of fat cells. The deficit of support-muscle loading was considered to cause the disturbance in skeletal bone tissue development.

The Role of Vitamin D in the Bone Changes Associated with Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Halloran, B. P.; Bikle, D. D.; Holton, E.; Levens, M. J.; Globus, R.

1985-01-01

The role of vitamin D in the change in bone metabolism was examined. The serum concentrations in rats sacrificed after 2, 5, 7, 10, 12 and 15 days of suspension was measured. Between days 1 and 5 of suspension and then gradually decreased towards normal between days 5 and 15. The time course of the changes in the circulating concentrations of 1,25(OH)2D and 24,25(OH)2D mirror almost precisely the changes in bone metabolism. The relationship between the changes in vitamin D metabolism and bone metabolism is investigated. Whether the bone changes are due to the change in serum concentration of 1,25(OH)2D or the changes in bone formation causing a reduction in Ca flux out of the serum pool and thereby suppressing 1,25(OH)2D production is examined. It is found that suspension had no effect on hormone concentration in the 1,25(OH)2D infused animals. Nevertheless, both vehicle and 1,25(OH)2D infused suspended rats exhibited the same reduction in bone mineral, and uptake of (45)Ca. It is suggested that the transitory reduction in circulating 1,25(OH)2D during suspension is not likely to cause the abnormalities in bone metabolism but rather that the changes in bone metabolism are primary and cause the fall in serum 1,25(OH)2D concentration. This supports the hypothesis that the metabolic abnormalities in bone associated with simulated weightlessness are due to the direct effect of unweighting on the bone.

Loading Configurations and Ground Reaction Forces During Treadmill Running in Weightlessness

NASA Technical Reports Server (NTRS)

DeWitt, John; Schaffner, Grant; Blazine, Kristi; Bentley, Jason; Laughlin, Mitzi; Loehr, James; Hagan, Donald

2003-01-01

Studies have shown losses in bone mineral density of 1-2% per month in critical weight bearing areas such as the proximal femur during long-term space flight (Grigoriev, 1998). The astronauts currently onboard the International Space Station (ISS) use a treadmill as an exercise countermeasure to bone loss that occurs as a result of prolonged exposure to weightlessness. A crewmember exercising on the treadmill is attached by a harness and loading device. Ground reaction forces are obtained through the loading device that pulls the crewn1ember towards the treadmill surface during locomotion. McCrory et al. (2002) found that the magnitude of the peak ground reaction force (pGRF) during horizontal suspension running, or simulated weightlessness, was directly related to the load applied to the subject. It is thought that strain magnitude and strain rate affects osteogenesis, and is a function of the magnitude and rate of change of the ground reaction force. While it is not known if a minimum stimulus exists for osteogenesis, it has been hypothesized that in order to replicate the bone formation occurring in normal gravity (1 G), the exercise in weightlessness should mimic the forces that occur on earth. Specifically, the pGRF obtained in weightlessness should be comparable to that achieved in 1 G.

Alendronate and Resistive Exercise Countermeasures Against Bed Rest-Induced Bone Loss: Biochemical Markers of Bone and Calcium Metabolism

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Nillen, Jeannie L.; Davis-Street, Janis E.; DeKerlegand, Diane E.; LeBlanc, Adrian; Shackelford, Linda C.

2001-01-01

Weightlessness-induced bone loss must be counteracted to ensure crew health during extendedduration space missions. Studies were conducted to assess two bone loss countermeasures in a ground-based model: horizontal bed rest. Following a 3-wk ambulatory adaptation period, male and female subjects (aged 21-56 y) completed a 17-wk bed rest protocol. Subjects were assigned to one of three treatments: alendronate (ALEN; 10 mg/d, n=6), resistive exercise (RE; 1.5 h/d, 6 d/wk, n=8), or control (CN; no countermeasure, n=8). Dietary intake was adjusted to maintain body weight. Endocrine and biochemical indices were measured in blood and urine using standard laboratory methods. All data reported are expressed as percent change from individual pre-bedrest data. Serum calcium changed little during bed rest, and tended to decrease (4-8%) in ALEN subjects. In RE subjects, bone alkaline phosphatase and osteocalcin were increased >65 and >30%, respectively, during bed rest, while these were unchanged or decreased in ALEN and CN subjects. Urinary calcium was increased 50% in CN subjects, but was unchanged or decreased in both ALEN and RE groups. Urinary n-telopeptide excretion was increased 40-50% in CN and RE subjects, but decreased 20% in ALEN subjects. Pyridinium crosslink and deoxypyridinoline excretion were increased 20-50% during bed rest. These data suggest that RE countermeasures are effective at increasing markers of bone formation in an analog of weightlessness, while ALEN reduces markers of bone resorption. Counteracting the bone loss of space flight may require both pharmacologic and exercise countermeasures.

Comparison between the weightlessness syndrome and aging

NASA Technical Reports Server (NTRS)

Miquel, J.

1982-01-01

The similarity of detrimental effects of normal aging and of exposure to space weightlessness is discussed. The effects include: the reduction in cardiac output, increase in blood pressure, decrease in respiratory vital capacity, decrease in lean body weight and muscle mass, collagen and fat infiltration of muscle, bone demineralization, and a decrease in urinary excretion of total 17-hydroxicorticosteroids. It is also noted that dispite the accelerated aging of organisms, if animals or human subjects were to spend their entire lives in weightlessness, their lifespans might be significantly increased because of a reduction in metabolic rate. Experimental results are cited.

Osteoblast histogenesis in periodontal ligament and tibial metaphysis during simulated weightlessness

NASA Technical Reports Server (NTRS)

Fielder, Paul J.; Morey, Emily R.; Roberts, W. Eugene

1986-01-01

Utilizing the nuclear morphometric assay for osteoblast histogenesis, the effect of simulated weightlessness (SW) on the relative numbers of the periodontal ligament (PDL) osteoblast progenitors and on the total number of osteogenic cells was determined in rats. Weightlessness was simulated by subjecting rats to continuous 30-deg head-down posture using a modified back-harness device of Morey (1979). The response of a partially unloaded, weight-bearing bone, tibial primary spongiosa (PS), was compared to a normally loaded, nonweight-bearing PDL bone. Data indicated a similar differentiation sequence in PS and PDL, which suggests that these bones might be sensitive to the same systemic factors. Preosteoblast numbers were seen to decrease in both nonweight-bearing and weight-bearing bones during SW (compared with rats not exposed to SW), indicating the importance of systemic mediators, such as cephalad fluid shift, physiological stress, and/or growth retardation.

Skeletal Micro-RNA Responses to Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Thomas, Nicholas J.; Choi, Catherine Y.; Alwood, Joshua S.

2016-01-01

Astronauts lose bone structure during long-duration spaceflight. These changes are due, in part, to insufficient bone formation by the osteoblast cells. Little is known about the role that small (approximately 22 nucleotides), non-coding micro-RNAs (miRNAs) play in the osteoblast response to microgravity. We hypothesize that osteoblast-lineage cells alter their miRNA status during microgravity exposure, contributing to impaired bone formation during weightlessness. To simulate weightlessness, female mice (C57BL/6, Charles River, 10 weeks of age, n = 7) were hindlimb unloaded up to 12 days. Age-matched and normally ambulating mice served as controls (n=7). To assess the expression of miRNAs in skeletal tissue, the tibia was collected ex vivo and cleaned of soft-tissue and marrow. Total RNA was collected from tibial bone and relative abundance was measured for miRNAs of interest using quantitative real time PCR array looking at 372 unique and well-characterized mature miRNAs using the delta-delta Ct method. Transcripts of interest were normalized to an average of 6 reference RNAs. Preliminary results show that hindlimb unloading decreased the expression of 14 miRNAs to less than 0.5 times that of the control levels and increased the expression of 5 miRNAs relative to the control mice between 1.2-1.5-fold (p less than 0.05, respectively). Using the miRSystem we assessed overlapping target genes predicted to be regulated by multiple members of the 19 differentially expressed miRNAs as well as in silico predicted targets of our individual miRNAs. Our miRsystem results indicated that a number of our differentially expressed miRNAs were regulators of genes related to the Wnt-Beta Catenin pathway-a known regulator of bone health-and, interestingly, the estrogen-mediated cell-cycle regulation pathway, which may indicate that simulated weightlessness modulated systemic hormonal levels or hormonal transduction that additionally contributed to bone loss. We plan to follow up

A "Bony" Proposition: Pathways Mediating Responses to Simulated Weightlessness and Radiation

NASA Technical Reports Server (NTRS)

Tahimic, Candice; Globus, Ruth

2016-01-01

There is evidence that weightlessness and radiation, two elements of the spaceflight environment, can lead to detrimental changes in human musculoskeletal tissue, including bone loss and muscle atrophy. This bone loss is thought to be brought about by the increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. My current area of research focuses on understanding the mechanistic basis for the responses of bone to the spaceflight environment using earth-based animal and cellular models. The overarching goal is to identify molecular targets to prevent bone loss in space exploration and earth-based scenarios of radiotherapy, accidental radiation exposure and reduced mobility. In this talk, I will highlight two signaling pathways that potentially play a role in the response of bone to spaceflight-like conditions. Firstly, I will discuss the role of insulin-like growth factor 1 (IGF1) signaling as it pertains to the recovery of bone from simulated weightlessness (rodent hindlimb unloading model). Secondly, I will share recent findings from our study that aims to understand the emerging role of autophagy in maintaining the balance between bone formation and resorption (bone homeostasis) as well as normal skeletal structure.

Alterations in gut transport of minerals and in binding proteins during simulated weightlessness

NASA Technical Reports Server (NTRS)

Bikle, D. D.

1984-01-01

The structural components of the skeleton develop and are maintained in a 1 g environment, shaped by the mechanical load to which they are constantly exposed. Altering such a mechanical load by reducing the gravitational force imposed on the system, as in space flight, has profound effects on the skeleton and permits an exploration of the molecular events which regulate normal skeletal homeostasis. The objective was to determine whether simulated weightlessness reduced intestinal calcium transport, and if so, to determine the molecular mechanisms for such an effect. A nonstressful tail suspension in which the rats gained weight normally while suspended was used to simulate weightlessness. A significant change in intestinal calcium transport was not demonstrated. However, a cyclic change in bone formation with suspension was shown. Based on these observations, the objective changed to determination of the hormonal regulation of bone formation during simulated weightlessness.

Calcium and bone metabolism during space flight

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Heer, Martina

2002-01-01

Weightlessness induces bone loss. Understanding the nature of this loss and developing means to counteract it are significant challenges to potential human exploration missions. This article reviews the existing information from studies of bone and calcium metabolism conducted during space flight. It also highlights areas where nutrition may play a specific role in this bone loss, and where countermeasures may be developed to mitigate that loss.

Comparison of bone histomorphometry and μCT for evaluating bone quality in tail-suspended rats

NASA Astrophysics Data System (ADS)

Sun, Lian-Wen; Huang, Yun-Fei; Wang, Ying; Luan, Hui-Qin; Fan, Yu-Bo

2014-10-01

Astronauts often suffer from microgravity-induced osteoporosis due to their time in space. Bone histomorphometry, the 'gold standard' technique for detecting bone quality, is widely used in the evaluation of osteoporosis. This study investigates whether μCT has the same application value as histomorphometry in the evaluation of weightlessness-induced bone loss. A total of 24 SD rats were distributed into three groups (n = 8, each): tail-suspension (TS), TS plus active exercise (TSA), and control (CON). After 21 days, bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) and μCT, and microstructure was measured by μCT and histomorphometry. BMD was found to have decreased significantly in TS and TSA compared with the CON group. The results of the μCT measurements showed that a change in BMD mainly occurred in the trabecular bone, and the trabecular BMD increased significantly in the TSA compared with the TS group. The comparison of μCT and histomorphometry showed that TS led to a significant decrease in bone volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N), and it led to an increase in trabecular separation (Tb.Sp). However, active exercise can prevent these changes. Significant differences in most parameters between TSA and CON were found by μCT but not by histomorphometry. Additionally, the parameters of these two methods are highly correlated. Therefore, the application value of μCT is as good as histomorphometry and DXA in the diagnosis of weightlessness-induced osteoporosis and is even better in evaluating the efficacy of exercise.

[Effect of aerospace weightlessness on cognitive functions and the relative dialectical analysis of Chinese medicine].

PubMed

Dong, Li; Liu, Xin-Min; Wu, Li-Sha; Yang, Si-Jin; Wang, Qiong

2014-03-01

Aerospace medicine has paid more and more attention to abnormal changes of physiological functions induced by weightlessness and studies on their prevention during space flight. In this paper, the effect of space weightlessness on cognitive functions was introduced. We tried to analyze the correlation between the cognitive function changes and relevant Chinese medical syndromes, thus providing a potential available way to prevent and treat weightlessness induced cognitive deficit during space flight.

Changes of brain response induced by simulated weightlessness

NASA Astrophysics Data System (ADS)

Wei, Jinhe; Yan, Gongdong; Guan, Zhiqiang

The characteristics change of brain response was studied during 15° head-down tilt (HDT) comparing with 45° head-up tilt (HUT). The brain responses evaluated included the EEG power spectra change at rest and during mental arithmetic, and the event-related potentials (ERPs) of somatosensory, selective attention and mental arithmetic activities. The prominent feature of brain response change during HDT revealed that the brain function was inhibited to some extent. Such inhibition included that the significant increment of "40Hz" activity during HUT arithmetic almost disappeared during HDT arithmetic, and that the positive-potential effect induced by HDT presented in all kinds of ERPs measured, but the slow negative wave reflecting mental arithmetic and memory process was elongated. These data suggest that the brain function be affected profoundly by the simulated weightlessness, therefore, the brain function change during space flight should be studied systematically.

Does Simulated Spaceflight Modify Epigenetic Status During Bone Remodeling?

NASA Technical Reports Server (NTRS)

Thomas, Nicholas J.; Stevick, Rebecca J.; Tran, Luan H.; Nalavadi, Mohit O.; Almeida, Eduardo A.C.; Globus, Ruth K.; Alwood, Joshua S.

2015-01-01

Little is known about the effects of spaceflight conditions on epigenetics. The term epigenetics describes changes to the genome that can affect expression of a gene without changes to the sequence of DNA. Epigenetic processes are thought to underlie cellular differentiation, where transcription of specific genes occurs in response to key stimuli, and may be heritable - passing from one cell to its daughter cell. We hypothesize that the mechanical environment during spaceflight, namely microgravity-induced weightlessness or exercise regulate gene expression in the osteoblast-lineage cells both to control bone formation by osteoblasts and bone resorption by osteoclasts, which continually shapes bone structure throughout life. Similarly we intend to evaluate how radiation regulates these same bone cell activity and differentiation related genes. We further hypothesize that the regulation in bone cell gene expression is at least partially controlled through epigenetic mechanisms of methylation or small non-coding RNA (microRNAs). We have acquired preliminary data suggesting that global genome methylation is modified in response to axial compression of the tibia - a model of exercise. We intend to pursue these hypotheses wherein we will evaluate changes in gene expression and, congruently, changes in epigenetic state in bones from mice subjected to the aforementioned conditions: hindlimb unloading to simulate weightlessness, axial compression of the tibia, or radiation exposure in order to gain insight into the role of epigenetics in spaceflight-induced bone loss.

From Milk to Bones, Moving Calcium Through the Body: Calcium Kinetics During Space Flight

NASA Technical Reports Server (NTRS)

Smith, Scott; Bloomberg, Jacob; Lee, Angie (Technical Monitor)

2002-01-01

Did you know that when astronauts are in space, their height increases about two inches? This happens because the weightlessness of space allows the spine, usually compressed in Earth's gravity, to expand. While this change is relatively harmless, other more serious things can happen with extended stays in weightlessness, notably bone loss. From previous experiments, scientists have observed that astronauts lose bone mass at a rate of about one percent per month during flight. Scientists know that bone is a dynamic tissue - continually being made and repaired by specialized bone cells throughout life. Certain cells produce new bone, while other cells are responsible for removing and replacing old bone. Research on the mechanisms of bone metabolism and the effects of space flight on its formation and repair are part of the exciting studies that will be performed during STS-107. Calcium plays a central role because 1) it gives strength and structure to bone and 2) all types of cells require it to function normally. Ninety-nine percent of calcium in the body is stored in the skeleton. However, calcium may be released, or resorbed, from bone to provide for other tissues when you are not eating. To better understand how and why weightlessness induces bone loss, astronauts will participate in a study of calcium kinetics - that is, the movement of calcium through the body, including absorption from food, and its role in the formation and breakdown of bone.

Effect of simulated weightlessness on exercise-induced anaerobic threshold

NASA Technical Reports Server (NTRS)

Convertino, V. A.; Karst, G. M.; Kirby, C. R.; Goldwater, D. J.

1986-01-01

The effect of simulated weightlessness, induced by ten days of continuous bedrest (BR) in the -6 deg head-down position, on the exercise-induced anaerobic threshold (AT) was determined by comparing specific ventilatory and gas-exchange measurements during an incremental ergometer test performed before and after BR. The primary index for determining the exercise-induced AT values of each subject was visual identification of the workrate or oxygen uptake (VO2) at which the ratio of the expired minute ventilation volume (VE) to VO2 exhibited a systematic increase without a concomitant increase in the VE/VCO2 value. Following BR, the mean VO2max of the subjects decreased by 7.0 percent, and the AT decreased from a mean of 1.26 L/min VO2 before BR to 0.95 L/min VO2 after BR. The decrease in AT was manifested by a decrease in both absolute and relative workrates. The change in AT correlated significantly with the change in plasma volume but not with the change in VO2max. The results suggest that the reduction in AT cannot be completely explained by the reduction in VO2, and that the AT decrease is associated with the reduction in intravascular fluid volume.

An optimized index of human cardiovascular adaptation to simulated weightlessness

NASA Technical Reports Server (NTRS)

Wang, M.; Hassebrook, L.; Evans, J.; Varghese, T.; Knapp, C.

1996-01-01

Prolonged exposure to weightlessness is known to produce a variety of cardiovascular changes, some of which may influence the astronaut's performance during a mission. In order to find a reliable indicator of cardiovascular adaptation to weightlessness, we analyzed data from nine male subjects after a 24-hour period of normal activity and after a period of simulated weightlessness produced by two hours in a launch position followed by 20 hours of 6 degrees head-down tilt plus pharmacologically induced diuresis (furosemide). Heart rate, arterial pressure, thoracic fluid index, and radial flow were analyzed. Autoregressive spectral estimation and decomposition were used to obtain the spectral components of each variable from the subjects in the supine position during pre- and post-simulated weightlessness. We found a significant decrease in heart rate power and an increase in thoracic fluid index power in the high frequency region (0.2-0.45 Hz) and significant increases in radial flow and arterial pressure powers in the low frequency region (<0.2 Hz) in response to simulated weightlessness. However, due to the variability among subjects, any single variable appeared limited as a dependable index of cardiovascular adaptation to weightlessness. The backward elimination algorithm was then used to select the best discriminatory features from these spectral components. Fisher's linear discriminant and Bayes' quadratic discriminant were used to combine the selected features to obtain an optimal index of adaptation to simulated weightlessness. Results showed that both techniques provided improved discriminant performance over any single variable and thus have the potential for use as an index to track adaptation and prescribe countermeasures to the effects of weightlessness.

Calcium and Bone Metabolism During Spaceflight

NASA Technical Reports Server (NTRS)

Smith, Scott M.

2002-01-01

The ability to understand and counteract weightlessness-induced bone loss will be critical for crew health and safety during and after space station or exploration missions lasting months or years, respectively. Until its deorbit in 2001 , the Mir Space Station provided a valuable platform for long-duration space missions and life sciences research. Long-duration flights are critical for studying bone loss, as the 2- to 3-week Space Shuttle flights are not long enough to detect changes in bone mass. This review will describe human spaceflight data, focusing on biochemical surrogates of bone and calcium metabolism. This subject has been reviewed previously. 1-

Cardiovascular, renal, electrolyte, and hormonal changes in man during gravitational stress, weightlessness, and simulated weightlessness: Lower body positive pressure applied by the antigravity suit. Thesis - Oslo Univ.

NASA Technical Reports Server (NTRS)

Kravik, Stein E.

1989-01-01

Because of their erect posture, humans are more vulnerable to gravitational changes than any other animal. During standing or walking man must constantly use his antigravity muscles and his two columns, his legs, to balance against the force of gravity. At the same time, blood is surging downward to the dependent portions of the body, draining blood away from the brain and heart, and requiring a series of complex cardiovascular adjustments to maintain the human in a bipedal position. It was not until 12 April 1961, when Yuri Gagarin became the first human being to orbit Earth, that we could confirm man's ability to maintain vital functions in space -- at least for 90 min. Nevertheless, man's adaptation to weightlessness entails the deconditioning of various organs in the body. Muscles atrophy, and calcium loss leads to loss of bone strength as the demands on the musculoskeletal system are almost nonexistent in weightlessness. Because of the lack of hydrostatic pressures in space, blood rushes to the upper portions of the body, initiating a complex series of cardioregulatory responses. Deconditioning during spaceflight, however, first becomes a potentially serious problem in humans returning to Earth, when the cardiovascular system, muscles and bones are suddenly exposed to the demanding counterforce of gravity -- weight. One of the main purposes of our studies was to test the feasibility of using Lower Body Positive Pressure, applied with an antigravity suit, as a new and alternative technique to bed rest and water immersion for studying cardioregulatory, renal, electrolyte, and hormonal changes in humans. The results suggest that Lower Body Positive Pressure can be used as an analog of microgravity-induced physiological responses in humans.

[Counteracting effects of intermittent head-up tilt on simulated-weightlessness induced atrophy of anti-gravity muscles].

PubMed

Liu, C; Zhang, L F; Zhang, L N; Ni, H Y; Zhang, Y Q; Sun, L

2000-12-01

Objective. To study the efficacy of intermittent + Gz (45 degrees head-up tilt, HUT) exposures in preventing or alleviating atrophic changes in hind limb muscles induced by simulated weightlessness. Method. Male Sprague-Dawley (SD) rats were assigned randomly to one of three groups: simultaneous control (CON), simulated weightlessness (SUS), and SUS plus 6 h/d HUT (SUS + HUT). Muscles examined included soleus (SOL), medial gastrocnemius (correction from grastrocnemius) (MG), lateral gastrocnemius (LG) and extensor digitorum longus (EDL). Sections were treated with an adenosinetriphosphatase (ATPase) stain or alkaline phosphatase stain. The cross-sectional areas (CSA) of fibers, the relative proportion of type I fiber and the ratio of capillaries/fibers (C/F) were measured using Leica image analysis system. Result. Compared with CON, the wet weight of hind limb muscles in SUS were significantly reduced. The changes of wet weight in different groups were various. The C/F ratios of all muscles were significantly reduced. SUS + HUT rats showed significant increases in SOL and MG wet weight, and the relative counter-effects of intermittent HUT were 93.4% and 34.8%, respectively. In SUS + HUT group, the CSA of both type I and II fibers and relative proportion of type I fibers were completely recovered in SOL, and partially recovered in MG, while the counter-effects were much less obvious in the fibers of LG and EDL. However, HUT resulted in a significant recovery of the C/F ratios in all muscles. Conclusion. The present study demonstrated that intermittent HUT is effective in counteracting the atrophy induced by simulated weightlessness. The result that reactivity to HUT varied among different muscles suggests that the intermittent artificial gravity should be complemented with other countermeasures.

Amino acid supplementation alters bone metabolism during simulated weightlessness

NASA Technical Reports Server (NTRS)

Zwart, S. R.; Davis-Street, J. E.; Paddon-Jones, D.; Ferrando, A. A.; Wolfe, R. R.; Smith, S. M.

2005-01-01

High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

So You Want to Go to Mars: Bones and Matters of the Heart

NASA Technical Reports Server (NTRS)

Tahimic, Candice; Globus, Ruth; Torres, Samantha; Steczina, Sonette

2017-01-01

There is evidence that weightlessness and radiation, two elements of the spaceflight environment, can lead to detrimental changes in human musculoskeletal tissue, including bone loss and muscle atrophy. This bone loss is thought to be brought about by the increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. Collectively, our research team aims to understand the molecular mechanisms underlying the responses of mammalian tissue to the spaceflight environment using earth-based animal and cellular models. The overarching goal is to identify molecular targets to prevent tissue decrements induced by spaceflight and earth-based scenarios of radiotherapy, accidental radiation exposure and reduced mobility. In this talk, I will provide an overview of skeletal and cardiovascular responses to spaceflight and will highlight our research progress on understanding the role of reactive oxygen species (ROS) signaling in skeletal responses to radiation and simulated weightlessness.

Perspective on the impact of weightlessness on calcium and bone metabolism

NASA Technical Reports Server (NTRS)

Holick, M. F.

1998-01-01

As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%-2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity's effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts' bone health.

Perspective on the impact of weightlessness on calcium and bone metabolism.

PubMed

Holick, M F

1998-05-01

As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%-2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity's effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts' bone health.

Preadapting to Weightlessness

NASA Technical Reports Server (NTRS)

Reschke, M. F.; Parker, D. E.; Arrott, A. P.

1986-01-01

Report discusses physiological and physical concepts of proposed training system to precondition astronauts to weightless environment. System prevents motion sickness, often experienced during early part of orbital flight. Also helps prevent seasickness and other forms of terrestrial motion sickness, often experienced during early part of orbital flight. Training affects subject's perception of inner-ear signals, visual signals, and kinesthetic motion perception. Changed perception resembles that of astronauts who spent many days in space and adapted to weightlessness.

Laparoscopic surgery in weightlessness

NASA Technical Reports Server (NTRS)

Campbell, M. R.; Billica, R. D.; Jennings, R.; Johnston, S. 3rd

1996-01-01

BACKGROUND: Performing a surgical procedure in weightlessness has been shown not to be any more difficult than in a 1g environment if the requirements for the restraint of the patient, operator, and surgical hardware are observed. The feasibility of performing a laparoscopic surgical procedure in weightlessness, however, has been questionable. Concerns have included the impaired visualization from the lack of gravitational retraction of the bowel and from floating debris such as blood. METHODS: In this project, laparoscopic surgery was performed on a porcine animal model in the weightlessness of parabolic flight. RESULTS: Visualization was unaffected due to the tethering of the bowel by the elastic mesentery and the strong tendency for debris and blood to adhere to the abdominal wall due to surface tension forces. CONCLUSIONS: There are advantages to performing a laparoscopic instead of an open surgical procedure in a weightless environment. These will become important as the laparoscopic support hardware is miniaturized from its present form, as laparoscopic technology becomes more advanced, and as more surgically capable crew medical officers are present in future long-duration space-exploration missions.

Intracranial pressure increases during weightlessness: A parabolic flights study

NASA Astrophysics Data System (ADS)

Denise, P.; Normand, H.; Buzer, L.; Duretete, A.; Avan, P.

2005-08-01

The fluid shift induced by weightlessness likely induces an elevated intracranial pressure (ICP). This factor may contribute to space adaptation syndrome (SAS). Recently, it has been shown that ICP can be monitored every few seconds non invasively by otoacoustic emissions (OAE). The OAE of 6 subjects were measured along the course of parabolic flights aboard the zero-gravity A300 Airbus. Built-in noise rejection and signal processing techniques enabled valid OAE signals to be collected and analyzed online in 4 of 6 subjects. On average, the phase of 1 kHz- OAE rotated by -41° from 1 to 1.8 g, and by +78.7° at 0 g relative to 1 g. From reference invasive ICP measurements in a control group of neurosurgery patients, it is possible to infer that ICP increased by about 34 mmHg in transient weightlessness.

Musculoskeletal adaptations to weightlessness and development of effective countermeasures

NASA Technical Reports Server (NTRS)

Baldwin, K. M.; White, T. P.; Arnaud, S. B.; Edgerton, V. R.; Kraemer, W. J.; Kram, R.; Raab-Cullen, D.; Snow, C. M.

1996-01-01

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.

Objects Mental Rotation under 7 Days Simulated Weightlessness Condition: An ERP Study

PubMed Central

Wang, Hui; Duan, Jiaobo; Liao, Yang; Wang, Chuang; Li, Hongzheng; Liu, Xufeng

2017-01-01

During the spaceflight under weightlessness condition, human's brain function may be affected by the changes of physiological effects along with the distribution of blood and body fluids to the head. This variation of brain function will influence the performance of astronauts and therefore create possible harm to flight safety. This study employs 20 male subjects in a 7-day−6° head-down tilted (HDT) bed rest model to simulate physiological effects under weightlessness condition, and use behavioral, electrophysiological techniques to compare the changes of mental rotation ability (MR ability) before and after short-term simulated weightlessness state. Behavioral results suggested that significant linear relationship existed between the rotation angle of stimuli and the reaction time, which means mental rotation process do happen during the MR task in simulated weightlessness state. In the first 3 days, the P300 component induced by object mental rotation followed the “down-up-down” pattern. In the following 4 days it changed randomly. On HDT D2, the mean of the amplitude of the P300 was the lowest, while increased gently on HDT D3. There was no obvious changing pattern of the amplitude of P300 observed after 3 days of HDT. Simulated weightlessness doesn't change the basic process of mental rotation. The effect of simulated weightlessness is neural mechanism of self-adaptation. MR ability didn't bounce back to the original level after HDT test. PMID:29270115

Objects Mental Rotation under 7 Days Simulated Weightlessness Condition: An ERP Study.

PubMed

Wang, Hui; Duan, Jiaobo; Liao, Yang; Wang, Chuang; Li, Hongzheng; Liu, Xufeng

2017-01-01

During the spaceflight under weightlessness condition, human's brain function may be affected by the changes of physiological effects along with the distribution of blood and body fluids to the head. This variation of brain function will influence the performance of astronauts and therefore create possible harm to flight safety. This study employs 20 male subjects in a 7-day-6° head-down tilted (HDT) bed rest model to simulate physiological effects under weightlessness condition, and use behavioral, electrophysiological techniques to compare the changes of mental rotation ability (MR ability) before and after short-term simulated weightlessness state. Behavioral results suggested that significant linear relationship existed between the rotation angle of stimuli and the reaction time, which means mental rotation process do happen during the MR task in simulated weightlessness state. In the first 3 days, the P300 component induced by object mental rotation followed the "down-up-down" pattern. In the following 4 days it changed randomly. On HDT D2, the mean of the amplitude of the P300 was the lowest, while increased gently on HDT D3. There was no obvious changing pattern of the amplitude of P300 observed after 3 days of HDT. Simulated weightlessness doesn't change the basic process of mental rotation. The effect of simulated weightlessness is neural mechanism of self-adaptation. MR ability didn't bounce back to the original level after HDT test.

Bed Rest and Immobilization: Risk Factors for Bone Loss

MedlinePlus

... Loss Bed Rest and Immobilization: Risk Factors for Bone Loss Like muscle, bone is living tissue that ... bones adjust to the state of weightlessness. Maintaining Bone Health In general, healthy people who undergo prolonged ...

Bone Analyzer

NASA Technical Reports Server (NTRS)

1985-01-01

The danger of disuse osteoporosis under weightless condition in space led to extensive research into measurements of bone stiffness and mass by the Biomedical Research Division of Ames and Stanford University. Through its Technology Utilization Program, NASA funded an advanced SOBSA, a microprocessor-controlled bone probe system. SOBSA determines bone stiffness by measuring responses to an electromagnetic shaker. With this information, a physician can identify bone disease, measure deterioration and prescribe necessary therapy. The system is now undergoing further testing.

Calcitonin control of calcium metabolism during weightlessness

NASA Technical Reports Server (NTRS)

Soliman, Karam F. A.

1993-01-01

The main objective of this proposal is to elucidate calcitonin role in calcium homeostasis during weightlessness. In this investigation our objectives are to study: the effect of weightlessness on thyroid and serum calcitonin, the effect of weightlessness on the circadian variation of calcitonin in serum and the thyroid gland, the role of light as zeitgeber for calcitonin circadian rhythm, the circadian pattern of thyroid sensitivity to release calcitonin in response to calcium load, and the role of serotonin and norepinephrine in the control of calcitonin release. The main objective of this research/proposal is to establish the role of calcitonin in calcium metabolism during weightlessness condition. Understanding the mechanism of these abnormalities will help in developing therapeutic means to counter calcium imbalance in spaceflights.

The temporal response of bone to unloading

NASA Technical Reports Server (NTRS)

Globus, R. K.; Bikle, D. D.; Morey-Holton, E.

1984-01-01

Rats were suspended by their tails with the forelimbs bearing the weight load to simulate the weightlessness of space flight. Growth in bone mass ceased by 1 week in the hindlimbs and lumbar vertebrae in growing rats, while growth in the forelimbs and cervical vertebrae remained unaffected. The effects of selective skeletal unloading on bone formation during 2 weeks of suspension was investigated using radio iostope incorporation (with Ca-45 and H-3 proline) and histomorphometry (with tetracycline labeling). The results of these studies were confirmed by histomorphometric measurements of bone formation using triple tetracycline labeling. This model of simulated weightlessness results in an initial inhibition of bone formation in the unloaded bones. This temporary cessation of bone formation is followed in the accretion of bone mass, which then resumes at a normal rate by 14 days, despite continued skeletal unloading. This cycle of inhibition and resumption of bone formation has profound implication for understanding bone dynamics durng space flight, immobilization, or bed rest and offers an opportunity to study the hormonal and mechanical factors that regulate bone formation.

Effects of weightlessness on body composition in the rat

NASA Technical Reports Server (NTRS)

Pitts, G. C.; Ushakov, A. S.; Pace, N.; Smith, A. H.; Rahlmann, D. F.; Smirnova, T. A.

1983-01-01

The effects of weightlessness on the body composition of rats were investigated using 5 male rats exposed to 18.5 days of weightlessness on the COSMOS 1129 biosatellite and killed after reentry. The animals were immediately dissected and the three major body divisions (musculoskeletal system, skin, and pooled viscera) were analyzed for fat, water, solids, and six elements. These results were determined as percentages of the fat-free body or its components and then compared with two groups of terrestrial controls, one of which was subjected to a flight simulation in a spacecraft mock-up while the other was under standard vivarium conditions. Compared with the control groups, the flight group was found to exhibit a reduced fraction of total body water, a net shift of body water from skin to viscera, a marked diminution in the fraction of extracellular water in the fat-free body, a marked reduction in the fraction of bone mineral, no change in the quantity of stored fat or adrenal masses, and a net increase in total muscle mass as indicated by total body creatine, protein, and body cell mass.

Bone mineral measurement from Apollo experiment M-078. [derangement of bone mineral metabolism in spacecrews

NASA Technical Reports Server (NTRS)

Vogel, J. M.; Rambaut, P. C.; Smith, M. C., Jr.

1974-01-01

Loss of mineral from bone during periods of immobilization, recumbency, or weightlessness is examined. This report describes the instrumentation, technique, and bone mineral changes observed preflight and postflight for the Apollo 14, 15, and 16 missions. The bone mineral changes documented during the Apollo Program are reviewed, and their relevance to future missions is discussed.

Electrostatic demonstration of free-fall weightlessness

NASA Astrophysics Data System (ADS)

Balukovic, Jasmina; Slisko, Josip; Corona Cruz, Adrian

2015-05-01

The phenomena of free-fall weightlessness have been demonstrated to students for many years in a number of different ways. The essential basis of all these demonstrations is the fact that in free-falling, gravitationally accelerated systems, the weight force and weight-related forces (for example, friction and hydrostatic forces) disappear. In this article, an original electrostatic demonstration of weightlessness is presented. A charged balloon fixed at the opening of a plastic container cannot lift a light styrofoam sphere sitting on the bottom when the container is at rest. However, while the system is in free-fall, the sphere becomes weightless and the charged balloon is able to lift it electrostatically.

The Effects of Simulated Weightlessness on Susceptibility to Viral and Bacterial Infections Using a Murine Model

NASA Technical Reports Server (NTRS)

Gould, C. L.

1985-01-01

Certain immunological responses may be compromised as a result of changes in environmental conditions, such as the physiological adaptation to and from the weightlessness which occurs during space flight and recovery. A murine antiorthostatic model was developed to simulate weightlessness. Using this model, the proposed study will determine if differences in susceptibility to viral and bacterial infections exist among mice suspended in an antiorthostatic orientation to simulate weightlessness, mice suspended in an orthostatic orientation to provide a stressful situation without the condition of weightlessness simulation, and non-suspended control mice. Inbred mouse strains which are resistant to the diabetogenic effects of the D variant of encephalomyocarditis virus (EMC-D) and the lethal effects of Salmonella typhimurium will be evaluated. Glucose tolerance tests will be performed on all EMC-D-infected and non-infected control groups. The incidence of EMC-D-induced diabetes and the percentage survival of S. typhimurium-infected animals will be determined in each group. An additional study will determine the effects of simulated weightlessness on murine responses to exogenous interferon.

Influence of stress, weightlessness, and simulated weightlessness on differentiation of preosteoblasts

NASA Technical Reports Server (NTRS)

Roberts, W. E.

1984-01-01

The effects of 18.5 days of weightlessness aboard a satellite, stress of restricted feeding, stress of noise and vibration to simulate space flight and 21 days of head down suspension via the Morey-Holton model for simulated weightlessness was studied. Nuclear size of fibroblastlike cells in PDL on the anterior surface of maxillary first molars was classified as: (1) A-cells, self perpetuating precursors with a nuclear volume 80 micron B-cells, nonosteogenic fibroblasts with a nuclear volume of 80-119 micron 3, C-cells, preosteoblasts that are in G1 stage of the cell cycle with a nuclear size of 120-170 micro, and D-cells, preosteoblasts that are in G2 stage of the cell cycle with a nuclear size 170 micro.

Analysis of human microcirculation in weightlessness: Study protocol and pre-study experiments.

PubMed

Bimpong-Buta, Nana-Yaw; Jirak, Peter; Wernly, Bernhard; Lichtenauer, Michael; Masyuk, Maryna; Muessig, Johanna Maria; Braun, Kristina; Kaya, Sema; Kelm, Malte; Jung, Christian

2018-04-14

In weightlessness, alterations in organ systems have been reported. The microcirculation consists of a network of blood vessels with diameters of a few μm. It is considered the largest part of the circulatory system of the human body and essential for exchange of gas, nutrients and waste products. An investigation of the microcirculation in weightlessness seems warranted but has not yet been performed. In this paper, we outline a study in which we will investigate the possible interrelations between weightlessness and microcirculation. We will induce weightlessness in the course of parabolic flight maneuvers, which will be conducted during a parabolic flight campaign. In this study protocol also an evaluation of a possible influence of parabolic flight premedication on microcirculation will be described. The microcirculation will be investigated by sublingual intravital measurements applying sidestream darkfield microscopy. Parameters of macrocirculation such as heart rate, blood pressure and blood oxygenation will also be investigated. In our pre-study experiments, neither dimenhydrinate nor scopolamine altered microcirculation. As the application of motion sickness therapy did not alter microcirculation, it will be applied during the parabolic flight maneuvers of the campaign. Our results might deepen the understanding of microcirculation on space missions and on earth.

Effects of Inactivity and Exercise on Bone.

ERIC Educational Resources Information Center

Smith, Everett L.; Gilligan, Catherine

1987-01-01

Research has shown that bone tissue responds to the forces of gravity and muscle contraction. The benefits of weight-bearing exercise in preventing or reversing bone mass loss related to osteoporosis is reviewed. The effects of weightlessness and immobilization, and the possible effects of athletic amenorrhea, on bone mineral density are…

Three-dimensional ballistocardiography in weightlessness

NASA Technical Reports Server (NTRS)

Scano, A.

1981-01-01

An experiment is described the aim of which is to record a three dimensional ballistocardiogram under the condition of weightlessness and to compare it with tracings recorded on the same subject on the ground as a means of clarifying the meaning of ballistocardiogram waves in different physiological and perphaps pathological conditions. Another purpose is to investigate cardiovascular and possibly fluid adaptations to weightlessness from data collected almost simultaneously on the same subjects during the other cardiovascular during the other cardiovascular and metabolic experiments.

Evaluation of the response of rat skeletal muscle to a model of weightlessness

NASA Technical Reports Server (NTRS)

Templeton, G. H.; Padalino, M.; Glasberg, M.; Manton, J.; Silver, P.; Sutko, J.

1982-01-01

Suspension of rats in a head-down tilt position such that their hind limbs are non-load bearing has been proposed as a model for weightlessness. Changes observed in metabolism, bone formation (Morey et al., 1979), and muscle catabolism (Mussachia et al., 1980) support the validity of the model. To further document this model, the effects of suspension on the mechanical, biochemical and histochemical characteristics of two hind limb skeletal muscles, the gastrocnemius and the soleus, are investigated.

Bone and Calcium Metabolism During Space Flight

NASA Technical Reports Server (NTRS)

Smith, Scott M.

2004-01-01

Understanding bone loss during space flight is one of the most critical challenges for maintaining astronaut health on space exploration missions. Flight and ground-based studies have been conducted to better understand the nature and mechanisms of weightlessness-induced bone loss, and to identify a means to counteract the loss. Maintenance of bone health requires a balance between bone formation and bone resorption. Early space research identified bone loss as a critical health issue, but could not provide a distinction between the bone formation and breakdown processes. The recent identification of collagen crosslinks as markers of bone resorption has made possible a clear understanding that a decrease in bone resorption is an important effect of space flight, with bone formation being unchanged or only slightly decreased. Calcium regulatory factors have also been studied, in an attempt to understand their role in bone loss. The lack of ultraviolet light exposure and insufficient dietary sources of vitamin D often lead to reduced vitamin D stores on long-duration flights. Serum parathyroid hormone (PTH) concentrations are decreased during flight compared to before flight, although small subject numbers often make this hard to document statistically. As expected, reduced PTH concentrations are accompanied by reduced 1,25-dihydroxyvitamin D concentrations. Calcium kinetic studies during space flight confirm and extend the information gained from biochemical markers of bone metabolism. Calcium kinetic studies demonstrate that bone resorption is increased, bone formation is unchanged or decreased, and dietary calcium absorption is reduced during space flight. Evaluations have also been conducted of countermeasures, including dietary, exercise, and pharmacological treatments. In recent studies, many potential countermeasures show promise at mitigating bone loss in ground-based analogs of weightlessness (e.g., bed rest), but require further ground and flight testing to

Mass discrimination during weightlessness

NASA Technical Reports Server (NTRS)

Ross, H.

1981-01-01

An experiment concerned with the ability of astronauts to discriminate between the mass of objects when both the objects and the astronauts are in weightless states is described. The main object of the experiment is to compare the threshold for weight-discrimination on Earth with that for mass-discrimination in orbit. Tests will be conducted premission and postmission and early and late during the mission while the crew is experiencing weightlessness. A comparison of early and late tests inflight and postflight will reveal the rate of adaptation to zero-gravity and 1-g. The mass discrimination box holds 24 balls which the astronaut will compare to one another in a random routine.

Regulation of Bone Formation During Disuse by miRNA

NASA Technical Reports Server (NTRS)

Thomas, Nicholas; Choi, Catherine Y.; Alwood, Joshua S.

2016-01-01

Astronauts lose bone structure during long-duration spaceflight. These changes are due, in part, to insufficient bone formation by the osteoblast cells. Little is known about the role that small (approximately 22 nucleotide), non-coding micro-RNAs (miRNAs) play in the osteoblast response to microgravity. We hypothesize that osteoblast-lineage cells alter their miRNA status during microgravity exposure, contributing to impaired bone formation during weightlessness. To simulate weightlessness, female mice (C57BL/6, Charles River, 10 weeks of age, n = 6) were hindlimb unloaded for 12 days. Age-matched and normally ambulating mice served as controls (n=6). To assess the expression of miRNAs in skeletal tissue, the right and left tibia of the mice were collected ex vivo and cleaned of soft-tissue and marrow. Total RNA was collected from tibial bone and relative abundance was measured for miRNAs of interest using quantitative real time PCR array looking at 372 unique and well-characterized mature miRNAs using the delta-delta Ct method. Transcripts of interest were normalized to an average of 6 reference RNAs. Preliminary results show that hindlimb unloading decreased the expression of 14 miRNAs to less than 1.4-2.9X control levels and increased the expression of 5 miRNAs relative to the control mice greater than 1-2-1.5X (p less than 0.05, respectively). Using the miRSystem we assessed overlapping target genes predicted to be regulated by multiple members of the 19 differentially expressed miRNAs as well as in silico predicted targets of our individual miRNAs. Our miRSystem results indicated that a number of our differentially expressed miRNAs were regulators of genes related to the Wnt-Beta Catenin pathway-a known regulator of bone health-and, interestingly, the estrogen-mediated cell-cycle regulation pathway, which may indicate that simulated weightlessness induced systemic hormonal changes that contributed to bone loss. We plan to follow up these findings by measuring

Gravity, calcium, and bone - Update, 1989

NASA Technical Reports Server (NTRS)

Arnaud, Sara B.; Morey-Holton, Emily

1990-01-01

Recent results obtained on skeletal adaptation, calcium metabolism, and bone browth during short-term flights and ground simulated-microgravity experiments are presented. Results demonstrate that two principal components of calcium metabolism respond within days to changes in body position and to weightlessness: the calcium endocrine system and bone characteristics. Furthermore, results of recent studies imply that bone biomechanics are more severely affected by spaceflight exposures than is the bone mass.

The effects of prolonged weightlessness and reduced gravity environments on human survival.

PubMed

Taylor, R L

1993-03-01

The manned exploration of the solar system and the surfaces of some of the smaller planets and larger satellites requires that we are able to keep the adverse human physiological response to long term exposure to near zero and greatly reduced gravity environments within acceptable limits consistent with metabolic function. This paper examines the physiological changes associated with microgravity conditions with particular reference to the weightless demineralizatoin of bone (WDB). It is suggested that many of these changes are the result of physical/mechanical processes and are not primarily a medical problem. There are thus two immediately obvious and workable, if relatively costly, solutions to the problem of weightlessness. The provision of a near 1 g field during prolonged space flights, and/or the development of rapid transit spacecraft capable of significant acceleration and short flight times. Although these developments could remove or greatly ameliorate the effects of weightlessness during long-distance space flights there remains a problem relating to the long term colonization of the surfaces of Mars, the Moon, and other small solar system bodies. It is not yet known whether or not there is a critical threshold value of 'g' below which viable human physiological function cannot be sustained. If such a threshold exists permanent colonization may only be possible if the threshold value of 'g' is less than that at the surface of the planet on which we wish to settle.

Blood circulation under conditions of weightlessness

NASA Technical Reports Server (NTRS)

Kastyan, I. I.; Kopanev, V. I.

1980-01-01

Experimental materials and published data on the problem of blood circulation in man and animals under conditions of short and long term weightlessness are summarized. The data obtained allow the conclusion, that when humans spent 5 days in a weightless state their blood circulation was not essentially distributed. Some features of the functioning of the cardiovascular system are pointed out: delay of adaptation rate, increase in lability, etc. There is a discussion of the physiological mechanisms for the direct and indirect effect of weightlessness. The direct effect comprise the complex of reactions caused by the significant fall in hydrostatic pressure and the indirect embraces all the reactions arising in the organism resulting from disturbance of the systematic character of the analyzers that take part in the analysis of space realtions and the body's orientation in space.

Surgical Instrument Restraint in Weightlessness

NASA Technical Reports Server (NTRS)

Campbell, Mark R.; Dawson, David L.; Melton, Shannon; Hooker, Dona; Cantu, Hilda

2000-01-01

Performing a surgical procedure during spaceflight will become more likely with longer duration missions in the near future. Minimal surgical capability has been present on previous missions as the definitive medical care time was short and the likelihood of surgical events too low to justify surgical hardware availability. Early demonstrations of surgical procedures in the weightlessness of parabolic flight indicated the need for careful logistical planning and restraint of surgical hardware. The consideration of human ergonomics also has more impact in weightlessness than in the conventionall-g environment. Three methods of surgical instrument restraint - a Minor Surgical Kit (MSK), a Surgical Restraint Scrub Suit (SRSS), and a Surgical Tray (ST) were evaluated in parabolic flight surgical procedures. The Minor Surgical Kit was easily stored, easily deployed, and demonstrated the best ability to facilitate a surgical procedure in weightlessness. Important factors in this surgical restraint system include excellent organization of supplies, ability to maintain sterility, accessibility while providing secure restraint, ability to dispose of sharp items and biological trash, and ergonomical efficiency.

The importance of weightlessness and tides in teaching gravitation

NASA Astrophysics Data System (ADS)

Galili, I.; Lehavi, Y.

2003-11-01

We examine the presentation of the weight, weightlessness, and tides in university-level physics textbooks. Introductory textbooks often do not discuss tidal forces even though their understanding would be useful for understanding weightlessness. The explanations of tides often miss the free gravitational motion of both interacting objects, which is essential for the symmetry of tidal deformation. The shortcomings in the explanations of weightlessness and tides as provided by students and teachers are compared to textbook discussions. We suggest that an explicit discussion of the different definitions of weight and a synergetic presentation of weightlessness and tides might lead to a better understanding of gravitation. Our approach is illustrated by examples of tidal effects appropriate for introductory courses.

Evidence that Resorption of Bone by Rat Peritoneal Macrophages Occurs in an Acidic Environment

NASA Technical Reports Server (NTRS)

Blair, H. C.

1985-01-01

Skeletal loss in space, like any form of osteoporosis, reflects a relative imbalance of the activities of cells resorbing (degrading) or forming bone. Consequently, prevention of weightlessness induced bone loss may theoretically be accomplished by (1) stimulating bone formation or (2) inhibiting bone resorption. This approach, however, requires fundamental understanding of the mechanisms by which cells form or degrade bone, information not yet at hand. An issue central to bone resorption is the pH at which resorption takes place. The pH dependent spectral shift of a fluorescent dye (fluorescein isothiocyanate) conjugated to bone matrix was used to determine the pH at the resorptive cell bone matrix interface. Devitalized rat bone was used as the substrate, and rat peritoneal macrophages were used as the bone resorbing cells. The results suggest that bone resorption is the result of generation of an acidic microenvironment at the cell matrix junction.

'Weightless' acrylic painting by Jack Kroehnke

NASA Technical Reports Server (NTRS)

1987-01-01

'Weightless' acrylic painting by Jack Kroehnke depicts STS-26 Discovery, Orbiter Vehicle (OV) 103, Mission Specialist (MS) David C. Hilmers participating in extravehicular activity (EVA) simulation in JSC Weightless Environment Training Facility (WETF) Bldg 29. In the payload bay (PLB) mockup, Hilmers, wearing extravehicular mobility unit (EMU), holds onto the mission-peculiar equipment support structure in foreground while SCUBA-equipped diver monitors activity overhead and camera operator records EVA procedures. Copyrighted art work for use by NASA.

The Effect of Part-simulation of Weightlessness on Human Control of Bilateral Teleoperation: Neuromotor Considerations

NASA Technical Reports Server (NTRS)

Corker, K.; Bejczy, A. K.

1984-01-01

The effect of weightlessness on the human operator's performance in force reflecting position control of remote manipulators was investigated. A gravity compensation system was developed to simulate the effect of weightlessness on the operator's arm. A universal force reflecting hand controller (FRHC) and task simulation software were employed. Two experiments were performed because of anticipated disturbances in neuromotor control specification on the human operator in an orbital control environment to investigate: (1) the effect of controller stiffness on the attainment of a learned terminal position in the three dimensional controller space, and (2) the effect of controller stiffness and damping on force tracking of the contour of a simulated three dimensional cube using the part simulation of weightless conditions. The results support the extension of neuromotor control models, which postulate a stiffness balance encoding of terminal position, to three dimensional motion of a multilink system, confirm the existence of a disturbance in human manual control performance under gravity compensated conditions, and suggest techniques for compensation of weightlessness induced performance decrement through appropriate specification of hand controller response characteristics. These techniques are based on the human control model.

Leg Vascular Responsiveness During Acute Orthostasis Following Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Blamick, Cynthia A.; Goldwater, Danielle J.; Convertino, Victor A.

1988-01-01

Ten men (35-49 years old) underwent lower body negative pressure (LBNP) exposures before and offer 10 d of continuous 6 degrees head-down bedrest in order to predict the effect of weightlessness on the responsiveness of leg vasculature to an orthostatic stress. Heart rate (HR), mean arterial blood pressure (MAP), and Impedance rheographic indices of arterial pulse volume (APV) of the legs were measured during rest and at 1 min at -30 mm Hg LBNP. Bedrest-induced deconditioning was manifested by decreases (p less than 0.06) in plasma volume (17%), peak oxygen uptake (16%), and LBNP tolerance (17%). Resting HR was unchanged after bedrest, but HR was higher (p less than 0.05) at 1 min of -30 mm Hg LBNP after, compared with before bedrest. Responses of MAP to -30 mm Hg LBNP were not altered by bodrest. Resting APV was decreased (p less than 0.05) by simulated weightlessness. However, APV was reduced (p less than 0.05) from rest to 1 min -30 mm Hg LBNP by the same relative magnitude before and after bodrest (-21.4 +/- 3.4% and -20.5 +/- 2.7%, respectively). We conclude that peripheral arterial vasoconstriction, as indicated by reductions in APV during LBNP, was not affected by bedrest. These results suggest that there was no apparent alteration in responsiveness of the leg vasculature following simulated weightlessness. Therefore, it appears unlikely that control mechanisms of peripheral resistance contribute significantly to reduced orthostatic tolerance following space-flight.

The Role of GH/IGF-I Axis in Muscle Homeostasis During Weightlessness

NASA Technical Reports Server (NTRS)

Schwartz, Robert J.

1997-01-01

Exposure to reduced gravity during space travel profoundly alters the loads placed on bone and muscle. Astronauts suffer significant losses of muscle and bone strength during weightlessness. Exercise as a countermeasure is only partially effective in remedying severe muscle atrophy and bone demineralization. Similar wasting of muscles and bones affects people on Earth during prolonged bed rest or immobilization due to injury. In the absence of weight bearing activity, atrophy occurs primarily in the muscles that act in low power, routine movements and in maintaining posture. Hormonal disfunction could contribute in part to the loss of muscle and bone during spaceflight. Reduced levels of human Growth Hormone (hGH) were found in astronauts during space flight, as well as reduced GH secretory activity was observed from the anterior pituitary in 7-day space flight rats. Growth hormone has been shown to be required for maintenance of muscle mass and bone mineralization, in part by mediating the biosynthesis IGF-I, a small polypeptide growth factor. IGF biosynthesis and secretion plays an important role in potentiating muscle cell differentiation and has been shown to drive the expression of myogenin, a myogenic specific basic helix-loop-helix factor. IGF-I has also been shown to have an important role in potentiating muscle regeneration, repair and adult muscle hypertrophy.

Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

NASA Technical Reports Server (NTRS)

Halloran, B.; Weider, T.; Morey-Holton, E.

1999-01-01

The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

Gravity, Calcium, And Bone: Update, 1989

NASA Technical Reports Server (NTRS)

Arnaud, Sara B.; Morey-Holton, Emily

1992-01-01

Report reviews short-term flight and ground-based experiments on effects of 1 g and 0 g on skeletal adaptation, calcium metabolism, and growth processes. Results indicate two principal components of calcium metabolism-calcium endocrine system and bone - respond within days to changes in orientation of body in gravitation and to weightlessness. Effects of spaceflight or bed rest on biomechanics of bones more severe than on total body bone mass.

Laboratory simulation of the action of weightlessness on the human organism

NASA Technical Reports Server (NTRS)

Genin, A. M.

1977-01-01

A brief history of attemps by the U.S. and the U.S.S.R. to simulate weightlessness in the laboratory is presented. Model for laboratory modeling of weightlessness included the bed regimen, the clinostat, and water immersion. An outline of immediate physiological effects of weightlessness and long term effects is offered.

Reactions of animals and people under conditions of brief weightlessness

NASA Technical Reports Server (NTRS)

Kitayev-Smik, L. A.

1975-01-01

It has been shown that under brief weightlessness sensory reactions arise in a number of people, mainly those under these conditions for the first time, in the form of spatial and visual illusions, motor excitation, in which tonic and motor components can be distinguished, and vestibular-vegetative disturbances (nausea, vomiting, etc.). In repeated flights with creation of weightlessness, a decrease in the extent of expression and, then, disappearance of these reactions occurred in a significant majority of those studied. Experiments in weightlessness with the vision cut off and with the absence of vestibular functions in the subjects confirm the hypothesis that spatial conceptions of people in weightlessness depend on predominance of gravireceptor or visual afferent signals under these conditions.

NASA Facts, Weightlessness.

ERIC Educational Resources Information Center

National Aeronautics and Space Administration, Washington, DC.

Weightlessness and how it can be artificially produced is described in this pamphlet written for junior high school students. The pamphlet is one of the NASA Facts Science Series (each of which consists of four pages) and is designed to fit in the standard size three-ring notebook. Review questions, suggested activities, and references are…

Ability of commercial demineralized freeze-dried bone allograft to induce new bone formation.

PubMed

Schwartz, Z; Mellonig, J T; Carnes, D L; de la Fontaine, J; Cochran, D L; Dean, D D; Boyan, B D

1996-09-01

Demineralized freeze-dried bone allograft (DFDBA) has been used extensively in periodontal therapy. The rationale for use of DFDBA includes the fact that proteins capable of inducing new bone; i.e., bone morphogenetic proteins, can be isolated from bone grafts. Commercial bone banks have provided DFDBA to the dental practitioner for many years; however, these organizations have not verified the osteoinductive capacity of their DFDBA preparations. The aim of this study was to determine the ability of commercial DFDBA preparations to induce new bone formation. DFDBA with particle sizes ranging from 200 to 500 microns was received from six bone banks using various bone production methods. Different lots of DFDBA from the same tissue bank were sometimes available. A total of 14 lots were examined. The surface area of bone particles in each sample was measured morphometrically and the pH of a solution containing the particles after suspension in distilled water determined. Samples from each DFDBA lot were implanted intramuscularly (10 mg) or subcutaneously (20 mg) into three different animals and tissue biopsies harvested after 4 weeks. One sample from each tissue bank was implanted and harvested after 8 weeks. At harvest, each area where DFDBA had been implanted was excised and examined by light microscopy. The ability of DFDBA to produce new bone was evaluated and the amount of residual bone particles measured. The results show that bone particles from all tissue banks had a variety of shapes and sizes, both before implantation and after 1 or 2 months of implantation. The pH of particle suspensions also varied between batches, as well as between tissue banks. None of the DFDBA induced new bone formation when implanted subcutaneously. Intramuscular implants from three banks induced new bone formation after 1 and 2 months. DFDBA from two banks caused new bone formation only after 2 months. However, DFDBA from one bank did not induce new bone at all. Particle size before

Gravity, weightlessness and the genetic structures of organisms.

PubMed

Dubinin, N P; Vaulina, E N

1974-01-01

The whole evolution of life on earth has proceeded under the action of earth's gravity which must have influenced the structure and function of organisms. During space flights organisms are exposed to the entirely new condition of weightlessness, and to variations in gravity that produce various changes. Current flight data suggest that organisms most often respond to weightlessness by disturbances in physiological function, which are reversible after the brief exposures that have at present been possible. Only longer space flights will show whether these changes will be compensated, or will lead to alterations in the more important systems of organisms including their hereditary properties. There is evidence that weightlessness has a direct effect on genetic properties. Thus, in microspores of Tradescantia abnormal mitoses (that were not observed in the ground-based control) were recorded to an extent of 3%. The numerous changes in various vital systems suggest that for terrestrial organisms weightlessness is a factor which, if administered for a long time, may bring about serious disturbances in their activities and heredity. The higher the evolutionary position of the organism, the more pronounced the effect is likely to be.

Islet in weightlessness: Biological experiments on board COSMOS 1129 satellite

NASA Technical Reports Server (NTRS)

Zhuk, Y.

1980-01-01

Biological experiments planned as an international venture for COSMOS 1129 satellite include tests of: (1) adaptation of rats to conditions of weightlessness, and readaption to Earth's gravity; (2) possibility of fertilization and embryonic development in weightlessness; (3) heat exchange processes; (4) amount of gravity force preferred by fruit flies for laying eggs (given a choice of three centrifugal zones); (5) growth of higher plants from seeds; (6) effects of weightlessness on cells in culture and (7) radiation danger from heavy nuclei, and electrostatic protection from charged particles.

Changes in muscles accompanying non-weight-bearing and weightlessness

NASA Technical Reports Server (NTRS)

Tischler, M. E.; Henriksen, E. J.; Jaspers, S. R.; Jacob, S.; Kirby, C.

1989-01-01

Results of hindlimb suspension and space flight experiments with rats examine the effects of weightlessness simulation, weightlessness, and delay in postflight recovery of animals. Parameters examined were body mass, protein balance, amino acid metabolism, glucose and glycogen metabolism, and hormone levels. Tables show metabolic responses to unweighting of the soleus muscle.

Physiological problems of weightlessness

NASA Technical Reports Server (NTRS)

Vasilyev, P. V.; Kasyan, I. I.

1975-01-01

A brief review of the compensatory-adjusting body changes observed during and after human exposure to prolonged spaceflight is given. Pathological disturbances caused by increased functional hypokinesia and weightlessness loads affect the cardiovascular system, the nervous and hormonal systems, and the state of the skeletal musculo apparatus.

Altered bone turnover during spaceflight

NASA Technical Reports Server (NTRS)

Turner, R. T.; Morey, E. R.; Liu, C.; Baylink, D. J.

1982-01-01

Modifications in calcium metabolism during spaceflight were studied, using parameters that reflect bone turnover. Bone formation rate, medullary area, bone length, bone density, pore size distribution, and differential bone cell number were evaluated in growing rate both immediately after and 25 days after orbital spaceflights aboard the Soviet biological satellites Cosmos 782 and 936. The primary effect of space flight on bone turnover was a reversible inhibition of bone formation at the periosteal surface. A simultaneous increase in the length of the periosteal arrest line suggests that bone formation ceased along corresponding portions of that surface. Possible reasons include increased secretion of glucocorticoids and mechanical unloading of the skeleton due to near-weightlessness, while starvation and immobilization are excluded as causes.

Influence of Body Weight on Bone Mass, Architecture, and Turnover

PubMed Central

Iwaniec, Urszula T.; Turner, Russell T.

2016-01-01

Weight-dependent loading of the skeleton plays an important role in establishing and maintaining bone mass and strength. This review focuses on mechanical signaling induced by body weight as an essential mechanism for maintaining bone health. In addition, the skeletal effects of deviation from normal weight are discussed. The magnitude of mechanical strain experienced by bone during normal activities is remarkably similar among vertebrates, regardless of size, supporting the existence of a conserved regulatory mechanism, or mechanostat, that senses mechanical strain. The mechanostat functions as an adaptive mechanism to optimize bone mass and architecture based on prevailing mechanical strain. Changes in weight, due to altered mass, weightlessness (spaceflight), and hypergravity (modeled by centrifugation), induce an adaptive skeletal response. However, the precise mechanisms governing the skeletal response are incompletely understood. Furthermore, establishing whether the adaptive response maintains the mechanical competence of the skeleton has proven difficult, necessitating development of surrogate measures of bone quality. The mechanostat is influenced by regulatory inputs to facilitate non-mechanical functions of the skeleton, such as mineral homeostasis, as well as hormones and energy/nutrient availability that support bone metabolism. While the skeleton is very capable of adapting to changes in weight, the mechanostat has limits. At the limits, extreme deviations from normal weight and body composition are associated with impaired optimization of bone strength to prevailing body size. PMID:27352896

Biochemical changes in bone in a model of weightlessness

NASA Technical Reports Server (NTRS)

Mechanic, Gerald L.

1986-01-01

The amounts of nonmineralized and mineralized collagen in bone from control, immobilized, and immobilized reambulated monkeys were examined. In order to understand structure function relationships of bone collagen and the reponse of a variety of conditions on control of the three dimensional structure of the collagen fibril, the stereochemistry of the cross-linking reactions as well as the stereospecific packing of the collagen molecules were studied.

The regulation of fluid and electrolyte metabolism in weightlessness

NASA Technical Reports Server (NTRS)

Leach, C. S.; Johnson, P. C.; Cintron, N. M.

1986-01-01

Endocrine and biochemical changes in astronauts caused by weightlessness are discussed. Translocation of fluid from the extremities to the head and chest at the onset of weightlessness is thought to lead to the establishment of a lower blood volume as an adaptation to microgravity. Results of Skylab experiments indicate that several other regulatory systems have lower homeostatic set points during space flight. Inflight blood samples from three Spacelab flights show increased antidiuretic hormone throughout these short flights and decreased aldosterone and cortisol after 3 days. Results help to explain blood hypoosmolality and hyponatremia but do not explain what happens between the onset of weightlessness and hormone changes. Other factors such as natriuretic peptides and changes in renal function are being studied to elucidate the physiologic adaptation mechanisms.

Respiration, respiratory metabolism and energy consumption under weightless conditions

NASA Technical Reports Server (NTRS)

Kasyan, I. I.; Makarov, G. F.

1975-01-01

Changes in the physiological indices of respiration, respiratory metabolism and energy consumption in spacecrews under weightlessness conditions manifest themselves in increased metabolic rates, higher pulmonary ventilation volume, oxygen consumption and carbon dioxide elimination, energy consumption levels in proportion to reduction in neuroemotional and psychic stress, adaptation to weightlessness and work-rest cycles, and finally in a relative stabilization of metabolic processes due to hemodynamic shifts.

Mechanical Factors and Bone Health: Effects of Weightlessness and Neurologic Injury

PubMed Central

Amin, Shreyasee

2014-01-01

Bone is a dynamic tissue with homeostasis governed by many factors. Among them, mechanical stimuli appear to be particularly critical for bone structure and strength. With removal of mechanical stimuli, a profound bone loss occurs, as best observed in the extreme examples following exposure to space flight or neurologic impairment. This review provides an overview of the changes in bone density and structure that occur during and after space flight as well as following neurologic injury from stroke and spinal cord injury. It also discusses the potential mechanisms through which mechanical stimuli are postulated to act on bone tissue. PMID:20425519

A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss

PubMed Central

Lozano, Alysia; Wright, Courtney; Vardanyan, Anna; King, Tamara; Largent-Milnes, Tally M.; Nelson, Mark; Jimenez-Andrade, Juan Miguel; Mantyh, Patrick W; Vanderah, Todd W.

2010-01-01

Aims Cannabinoid CB2 agonists have been shown to alleviate behavioral signs of inflammatory and neuropathic pain in animal models. AM1241, a CB2 agonist, does not demonstrate central nervous system side-effects seen with CB1 agonists such as hypothermia and catalepsy. Metastatic bone cancer causes severe pain in patients and is treated with analgesics such as opiates. Recent reports suggest that sustained opiates can produce paradoxical hyperalgesic actions and enhance bone destruction in a murine model of bone cancer. In contrast, CB2 selective agonists have been shown to reduce bone loss associated with a model of osteoporosis. Here we tested whether a CB2 agonist administered over a 7 day period inhibits bone cancer-induced pain as well as attenuates cancer-induced bone degradation. Main Methods A murine bone cancer model was used in which osteolytic sarcoma cells were injected into the intramedullary space of the distal end of the femur. Behavioral and radiographic image analysis was performed at days 7, 10 and 14 after injection of tumor cells into the femur. Key Findings Osteolytic sarcoma within the femur produced spontaneous and touch evoked behavioral signs of pain within the tumor-bearing limb. The systemic administration of AM1241 acutely or for 7 days significantly attenuated spontaneous and evoked pain in the inoculated limb. Sustained AM1241 significantly reduced bone loss and decreased the incidence of cancer-induced bone fractures. Significance These findings suggest a novel therapy for cancer-induced bone pain, bone loss and bone fracture while lacking many unwanted side effects seen with current treatments for bone cancer pain. PMID:20176037

Effects of ionizing radiation on bone cell differentiation in an experimental murine bone cell model

NASA Astrophysics Data System (ADS)

Baumstark-Khan, Christa; Lau, Patrick; Hellweg, Christine; Reitz, Guenther

During long-term space travel astronauts are exposed to a complex mixture of different radiation types under conditions of dramatically reduced weight-bearing activity. It has been validated that astronauts loose a considerable amount of bone mass at a rate up to one to two percent each month in space. Therapeutic doses of ionizing radiation cause bone damage and increase fracture risks after treatment for head-and-neck cancer and in pelvic irradiation. For low radiation doses, the possibility of a disturbed healing potential of bone was described. Radiation induced damage has been discussed to inflict mainly on immature and healing bone. Little is known about radiation effects on bone remodelling and even less on the combined action of microgravity and radiation. Bone remodelling is a life-long process performed by balanced action of cells from the osteoblast and osteoclast lineages. While osteoblasts differentiate either into bone-lining cells or into osteocytes and play a crucial role in bone matrix synthesis, osteoclasts are responsible for bone resorption. We hypothesize that the balance between bone matrix assembly by osteocytes and bone degradation by osteoclasts is modulated by microgravity as well as by ionizing radiation. To address this, a cell model consisting of murine cell lines with the potential to differentiate into bone-forming osteoblasts (OCT-1, MC3T3-E1 S24, and MC3T3-E1 S4) was used for studying radiation response after exposure to simulated components of cosmic radiation. Cells were exposed to graded doses of 150 kV X-rays, α particles (0.525 MeV/u, 160 keV/µm; PTB, Braunschweig, Germany) and accelerated heavy ions (75 MeV/u carbon, 29 keV/µm; 95 MeV/u argon, 230 keV/µm; GANIL, Caen, France). Cell survival was measured as colony forming ability; cell cycle progression was analyzed via fluorescence-activated cell scanning (FACS) by measurement of the content of propidium iodide-stained DNA, DNA damage was visualized by γH2AX

Hydrogen and hydrocarbon diffusion flames in a weightless environment

NASA Technical Reports Server (NTRS)

Haggard, J. B., Jr.; Cochran, T. H.

1973-01-01

An experimental investigation was performed on laminar hydrogen-, ethylene-, and propylene-air diffusion burning in a weightless environment. The flames burned on nozzles with radii ranging from 0.051 to 0.186 cm with fuel Reynolds numbers at the nozzle exit from 9 to 410. Steady-state diffusion flames existed in a weightless environment for all the fuels tested. A correlation was obtained for their axial length as a function of Schmidt number, Reynolds numbers, and stoichiometric mole fraction. The maximum flame radii were correlated with the ratio of nozzle radius to average fuel velocity. The flames of ethylene and propylene on nozzles with radii 0.113 or larger appeared to be constantly changing color and/or length throughout the test. No extinguishment was observed for any of the gases tested within the 2.2 seconds of weightlessness.

Artificial Gravity as a Bone Loss Countermeasure in Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Smith, S. M.; Zwart, S. R.; Crawford, G. E.; Gillman, P. L.; LeBlanc, A.; Shackelford, L. C.; Heer, M. A.

2007-01-01

The impact of microgravity on the human body is a significant concern for space travelers. We report here initial results from a pilot study designed to explore the utility of artificial gravity (AG) as a countermeasure to the effects of microgravity, specifically to bone loss. After an initial phase of adaptation and testing, 15 male subjects underwent 21 days of 6 head-down bed rest to simulate the deconditioning associated with space flight. Eight of the subjects underwent 1 h of centrifugation (AG, 1 gz at the heart, 2.5 gz at the feet) each day for 21 days, while 7 of the subjects served as untreated controls (CN). Blood and urine were collected before, during, and after bed rest for bone marker determinations. At this point, preliminary data are available on the first 8 subjects (6 AG, and 2 CN). Comparing the last week of bed rest to before bed rest, urinary excretion of the bone resorption marker n-telopeptide increased 95 plus or minus 59% (mean plus or minus SD) in CN but only 32 plus or minus 26% in the AG group. Similar results were found for another resorption marker, helical peptide (increased 57 plus or minus 0% and 35 plus or minus 13% in CN and AG respectively). Bone-specific alkaline phosphatase, a bone formation marker, did not change during bed rest. At this point, sample analyses are continuing, including calcium tracer kinetic studies. These initial data demonstrate the potential effectiveness of short-radius, intermittent AG as a countermeasure to the bone deconditioning that occurs during bed rest.

A Systems Approach to the Physiology of Weightlessness

NASA Technical Reports Server (NTRS)

White, Ronald J.; Leonard, Joel I.; Rummel, John A.; Leach, Carolyn S.

1991-01-01

A systems approach to the unraveling of the complex response pattern of the human subjected to weightlessness is presented. The major goal of this research is to obtain an understanding of the role that each of the major components of the human system plays following the transition to and from space. The cornerstone of this approach is the utilization of a variety of mathematical models in order to pose and test alternative hypotheses concerned with the adaptation process. An integrated hypothesis for the human physiological response to weightlessness is developed.

Perception of linear acceleration in weightlessness

NASA Technical Reports Server (NTRS)

Arrott, Anthony P.; Young, Laurence R.; Merfeld, Daniel M.

1991-01-01

Tests of the perception and use of linear acceleration sensory information were performed on the science crews of the Spacelab 1 (SL-1) and D-1 missions using linear 'sleds' in-flight (D-1) and pre-post flight. The time delay between the acceleration step stimulus and the subjective response was consistently reduced during weightlessness, but was neither statistically significant nor of functional importance. Increased variability of responses when going from one environment to the other was apparent from measurements on the first day of the mission and in the first days post-flight. Subjective reports of perceived motion during sinusoidal oscillation in weightlessness were qualitatively similar to reports on earth. In a closed-loop motion nulling task, enhanced performance was observed post-flight in all crewmembers tested in the Y or Z axes.

Perception of linear acceleration in weightlessness

NASA Technical Reports Server (NTRS)

Arrott, A. P.; Young, L. R.; Merfeld, D. M.

1990-01-01

Tests of the perception and use of linear acceleration sensory information were performed on the science crews of the Spacelab 1 (SL-1) and D-1 missions using linear "sleds" in-flight (D-1) and pre-post flight. The time delay between the acceleration step stimulus and the subjective response was consistently reduced during weightlessness, but was neither statistically significant nor of functional importance. Increased variability of responses when going from one environment to the other was apparent from measurements on the first day of the mission and in the first days post-flight. Subjective reports of perceived motion during sinusoidal oscillation in weightlessness were qualitatively similar to reports on earth. In a closed-loop motion nulling task, enhanced performance was observed post-flight in all crewmembers tested in the Y or Z axes.

[Morphological changes on cochlear hair cells of rats in simulated weightlessness and inboard noise].

PubMed

2017-06-18

To observe the morphological changes on cochlear hair cells of rats in simulated weightlessness and inboard noise and to investigate the different changes in three turns of hair cells. Thirty-two healthy SD rats, all males, were randomly divided into four groups: control group, weightlessness group, noise group and weightlessness+noise groups (n=8). Then rats were exposed to -30° head down tilt as simulated weightlessness and inboard noise including steady-state noise which was (72±2) dB SPL and impulse noise up to 160 dB SPL in spaceship environment. The control group was kept in normal condition for 8 weeks. Bilateral auditory brainstem response (ABR) thresholds were tested before and after exposure respectively, and immunofluorescence staining and scanning electron microscopy (SEMs) of basilar membrane were applied after exposure. ABR threshold shifts of each group were higher after exposure. There was difference between ABRs of the experiment groups before and after exposure (P<0.05). IF showed that the inner hair cells (IHCs) missing was the main damage in the basal turn of weightlessness group, the hair cells in the middle turn were swell and in the top turn, the hair cells were not clear. In noise group, the main loss happened in the outer hair cells (OHCs) of the outermost layer. In weightlessness+noise group, the nuclear missing in the basal turn was apparent, and mainly happened at the outermost layer. Meanwhile, the missing of hair cells in the middle turn and top turn was seen at the innermost layer. SEM showed that the cilia in the basal turn of weightlessness group were serious lodging, and occasional absence. Furthermore, the basal cilia in noise group became lodged and absent, and the other two turns were seriously missing. And in weightlessness+noise group, the cilia missing in the basal turn was apparently seen. The damage degree of the four groups: weightlessness+noise group>noise group>weightlessness group>control group and the damage degree

Lower body negative pressure treadmill exercise as a countermeasure for bed rest-induced bone loss in female identical twins.

PubMed

Zwart, Sara R; Hargens, Alan R; Lee, Stuart M C; Macias, Brandon R; Watenpaugh, Donald E; Tse, Kevin; Smith, Scott M

2007-02-01

Supine weight-bearing exercise within lower body negative pressure (LBNP) alleviates some of the skeletal deconditioning induced by simulated weightlessness in men. We examined this potential beneficial effect in women. Because dietary acid load affected the degree of bone resorption in men during bed rest, we also investigated this variable in women. Subjects were 7 pairs of female identical twins assigned at random to 2 groups, sedentary bed rest (control) or bed rest with supine treadmill exercise within LBNP. Dietary intake was controlled and monitored. Urinary calcium and markers of bone resorption were measured before bed rest and on bed rest days 5/6, 12/13, 19/20, and 26/27. Bone mineral content was assessed by dual-energy X-ray absorptiometry before and after bed rest. Data were analyzed by repeated-measures two-way analysis of variance. Pearson correlation coefficients were used to define the relationships between diet and markers of bone metabolism and to estimate heritability of markers. During bed rest, all markers of bone resorption and urinary calcium and phosphorus increased (P<0.001); parathyroid hormone (P=0.06), bone-specific alkaline phosphatase (P=0.06), and 1,25-dihydroxyvitamin D (P=0.09) tended to decrease. LBNP exercise tended to mitigate bone density loss. The ratio of dietary animal protein to potassium was positively correlated with urinary calcium excretion for all weeks of bed rest in the control group, but only during weeks 1 and 3 in the exercise group. Pre-bed rest data suggested that many markers of bone metabolism have strong genetic determinants. Treadmill exercise within LBNP had less of a protective effect on bone resorption during bed rest in women than previously published results had shown for its effect in men, but the same trends were observed for both sexes. Dietary acid load of these female subjects was significantly correlated with calcium excretion but not with other bone resorption markers.

Lower body negative pressure treadmill exercise as a countermeasure for bed rest-induced bone loss in female identical twins

PubMed Central

Zwart, Sara R.; Hargens, Alan R.; Lee, Stuart M. C.; Macias, Brandon R.; Watenpaugh, Donald E.; Tse, Kevin; Smith, Scott M.

2007-01-01

Supine weight-bearing exercise within lower body negative pressure (LBNP) alleviates some of the skeletal deconditioning induced by simulated weightlessness in men. We examined the potential beneficial effect in women. Because dietary acid load affected the degree of bone resorption in men during bed rest, we also investigated this variable in women. Subjects were 7 pairs of female identical twins assigned at random to 2 groups, sedentary bed rest (control) or bed rest with supine treadmill exercise within LBNP. Dietary intake was controlled and monitored. Urinary calcium and markers of bone resorption were measured before bed rest (BR) and on BR days 5/6, 12/13, 19/20, and 26/27. Bone mineral content was assessed by dual-energy X-ray absorptiometry before and after bed rest. Data were analyzed by repeated measures two-way analysis of variance. Pearson correlation coefficients were used to define the relationships between diet and markers of bone metabolism, and to estimate heritability of markers. During bed rest, all markers of bone resorption and urinary calcium and phosphorus increased (P < 0.001); parathyroid hormone (P = 0.06), bone-specific alkaline phosphatase (P = 0.06), and 1,25-dihydroxyvitamin D (P = 0.09) tended to decrease. LBNP exercise tended to mitigate bone density loss. The ratio of dietary animal protein to potassium was positively correlated with urinary calcium excretion for all weeks of bed rest in the control group, but only during weeks 1 and 3 for the exercise group. Pre-bed rest data suggested that many markers of bone metabolism have strong genetic determinants. Treadmill exercise within LBNP had less of a protective effect on bone resorption during bed rest in women than previously-published results had shown for its effect in men, but the same trends were observed for both sexes. Dietary acid load of these female subjects was significantly correlated with calcium excretion but not with other bone resorption markers. PMID:17070743

Abnormal bone formation induced by implantation of osteosarcoma-derived bone-inducing substance in the X-linked hypophosphatemic mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshikawa, H.; Masuhara, K.; Takaoka, K.

1985-01-01

The X-linked hypophosphatemic mouse (Hyp) has been proposed as a model for the human familial hypophosphatemia (the most common form of vitamin D-resistant rickets). An osteosarcoma-derived bone-inducing substance was subcutaneously implanted into the Hyp mouse. The implant was consistently replaced by cartilage tissue at 2 weeks after implantation. The cartilage matrix seemed to be normal, according to the histological examination, and 35sulphur (TVS) uptake was also normal. Up to 4 weeks after implantation the cartilage matrix was completely replaced by unmineralized bone matrix and hematopoietic bone marrow. Osteoid tissue arising from the implantation of bone inducing substance in the Hypmore » mouse showed no radiologic or histologic sign of calcification. These findings suggest that the abnormalities of endochondral ossification in the Hyp mouse might be characterized by the failure of mineralization in cartilage and bone matrix. Analysis of the effects of bone-inducing substance on the Hyp mouse may help to give greater insight into the mechanism and treatment of human familial hypophosphatemia.« less

One-month spaceflight compromises the bone microstructure, tissue-level mechanical properties, osteocyte survival and lacunae volume in mature mice skeletons.

PubMed

Gerbaix, Maude; Gnyubkin, Vasily; Farlay, Delphine; Olivier, Cécile; Ammann, Patrick; Courbon, Guillaume; Laroche, Norbert; Genthial, Rachel; Follet, Hélène; Peyrin, Françoise; Shenkman, Boris; Gauquelin-Koch, Guillemette; Vico, Laurence

2017-06-01

The weightless environment during spaceflight induces site-specific bone loss. The 30-day Bion-M1 mission offered a unique opportunity to characterize the skeletal changes after spaceflight and an 8-day recovery period in mature male C57/BL6 mice. In the femur metaphysis, spaceflight decreased the trabecular bone volume (-64% vs. Habitat Control), dramatically increased the bone resorption (+140% vs. Habitat Control) and induced marrow adiposity invasion. At the diaphysis, cortical thinning associated with periosteal resorption was observed. In the Flight animal group, the osteocyte lacunae displayed a reduced volume and a more spherical shape (synchrotron radiation analyses), and empty lacunae were highly increased (+344% vs. Habitat Control). Tissue-level mechanical cortical properties (i.e., hardness and modulus) were locally decreased by spaceflight, whereas the mineral characteristics and collagen maturity were unaffected. In the vertebrae, spaceflight decreased the overall bone volume and altered the modulus in the periphery of the trabecular struts. Despite normalized osteoclastic activity and an increased osteoblast number, bone recovery was not observed 8 days after landing. In conclusion, spaceflight induces osteocyte death, which may trigger bone resorption and result in bone mass and microstructural deterioration. Moreover, osteocyte cell death, lacunae mineralization and fatty marrow, which are hallmarks of ageing, may impede tissue maintenance and repair.

Bone mineral measurement: Skylab experiment M-078.

PubMed

Vogel, J M

1975-01-01

The observation that bone mineral is lost in patients who are either immobilized or remain in bed for extended periods of time formed the basis for the concern that large amounts of bone mineral may be lost during long periods of weightlessness. This concern was magnified when early X-ray densitometry studies suggested that rather large amounts of mineral could be lost during rather short periods of weightlessness (4-14 days). Even though these Gemini results have recently been modified, they still reflect substantial losses in the upper extremity. This led to a series of prolonged bed-rest studies (30-36 weeks) which, in addition to careful calcium balance, also employed a newer, more precise method of estimating bone mineral in the radius, ulna, and os calcis. It employed an essentially monoenergetic photon source (125I) and a scintillation detector operating in a rectilinear scanning mode to measure bone mineral by the absorptiometric technique. Bed-rest studies revealed variable mineral losses but suggested that little if any is lost during 4-6 weeks, with variable amounts being lost in 8 weeks. Losses up to 40% were noted in the os calcis after 9 months, with essentially none in the radius and ulna. When this technique was employed during the Apollo 14, 15, and 16 missions, only one crewman (CMP Apollo 15) showed significant losses in the os calcis and none in the radius or ulna. These results were, therefore, in concert with the bed-rest data but at variance with the earlier Gemini data. The variability observed during bed rest was reconciled when it was observed that the rate of loss could be correlated with the initial 24-hour urinary hydroxyproline excretion and the initial os calcis mineral content. Prediction terms were established. Measurements of the SL-II crew after 28 days of weightlessness revealed no significant bone mineral losses. The Skylab data lie within the predicted limits obtained from the bed-rest data. The relevance of the prediction

Effects of prolonged weightlessness on the humoral immune response of humans

NASA Technical Reports Server (NTRS)

Voss, E. W., Jr.

1981-01-01

An experiment to examine the possible interrelationship of various classes of immunoglobulins by utilizing the effect of weightlessness as a stress factor and subsequently measuring inhibitory, compensatory, or enhancing interrelationships. A second objective of the experiment is to investigate the state of immune competency under conditions of sustained weightlessness.

The effect of simulated weightlessness on hypobaric decompression sickness

NASA Technical Reports Server (NTRS)

Balldin, Ulf I.; Pilmanis, Andrew A.; Webb, James T.

2002-01-01

BACKGROUND: A discrepancy exists between the incidence of ground-based decompression sickness (DCS) during simulated extravehicular activity (EVA) at hypobaric space suit pressure (20-40%) and crewmember reports during actual EVA (zero reports). This could be due to the effect of gravity during ground-based DCS studies. HYPOTHESIS: At EVA suit pressures of 29.6 kPa (4.3 psia), there is no difference in the incidence of hypobaric DCS between a control group and group exposed to simulated weightlessness (supine body position). METHODS: Male subjects were exposed to a hypobaric pressure of 29.6 kPa (4.3 psi) for up to 4 h. The control group (n = 26) pre-oxygenated for 60 min (first 10 min exercising) before hypobaric exposure and walking around in the altitude chamber. The test group (n = 39) remained supine for a 3 h prior to and during the 60-min pre-oxygenation (also including exercise) and at hypobaric pressure. DCS symptoms and venous gas emboli (VGE) at hypobaric pressure were registered. RESULTS: DCS occurred in 42% in the control and in 44% in simulated weightlessness group (n.s.). The mean time for DCS to develop was 112 min (SD +/- 61) and 123 min (+/- 67), respectively. VGE occurred in 81% of the control group subjects and in 51% of the simulated weightlessness subjects (p = 0.02), while severe VGE occurred in 58% and 33%, respectively (p = 0.08). VGE started after 113 min (+/- 43) in the control and after 76 min (+/- 64) in the simulated weightlessness group. CONCLUSIONS: No difference in incidence of DCS was shown between control and simulated weightlessness conditions. VGE occurred more frequently during the control condition with bubble-releasing arm and leg movements.

Effects of simulated weightlessness on regional blood flow specifically during cardiovascular stress

NASA Technical Reports Server (NTRS)

Harrison, D. C.

1986-01-01

Significant changes in the cardiovasular system of humans and animals have been observed following exposure to prolonged periods of weightlessness during space flight. Although adaption to weightlessness is relatively uncomplicated, marked changes in cardiovascular deconditioning become evident upon return to normal gravity, including orthostatic hypotension and tachycardia. Some evidence that myocardial degeneration occurs has been demonstrated in animals who have been immobilized for two months. Also, evidence of possible loss of myocardial mass following manned space flight has been obtained by means of echocardiographic studies. These findings have serious implications in light of the increasing frequency and duration of Space Shuttle missions and the prospect of extended space station missions in the future. A number of both military and civilian investigators, including middle-aged scientists, will probably encounter prolonged periods of weightlessness. It has been imperative, therefore, to determine the effects of prolonged weightlessness on cardiovascular deconditioning and whether such effects are cumulative or reversible. The research project conducted under NASA Cooperative Agreement NCC 2-126 was undertaken to determine the effects of prolonged simulated weightlessness on regional blood flow. Research results are reported in the three appended publications.

Float-zone processing in a weightless environment

NASA Technical Reports Server (NTRS)

Fowle, A. A.; Haggerty, J. S.; Perron, R. R.; Strong, P. F.; Swanson, J. L.

1976-01-01

The results were reported of investigations to: (1) test the validity of analyses which set maximum practical diameters for Si crystals that can be processed by the float zone method in a near weightless environment, (2) determine the convective flow patterns induced in a typical float zone, Si melt under conditions perceived to be advantageous to the crystal growth process using flow visualization techniques applied to a dimensionally scaled model of the Si melt, (3) revise the estimates of the economic impact of space produced Si crystal by the float zone method on the U.S. electronics industry, and (4) devise a rational plan for future work related to crystal growth phenomena wherein low gravity conditions available in a space site can be used to maximum benefit to the U.S. electronics industry.

Prevention of glucocorticoid induced bone changes with beta-ecdysone

PubMed Central

Dai, Weiwei; Jiang, Li; Lay, Yu-An Evan; Chen, Haiyan; Jin, Guoqin; Zhang, Hongliang; Kot, Alex; Ritchie, Robert O.; Lane, Nancy E.; Yao, Wei

2015-01-01

Beta-ecdysone (βEcd) is a phytoecdysteroid found in the dry roots and seeds of the asteraceae and achyranthes plants, and is reported to increase osteogenesis in vitro. Since glucocorticoid (GCs) excess is associated with a decrease in bone formation, the purpose of this study was to determine if treatment with βEcd could prevent GC-induced osteoporosis. Two-month-old male Swiss-Webster mice (n=8-10/group) were randomized to either placebo or slow release prednisolone pellets (3.3mg/kg/d) and treated with vehicle control or βEcd (0.5mg/kg/d) for 21 days. GC treatment inhibited age-dependent trabecular gain and cortical bone expansion and this was accompanied by a 30-50% lower bone formation rate (BFR) at both the endosteal and periosteal surfaces. Mice treated with only βEcd significantly increased bone formation on endosteal and periosteal bone surfaces, and increased cortical bone mass were their controls to compare to GC alone. Concurrent treatment of βEcd and GC completely prevented the GC-induced reduction in BFR, trabecular bone volume and partially prevented cortical bone loss. In vitro studies determined that βEcd prevented the GC increase in autophagy of the bone marrow stromal cells as well as in whole bone. In summary, βEcd prevented GC induced changes in bone formation, bone cell viability and bone mass. Additional studies are warranted of βEcd for the treatment of GC induced bone loss. PMID:25585248

A comparison of autonomic responses in humans induced by two simulation models of weightlessness: lower body positive pressure and 6 degrees head-down tilt.

PubMed

Fu, Q; Sugiyama, Y; Kamiya, A; Mano, T

2000-04-12

Six-degree head-down tilt (HDT) is well accepted as an effective weightlessness model in humans. However, some researchers utilized lower body positive pressure (LBPP) to simulate the cardiovascular and renal effects of a decreased gravitational stress. In order to determine whether LBPP was a suitable model for simulated weightlessness, we compared the differences between these two methods. Ten healthy males, aged 21-41 years, were subjected to graded LBPP at 10, 20 and 30 mmHg, as well as 6 degrees HDT. Muscle sympathetic nerve activity (MSNA) was microneurographically recorded from the tibial nerve along with cardiovascular variables. We found that MSNA decreased by 27% to a similar extent both at low levels of LBPP (10 and 20 mmHg) and HDT. However, at a high level of LBPP (30 mmHg), MSNA tended to increase. Mean arterial pressure was elevated significantly by 11% (10 mmHg) at 30 mmHg LBPP, but remained unchanged at low levels of LBPP and HDT. Heart rate did not change during the entire LBPP and HDT procedures. Total peripheral resistance markedly increased by 36% at 30 mmHg LBPP, but decreased by 9% at HDT. Both stroke volume and cardiac output tended to decrease at 30 mmHg LBPP, but increased at HDT. These results suggest that although both LBPP and HDT induce fluid shifts from the lower body toward the thoracic compartment, autonomic responses are different, especially at LBPP greater than 20 mmHg. We note that high levels of LBPP (>20 mmHg) activate not only cardiopulmonary and arterial baroreflexes, but also intramuscular mechanoreflexes, while 6 degrees HDT only activates cardiopulmonary baroreflexes. We conclude that LBPP is not a suitable model for simulated weightlessness in humans.

Novel Radiomitigator for Radiation-Induced Bone Loss

NASA Technical Reports Server (NTRS)

Schreurs, A-S; Shirazi-fard, Y.; Terada, M.; Alwood, J. S.; Steczina, S.; Medina, C.; Tahimic, C. G. T.; Globus, R. K.

2016-01-01

Radiation-induced bone loss can occur with radiotherapy patients, accidental radiation exposure and during long-term spaceflight. Bone loss due to radiation is due to an early increase in oxidative stress, inflammation and bone resorption, resulting in an imbalance in bone remodeling. Furthermore, exposure to high-Linear Energy Transfer (LET) radiation will impair the bone forming progenitors and reduce bone formation. Radiation can be classified as high-LET or low-LET based on the amount of energy released. Dried Plum (DP) diet prevents bone loss in mice exposed to total body irradiation with both low-LET and high-LET radiation. DP prevents the early radiation-induced bone resorption, but furthermore, we show that DP protects the bone forming osteoblast progenitors from high-LET radiation. These results provide insight that DP re-balances the bone remodeling by preventing resorption and protecting the bone formation capacity. This data is important considering that most of the current osteoporosis treatments only block the bone resorption but do not protect bone formation. In addition, DP seems to act on both the oxidative stress and inflammation pathways. Finally, we have preliminary data showing the potential of DP to be radio-protective at a systemic effect and could possible protect other tissues at risk of total body-irradiation such as skin, brain and heart.

Prevention of glucocorticoid induced bone changes with beta-ecdysone.

PubMed

Dai, Weiwei; Jiang, Li; Lay, Yu-An Evan; Chen, Haiyan; Jin, Guoqin; Zhang, Hongliang; Kot, Alexander; Ritchie, Robert O; Lane, Nancy E; Yao, Wei

2015-05-01

Beta-ecdysone (βEcd) is a phytoecdysteroid found in the dry roots and seeds of the asteraceae and achyranthes plants, and is reported to increase osteogenesis in vitro. Since glucocorticoid (GC) excess is associated with a decrease in bone formation, the purpose of this study was to determine if treatment with βEcd could prevent GC-induced osteoporosis. Two-month-old male Swiss-Webster mice (n=8-10/group) were randomized to either placebo or slow release prednisolone pellets (3.3mg/kg/day) and treated with vehicle control or βEcd (0.5mg/kg/day) for 21days. GC treatment inhibited age-dependent trabecular gain and cortical bone expansion and this was accompanied by a 30-50% lower bone formation rate (BFR) at both the endosteal and periosteal surfaces. Mice treated with only βEcd significantly increased bone formation on the endosteal and periosteal bone surfaces, and increased cortical bone mass were their controls to compare to GC alone. Concurrent treatment of βEcd and GC completely prevented the GC-induced reduction in BFR, trabecular bone volume and partially prevented cortical bone loss. In vitro studies determined that βEcd prevented the GC increase in autophagy of the bone marrow stromal cells as well as in whole bone. In summary, βEcd prevented GC induced changes in bone formation, bone cell viability and bone mass. Additional studies are warranted of βEcd for the treatment of GC induced bone loss. Copyright © 2015 Elsevier Inc. All rights reserved.

Responses of Cardiac Tissue to Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Tahimic, Candice; Steczina, Sonette; Terada, Masahiro; Shirazi-Fard, Yasaman; Schreurs, Ann-Sofie; Goukassian, David; Globus, Ruth

2017-01-01

Our current study aims to determine the molecular mechanisms that underlie these cardiac changes in response to spaceflight. The central hypothesis of our study is that long duration simulated weightlessness and subsequent recovery causes select and persistent changes in gene expression and oxidative defense-related pathways. In this study, we will first conduct general analyses of three-month old male and female animals, focusing on two key long-duration time points, (i.e. after 90 days of simulated weightlessness (HU) and after 90 days recovery from 90 days of HU. Both rat-specific gene arrays and qPCR will be performed focusing on genes already implicated in oxidative stress responses and cardiac disease. Gene expression analyses will be complemented by biochemical tests of frozen tissue lysates for select markers of oxidative damage.

Simulated weightlessness - Effects on bioenergetic balance

NASA Technical Reports Server (NTRS)

Jordan, J. P.; Sykes, H. A.; Crownover, J. C.; Schatte, C. L.; Simmons, J. B., II; Jordan, D. P.

1980-01-01

As a prelude to a flight experiment, an attempt was made to separate energy requirements associated with gravity from all other metabolic needs. The biological effects of weightlessness were simulated by suspending animals in a harness so that antigravity muscles were not supporting the body. Twelve pairs of rats were allowed to adapt to wearing a harness for 5 d. Experimental animals were then suspended in harness for 7 d followed by recovery for 7 d. Control animals were harnessed but never suspended. Oxygen consumption, carbon dioxide production and rate of (C-14)O2 expiration from radio-labeled glucose were monitored on selected days. Food intake and body mass were recorded daily. Metabolic rate decreased in experimental animals during 7 d of suspension and returned to normal during recovery. Although some of the metabolic changes may have related to variation in food intake, simulated weightlessness appears to directly affect bioenergetic balance.

Human Cardiovascular Adaptation to Weightlessness

NASA Technical Reports Server (NTRS)

Norsk, Peter

2011-01-01

Entering weightlessness (0 G) induces immediately a shift of blood and fluid from the lower to the upper parts of the body inducing expansion of the cardiac chambers (Bungo et al. 1986; Charles & Lathers 1991; Videbaek & Norsk 1997). For many years the effects of sudden 0 G on central venous pressure (CVP) was discussed, and it puzzled researchers that CVP compared to the 1-G supine position decreased during the initial hours of spaceflight, when at the same time left atrial diameter increased (Buckey et al. 1996). By measuring esophageal pressure as an estimate of inter-pleural pressure, it was later shown that this pressure decreases more than CVP does during 0 G induced by parabolic flights (Videbaek & Norsk 1997). Thus, transmural CVP is increased, which distends the cardiac chambers. This unique lung-heart interaction whereby 1) inter-pleural pressure decreases and 2) central blood volume is expanded is unique for 0 G. Because transmural CVP is increased, stroke volume increases according to the law of Frank-Starling leading to an increase in cardiac output, which is maintained increased during months of 0 G in space to levels of some 25% above that of the 1-G seated position (Norsk unpublished). Simultaneously, sympathetic nervous activity is at the level of the upright 1-G posture, which is difficult to explain based on the high stroke volume and decreased blood pressure and systemic vascular resistance. This paradox should be explored and the mechanisms revealed, because it might have implications for estimating the cardiovascular risk of travelling in space.

Ability of commercial demineralized freeze-dried bone allograft to induce new bone formation is dependent on donor age but not gender.

PubMed

Schwartz, Z; Somers, A; Mellonig, J T; Carnes, D L; Dean, D D; Cochran, D L; Boyan, B D

1998-04-01

Demineralized freeze-dried bone allografts (DFDBA) have been used extensively in periodontal therapy. DFDBA is used because it contains bone morphogenetic protein (BMP), which induces new bone formation during the healing process. Most commercial bone banks do not verify the presence or activity of BMP in DFDBA nor the ability of DFDBA to induce new bone. Recently, we showed that different bone bank preparations of DFDBA, even from the same bank, varied considerably in their ability to induce new bone, suggesting inherent differences in the quality of the material. Therefore, we examined whether donor age or gender contributed to the variability seen with these preparations. Twenty-seven batches of DFDBA from different donors were donated by one bone bank which had been shown previously to supply DFDBA that was consistently able to induce new bone formation. Each batch was implanted bilaterally in the thigh muscle of nude mice. After 56 days, the implants were excised and examined by light microscopy and histomorphometry. Seventy percent of the preparations tested induced new bone formation. Most of these preparations produced ossicles containing cortical bone surrounding bone marrow-like tissue. The ability to induce bone appears to be age-dependent, with DFDBA from older donors being less likely to have strong bone-inducing activity. By contrast, no difference in ability to induce new bone was noticed between male or female donors. The results of this study confirm that commercial preparations of DFDBA differ in their ability to induce new bone formation. In fact, some of the batches had no activity at all. The ability of DFDBA to induce new bone formation is suggested to be age-dependent, but not gender-dependent by our study. These results indicate that commercial bone banks need to verify the ability of DFDBA to induce new bone formation and should reconsider the advisability of using bone from older donors.

Effect of simulated weightlessness on the expression of Cbfα1 induced by fluid shear stress in MG-63 osteosarcoma cells.

NASA Astrophysics Data System (ADS)

Yang, Z.; Zhang, S.; Wang, B.; Sun, X. Q.

Objective The role of mechanical load in the functional regulation of osteoblasts becomes an emphasis in osseous biomechanical researches recently This study was aim to explore the effect of flow shear stress on the expression of Cbf alpha 1 in human osteosarcoma cells and to survey its functional alteration in simulated weightlessness Method After cultured for 72 h in two different gravitational environments i e 1G terrestrial gravitational condition and simulated weightlessness condition human osteosarcoma cells MG-63 were treated with 0 5 Pa or 1 5 Pa fluid shear stress FSS in a flow chamber for 15 30 60 min respectively The total RNA in cells was isolated Transcription PCR analysis was made to examine the gene expression of Cbf alpha 1 And the total protein of cells was extracted and the expression of Cbf alpha 1 protein was detected by means of Western Blotting Results MG-63 cultured in 1G condition reacted to FSS treatment with an enhanced expression of Cbf alpha 1 Compared with no FSS control group Cbf alpha 1 mRNA and protein expression increased significantly at 30 and 60 min with the treatment of FSS P 0 01 And there was remarkable difference on the Cbf alpha 1 mRNA and protein expression between the treatments of 0 5 Pa and 1 5 Pa FSS at 30 min or 60 min P 0 01 As to the osteoblasts cultured in simulated weightlessness by using clinostat the expression of Cbf alpha 1 was significantly different between 1G and simulated weightlessness conditions at each test time P 0 05 Compared with no FSS

Influences of chemical sympathectomy and simulated weightlessness on male and female rats

NASA Technical Reports Server (NTRS)

Woodman, Christopher R.; Stump, Craig S.; Stump, Jane A.; Sebastian, Lisa A.; Rahman, Z.; Tipton, Charles M.

1991-01-01

Consideration is given to a study aimed at determining whether the sympathetic nervous system is associated with the changes in maximum oxygen consumption (VO2max), run time, and mechanical efficiency observed during simulated weightlessness in male and female rats. Female and male rats were compared for food consumption, body mass, and body composition in conditions of simulated weightlessness to provide an insight into how these parameters may influence aerobic capacity and exercise performance. It is concluded that chemical sympathectomy and/or a weight-bearing stimulus will attenuate the loss in VO2max associated with simulated weightlessness in rats despite similar changes in body mass and composition. It is noted that the mechanisms remain unclear at this time.

Work/control stations in Space Station weightlessness

NASA Technical Reports Server (NTRS)

Willits, Charles

1990-01-01

An ergonomic integration of controls, displays, and associated interfaces with an operator, whose body geometry and dynamics may be altered by the state of weightlessness, is noted to rank in importance with the optimal positioning of controls relative to the layout and architecture of 'body-ported' work/control stations applicable to the NASA Space Station Freedom. A long-term solution to this complex design problem is envisioned to encompass the following features: multiple imaging, virtual optics, screen displays controlled by a keyboard ergonomically designed for weightlessness, cursor control, a CCTV camera, and a hand-controller featuring 'no-grip' vernier/tactile positioning. This controller frees all fingers for multiple-switch actuations, while retaining index/register determination with the hand controller. A single architectural point attachment/restraint may be used which requires no residual muscle tension in either brief or prolonged operation.

Reloading partly recovers bone mineral density and mechanical properties in hind limb unloaded rats

NASA Astrophysics Data System (ADS)

Zhao, Fan; Li, Dijie; Arfat, Yasir; Chen, Zhihao; Liu, Zonglin; Lin, Yu; Ding, Chong; Sun, Yulong; Hu, Lifang; Shang, Peng; Qian, Airong

2014-12-01

Skeletal unloading results in decreased bone formation and bone mass. During long-term space flight, the decreased bone mass is impossible to fully recover. Therefore, it is necessary to develop the effective countermeasures to prevent spaceflight-induced bone loss. Hindlimb Unloading (HLU) simulates effects of weightlessness and is utilized extensively to examine the response of musculoskeletal systems to certain aspects of space flight. The purpose of this study is to investigate the effects of a 4-week HLU in rats and subsequent reloading on the bone mineral density (BMD) and mechanical properties of load-bearing bones. After HLU for 4 weeks, the rats were then subjected to reloading for 1 week, 2 weeks and 3 weeks, and then the BMD of the femur, tibia and lumbar spine in rats were assessed by dual energy X-ray absorptiometry (DXA) every week. The mechanical properties of the femur were determined by three-point bending test. Dry bone and bone ash of femur were obtained through Oven-Drying method and were weighed respectively. Serum alkaline phosphatase (ALP) and serum calcium were examined through ELISA and Atomic Absorption Spectrometry. The results showed that 4 weeks of HLU significantly decreased body weight of rats and reloading for 1 week, 2 weeks or 3 weeks did not recover the weight loss induced by HLU. However, after 2 weeks of reloading, BMD of femur and tibia of HLU rats partly recovered (+10.4%, +2.3%). After 3 weeks of reloading, the reduction of BMD, energy absorption, bone mass and mechanical properties of bone induced by HLU recovered to some extent. The changes in serum ALP and serum calcium induced by HLU were also recovered after reloading. Our results indicate that a short period of reloading could not completely recover bone after a period of unloading, thus some interventions such as mechanical vibration or pharmaceuticals are necessary to help bone recovery.

Effect of 5E Teaching Model on Student Teachers' Understanding of Weightlessness

ERIC Educational Resources Information Center

Tural, Guner; Akdeniz, Ali Riza; Alev, Nedim

2010-01-01

Weight is one of the basic concepts of physics. Its gravitational definition accommodates difficulties for students to understand the state of weightlessness. The aim of this study is to investigate the effect of materials based on 5E teaching model and related to weightlessness on science student teachers' learning. The sample of the study was 9…

Ultrasonically-induced electrical potentials in demineralized bovine cortical bone

NASA Astrophysics Data System (ADS)

Mori, Shunki; Makino, Taiki; Koyama, Daisuke; Takayanagi, Shinji; Yanagitani, Takahiko; Matsukawa, Mami

2018-04-01

While the low-intensity pulsed ultrasound technique has proved useful for healing of bone fractures, the ultrasound healing mechanism is not yet understood. To understand the initial physical effects of the ultrasound irradiation process on bone, we have studied the anisotropic piezoelectric properties of bone in the MHz range. Bone is known to be composed of collagen and hydroxyapatite (HAp) and shows strong elastic anisotropy. In this study, the effects of HAp on the piezoelectricity were investigated experimentally. To remove the HAp crystallites from the bovine cortical bone, demineralization was performed using ethylene diamine tetra-acetic acid (EDTA) solutions. To investigate the piezoelectricity, we have fabricated ultrasound transducers using the cortical bone or demineralized cortical bone. The induced electrical potentials due to the piezoelectricity were observed as the output of these transducers under pulsed ultrasound irradiation in the MHz range. The cortical bone transducer (before mineralization) showed anisotropic piezoelectric behavior. When the ultrasound irradiation was applied normal to the transducer surface, the observed induced electrical potentials had minimum values. The potential increased under off-axis ultrasound irradiation with changes in polarization. In the demineralized bone transducer case, however, the anisotropic behavior was not observed in the induced electrical potentials. These results therefore indicate that the HAp crystallites affect the piezoelectric characteristics of bone.

Modulation of bone remodeling via mechanically activated ion channels

NASA Technical Reports Server (NTRS)

Duncan, Randall L. (Principal Investigator)

1996-01-01

A critical factor in the maintenance of bone mass is the physical forces imposed upon the skeleton. Removal of these forces, such as in a weightless environment, results in a rapid loss of bone, whereas application of exogenous mechanical strain has been shown to increase bone formation. Numerous flight and ground-based experiments indicate that the osteoblast is the key bone cell influenced by mechanical stimulation. Aside from early transient fluctuations in response to unloading, osteoclast number and activity seem unaffected by removal of strain. However, bone formation is drastically reduced in weightlessness and osteoblasts respond to mechanical strain with an increase in the activity of a number of second messenger pathways resulting in increased anabolic activity. Unfortunately, the mechanism by which the osteoblast converts physical stimuli into a biochemical message, a process we have termed biochemical coupling, remains elusive. Prior to the application of this grant, we had characterized a mechanosensitive, cation nonselective channel (SA-cat) in osteoblast-like osteosarcoma cells that we proposed is the initial signalling mechanism for mechanotransduction. During the execution of this grant, we have made considerable progress to further characterize this channel as well as to determine its role in the osteoblastic response to mechanical strain. To achieve these goals, we combined electrophysiologic techniques with cellular and molecular biology methods to examine the role of these channels in the normal function of the osteoblast in vitro.

Bone-Inspired Spatially Specific Piezoelectricity Induces Bone Regeneration

PubMed Central

Yu, Peng; Ning, Chengyun; Zhang, Yu; Tan, Guoxin; Lin, Zefeng; Liu, Shaoxiang; Wang, Xiaolan; Yang, Haoqi; Li, Kang; Yi, Xin; Zhu, Ye; Mao, Chuanbin

2017-01-01

The extracellular matrix of bone can be pictured as a material made of parallel interspersed domains of fibrous piezoelectric collagenous materials and non-piezoelectric non-collagenous materials. To mimic this feature for enhanced bone regeneration, a material made of two parallel interspersed domains, with higher and lower piezoelectricity, respectively, is constructed to form microscale piezoelectric zones (MPZs). The MPZs are produced using a versatile and effective laser-irradiation technique in which K0.5Na0.5NbO3 (KNN) ceramics are selectively irradiated to achieve microzone phase transitions. The phase structure of the laser-irradiated microzones is changed from a mixture of orthorhombic and tetragonal phases (with higher piezoelectricity) to a tetragonal dominant phase (with lower piezoelectricity). The microzoned piezoelectricity distribution results in spatially specific surface charge distribution, enabling the MPZs to bear bone-like microscale electric cues. Hence, the MPZs induce osteogenic differentiation of stem cells in vitro and bone regeneration in vivo even without being seeded with stem cells. The concept of mimicking the spatially specific piezoelectricity in bone will facilitate future research on the rational design of tissue regenerative materials. PMID:28900517

Effects of microgravity on bone and calcium homeostasis

NASA Astrophysics Data System (ADS)

Zérath, E.

Mechanical function is known to be of crucial importance for the maintenance of bone tissue. Gravity on one hand and muscular effort on the other hand are required for normal skeletal structure. It has been shown by numerous experimental studies that loss of total-body calcium, and marked skeletal changes occur in people who have flown in space. However, most of the pertinent investigations have been conducted on animal models, including rats and non-human primates, and a reasonably clear picture of bone response to spaceflight has emerged during the past few years. Osteopenia induced by microgravity was found to be associated with reduction in both cortical and trabecular bone formation, alteration in mineralization patterns, and disorganization of collagen, and non-collagenous protein metabolism. Recently, cell-culture techniques have offered a direct approach of altered gravity effects at the osteoblastic-cell level. But the fundamental mechanisms by which bone and calcium are lost during spaceflight are not yet fully known. Infrequenccy and high financial cost of flights have created the necessity to develop on-Earth models designed to mimic weightlessness effects. Antiorthostatic suspension devices are now commonly used to obtain hindlimb unloading in rats, with skeletal effects similar to those observed after spaceflight. Therefore, actual and ``simulated'' spaceflights, with investigations conducted at whole body and cellular levels, are needed to elucidate pathogeny of bone loss in space, to develop effective countermeasures, and to study recovery processes of bone changes after return to Earth.

Epigallocatechin gallate (EGCG) suppresses lipopolysaccharide-induced inflammatory bone resorption, and protects against alveolar bone loss in mice.

PubMed

Tominari, Tsukasa; Matsumoto, Chiho; Watanabe, Kenta; Hirata, Michiko; Grundler, Florian M W; Miyaura, Chisato; Inada, Masaki

2015-01-01

Epigallocatechin gallate (EGCG), a major polyphenol in green tea, possesses antioxidant properties and regulates various cell functions. Here, we examined the function of EGCG in inflammatory bone resorption. In calvarial organ cultures, lipopolysaccharide (LPS)-induced bone resorption was clearly suppressed by EGCG. In osteoblasts, EGCG suppressed the LPS-induced expression of COX-2 and mPGES-1 mRNAs, as well as prostaglandin E2 production, and also suppressed RANKL expression, which is essential for osteoclast differentiation. LPS-induced bone resorption of mandibular alveolar bones was attenuated by EGCG in vitro, and the loss of mouse alveolar bone mass was inhibited by the catechin in vivo.

Calcium and Bone Homeostasis During 4-6 Months Space Flight

NASA Technical Reports Server (NTRS)

Smith, Scott M.; OBrien, K.; Wastney, M.; Morukov, B.; Larina, I.; Abrams, S.; Lane, H.; Nillen, J.; Davis-Street, J.; Paloski, W. H. (Technical Monitor)

2000-01-01

Bone and calcium homeostasis are altered by weightlessness. We previously reported calcium studies on three subjects from the first joint US/Russian mission to Mir. We report here data on an additional three male subjects, whose stays on Mir were 4 (n= 1) and 6 (n=2) mos. Data were collected before, during, and after the missions. Inflight studies were conducted at 2-3 mos. Endocrine and biochemical indices were measured, along with 3-wk calcium tracer studies. Percent differences are reported compared to preflight. Ionized calcium was unchanged (2.8 +/-2.1 %) during flight. Calcium absorption was variable inflight, but was decreased after landing. Vitamin D stores were decreased 35 +/-24% inflight, similar to previous reports. Serum PTH was decreased 59 +/-9% during flight (greater than we previously reported), while 1,25(OH)(sub 2)-Vitamin D was decreased in 2 of 3 subjects. Markers of bone resorption (e.g., crosslinks) were increased in all subjects. Bone-specific alkaline phosphatase was decreased (n=1) or unchanged (n=2), while osteocalcin was decreased 34 +/-23%. Previously presented data showed that inflight bone loss is associated with increased resorption and unchanged/decreased formation. The data reported here support these earlier findings. These studies will help to extend our understanding of space flight-induced bone loss, and of bone loss associated with diseases such as osteoporosis or paralysis.

Bion 11 Spaceflight Project: Effect of Weightlessness on Single Muscle Fiber Function in Rhesus Monkeys

NASA Technical Reports Server (NTRS)

Fitts, Robert H.; Romatowski, Janell G.; Widrick, Jeffrey J.; DeLaCruz, Lourdes

1999-01-01

Although it is well known that microgravity induces considerable limb muscle atrophy, little is known about how weightlessness alters cell function. In this study, we investigated how weightlessness altered the functional properties of single fast and slow striated muscle fibers. Physiological studies were carried out to test the hypothesis that microgravity causes fiber atrophy, a decreased peak force (Newtons), tension (Newtons/cross-sectional area) and power, an elevated peak rate of tension development (dp/dt), and an increased maximal shortening velocity (V(sub o)) in the slow type I fiber, while changes in the fast-twitch fiber are restricted to atrophy and a reduced peak force. For each fiber, we determined the peak force (P(sub o)), V(sub o), dp/dt, the force-velocity relationship, peak power, the power-force relationship, the force-pCa relationship, and fiber stiffness. Biochemical studies were carried out to assess the effects of weightlessness on the enzyme and substrate profile of the fast- and slow-twitch fibers. We predicted that microgravity would increase resting muscle glycogen and glycolytic metabolism in the slow fiber type, while the fast-twitch fiber enzyme profile would be unaltered. The increased muscle glycogen would in part result from an elevated hexokinase and glycogen synthase. The enzymes selected for study represent markers for mitochondrial function (citrate synthase and 0-hydroxyacyl-CoA dehydrogenase), glycolysis (Phosphofructokinase and lactate dehydrogenase), and fatty acid transport (Carnitine acetyl transferase). The substrates analyzed will include glycogen, lactate, adenosine triphosphate, and phosphocreatine.

Unloading-induced bone loss was suppressed in gold-thioglucose treated mice.

PubMed

Hino, K; Nifuji, A; Morinobu, M; Tsuji, K; Ezura, Y; Nakashima, K; Yamamoto, H; Noda, M

2006-10-15

Loss of mechanical stress causes bone loss. However, the mechanisms underlying the unloading-induced bone loss are largely unknown. Here, we examined the effects of gold-thioglucose (GTG) treatment, which destroys ventromedial hypothalamus (VMH), on unloading-induced bone loss. Unloading reduced bone volume in control (saline-treated) mice. Treatment with GTG-reduced bone mass and in these GTG-treated mice, unloading-induced reduction in bone mass levels was not observed. Unloading reduced the levels of bone formation rate (BFR) and mineral apposition rate (MAR). GTG treatment also reduced these parameters and under this condition, unloading did not further reduce the levels of BFR and MAR. Unloading increased the levels of osteoclast number (Oc.N/BS) and osteoclast surface (Oc.S/BS). GTG treatment did not alter the basal levels of these bone resorption parameters. In contrast to control, GTG treatment suppressed unloading-induced increase in the levels of Oc.N/BS and Oc.S/BS. Unloading reduced the levels of mRNA expression of the genes encoding osteocalcin, type I collagen and Cbfa1 in bone. In contrast, GTG treatment suppressed such unloading-induced reduction of mRNA expression. Unloading also enhanced the levels of fat mass in bone marrow and mRNA expression of the genes encoding PPARgamma2, C/EBPalpha, and C/EBPbeta in bone. In GTG-treated mice, unloading did not increase fat mass and the levels of fat-related mRNA expression. These results indicated that GTG treatment suppressed unloading-induced alteration in bone loss. 2006 Wiley-Liss, Inc.

Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption

PubMed Central

van't Hof, R. J.; Armour, K. J.; Smith, L. M.; Armour, K. E.; Wei, X. Q.; Liew, F. Y.; Ralston, S. H.

2000-01-01

Nitric oxide has been suggested to be involved in the regulation of bone turnover, especially in pathological conditions characterized by release of bone-resorbing cytokines. The cytokine IL-1 is thought to act as a mediator of periarticular bone loss and tissue damage in inflammatory diseases such as rheumatoid arthritis. IL-1 is a potent stimulator of both osteoclastic bone resorption and expression of inducible nitric oxide synthase (iNOS) in bone cells and other cell types. In this study, we investigated the role that the iNOS pathway plays in mediating the bone-resorbing effects of IL-1 by studying mice with targeted disruption of the iNOS gene. Studies in vitro and in vivo showed that iNOS-deficient mice exhibited profound defects of IL-1-induced osteoclastic bone resorption but responded normally to calciotropic hormones such as 1,25 dihydroxyvitamin D3 and parathyroid hormone. Immunohistochemical studies and electrophoretic mobility shift assays performed on bone marrow cocultures from iNOS-deficient mice showed abnormalities in IL-1-induced nuclear translocation of the p65 component of NFκB and in NFκB-DNA binding, which were reversed by treatment with the NO donor S-nitroso-acetyl penicillamine. These results show that the iNOS pathway is essential for IL-1-induced bone resorption and suggest that the effects of NO may be mediated by modulating IL-1-induced nuclear activation of NFκB in osteoclast precursors. PMID:10869429

Mathematical modeling of fluid-electrolyte alterations during weightlessness

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1984-01-01

Fluid electrolyte metabolism and renal endocrine control as it pertains to adaptation to weightlessness were studied. The mathematical models that have been particularly useful are discussed. However, the focus of the report is on the physiological meaning of the computer studies. A discussion of the major ground based analogs of weightlessness are included; for example, head down tilt, water immersion, and bed rest, and a comparison of findings. Several important zero g phenomena are described, including acute fluid volume regulation, blood volume regulation, circulatory changes, longer term fluid electrolyte adaptations, hormonal regulation, and body composition changes. Hypotheses are offered to explain the major findings in each area and these are integrated into a larger hypothesis of space flight adaptation. A conceptual foundation for fluid electrolyte metabolism, blood volume regulation, and cardiovascular regulation is reported.

Effect of simulated weightlessness on the immune system in rats

NASA Technical Reports Server (NTRS)

Caren, L. D.; Mandel, A. D.; Nunes, J. A.

1980-01-01

Rats suspended in a model system designed to simulate many aspects of weightlessness were immunized with sheep red blood cells. Parameters measured on these and control rats included titers of anti-sheep red blood cell antibodies, serum immunoglobulin levels, spleen and thymus weights, hematocrits, and leukocyte differential counts on peripheral blood. No significant differences were found between test and weight-bearing, harnessed controls; however, the thymuses of animals in both these groups were significantly smaller than untreated cage controls. The lack of an effect of simulated weightlessness on the immune system is an interesting result, and its significance is discussed.

Second All-Union Seminar on Hydromechanics and Heat and Mass Exchange in Weightlessness, summaries of reports

NASA Astrophysics Data System (ADS)

Gershuni, G. Z.; Zhukhovitskiy, Y. M.

1984-07-01

s of reports are given which were presented at the Second All Union Seminar on Hydromechanics and Heat-Mass Transfer in Weightlessness. Topics include: (1) features of crystallization of semiconductor materials under conditions of microacceleration; (2) experimental results of crystallization of solid solutions of CDTE-HGTE under conditions of weightlessness; (3) impurities in crystals cultivated under conditions of weightlessness; and (4) a numerical investigation of the distribution of impurities during guided crystallization of a melt.

Second All-Union Seminar on Hydromechanics and Heat and Mass Exchange in Weightlessness, summaries of reports

NASA Technical Reports Server (NTRS)

Gershuni, G. Z. (Editor); Zhukhovitskiy, Y. M. (Editor)

1984-01-01

Abstracts of reports are given which were presented at the Second All Union Seminar on Hydromechanics and Heat-Mass Transfer in Weightlessness. Topics include: (1) features of crystallization of semiconductor materials under conditions of microacceleration; (2) experimental results of crystallization of solid solutions of CDTE-HGTE under conditions of weightlessness; (3) impurities in crystals cultivated under conditions of weightlessness; and (4) a numerical investigation of the distribution of impurities during guided crystallization of a melt.

Biomedical research on the International Space Station postural and manipulation problems of the human upper limb in weightlessness

NASA Astrophysics Data System (ADS)

Neri, Gianluca; Zolesi, Valfredo

2000-01-01

Accumulated evidence, based on information gathered on space flight missions and ground based models involving both humans and animals, clearly suggests that exposure to states of microgravity conditions for varying duration induces certain physiological changes; they involve cardiovascular deconditioning, balance disorders, bone weakening, muscle hypertrophy, disturbed sleep patterns and depressed immune responses. The effects of the microgravity on the astronauts' movement and attitude have been studied during different space missions, increasing the knowledge of the human physiology in weightlessness. The purpose of the research addressed in the present paper is to understand and to assess the performances of the upper limb, especially during grasp. Objects of the research are the physiological changes related to the long-term duration spaceflight environment. Specifically, the changes concerning the upper limb are investigated, with particular regard to the performances of the hand in zero-g environments. This research presents also effects on the Earth, improving the studies on a number of pathological states, on the health care and the rehabilitation. In this perspective, a set of experiments are proposed, aimed at the evaluation of the effects of the zero-g environments on neurophysiology of grasping movements, fatigue assessment, precision grip. .

Yeast-incorporated gallium attenuates glucocorticoid-induced bone loss in rats by inhibition of bone resorption.

PubMed

Ren, Zhaozhou; Yang, Liqing; Xue, Feng; Meng, Qingjie; Wang, Kejia; Wu, Xian; Ji, Chao; Jiang, Teng; Liu, Da; Zhou, Long; Zhang, Jing; Fu, Qin

2013-06-01

Glucocorticoids (GC) are potent anti-inflammatory agents and widely used for the treatment of many immune-mediated and inflammatory diseases, whereas GC-induced osteoporosis (GIOP) is the most common cause of secondary osteoporosis and significantly increases the patients' morbidity and mortality. GIOP is characterized as diminished osteogenesis and accelerated bone resorption. Yeast-incorporated gallium (YG) as an organic compound not only reduces elements-associated toxicity, but also maintains its therapeutic effect on improving bone loss or promoting fracture healing in ovariectomized female rats. The aim of this study was to examine whether YG could prevent GC-induced bone loss. Five-month-old male Sprague-Dawley rats were randomly divided into three groups (n = 6): two groups were administered dexamethasone (0.1 mg/kg/day) or vehicle (PBS) subcutaneously for 5 weeks; one other group was received dexamethasone subcutaneously and YG (120 μg/kg/day) orally. Trabecular bone microarchitectural parameters, bone mineral density (BMD), bone strength, body weight, and serum biochemical markers of bone resorption and formation were examined. Compared to the GC alone group, treatment with YG not only prevented microarchitectural deterioration of trabecular bone volume relative to tissue volume, trabecular number, and trabecular separation, but also significantly improved BMD, mechanical strength, and body weight in GC-treated rats. Moreover, YG decreased tartrate-resistant acid phosphatase 5b level but failed to change alkaline phosphatase level in GC-treated rats. This is the first study to show that YG prominently attenuates bone loss and microarchitectural deterioration and inhibits the increased bone resorption in GIOP. It implies that YG might be an alternative therapy for prevention of GC-induced bone loss in humans.

Correlation of macro and micro cardiovascular function during weightlessness and simulated weightlessness

NASA Technical Reports Server (NTRS)

Hutchins, P. M.; Marshburn, T. H.; Smith, T. L.; Osborne, S. W.; Lynch, C. D.; Moultsby, S. J.

1988-01-01

The investigation of cardiovascular function necessarily involves a consideration of the exchange of substances at the capillary. If cardiovascular function is compromised or in any way altered during exposure to zero gravity in space, then it stands to reason that microvascular function is also modified. We have shown that an increase in cardiac output similar to that reported during simulated weightlessness is associated with a doubling of the number of post-capillary venules and a reduction in the number of arterioles by 35%. If the weightlessness of space travel produces similar changes in cardiopulmonary volume and cardiac output, a reasonable expectation is that astronauts will undergo venous neovascularization. We have developed an animal model in which to correlate microvascular and systemic cardiovascular function. The microcirculatory preparation consists of a lightweight, thermo-neutral chamber implanted around intact skeletal muscle on the back of a rat. Using this technique, the performed microvasculature of the cutaneous maximus muscle may be observed in the conscious, unanesthetized animal. Microcirculatory variables which may be obtained include venular and arteriolar numbers, lengths and diameters, single vessel flow velocities, vasomotion, capillary hematocrit anastomoses and orders of branching. Systemic hemodynamic monitoring of cardiac output by electromagnetic flowmetry, and arterial and venous pressures allows correlation of macro- and microcirculatory changes at the same time, in the same animal. Observed and calculated hemodynamic variables also include pulse pressure, heart rate, stroke volume, total peripheral resistance, aortic compliance, minute work, peak aortic flow velocity and systolic time interval. In this manner, an integrated assessment of total cardiovascular function may be obtained in the same animal without the complicating influence of anesthetics.

Electromyographic analysis of skeletal muscle changes arising from 9 days of weightlessness in the Apollo-Soyuz space mission

NASA Technical Reports Server (NTRS)

Lafevers, E. V.; Nicogossian, A. E.; Hursta, W. N.

1976-01-01

Both integration and frequency analyses of the electromyograms from voluntary contractions were performed in one crewman of the Apollo-Soyuz Test Project mission. Of particular interest were changes in excitability, electrical efficiency, and fatigability. As a result of 9 days of weightlessness, muscle excitability was shown to increase; muscle electrical efficiency was found to decrease in calf muscles and to increase in arm muscles; and fatigability was found to increase significantly, as shown by spectral power shifts into lower frequencies. It was concluded from this study that skeletal muscles are affected by the disuse of weightlessness early in the period of weightlessness, antigravity muscles seem most affected by weightlessness, and exercise may abrogate the weightlessness effect. It was further concluded that electromyography is a sensitive tool for measuring spaceflight muscle effects.

Local vibration enhanced the efficacy of passive exercise on mitigating bone loss in hindlimb unloading rats

NASA Astrophysics Data System (ADS)

Huang, Yunfei; Luan, Huiqin; Sun, Lianwen; Bi, Jingfang; Wang, Ying; Fan, Yubo

2017-08-01

Spaceflight induced bone loss is seriously affecting astronauts. Mechanical stimulation from exercise has been shown to restrain bone resorption as well as improve bone formation. Current exercise countermeasures in space cannot prevent it completely. Active exercise may convert to passive exercise in some ways because of the loss of gravity stimulus and inertia of exercise equipment. The aim of this study was to compare the efficacy of passive exercise or/and local vibration on counteracting the deterioration of the musculoskeletal system, including bone, muscle and tendons in tail-suspended rats. We hypothesized that local vibration could enhance the efficacy of passive exercise on countering bone loss. 40 Sprague Dawley rats were randomly distributed into five groups (n = 8, each): tail-suspension (TS), TS+35 Hz vibration (TSV), TS + passive exercise (TSP), TS + passive exercise coupled with 35 Hz vibration (TSPV) and control (CON). Passive exercise or/and local vibration was performed for 21 days. On day 0 and 21, bone mineral density (BMD) was observed by dual energy X-ray absorptiometry (DXA), and trabecular microstructure was evaluated by microcomputer tomography (μCT) analysis in vivo. Mechanical properties of tibia and tendon were determined by a mechanical testing system. Soleus and bone ash weight was tested by an electronic balance. Results showed that the passive exercise could not prevent the decrease of trabecular BMD, microstructure and bone ash weight induced by TS, whereas vibration and passive exercise coupled with local vibration (PV) could. Biomechanical properties of the tibia and tendon in TSPV group significantly increased compared with TS group. In summary, PV in this study was the best method in preventing weightlessness-induced bone loss. Consistent with our hypothesis, local vibration partly enhanced the effect of passive exercise. Furthermore, this study will be useful in improving countermeasure for astronauts, but also for the

The Role of Hedgehog Signaling in Tumor Induced Bone Disease

PubMed Central

Cannonier, Shellese A.; Sterling, Julie A.

2015-01-01

Despite significant progress in cancer treatments, tumor induced bone disease continues to cause significant morbidities. While tumors show distinct mutations and clinical characteristics, they behave similarly once they establish in bone. Tumors can metastasize to bone from distant sites (breast, prostate, lung), directly invade into bone (head and neck) or originate from the bone (melanoma, chondrosarcoma) where they cause pain, fractures, hypercalcemia, and ultimately, poor prognoses and outcomes. Tumors in bone secrete factors (interleukins and parathyroid hormone-related protein) that induce RANKL expression from osteoblasts, causing an increase in osteoclast mediated bone resorption. While the mechanisms involved varies slightly between tumor types, many tumors display an increase in Hedgehog signaling components that lead to increased tumor growth, therapy failure, and metastasis. The work of multiple laboratories has detailed Hh signaling in several tumor types and revealed that tumor establishment in bone can be controlled by both canonical and non-canonical Hh signaling in a cell type specific manner. This review will explore the role of Hh signaling in the modulation of tumor induced bone disease, and will shed insight into possible therapeutic interventions for blocking Hh signaling in these tumors. PMID:26343726

The Beginnings of Airborne Weightlessness Research.

DTIC Science & Technology

1985-01-01

experiments in aircraft with humans and test animals (water turtles) which were published at the 4th International Astronautical Congress in Zurich...EXPERIMENTS ON WEIGHTLESSNESS WHICH I CONDUCTED IN THE UNITED STATES .......... 15 HUMAN REACTIONS DURING FLIGHT TO ACCELERATION PRECEDED BY OR FOLLOWED BY...The astronautical pioneers Tsiolkovsky, Goddard, and Oberth first considered the possible effects of spaceflight *i on humans early in the twentieth

Probiotics Protect Mice from Ovariectomy-Induced Cortical Bone Loss

PubMed Central

Ohlsson, Claes; Engdahl, Cecilia; Fåk, Frida; Andersson, Annica; Windahl, Sara H.; Farman, Helen H.; Movérare-Skrtic, Sofia; Islander, Ulrika; Sjögren, Klara

2014-01-01

The gut microbiota (GM) modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx) results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L) strain, L. paracasei DSM13434 (L. para) or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix) given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh) treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice. PMID:24637895

Probiotics protect mice from ovariectomy-induced cortical bone loss.

PubMed

Ohlsson, Claes; Engdahl, Cecilia; Fåk, Frida; Andersson, Annica; Windahl, Sara H; Farman, Helen H; Movérare-Skrtic, Sofia; Islander, Ulrika; Sjögren, Klara

2014-01-01

The gut microbiota (GM) modulates the hosts metabolism and immune system. Probiotic bacteria are defined as live microorganisms which when administered in adequate amounts confer a health benefit on the host and can alter the composition of the GM. Germ-free mice have increased bone mass associated with reduced bone resorption indicating that the GM also regulates bone mass. Ovariectomy (ovx) results in bone loss associated with altered immune status. The purpose of this study was to determine if probiotic treatment protects mice from ovx-induced bone loss. Mice were treated with either a single Lactobacillus (L) strain, L. paracasei DSM13434 (L. para) or a mixture of three strains, L. paracasei DSM13434, L. plantarum DSM 15312 and DSM 15313 (L. mix) given in the drinking water during 6 weeks, starting two weeks before ovx. Both the L. para and the L. mix treatment protected mice from ovx-induced cortical bone loss and bone resorption. Cortical bone mineral content was higher in both L. para and L. mix treated ovx mice compared to vehicle (veh) treated ovx mice. Serum levels of the resorption marker C-terminal telopeptides and the urinary fractional excretion of calcium were increased by ovx in the veh treated but not in the L. para or the L. mix treated mice. Probiotic treatment reduced the expression of the two inflammatory cytokines, TNFα and IL-1β, and increased the expression of OPG, a potent inhibitor of osteoclastogenesis, in cortical bone of ovx mice. In addition, ovx decreased the frequency of regulatory T cells in bone marrow of veh treated but not probiotic treated mice. In conclusion, treatment with L. para or the L. mix prevents ovx-induced cortical bone loss. Our findings indicate that these probiotic treatments alter the immune status in bone resulting in attenuated bone resorption in ovx mice.

Force-induced bone growth and adaptation: A system theoretical approach to understanding bone mechanotransduction

NASA Astrophysics Data System (ADS)

Maldonado, Solvey; Findeisen, Rolf

2010-06-01

The modeling, analysis, and design of treatment therapies for bone disorders based on the paradigm of force-induced bone growth and adaptation is a challenging task. Mathematical models provide, in comparison to clinical, medical and biological approaches an structured alternative framework to understand the concurrent effects of the multiple factors involved in bone remodeling. By now, there are few mathematical models describing the appearing complex interactions. However, the resulting models are complex and difficult to analyze, due to the strong nonlinearities appearing in the equations, the wide range of variability of the states, and the uncertainties in parameters. In this work, we focus on analyzing the effects of changes in model structure and parameters/inputs variations on the overall steady state behavior using systems theoretical methods. Based on an briefly reviewed existing model that describes force-induced bone adaptation, the main objective of this work is to analyze the stationary behavior and to identify plausible treatment targets for remodeling related bone disorders. Identifying plausible targets can help in the development of optimal treatments combining both physical activity and drug-medication. Such treatments help to improve/maintain/restore bone strength, which deteriorates under bone disorder conditions, such as estrogen deficiency.

Germination of pine seed in weightlessness (investigation in Kosmos 782)

NASA Technical Reports Server (NTRS)

Platonova, R. N.; Parfenov, G. P.; Olkhovenko, V. P.; Karpova, N. I.; Pichugov, M. Y.

1978-01-01

An investigation was made of the orientation of aboveground and underground organs of pine plants grown from seed in weightlessness. Orientation was found to be caused by the position of the seeds relative to the substrate surface. Normal growth was manifest only for the plants grown from seed oriented with embryo toward the substrate. Differences were noted between experiment and control as to the quantitative content of nucleoli in the meristematic cells of the rootlets and the shape of cells in the cotyledonous leaflets. No complete agreement was found between data obtained in weightlessness and when gravity was compensated (clinostat treatment with horizontal rotation).

Effects of spaceflight and simulated weightlessness on longitudinal bone growth

NASA Technical Reports Server (NTRS)

Sibonga, J. D.; Zhang, M.; Evans, G. L.; Westerlind, K. C.; Cavolina, J. M.; Morey-Holton, E.; Turner, R. T.

2000-01-01

Indirect measurements have suggested that spaceflight impairs bone elongation in rats. To test this possibility, our laboratory measured, by the fluorochrome labeling technique, bone elongation that occurred during a spaceflight experiment. The longitudinal growth rate (LGR) in the tibia of rats in spaceflight experiments (Physiological Space Experiments 1, 3, and 4 and Physiological-Anatomical Rodent Experiment 3) and in two models of skeletal unloading (hind-limb elevation and unilateral sciatic neurotomy) were calculated. The effects of an 11 day spaceflight on gene expression of cartilage matrix proteins in rat growth plates were also determined by northern analysis and are reported for the first time in this study. Measurements of longitudinal growth indicate that skeletal unloading generally did not affect LGR, regardless of age, strain, gender, duration of unloading, or method of unloading. There was, however, one exception with 34% suppression in LGR detected in slow-growing, ovariectomized rats skeletally unloaded for 8 days by hind-limb elevation. This detection of reduced LGR by hind-limb elevation is consistent with changes in steady-state mRNA levels for type II collagen (-33%) and for aggrecan (-53%) that were detected in rats unloaded by an 11 day spaceflight. The changes detected in gene expression raise concern that spaceflight may result in changes in the composition of extracellular matrix, which could have a negative impact on conversion of growth-plate cartilage into normal cancellous bone by endochondral ossification.

External Load Affects Ground Reaction Force Parameters Non-uniformly during Running in Weightlessness

NASA Technical Reports Server (NTRS)

DeWitt, John; Schaffner, Grant; Laughlin, Mitzi; Loehr, James; Hagan, R. Donald

2004-01-01

Long-term exposure to microgravity induces detrimefits to the musculcskdetal system (Schneider et al., 1995; LeBlanc et al., 2000). Treadmill exercise is used onboard the International Space Station as an exercise countermeasure to musculoskeletal deconditioning due to spaceflight. During locomotive exercise in weightlessness (0G), crewmembers wear a harness attached to an external loading mechanism (EL). The EL pulls the crewmember toward the treadmill, and provides resistive load during the impact and propulsive phases of gait. The resulting forces may be important in stimulating bone maintenance (Turner, 1998). The EL can be applied via a bungee and carabineer clip configuration attached to the harness and can be manipulated to create varying amounts of load levels during exercise. Ground-based research performed using a vertically mounted treadmill found that peak ground reaction forces (GRF) during running at an EL of less than one body weight (BW) are less than those that occur during running in normal gravity (1G) (Davis et al., 1996). However, it is not known how the GRF are affected by the EL in a true OG environment. Locomotion while suspended may result in biomechanics that differ from free running. The purpose of this investigation was to determine how EL affects peak impact force, peak propulsive force, loading rate, and impulse of the GRF during running in 0G. It was hypothesized that increasing EL would result in increases in each GRF parameter.

Space flight and bone formation.

PubMed

Doty, St B

2004-12-01

Major physiological changes which occur during spaceflight include bone loss, muscle atrophy, cardiovascular and immune response alterations. When trying to determine the reason why bone loss occurs during spaceflight, one must remember that all these other changes in physiology and metabolism may also have impact on the skeletal system. For bone, however, the role of normal weight bearing is a major concern and we have found no adequate substitute for weight bearing which can prevent bone loss. During the study of this problem, we have learned a great deal about bone physiology and increased our knowledge about how normal bone is formed and maintained. Presently, we do not have adequate ground based models which can mimic the tissue loss that occurs in spaceflight but this condition closely resembles the bone loss seen with osteoporosis. Although a normal bone structure will respond to application of mechanical force and weight bearing by forming new bone, a weakened osteoporotic bone may have a tendency to fracture. The study of the skeletal system during weightless conditions will eventually produce preventative measures and form a basis for protecting the crew during long term space flight. The added benefit from these studies will be methods to treat bone loss conditions which occur here on earth.

Space flight and bone formation

NASA Technical Reports Server (NTRS)

Doty, St B.

2004-01-01

Major physiological changes which occur during spaceflight include bone loss, muscle atrophy, cardiovascular and immune response alterations. When trying to determine the reason why bone loss occurs during spaceflight, one must remember that all these other changes in physiology and metabolism may also have impact on the skeletal system. For bone, however, the role of normal weight bearing is a major concern and we have found no adequate substitute for weight bearing which can prevent bone loss. During the study of this problem, we have learned a great deal about bone physiology and increased our knowledge about how normal bone is formed and maintained. Presently, we do not have adequate ground based models which can mimic the tissue loss that occurs in spaceflight but this condition closely resembles the bone loss seen with osteoporosis. Although a normal bone structure will respond to application of mechanical force and weight bearing by forming new bone, a weakened osteoporotic bone may have a tendency to fracture. The study of the skeletal system during weightless conditions will eventually produce preventative measures and form a basis for protecting the crew during long term space flight. The added benefit from these studies will be methods to treat bone loss conditions which occur here on earth.

Dexamethasone Enhances Osteogenic Differentiation of Bone Marrow- and Muscle-Derived Stromal Cells and Augments Ectopic Bone Formation Induced by Bone Morphogenetic Protein-2

PubMed Central

Yuasa, Masato; Yamada, Tsuyoshi; Taniyama, Takashi; Masaoka, Tomokazu; Xuetao, Wei; Yoshii, Toshitaka; Horie, Masaki; Yasuda, Hiroaki; Uemura, Toshimasa; Okawa, Atsushi; Sotome, Shinichi

2015-01-01

We evaluated whether dexamethasone augments the osteogenic capability of bone marrow-derived stromal cells (BMSCs) and muscle tissue-derived stromal cells (MuSCs), both of which are thought to contribute to ectopic bone formation induced by bone morphogenetic protein-2 (BMP-2), and determined the underlying mechanisms. Rat BMSCs and MuSCs were cultured in growth media with or without 10-7 M dexamethasone and then differentiated under osteogenic conditions with dexamethasone and BMP-2. The effects of dexamethasone on cell proliferation and osteogenic differentiation, and also on ectopic bone formation induced by BMP-2, were analyzed. Dexamethasone affected not only the proliferation rate but also the subpopulation composition of BMSCs and MuSCs, and subsequently augmented their osteogenic capacity during osteogenic differentiation. During osteogenic induction by BMP-2, dexamethasone also markedly affected cell proliferation in both BMSCs and MuSCs. In an in vivo ectopic bone formation model, bone formation in muscle-implanted scaffolds containing dexamethasone and BMP-2 was more than two fold higher than that in scaffolds containing BMP-2 alone. Our results suggest that dexamethasone potently enhances the osteogenic capability of BMP-2 and may thus decrease the quantity of BMP-2 required for clinical application, thereby reducing the complications caused by excessive doses of BMP-2. Highlights: 1. Dexamethasone induced selective proliferation of bone marrow- and muscle-derived cells with higher differentiation potential. 2. Dexamethasone enhanced the osteogenic capability of bone marrow- and muscle-derived cells by altering the subpopulation composition. 3. Dexamethasone augmented ectopic bone formation induced by bone morphogenetic protein-2. PMID:25659106

Nell-1-Induced Bone Regeneration in Calvarial Defects

PubMed Central

Aghaloo, Tara; Cowan, Catherine M.; Chou, Yu-Fen; Zhang, Xinli; Lee, Haofu; Miao, Steve; Hong, Nichole; Kuroda, Shun’ichi; Wu, Benjamin; Ting, Kang; Soo, Chia

2006-01-01

Many craniofacial birth defects contain skeletal components requiring bone grafting. We previously identified the novel secreted osteogenic molecule NELL-1, first noted to be overexpressed during premature bone formation in calvarial sutures of craniosynostosis patients. Nell-1 overexpression significantly increases differentiation and mineralization selectively in osteoblasts, while newborn Nell-1 transgenic mice significantly increase premature bone formation in calvarial sutures. In the current study, cultured calvarial explants isolated from Nell-1 transgenic newborn mice (with mild sagittal synostosis) demonstrated continuous bone growth and overlapping sagittal sutures. Further investigation into gene expression cascades revealed that fibroblast growth factor-2 and transforming growth factor-β1 stimulated Nell-1 expression, whereas bone morphogenetic protein (BMP)-2 had no direct effect. Additionally, Nell-1-induced osteogenesis in MC3T3-E1 osteoblasts through reduction in the expression of early up-regulated osteogenic regulators (OSX and ALP) but induction of later markers (OPN and OCN). Grafting Nell-1 protein-coated PLGA scaffolds into rat calvarial defects revealed the osteogenic potential of Nell-1 to induce bone regeneration equivalent to BMP-2, whereas immunohistochemistry indicated that Nell-1 reduced osterix-producing cells and increased bone sialoprotein, osteocalcin, and BMP-7 expression. Insights into Nell-1-regulated osteogenesis coupled with its ability to stimulate bone regeneration revealed a potential therapeutic role and an alternative to the currently accepted techniques for bone regeneration. PMID:16936265

Bone mineral measurement using dual energy x ray densitometry

NASA Technical Reports Server (NTRS)

Smith, Steven W.

1989-01-01

Bone mineral measurements before and after space missions have shown that weightlessness greatly accelerates bone demineralization. Bone mineral losses as high as 1 to 3 percent per month were reported. Highly precise instrumentation is required to monitor this loss and thereby test the efficacy of treatment. During the last year, a significant improvement was made in Dual-Photon Absorptiometry by replacing the radioactive source with an x ray tube. Advantages of this system include: better precision, lower patient dose, better spacial resolution, and shorter scan times. The high precision and low radiation dose of this technique will allow detection of bone mineral changes of less than 1 percent with measurements conducted directly at the sites of interest. This will allow the required bone mineral studies to be completed in a shorter time with greater confidence.

Calcium hydroxide suppresses Porphyromonas endodontalis lipopolysaccharide-induced bone destruction.

PubMed

Guo, J; Yang, D; Okamura, H; Teramachi, J; Ochiai, K; Qiu, L; Haneji, T

2014-05-01

Porphyromonas endodontalis and its main virulence factor, lipopolysaccharide (LPS), are associated with the development of periapical diseases and alveolar bone loss. Calcium hydroxide is commonly used for endodontic therapy. However, the effects of calcium hydroxide on the virulence of P. endodontalis LPS and the mechanism of P. endodontalis LPS-induced bone destruction are not clear. Calcium hydroxide rescued the P. endodontalis LPS-suppressed viability of MC3T3-E1 cells and activity of nuclear factor-κB (NF-κB) in these cells, resulting in the reduced expression of interleukin-6 and tumor necrosis factor-α. In addition, calcium hydroxide inhibited P. endodontalis LPS-induced osteoclastogenesis by decreasing the activities of NF-κB, p38, and ERK1/2 and the expression of nuclear factor of activated T-cell cytoplasmic 1 in RAW264.7 cells. Calcium hydroxide also rescued the P. endodontalis LPS-induced osteoclastogenesis and bone destruction in mouse calvaria. Taken together, our present results indicate that calcium hydroxide suppressed bone destruction by attenuating the virulence of P. endodontalis LPS on bone cells.

Osteoclast TGF-β Receptor Signaling Induces Wnt1 Secretion and Couples Bone Resorption to Bone Formation

PubMed Central

Weivoda, Megan M; Ruan, Ming; Pederson, Larry; Hachfeld, Christine; Davey, Rachel A; Zajac, Jeffrey D; Westendorf, Jennifer J; Khosla, Sundeep; Oursler, Merry Jo

2016-01-01

Osteoblast-mediated bone formation is coupled to osteoclast-mediated bone resorption. These processes become uncoupled with age, leading to increased risk for debilitating fractures. Therefore, understanding how osteoblasts are recruited to sites of resorption is vital to treating age-related bone loss. Osteoclasts release and activate TGF-β from the bone matrix. Here we show that osteoclastspecific inhibition of TGF-β receptor signaling in mice results in osteopenia due to reduced osteoblast numbers with no significant impact on osteoclast numbers or activity. TGF-β induced osteoclast expression of Wnt1, a protein crucial to normal bone formation, and this response was blocked by impaired TGF-β receptor signaling. Osteoclasts in aged murine bones had lower TGF-β signaling and Wnt1 expression in vivo. Ex vivo stimulation of osteoclasts derived from young or old mouse bone marrow macrophages showed no difference in TGF-β–induced Wnt1 expression. However, young osteoclasts expressed reduced Wnt1 when cultured on aged mouse bone chips compared to young mouse bone chips, consistent with decreased skeletal TGF-β availability with age. Therefore, osteoclast responses to TGF-β are essential for coupling bone resorption to bone formation, and modulating this pathway may provide opportunities to treat age-related bone loss. PMID:26108893

GEMINI-TITAN (GT)-3 - WEIGHTLESSNESS EXPERIMENT - AMES RESEARCH CENTER (ARC), CA

NASA Image and Video Library

1965-03-01

S65-18762 (March 1965) --- Effects of the weightless environment on cell division, the basic growth process for living tissue, will be studied during the Gemini-Titan 3 flight scheduled for March 23, 1965. A spiny black sea urchin (upper left) is stimulated by mild electric shock or potassium chloride. As a result it sheds many thousands of eggs. When fertilized, these eggs become actively dividing cells very similar in basic processes to cells of other animals, including humans. These pictures show stages of cell division. At upper right is a single cell; at lower right cell divisions have produced many cells. Cell photos are magnified about 700 times, and all cells shown are too small to be seen by the naked eye. (Photos at upper right and lower left are of sea urchin eggs. Group of cells at lower right are from a sand dollar, which like the sea urchin, is an Echinoderm. Its eggs are virtually identical and are used interchangeably with those of the sea urchin in NASA Ames Center weightlessness experiments.) The Gemini experiment will involve cell division like that shown here. This will take place during several hours of weightlessness aboard the Gemini spacecraft. The experiment will be flown back to laboratories at Cape Kennedy after spacecraft recovery. It has been designed so that any abnormal cell division found by postflight analysis should suggest that the weightless environment has effects on individual cells. This might mean hazards for prolonged periods of manned spaceflight.

Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice

PubMed Central

Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

2015-01-01

Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia. PMID:26664256

Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice.

PubMed

Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; Yamada, Kumiko; Kubo, Kin-ya

2015-01-01

Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a wooden stick to chew during the experimental period. Quantitative micro-computed tomography, histologic analysis, and biochemical markers were used to evaluate the bone response. The stress/chewing group exhibited significantly attenuated stress-induced increases in serum corticosterone levels, suppressed bone formation, enhanced bone resorption, and decreased trabecular bone mass in the vertebrae and distal femurs, compared with mice in the stress group. Active mastication during exposure to chronic stress alleviated chronic stress-induced bone density loss in B6 mice. Active mastication during chronic psychologic stress may thus be an effective strategy to prevent and/or treat chronic stress-related osteopenia.

Cardiovascular adaptations in weightlessness: The influence of in-flight exercise programs on the cardiovascular adjustments during weightlessness and upon returning to Earth

NASA Technical Reports Server (NTRS)

Bennett, C. H.

1981-01-01

The effect of in-flight exercise programs on astronauts' cardiovascular adjustments during spaceflight weightlessness and upon return to Earth was studied. Physiological changes in muscle strength and volume, cardiovascular responses during the application of lower body negative pressure, and metabolic activities during pre-flight and flight tests were made on Skylab crewmembers. The successful completion of the Skylab missions showed that man can perform submaximal and maximal aerobic exercise in the weightless enviroment without detrimental trends in any of the physiologic data. Exercise tolerance during flight was unaffected. It was only after return to Earth that a tolerance decrement was noted. The rapid postflight recovery of orthostatic and exercise tolerance following two of the three Skylab missions appeared to be directly related to total in-flight exercise as well as to the graded, regular program of exercise performed during the postflight debriefing period.

The impact of microgravity on bone in humans.

PubMed

Grimm, Daniela; Grosse, Jirka; Wehland, Markus; Mann, Vivek; Reseland, Janne Elin; Sundaresan, Alamelu; Corydon, Thomas Juhl

2016-06-01

Experiencing real weightlessness in space is a dream for many of us who are interested in space research. Although space traveling fascinates us, it can cause both short-term and long-term health problems. Microgravity is the most important influence on the human organism in space. The human body undergoes dramatic changes during a long-term spaceflight. In this review, we will mainly focus on changes in calcium, sodium and bone metabolism of space travelers. Moreover, we report on the current knowledge on the mechanisms of bone loss in space, available models to simulate the effects of microgravity on bone on Earth as well as the combined effects of microgravity and cosmic radiation on bone. The available countermeasures applied in space will also be evaluated. Copyright © 2016 Elsevier Inc. All rights reserved.

Perception of time under conditions of brief weightlessness

NASA Technical Reports Server (NTRS)

Lebedev, V. I.; Chekidra, I. F.; Kolosov, I. A.

1975-01-01

Results of experiments under conditions of brief weightlessness confirmed the theoretical concepts of the dependence of time perception on the emotional state of a man. The time test, together with other methods, can be used to precisely define the emotional state of subjects in stress situations.

Effects of weightlessness in man.

NASA Technical Reports Server (NTRS)

Berry, C. A.

1973-01-01

The program for the Apollo 16 flight was designed to include both safeguards against and investigations of the physiological problems arising from increase in the period of manned space flight. Precautions included the provision of a controlled diet with high potassium content, carefully controlled work loads and work-rest cycles, and an emergency cardiology consultation service, and investigations were made to enable preflight vs postflight comparisons of metabolic, cardiovascular, and central nervous system data. Results of these investigations indicate that adjustment to weightlessness can be satisfactorily assisted by appropriate countermeasures, including attention to diet.

Second All-Union Seminar on Hydromechanics and Heat-Mass Transfer in Weightlessness. Abstracts of reports: Table of contents

NASA Technical Reports Server (NTRS)

Gershuni, G. Z.; Zhukhovitskiy, Y. M.

1984-01-01

Abstracts of reports are given which were presented at the Second All Union Seminar on Hydromechanics and Heat-Mass Transfer in Weightlessness. Topics inlcude: (1) features of crystallization of semiconductor materials under conditions of microacceleration; (2) experimental results of crystallization of solid solutions of CDTE-HGTE under conditions of weightlessness; (3) impurities in crystals cultivated under conditions of weightlessness; and (4) a numerical investigation of the distribution of impurities during guided crystallization of a melt.

Second All-Union Seminar on Hydromechanics and Heat-Mass Transfer in Weightlessness. Abstracts of reports: Table of contents

NASA Astrophysics Data System (ADS)

Gershuni, G. Z.; Zhukhovitskiy, Y. M.

1984-01-01

s of reports are given which were presented at the Second All Union Seminar on Hydromechanics and Heat-Mass Transfer in Weightlessness. Topics inlcude: (1) features of crystallization of semiconductor materials under conditions of microacceleration; (2) experimental results of crystallization of solid solutions of CDTE-HGTE under conditions of weightlessness; (3) impurities in crystals cultivated under conditions of weightlessness; and (4) a numerical investigation of the distribution of impurities during guided crystallization of a melt.

Evidence Report: Risk of Bone Fracture due to Spaceflight-Induced Changes to Bone

NASA Technical Reports Server (NTRS)

Sibonga, Jean D.; Evans, Harlan J.; Smith, Scott A.; Spector, Elisabeth R.; Yardley, Greg; Myer, Jerry

2017-01-01

Given that spaceflight may induce adverse changes in bone ultimate strength with respect to mechanical loads during and post-mission, there is a possibility a fracture may occur for activities otherwise unlikely to induce fracture prior to initiating spaceflight.

Irradiation induces bone injury by damaging bone marrow microenvironment for stem cells

PubMed Central

Cao, Xu; Wu, Xiangwei; Frassica, Deborah; Yu, Bing; Pang, Lijuan; Xian, Lingling; Wan, Mei; Lei, Weiqi; Armour, Michael; Tryggestad, Erik; Wong, John; Wen, Chun Yi; Lu, William Weijia; Frassica, Frank J.

2011-01-01

Radiation therapy can result in bone injury with the development of fractures and often can lead to delayed and nonunion of bone. There is no prevention or treatment for irradiation-induced bone injury. We irradiated the distal half of the mouse left femur to study the mechanism of irradiation-induced bone injury and found that no mesenchymal stem cells (MSCs) were detected in irradiated distal femora or nonirradiated proximal femora. The MSCs in the circulation doubled at 1 week and increased fourfold after 4 wk of irradiation. The number of MSCs in the proximal femur quickly recovered, but no recovery was observed in the distal femur. The levels of free radicals were increased threefold at 1 wk and remained at this high level for 4 wk in distal femora, whereas the levels were increased at 1 wk and returned to the basal level at 4 wk in nonirradiated proximal femur. Free radicals diffuse ipsilaterally to the proximal femur through bone medullary canal. The blood vessels in the distal femora were destroyed in angiographic images, but not in the proximal femora. The osteoclasts and osteoblasts were decreased in the distal femora after irradiation, but no changes were observed in the proximal femora. The total bone volumes were not affected in proximal and distal femora. Our data indicate that irradiation produces free radicals that adversely affect the survival of MSCs in both distal and proximal femora. Irradiation injury to the vasculatures and the microenvironment affect the niches for stem cells during the recovery period. PMID:21220327

Irradiation induces bone injury by damaging bone marrow microenvironment for stem cells.

PubMed

Cao, Xu; Wu, Xiangwei; Frassica, Deborah; Yu, Bing; Pang, Lijuan; Xian, Lingling; Wan, Mei; Lei, Weiqi; Armour, Michael; Tryggestad, Erik; Wong, John; Wen, Chun Yi; Lu, William Weijia; Frassica, Frank J

2011-01-25

Radiation therapy can result in bone injury with the development of fractures and often can lead to delayed and nonunion of bone. There is no prevention or treatment for irradiation-induced bone injury. We irradiated the distal half of the mouse left femur to study the mechanism of irradiation-induced bone injury and found that no mesenchymal stem cells (MSCs) were detected in irradiated distal femora or nonirradiated proximal femora. The MSCs in the circulation doubled at 1 week and increased fourfold after 4 wk of irradiation. The number of MSCs in the proximal femur quickly recovered, but no recovery was observed in the distal femur. The levels of free radicals were increased threefold at 1 wk and remained at this high level for 4 wk in distal femora, whereas the levels were increased at 1 wk and returned to the basal level at 4 wk in nonirradiated proximal femur. Free radicals diffuse ipsilaterally to the proximal femur through bone medullary canal. The blood vessels in the distal femora were destroyed in angiographic images, but not in the proximal femora. The osteoclasts and osteoblasts were decreased in the distal femora after irradiation, but no changes were observed in the proximal femora. The total bone volumes were not affected in proximal and distal femora. Our data indicate that irradiation produces free radicals that adversely affect the survival of MSCs in both distal and proximal femora. Irradiation injury to the vasculatures and the microenvironment affect the niches for stem cells during the recovery period.

GEMINI-TITAN (GT)-III - WEIGHTLESSNESS EXPERIMENT - AMES RESEARCH CENTER (ARC), CA

NASA Image and Video Library

1965-03-19

S65-18766 (March 1965) --- Diagram of experiment planned for the Gemini-Titan 3 mission scheduled on March 23, 1965, to find out if there are effects of weightlessness on individual living cells. The round canister (top) shows the experiment package. It will contain eight identical chambers, each with sections of sperm, eggs and fixative. Cells are eggs of the spiny, black sea animal, the sea urchin. Bottom panel shows the three stages of each chamber. From left in the first stage, sperm, eggs and fixative are separated. By turning the handle, astronauts will fertilize a certain portion of the eggs, which will begin to divide. At 20 minutes after launch, further turns of the handle will force fixative into two chambers and stop cell division. At 70 minutes after launch, cell division in four more chambers will be stopped, and just prior to re-entry, growth of the remaining two chambers will be terminated by a turn of the handle. This system will allow study after the flight of how cells divided after various time periods in weightlessness. Abnormalities would suggest weightlessness effects on living tissue and possible hazard to prolonged manned spaceflight.

Potential benefits of maximal exercise just prior to return from weightlessness

NASA Technical Reports Server (NTRS)

Convertino, Victor A.

1987-01-01

The purpose of this study was to determine whether performance of a single maximal bout of exercise during weightlessness within hours of return to earth would enhance recovery of aerobic fitness and physical work capacities under a 1G environment. Ten healthy men were subjected to a 10-d bedrest period in the 6-deg headdown position. A graded maximal supine cycle ergometer test was performed before and at the end of bedrest to simulate exercise during weightlessness. Following 3 h of resumption of the upright posture, a second maximal exercise test was performed on a treadmill to measure work capacity under conditions of 1G. Compared to before bedrest, peak oxygen consumption, V(O2), decreased by 8.7 percent and peak heart rate (HR) increased by 5.6 percent in the supine cycle test at the end of bedrest. However, there were no significant changes in peak V(O2) and peak HR in the upright treadmill test following bedrest. These data suggest that one bout of maximal leg exercise prior to return from 10 d of weightlessness may be adequate to restore preflight aerobic fitness and physical work capacity.

Naringin ameliorates bone loss induced by sciatic neurectomy and increases Semaphorin 3A expression in denervated bone.

PubMed

Ma, Xinlong; Lv, Jianwei; Sun, Xiaolei; Ma, Jianxiong; Xing, Guosheng; Wang, Ying; Sun, Lei; Wang, Jianbao; Li, Fengbo; Li, Yanjun; Zhao, Zhihu

2016-04-25

Naringin maintains bone mass in various osteoporosis models, while its effect on bone in disuse osteoporosis has not been reported. The present study explores whether naringin can prevent disuse osteoporosis induced by unilateral sciatic neurectomy (USN) and whether the Semaphorin 3A-induced Wnt/β-catenin signalling pathway is involved in the osteoprotection of naringin. Naringin dose-dependently prevented the deterioration of bone mineral density (BMD), trabecular structure and biomechanical strength in femur due to USN. Naringin increased bone formation but inhibited resorption, as indicated by bone-turnover markers in blood and urine and the histological staining of Osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) in femur. Semaphorin 3A (Sema3A) and active β-catenin protein decreased after USN and could be restored by naringin to the levels of the sham-operated rats. In addition, naringin in vitro promoted the differentiation of osteoblasts and inhibited osteoclastic differentiation. Our studies suggest that the down-regulation of Sema3A and the subsequent inactivation of Wnt/β-catenin signalling may be some of the mechanisms involved in USN-induced osteoporosis. Naringin could increase the expression of Sema3A and the activation of Wnt/β-catenin signalling to prevent disuse osteoporosis induced by denervation. Thus, naringin functions in bone maintenance and could be a promising therapeutic alternative in preventing disuse osteoporosis.

Naringin ameliorates bone loss induced by sciatic neurectomy and increases Semaphorin 3A expression in denervated bone

PubMed Central

Ma, Xinlong; Lv, Jianwei; Sun, Xiaolei; Ma, Jianxiong; Xing, Guosheng; Wang, Ying; Sun, Lei; Wang, Jianbao; Li, Fengbo; Li, Yanjun; Zhao, Zhihu

2016-01-01

Naringin maintains bone mass in various osteoporosis models, while its effect on bone in disuse osteoporosis has not been reported. The present study explores whether naringin can prevent disuse osteoporosis induced by unilateral sciatic neurectomy (USN) and whether the Semaphorin 3A-induced Wnt/β-catenin signalling pathway is involved in the osteoprotection of naringin. Naringin dose-dependently prevented the deterioration of bone mineral density (BMD), trabecular structure and biomechanical strength in femur due to USN. Naringin increased bone formation but inhibited resorption, as indicated by bone-turnover markers in blood and urine and the histological staining of Osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) in femur. Semaphorin 3A (Sema3A) and active β-catenin protein decreased after USN and could be restored by naringin to the levels of the sham-operated rats. In addition, naringin in vitro promoted the differentiation of osteoblasts and inhibited osteoclastic differentiation. Our studies suggest that the down-regulation of Sema3A and the subsequent inactivation of Wnt/β-catenin signalling may be some of the mechanisms involved in USN-induced osteoporosis. Naringin could increase the expression of Sema3A and the activation of Wnt/β-catenin signalling to prevent disuse osteoporosis induced by denervation. Thus, naringin functions in bone maintenance and could be a promising therapeutic alternative in preventing disuse osteoporosis. PMID:27109829

A TNF receptor loop peptide mimic blocks RANK ligand–induced signaling, bone resorption, and bone loss

PubMed Central

Aoki, Kazuhiro; Saito, Hiroaki; Itzstein, Cecile; Ishiguro, Masaji; Shibata, Tatsuya; Blanque, Roland; Mian, Anower Hussain; Takahashi, Mariko; Suzuki, Yoshifumi; Yoshimatsu, Masako; Yamaguchi, Akira; Deprez, Pierre; Mollat, Patrick; Murali, Ramachandran; Ohya, Keiichi; Horne, William C.; Baron, Roland

2006-01-01

Activating receptor activator of NF-κB (RANK) and TNF receptor (TNFR) promote osteoclast differentiation. A critical ligand contact site on the TNFR is partly conserved in RANK. Surface plasmon resonance studies showed that a peptide (WP9QY) that mimics this TNFR contact site and inhibits TNF-α–induced activity bound to RANK ligand (RANKL). Changing a single residue predicted to play an important role in the interaction reduced the binding significantly. WP9QY, but not the altered control peptide, inhibited the RANKL-induced activation of RANK-dependent signaling in RAW 264.7 cells but had no effect on M-CSF–induced activation of some of the same signaling events. WP9QY but not the control peptide also prevented RANKL-induced bone resorption and osteoclastogenesis, even when TNFRs were absent or blocked. In vivo, where both RANKL and TNF-α promote osteoclastogenesis, osteoclast activity, and bone loss, WP9QY prevented the increased osteoclastogenesis and bone loss induced in mice by ovariectomy or low dietary calcium, in the latter case in both wild-type and TNFR double-knockout mice. These results suggest that a peptide that mimics a TNFR ligand contact site blocks bone resorption by interfering with recruitment and activation of osteoclasts by both RANKL and TNF. PMID:16680194

Perception of linear acceleration in weightlessness

NASA Technical Reports Server (NTRS)

Arrott, A. P.; Young, L. R.

1987-01-01

Eye movements and subjective detection of acceleration were measured on human experimental subjects during vestibular sled acceleration during the D1 Spacelab Mission. Methods and results are reported on the time to detection of small acceleration steps, the threshold for detection of linear acceleration, perceived motion path, and CLOAT. A consistently shorter time to detection of small acceleration steps is found. Subjective reports of perceived motion during sinusoidal oscillation in weightlessness were qualitatively similar to reports on earth.

STS-60 Cosmonauts in Weightless Environment Training Facility (WETF) training

NASA Image and Video Library

1993-01-07

Russian Cosmonaut Vladimir Titov maneuvers a small life raft during bailout training at JSC's Weightless Environment Training Facility (WETF). Two SCUBA-equipped divers assisted Titov in the STS-60 training exercise.

Validation of a model for investigating red cell mass changes during weightlessness

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1976-01-01

The model, both the conceptual model and simulation model, provided a convenient framework on which to demonstrate the commonality between such diverse stresses as descent from altitude, red cell infusions, bed rest, and weightlessness. The results suggest that all of these stresses induce an increased blood hematocrit leading to tissue hyperoxia and eventual inhibition of the erythyocyte producing circuit until the hyperoxic condition is relieved. The erythropoietic system was acting, in these situations, as if it were an hematocrit sensor and regulator. In these terms the decreases in red cell mass during Skylab may be explained in terms of normal feedback regulation of the erythropoietic system in the face of sustained decreases in plasma colume.

Preadaptation to the stimulus rearrangement of weightlessness: Preliminary studies and concepts for trainer designs

NASA Technical Reports Server (NTRS)

Parker, D. E.; Reschke, M. F.

1988-01-01

An effort to develop preflight adaptation training (PAT) apparatus and procedures to adapt astronauts to the stimulus rearrangement of weightless spaceflight is being pursued. Based on the otolith tilt-translation reinterpretation model of sensory adaptation to weightlessness, two prototype preflight adaptation trainers (PAT) have been developed. These trainers couple pitch movement of the subject with translation of the visual surround. Subjects were exposed to this stimulus rearrangement for periods of 30 m. The hypothesis is that exposure to the rearrangement would attenuate vertical eye movements was supported by two experiments using the Miami University Seesaw (MUS) PAT prototype. The Dynamic Environment Simulator (DES) prototype failed to support this hypothesis; this result is attributed to a pecularity of the DES apparatus. A final experiment demonstrated that changes in vertical eye movements were not a consequence of fixation on an external target during exposure to a control condition. Together these experiments support the view that preflight adaptation training can alter eye movements in a manner consistent with adaptation to weightlessness. Following these initial studies, concepts for development of operational preflight trainers were proposed. The trainers are intended to: demonstrate the stimulus rearrangement of weightlessness; allow astronauts to train in altered sensory environment; modify sensory motor reflexes; and reduce/eliminate space motion sickness symptoms.

Challenges of Estimating Fracture Risk with DXA: Changing Concepts About Bone Strength and Bone Density.

PubMed

Licata, Angelo A

2015-07-01

Bone loss due to weightlessness is a significant concern for astronauts' mission safety and health upon return to Earth. This problem is monitored with bone densitometry (DXA), the clinical tool used to assess skeletal strength. DXA has served clinicians well in assessing fracture risk and has been particularly useful in diagnosing osteoporosis in the elderly postmenopausal population for which it was originally developed. Over the past 1-2 decades, however, paradoxical and contradictory findings have emerged when this technology was widely employed in caring for diverse populations unlike those for which it was developed. Although DXA was originally considered the surrogate marker for bone strength, it is now considered one part of a constellation of factors-described collectively as bone quality-that makes bone strong and resists fracturing, independent of bone density. These characteristics are beyond the capability of routine DXA to identify, and as a result, DXA can be a poor prognosticator of bone health in many clinical scenarios. New clinical tools are emerging to make measurement of bone strength more accurate. This article reviews the historical timeline of bone density measurement (dual X-ray absorptiometry), expands upon the clinical observations that modified the relationship of DXA and bone strength, discusses some of the new clinical tools to predict fracture risk, and highlights the challenges DXA poses in the assessment of fracture risk in astronauts.

Physiological effects of weightlessness: countermeasure system development for a long-term Chinese manned spaceflight.

PubMed

Wang, Linjie; Li, Zhili; Tan, Cheng; Liu, Shujuan; Zhang, Jianfeng; He, Siyang; Zou, Peng; Liu, Weibo; Li, Yinghui

2018-04-25

The Chinese space station will be built around 2020. As a national space laboratory, it will offer unique opportunities for studying the physiological effects of weightlessness and the efficacy of the countermeasures against such effects. In this paper, we described the development of countermeasure systems in the Chinese space program. To emphasize the need of the Chinese space program to implement its own program for developing countermeasures, we reviewed the literature on the negative physiological effects of weightlessness, the challenges of completing missions, the development of countermeasure devices, the establishment of countermeasure programs, and the efficacy of the countermeasure techniques in American and Russian manned spaceflights. In addition, a brief overview was provided on the Chinese research and development on countermeasures to discuss the current status and goals of the development of countermeasures against physiological problems associated with weightlessness.

A universal multilingual weightless neural network tagger via quantitative linguistics.

PubMed

Carneiro, Hugo C C; Pedreira, Carlos E; França, Felipe M G; Lima, Priscila M V

2017-07-01

In the last decade, given the availability of corpora in several distinct languages, research on multilingual part-of-speech tagging started to grow. Amongst the novelties there is mWANN-Tagger (multilingual weightless artificial neural network tagger), a weightless neural part-of-speech tagger capable of being used for mostly-suffix-oriented languages. The tagger was subjected to corpora in eight languages of quite distinct natures and had a remarkable accuracy with very low sample deviation in every one of them, indicating the robustness of weightless neural systems for part-of-speech tagging tasks. However, mWANN-Tagger needed to be tuned for every new corpus, since each one required a different parameter configuration. For mWANN-Tagger to be truly multilingual, it should be usable for any new language with no need of parameter tuning. This article proposes a study that aims to find a relation between the lexical diversity of a language and the parameter configuration that would produce the best performing mWANN-Tagger instance. Preliminary analyses suggested that a single parameter configuration may be applied to the eight aforementioned languages. The mWANN-Tagger instance produced by this configuration was as accurate as the language-dependent ones obtained through tuning. Afterwards, the weightless neural tagger was further subjected to new corpora in languages that range from very isolating to polysynthetic ones. The best performing instances of mWANN-Tagger are again the ones produced by the universal parameter configuration. Hence, mWANN-Tagger can be applied to new corpora with no need of parameter tuning, making it a universal multilingual part-of-speech tagger. Further experiments with Universal Dependencies treebanks reveal that mWANN-Tagger may be extended and that it has potential to outperform most state-of-the-art part-of-speech taggers if better word representations are provided. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pine seed germination under weightlessness (a study of the Kosmos 782 satellite)

NASA Technical Reports Server (NTRS)

Platonova, R. N.; Parfenov, G. P.; Olkhovenko, V. P.; Karpova, N. I.; Pichugov, M. Y.

1977-01-01

Orientation of the above and underground organs of pine plants, grown from seeds under weightlessness, was found to be determined by seed position on the substrate. Normal plant growth was observed only if the seed embryos were oriented toward the substrate. Some differences were noted between the experimental and control plants concerning the amount of nucleoli in the root meristematic cells and the cell shape in cotyledonous leaves. No complete similarity was found in experimental results obtained with plants under weightlessness and under compensated gravity. The seeds were obtained from Pinus silvestris, considered to be particularly suitable for this experiment.

S-Ketoprofen Inhibits Tenotomy-Induced Bone Loss and Dynamics in Weanling Rats

NASA Technical Reports Server (NTRS)

Zeng, Q. Q.; Jee, W. S. S.; Ke, H. Z.; Wechter, W. J.

1993-01-01

The objects of this study were to determine whether S-ketoprofen, a non-steroidal anti-inflammatory drug (NSAID), can prevent immobilization (tenotomy)-induced bone loss in weanling rats. Forty five 4 week-old Sprague-Dawley female rats were either sham-operated or subjected to knee tenotomy and treated simultaneously with 0, 0.02, 0.1, 0.5 or 2.5 mg of S-ketoprofen/kg per day for 21 days. We then studied double-fluorescent labeled proximal tibial longitudinal sections and tibial shaft cross sections using static and dynamic histomorphometry. Less cancellous bone mass in proximal tibial metaphyses was found in tenotomized controls than in basal (36%) and sham-operated (54%) controls. This was due to the inhibition of age-related bone gain and induced bone loss due to increased bone resorption and decreased bone formation. S-ketoprofen prevented both the inhibition of age-related bone gain and the stimulation of bone loss at the 2.5 mg/kg per day dose level, while it only prevented bone loss at the 0.5 mg/kg dose levels. In cancellous bone, dynamic histomorphometry showed that S-ketoprofen prevented the tenotomy induced decrease in bone formation and increase in bone resorption. In the tibial shaft, tenotomy inhibited the enlargement of total tissue area by depressing periosteal bone formation, and thus inhibited age-related cortical bone gain. S-ketoprofen treatment did not prevent this change at all dose levels, but reduced marrow cavity area to increase cortical bone area at the 0.1, 0.5 and 2.5 mg/kg per dose levels compared to tenotomy controls. However, the cortical bone area in the 0.1 and 0.5 mg dose-treated treated tenotomy rats was still lower than in the age-related controls. S-ketoprofen also prevented the increase in endocortical eroded perimeter induced by tenotomy. In summary, tenotomy inhibited age-related bone gain and stimulated bone loss in cancellous bone sites, and only inhibited age-related bone gain in cortical bone sites. S

Astronauts Hoffman and Seddon demonstrate effect of weightlessness on slinky

NASA Image and Video Library

1985-04-14

51D-06-015 (12-19 April 1985) --- Astronaut Jeffrey A. Hoffman and Rhea Seddon mission specialists, demonstrate the effect of weightlessness on a slinky toy in the mid-deck of the Space Shuttle Discovery.

Decursin from Angelica gigas suppresses RANKL-induced osteoclast formation and bone loss.

PubMed

Wang, Xin; Zheng, Ting; Kang, Ju-Hee; Li, Hua; Cho, Hyewon; Jeon, Raok; Ryu, Jae-Ha; Yim, Mijung

2016-03-05

Osteoclasts are the only cells capable of breaking down bone matrix, and excessive activation of osteoclasts is responsible for bone-destructive diseases. In this study, we investigated the effects of decursin from extract of Angelica gigas root on receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast formation using mouse bone marrow-derived macrophages (BMMs). Decursin inhibited RANKL-induced osteoclast formation without cytotoxicity. In particular, decursin maintains the characteristics of macrophages by blocking osteoclast differentiation by RANKL. Furthermore, the RANKL-stimulated bone resorption was diminished by decursin. Mechanistically, decursin blocked the RANKL-triggered ERK mitogen-activated protein kinases (MAPK) phosphorylation, which results in suppression of c-Fos and the nuclear factor of activated T cells (NFATc1) expression. In accordance with the in vitro study, decursin reduced lipopolysaccharide (LPS)- or ovariectomy (OVX)-induced bone loss in vivo. Therefore, decursin exerted an inhibitory effect on osteoclast formation and bone loss in vitro and in vivo. Decursin could be useful for the treatment of bone diseases associated with excessive bone resorption. Copyright © 2016 Elsevier B.V. All rights reserved.

The G-factor as a tool to learn more about bone structure and function.

PubMed

Zerath, E

1999-07-01

In normal life on earth, the locomotor system is exposed to two types of stimulation: gravity (passive stimulation) and motion (active stimulation). Both permanently combine, and the interactions between locomotion and gravity induce an overall recruitment which is repeated daily and maintains the bone tissue structure within the range of constraints to which it is adapted. This range is one of the basic hypotheses underlying the mechanical concepts of bone structure control, and it has been considered as logical to assume that weightlessness of spaceflight should produce bone loss since astronauts are outside of the terrestrial gravitational field of forces, no longer relying on muscular work to change positions or move. But, thirty years after the first changes in phospho-calcium metabolism were observed in astronauts after spaceflight, current knowledge does not provide a full understanding of this pathogeny, and prove the G-factor is now considered as an essential component of the experimental tools available to study bone physiology. The study of the physiology of bone tissue usually consists in the investigation of its two fundamental roles, i.e. reservoir of inorganic elements (calcium, phosphorus, magnesium) and mechanical support for soft tissues. Together with the combined action of muscles, tendons, and ligaments, this support permits motion and locomotion. These two functions rely on a sophisticated bone tissue architecture, and on the adaptability of this structure, with modeling and remodeling processes, themselves associated with the coupled activity of specialized bone cell populations.

A study of stress-free living bone and its application to space flight

NASA Technical Reports Server (NTRS)

Leblanc, A.; Spira, M.

1983-01-01

Observations of animals and human subjects in weightless space flight (Skylab and COSMOS) document altered bone metabolism. Bone metabolism is affected by a number of local and systemic factors. The calcification and growth of transplanted bone is independent of local muscle, nervous, and mechanical forces; therefore, transplanted bone would provide data on the role of local vs. systematic factors. Bone metabolism in living transplanted bone, devoid of stress, was investigated as a possible tool for the investigation of countermeasures against disuse bone loss. An animal model using Sprague-Dawley rats was developed for transplantation of femur bone tissue on a nutrient vascular pedicel. The long term course of these implants was assessed through the measure of regional and total bone mineral, blood flow, and methylene diphosphonate (MDP) uptake. Clomid, an estrogen agonist/antagonist, was shown to protect bone from disuse loss of minerals by retarding trabecular and cortical resorption.

Dihydroartemisinin attenuates lipopolysaccharide-induced osteoclastogenesis and bone loss via the mitochondria-dependent apoptosis pathway

PubMed Central

Dou, C; Ding, N; Xing, J; Zhao, C; Kang, F; Hou, T; Quan, H; Chen, Y; Dai, Q; Luo, F; Xu, J; Dong, S

2016-01-01

Dihydroartemisinin (DHA) is a widely used antimalarial drug isolated from the plant Artemisia annua. Recent studies suggested that DHA has antitumor effects utilizing its reactive oxygen species (ROS) yielding mechanism. Here, we reported that DHA is inhibitory on lipopolysaccharide (LPS)-induced osteoclast (OC) differentiation, fusion and bone-resorption activity in vitro. Intracellular ROS detection revealed that DHA could remarkably increase ROS accumulation during LPS-induced osteoclastogenesis. Moreover, cell apoptosis was also increased by DHA treatment. We found that DHA-activated caspase-3 increased Bax/Bcl-2 ratio during LPS-induced osteoclastogenesis. Meanwhile, the translocation of apoptotic inducing factor (AIF) and the release of cytochrome c from the mitochondria into the cytosol were observed, indicating that ROS-mediated mitochondrial dysfunction is crucial in DHA-induced apoptosis during LPS-induced osteoclastogenesis. In vivo study showed that DHA treatment decreased OC number, prevents bone loss, rescues bone microarchitecture and restores bone strength in LPS-induced bone-loss mouse model. Together, our findings indicate that DHA is protective against LPS-induced bone loss through apoptosis induction of osteoclasts via ROS accumulation and the mitochondria-dependent apoptosis pathway. Therefore, DHA may be considered as a new therapeutic candidate for treating inflammatory bone loss. PMID:27031959

Effect of weightlessness conditions on the somatic embryogenesis in the culture of carrot cells

NASA Technical Reports Server (NTRS)

Butenko, R. G.; Dmitriyeva, N. N.; Ongko, V.; Basyrova, L. V.

1977-01-01

A carrot cell culture seeded in Petri dishes in the United States and transported to the USSR was subjected to weightlessness for 20 days during the flight of Kosmos 782. The controls were cultures placed on a centrifuge (1 g) inside the satellite and cultures left on ground in the U.S.S.R. and the United States. A count of structures in the dishes after the flight showed that the number of developing embryonic structures and the extent of their differentiation in weightlessness did not reliably differ from the number and extent of differentiation in structures developed on the ground. Structures with long roots developed in weightlessness. Analysis of the root zones showed that these roots differed by the increased size of the zone of differentiated cells. The increased size of the zones of differentiated cells can indicate earlier development of embryonic structures.

The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate

PubMed Central

Song, Guodong; Habibovic, Pamela; Bao, Chongyun; Hu, Jing; van Blitterswijk, Clemens A.; Yuan, Huipin; Chen, Wenchuan; Xu, Hockin H.K.

2013-01-01

Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched beagle dog model to investigate BMSC homing via blood circulation to participate in ectopic bone formation via osteoinductive biomaterial. BMSCs of male dogs were injected into female femoral marrow cavity. The survival and stable chimerism of donor BMSCs in recipients were confirmed with polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH). Biphasic calcium phosphate (BCP) granules were implanted in dorsal muscles of female dogs. Y chromosomes were detected in samples harvested from female dogs which had received male BMSCs. At 4 weeks, cells with Y-chromosomes were distributed in the new bone matrix throughout the BCP granule implant. At 6 weeks, cells with Y chromosomes were present in newly mineralized woven bone. TRAP positive osteoclast-like cells were observed in 4-week implants, and the number of such cells decreased from 4 to 6 weeks. These results show that osteoprogenitors were recruited from bone marrow and homed to ectopic site to serve as a cell source for calcium phosphate-induced bone formation. In conclusion, BMSCs were demonstrated to migrate from bone marrow through blood circulation to non-osseous bioceramic implant site to contribute to ectopic bone formation in a canine model. BCP induced new bone in muscles without growth factor delivery, showing excellent osteoinductivity that could be useful for bone tissue engineering. PMID:23298780

Effects of Spaceflight on Cells of Bone Marrow Origin

PubMed Central

Özçivici, Engin

2013-01-01

Once only a subject for science fiction novels, plans for establishing habitation on space stations, the Moon, and distant planets now appear among the short-term goals of space agencies. This article reviews studies that present biomedical issues that appear to challenge humankind for long-term spaceflights. With particularly focus on cells of bone marrow origin, studies involving changes in bone, immune, and red blood cell populations and their functions due to extended weightlessness were reviewed. Furthermore, effects of mechanical disuse on primitive stem cells that reside in the bone marrow were also included in this review. Novel biomedical solutions using space biotechnology will be required in order to achieve the goal of space exploration without compromising the functions of bone marrow, as spaceflight appears to disrupt homeostasis for all given cell types. Conflict of interest:None declared. PMID:24385745

Zoledronate prevents lactation induced bone loss and results in additional post-lactation bone mass in mice.

PubMed

Wendelboe, Mette Høegh; Thomsen, Jesper Skovhus; Henriksen, Kim; Vegger, Jens Bay; Brüel, Annemarie

2016-06-01

In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation induced bone loss, and if Zln interferes with recovery of bone mass after lactation has ceased. Seventy-six 10-weeks-old NMRI mice were divided into the following groups: Baseline, Pregnant, Lactation, Lactation+Zln, Recovery, Recovery+Zln, and Virgin Control (age-matched). The lactation period was 12days, then the pups were removed, and thereafter recovery took place for 28days. Zln, 100μg/kg, was given s.c. on the day of delivery, and again 4 and 8days later. Mechanical testing, μCT, and dynamic histomorphometry were performed. At L4, lactation resulted in a substantial loss of bone strength (-55% vs. Pregnant, p<0.01), BV/TV (-40% vs. Pregnant, p<0.01), and trabecular thickness (Tb.Th) (-29% vs. Pregnant, p<0.001). Treatment with Zln completely prevented lactation induced loss of bone strength, BV/TV, and Tb.Th at L4. Full recovery of micro-architectural and mechanical properties was found 28days after weaning in vehicle-treated mice. Interestingly, the recovery group treated with Zln during the lactation period had higher BV/TV (+45%, p<0.01) and Tb.Th (+16%, p<0.05) compared with virgin controls. Similar results were found at the proximal tibia and femur. This indicates that Zln did not interfere with the bone formation taking place after weaning. On this background, we conclude that post-lactation bone formation is not dependent on a preceding lactation induced bone loss. Copyright © 2016 Elsevier Inc. All rights reserved.

Physiological changes in fast and slow muscle with simulated weightlessness

NASA Technical Reports Server (NTRS)

Dettbarn, W. D.; Misulis, K. E.

1984-01-01

A rat hindlimb suspension model of simulated weightlessness was used to examine the physiological characteristics of skeletal muscle. The physiological sequelae of hindlimb suspension were compared to those of spinal cord section, denervation by sciatic nerve crush, and control. Muscle examined were the predominantly slow (Type 1) soleus (SOL) and the predominantly fast (Type 2) extensor digitorum longus (EDL). Two procedures which alter motor unit activity, hindlimb suspension and spinal cord section, produce changes in characteristics of skeletal muscles that are dependent upon fiber type. The SOL develops characteristics more representative of a fast muscle, including smaller Type 1 fiber proportion and higher AChE activity. The EDL, which is already predominantly fast, loses most of its few Type 1 fibers, thus also becoming faster. These data are in agreement with the studies in which rats experienced actual weightlessness.

Intake of Fish and Omega-3 (n-3) Fatty Acids: Effect on Humans During Actual and Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Smith, S. M.; Pierson, D. L.; Mehta, S. K.; Zwart, S. R.

2011-01-01

Space flight has many negative effects on human physiology, including bone and muscle loss. Bone and muscle are two systems that are positively affected by dietary intake of fish and n-3 fatty acids. The mechanism is likely to be related to inhibition by n-3 fatty acids of inflammatory cytokines (such as TNF) and thus inhibition of downstream NF-kB activation. We have documented this effect in a 3-dimensional cell culture model, where NF-kB activation in osteoclasts was inhibited by eicosapentaenoic acid, an n-3 fatty acid. We have also indentified that NF-kB activation in peripheral blood mononuclear cells of Space Shuttle crews. We found that after Shuttle flights of 2 wk, expression of the protein p65 (evidence of NF-kB activation) was increased at landing (P less than 0.001). When evaluating the effects of n-3 fatty acid intake on bone breakdown after 60 d of bed rest (a weightlessness analog). We found that after 60 d of bed rest, greater intake of n-3 fatty acids was associated with less N-telopeptide excretion (Pearson r = -0.62, P less than 0.05). We also evaluated the relationship of fish intake and bone loss in astronauts after 4 to 6 mo missions on the International Space Station. Higher consumption of fish during flight was associated with higher bone mineral density (Pearson r = 0.46, P less than 0.05). Together, these findings provide evidence of the cellular mechanism by which n-3 fatty acids can inhibit bone loss, and preliminary human evidence of the potential for n-3 fatty acids to counteract bone loss associated with space flight. This study was supported by the NASA Human Research Program.

PULSED FOCUSED ULTRASOUND TREATMENT OF MUSCLE MITIGATES PARALYSIS-INDUCED BONE LOSS IN THE ADJACENT BONE: A STUDY IN A MOUSE MODEL

PubMed Central

Poliachik, Sandra L.; Khokhlova, Tatiana D.; Wang, Yak-Nam; Simon, Julianna C.; Bailey, Michael R.

2015-01-01

Bone loss can result from bed rest, space flight, spinal cord injury or age-related hormonal changes. Current bone loss mitigation techniques include pharmaceutical interventions, exercise, pulsed ultrasound targeted to bone and whole body vibration. In this study, we attempted to mitigate paralysis-induced bone loss by applying focused ultrasound to the midbelly of a paralyzed muscle. We employed a mouse model of disuse that uses onabotulinumtoxinA-induced paralysis, which causes rapid bone loss in 5 d. A focused 2 MHz transducer applied pulsed exposures with pulse repetition frequency mimicking that of motor neuron firing during walking (80 Hz), standing (20 Hz), or the standard pulsed ultrasound frequency used in fracture healing (1 kHz). Exposures were applied daily to calf muscle for 4 consecutive d. Trabecular bone changes were characterized using micro-computed tomography. Our results indicated that application of certain focused pulsed ultrasound parameters was able to mitigate some of the paralysis-induced bone loss. PMID:24857416

Micropore-induced capillarity enhances bone distribution in vivo in biphasic calcium phosphate scaffolds.

PubMed

Rustom, Laurence E; Boudou, Thomas; Lou, Siyu; Pignot-Paintrand, Isabelle; Nemke, Brett W; Lu, Yan; Markel, Mark D; Picart, Catherine; Wagoner Johnson, Amy J

2016-10-15

The increasing demand for bone repair solutions calls for the development of efficacious bone scaffolds. Biphasic calcium phosphate (BCP) scaffolds with both macropores and micropores (MP) have improved healing compared to those with macropores and no micropores (NMP), but the role of micropores is unclear. Here, we evaluate capillarity induced by micropores as a mechanism that can affect bone growth in vivo. Three groups of cylindrical scaffolds were implanted in pig mandibles for three weeks: MP were implanted either dry (MP-Dry), or after submersion in phosphate buffered saline, which fills pores with fluid and therefore suppresses micropore-induced capillarity (MP-Wet); NMP were implanted dry. The amount and distribution of bone in the scaffolds were quantified using micro-computed tomography. MP-Dry had a more homogeneous bone distribution than MP-Wet, although the average bone volume fraction, BVF‾, was not significantly different for these two groups (0.45±0.03 and 0.37±0.03, respectively). There was no significant difference in the radial bone distribution of NMP and MP-Wet, but the BVF‾, of NMP was significantly lower among the three groups (0.25±0.02). These results suggest that micropore-induced capillarity enhances bone regeneration by improving the homogeneity of bone distribution in BCP scaffolds. The explicit design and use of capillarity in bone scaffolds may lead to more effective treatments of large and complex bone defects. The increasing demand for bone repair calls for more efficacious bone scaffolds and calcium phosphate-based materials are considered suitable for this application. Macropores (>100μm) are necessary for bone ingrowth and vascularization. However, studies have shown that microporosity (<20μm) also enhances growth, but there is no consensus on the controlling mechanisms. In previous in vitro work, we suggested that micropore-induced capillarity had the potential to enhance bone growth in vivo. This work illustrates the

Bone growth and calcium balance during simulated weightlessness in the rat

NASA Technical Reports Server (NTRS)

Roer, Robert D.; Dillaman, Richard M.

1990-01-01

Rats, age 28 days, experiencing tail suspension in modified metabolic cages for 1, 2, and 3 wk were compared with littermate controls. Food and water consumption, urinary and fecal Ca excretion, and serum Ca were measured; hearts, fore- and hindlimb bones, skulls, and mandibles were removed for determination of wet, dry, and ash weights and Ca concentration and for histological examination. Weight gain and Ca intake and excretion were the same for both groups; both displayed net Ca gain. Suspended rats had significantly lower wet, dry, and ash weights of femora and tibiae. Dry weights of the humeri and radii/ulnae were moderately higher, and the skull and mandible dry and ash weights were significantly higher in suspended than in control rats. Cortical thickness of the femur, but not humerus, was less in suspended rats. The data are consistent with the hypothesis that bone growth is influenced by the cardiovascular changes associated with tail suspension.

Whole-Body Movements in Long-Term Weightlessness: Hierarchies of the Controlled Variables Are Gravity-Dependent.

PubMed

Casellato, Claudia; Pedrocchi, Alessandra; Ferrigno, Giancarlo

2017-01-01

Switching between contexts affects the mechanisms underlying motion planning, in particular it may entail reranking the variables to be controlled in defining the motor solutions. Three astronauts performed multiple sessions of whole-body pointing, in normogravity before launch, in prolonged weightlessness onboard the International Space Station, and after return. The effect of gravity context on kinematic and dynamic components was evaluated. Hand trajectory was gravity independent; center-of-mass excursion was highly variable within and between subjects. The body-environment effort exchange, expressed as inertial ankle momentum, was systematically lower in weightlessness than in normogravity. After return on Earth, the system underwent a rapid 1-week readaptation. The study indicates that minimizing the control effort is given greater weight when optimizing the motor plan in weightlessness compared to normogravity: the hierarchies of the controlled variables are gravity dependent.

Morphological and histochemical studies of bone and cartilage during periods of stimulated weightlessness

NASA Technical Reports Server (NTRS)

Doty, S. B.

1984-01-01

Rats which were subjected to spaceflight for 2-4 weeks showed considerable loss in ability to form new bone. Animals which are placed into nonweight bearing positions, as a model to simulate the absence of gravity here on the Earth's surface. Show a similar decline in new bone formation. It is suggested that the mechanisms underlying these changes may be the result of reduced transmission of gravitational force to the skeletal cells.

Markers of bone turnover in patients with epilepsy and their relationship to management of bone diseases induced by antiepileptic drugs.

PubMed

Hamed, Sherifa A

2016-01-01

Data from cross-sectional and prospective studies revealed that patients with epilepsy and on long-term treatment with antiepileptic drugs (AEDs) are at increased risk for metabolic bone diseases. Bone diseases were reported in about 50% of patients on AEDs. Low bone mineral density, osteopenia/osteoporosis, osteomalacia, rickets, altered concentration of bone turnover markers and fractures were reported with phenobarbital, phenytoin, carbamazepine, valproate, oxcarbazepine and lamotrigine. The mechanisms for AEDs-induced bone diseases are heterogeneous and include hypovitaminosis D, hypocalcemia and direct acceleration of bone loss and/or reduction of bone formation. This article reviews the evidence, predictors and mechanisms of AEDs-induced bone abnormalities and its clinical implications. For patients on AEDs, regular monitoring of bone health is recommended. Prophylactic administration of calcium and vitamin D is recommended for all patients. Treatment doses of calcium and vitamin D and even anti-resorptive drug therapy are reserved for patients at high risk of pathological fracture.

Thought Experiments in Teaching Free-Fall Weightlessness: A Critical Review and an Exploration of Mercury's Behavior in "Falling Elevator"

ERIC Educational Resources Information Center

Balukovic, Jasmina; Slisko, Josip; Cruz, Adrián Corona

2017-01-01

Different "thought experiments" dominate teaching approaches to weightlessness, reducing students' opportunities for active physics learning, which should include observations, descriptions, explanations and predictions of real phenomena. Besides the controversy related to conceptual definitions of weight and weightlessness, we report…

Botulinum Toxin Induces Muscle Paralysis and Inhibits Bone Regeneration in Zebrafish

PubMed Central

Recidoro, Anthony M.; Roof, Amanda C.; Schmitt, Michael; Worton, Leah E.; Petrie, Timothy; Strand, Nicholas; Ausk, Brandon J.; Srinivasan, Sundar; Moon, Randall T.; Gardiner, Edith M.; Kaminsky, Werner; Bain, Steven D.; Allan, Christopher H.; Gross, Ted S.; Kwon, Ronald Y.

2016-01-01

Intramuscular administration of Botulinum toxin (BTx) has been associated with impaired osteogenesis in diverse conditions of bone formation (e.g., development, growth, and healing), yet the mechanisms of neuromuscular-bone crosstalk underlying these deficits have yet to be identified. Motivated by the emerging utility of zebrafish (Danio rerio) as a rapid, genetically tractable, and optically transparent model for human pathologies (as well as the potential to interrogate neuromuscular-mediated bone disorders in a simple model that bridges in vitro and more complex in vivo model systems), in this study we developed a model of BTx-induced muscle paralysis in adult zebrafish, and examined its effects on intramembranous ossification during tail fin regeneration. BTx administration induced rapid muscle paralysis in adult zebrafish in a manner that was dose-dependent, transient, and focal, mirroring the paralytic phenotype observed in animal and human studies. During fin regeneration, BTx impaired continued bone ray outgrowth, morphology, and patterning, indicating defects in early osteogenesis. Further, BTx significantly decreased mineralizing activity and crystalline mineral accumulation, suggesting delayed late-stage osteoblast differentiation and/or altered secondary bone apposition. Bone ray transection proximal to the amputation site focally inhibited bone outgrowth in the affected ray, implicating intra- and/or inter-ray nerves in this process. Taken together, these studies demonstrate the potential to interrogate pathological features of BTx-induced osteoanabolic dysfunction in the regenerating zebrafish fin, define the technological toolbox for detecting bone growth and mineralization deficits in this process, and suggest that pathways mediating neuromuscular regulation of osteogenesis may be conserved beyond established mammalian models of bone anabolic disorders. PMID:24806738

The Lyme Disease Pathogen Borrelia burgdorferi Infects Murine Bone and Induces Trabecular Bone Loss.

PubMed

Tang, Tian Tian; Zhang, Lucia; Bansal, Anil; Grynpas, Marc; Moriarty, Tara J

2017-02-01

Lyme disease is caused by members of the Borrelia burgdorferi sensu lato species complex. Arthritis is a well-known late-stage pathology of Lyme disease, but the effects of B. burgdorferi infection on bone at sites other than articular surfaces are largely unknown. In this study, we investigated whether B. burgdorferi infection affects bone health in mice. In mice inoculated with B. burgdorferi or vehicle (mock infection), we measured the presence of B. burgdorferi DNA in bones, bone mineral density (BMD), bone formation rates, biomechanical properties, cellular composition, and two- and three-dimensional features of bone microarchitecture. B. burgdorferi DNA was detected in bone. In the long bones, increasing B. burgdorferi DNA copy number correlated with reductions in areal and trabecular volumetric BMDs. Trabecular regions of femora exhibited significant, copy number-correlated microarchitectural disruption, but BMD, microarchitectural, and biomechanical properties of cortical bone were not affected. Bone loss in tibiae was not due to increased osteoclast numbers or bone-resorbing surface area, but it was associated with reduced osteoblast numbers, implying that bone loss in long bones was due to impaired bone building. Osteoid-producing and mineralization activities of existing osteoblasts were unaffected by infection. Therefore, deterioration of trabecular bone was not dependent on inhibition of osteoblast function but was more likely caused by blockade of osteoblastogenesis, reduced osteoblast survival, and/or induction of osteoblast death. Together, these data represent the first evidence that B. burgdorferi infection induces bone loss in mice and suggest that this phenotype results from inhibition of bone building rather than increased bone resorption. Copyright © 2017 Tang et al.

Physiologic mechanisms of circulatory and body fluid losses in weightlessness identified by mathematical modeling

NASA Technical Reports Server (NTRS)

Simanonok, K. E.; Srinivasan, R. S.; Charles, J. B.

1993-01-01

Central volume expansion due to fluid shifts in weightlessness is believed to activate adaptive reflexes which ultimately result in a reduction of the total circulating blood volume. However, the flight data suggests that a central volume overdistention does not persist, in which case some other factor or factors must be responsible for body fluid losses. We used a computer simulation to test the hypothesis that factors other than central volume overdistention are involved in the loss of blood volume and other body fluid volumes observed in weightlessness and in weightless simulations. Additionally, the simulation was used to identify these factors. The results predict that atrial volumes and pressures return to their prebedrest baseline values within the first day of exposure to head down tilt (HDT) as the blood volume is reduced by an elevated urine formation. They indicate that the mechanisms for large and prolonged body fluid losses in weightlessness is red cell hemoconcentration that elevates blood viscosity and peripheral resistance, thereby lowering capillary pressure. This causes a prolonged alteration of the balance of Starling forces, depressing the extracellular fluid volume until the hematocrit is returned to normal through a reduction of the red cell mass, which also allows some restoration of the plasma volume. We conclude that the red cell mass becomes the physiologic driver for a large 'undershoot' of the body fluid volumes after the normalization of atrial volumes and pressures.

Protective effect of salidroside against bone loss via hypoxia-inducible factor-1α pathway-induced angiogenesis

PubMed Central

Li, Ling; Qu, Ye; Jin, Xin; Guo, Xiao Qin; Wang, Yue; Qi, Lin; Yang, Jing; Zhang, Peng; Li, Ling Zhi

2016-01-01

Hypoxia-inducible factor (HIF)-1α plays a critical role in coupling angiogenesis with osteogenesis during bone development and regeneration. Salidroside (SAL) has shown anti-hypoxic effects in vitro and in vivo. However, the possible roles of SAL in the prevention of hypoxia-induced osteoporosis have remained unknown. Two osteoblast cell lines, MG-63 and ROB, were employed to evaluate the effects of SAL on cell viability, apoptosis, differentiation and mineralization in vitro. Rats subjected to ovariectomy-induced bone loss were treated with SAL in vivo. Our results showed that pre-treatment with SAL markedly attenuated the hypoxia-induced reductions in cell viability, apoptosis, differentiation and mineralization. SAL down-regulated HIF-1α expression and inhibited its translocation; however, SAL increased its transcriptional activity and, consequently, up-regulated vascular endothelial growth factor (VEGF). In vivo studies further demonstrated that SAL caused decreases in the mineral, alkaline phosphatase (ALP), and BGP concentrations in the blood of ovariectomized (OVX) rats. Moreover, SAL improved the trabecular bone microarchitecture and increased bone mineral density in the distal femur. Additionally, SAL administration partially ameliorated this hypoxia via the HIF-1α-VEGF signalling pathway. Our results indicate that SAL prevents bone loss by enhancing angiogenesis and osteogenesis and that these effects are associated with the activation of HIF-1α signalling. PMID:27558909

Polymethoxy flavonoids, nobiletin and tangeretin, prevent lipopolysaccharide-induced inflammatory bone loss in an experimental model for periodontitis.

PubMed

Tominari, Tsukasa; Hirata, Michiko; Matsumoto, Chiho; Inada, Masaki; Miyaura, Chisato

2012-01-01

Nobiletin, a polymethoxy flavonoid (PMF), inhibits systemic bone resorption and maintains bone mass in estrogen-deficient ovariectomized mice. This study examined the anti-inflammatory effects of PMFs, nobiletin, and tangeretin on lipopolysaccharide (LPS)-induced bone resorption. Nobiletin and tangeretin suppressed LPS-induced osteoclast formation and bone resorption and suppressed the receptor activator of NFκB ligand-induced osteoclastogenesis in RAW264.7 macrophages. Nobiletin clearly restored the alveolar bone mass in a mouse experimental model for periodontitis by inhibiting LPS-induced bone resorption. PMFs may therefore provide a new therapeutic approach for periodontal bone loss.

Otolith mass asymmetry: natural, and after weightlessness and hypergravity

NASA Astrophysics Data System (ADS)

Lychakov, Dmitri

It is believed that otolith mass asymmetry (OA) can play an essential role in genesis of vestibular space disturbances in human subjects and fish. This review poster presents data on values and characters of OA in animals of various species and classes and on the effect of weightlessness and hypergravity on OA; the issue of the effect of OA on vestibular and auditory functions also is considered (Lychakov, Rebane, 2004, 2005; Lychakov et al., 2006, 2008). In symmetric vertebrates, OA was shown to be fluctuating, its coefficient chiχ ranges from - 0.2 to + 0.2 (±± 20%). It should be stressed that in the overwhelming majority of individuals absolute values of chiχ << 0.06. The low OA level enables the paired otolith organs to work in coordination; this is why the OA level is equally low regardless of the individual taxonomic and ecological position, size, age, and otolith growth rate. Individuals with the abnormally high OA level can experience difficulties in analyzing auditory and vestibular stimuli; therefore, most of such individuals are eliminated by natural selection. Unlike symmetric vertebrates, labyrinths of many Pleuronectiformes have pronounced OA. Otoliths in the lower labyrinth, on average, are significantly heavier than those in the upper labyrinth. The organs of flatfish represent the only example when OA, being directional, seem to play an essential role in lateralized behavior and are suggested to be used in the spatial localization of the source of sound. The short-term weightlessness and relatively weak hypergravity (<< 2g) do not affect OA. However, it cannot be ruled out that the long-term weightlessness and hypergravity >> 3g as well as some diseases and age-related changes can indirectly enhance OA and cause some functional disturbances. This work was partly supported by Russian grant RFFI 14-04-00601.

Mechanisms of diabetes mellitus-induced bone fragility.

PubMed

Napoli, Nicola; Chandran, Manju; Pierroz, Dominique D; Abrahamsen, Bo; Schwartz, Ann V; Ferrari, Serge L

2017-04-01

The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. However, in both T1DM and T2DM, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly so when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia, oxidative stress and the accumulation of advanced glycation endproducts that compromise collagen properties, increase marrow adiposity, release inflammatory factors and adipokines from visceral fat, and potentially alter the function of osteocytes. Additional factors including treatment-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus.

Effect of anisotropy on stress-induced electrical potentials in bovine bone using ultrasound irradiation

NASA Astrophysics Data System (ADS)

Matsukawa, S.; Makino, T.; Mori, S.; Koyama, D.; Takayanagi, S.; Mizuno, K.; Yanagitani, T.; Matsukawa, M.

2017-04-01

The bone fracture healing mechanism of the low-intensity pulsed ultrasound technique is not yet clearly understood. In our previous study, the electrical potentials induced in bone were successfully measured by focusing on piezoelectricity in the MHz range. Bone is composed of collagen and hydroxyapatite and has strong anisotropy. The purpose of this study is to investigate the effects of bone anisotropy on the electrical potentials induced by ultrasound irradiation. For this study, ultrasound bone transducers were fabricated using cortical bovine bone plates as piezoelectric devices. An ultrasound of 7.4 kPapeak-peak (i.e., the peak-to-peak pressure value) was used to irradiate the side surface of each bone plate. Electrical potentials induced in the bone plate were then measured by varying the wave propagation direction in the plate. The peak-to-peak values of these ultrasonically induced electrical potentials were found to vary with changes in the ultrasound propagation direction in the bone sample. The potential was maximized at an inclination of approximately 45° to the bone axis but was minimized around the three orthogonal directions. These maxima and minima ranged from 28 to 33 μVpeak-peak and from 5 to 12 μVpeak-peak, respectively. Additionally, our ultrasound results indicated a change in polarity due to bone anisotropy in the MHz range.

[Histomorphometric analysis of the bones of rats on board the Kosmos 1667 biosatellite].

PubMed

Kaplanskiĭ, A S; Durnova, G N; Sakharova, Z F; Il'ina-Kakueva, E I

1987-01-01

Bones of the rats flown on Cosmos-1667 were examined histologically and histomorphometrically. It was found that 7-day exposure to weightlessness led to osteoporosis in the spongy matter of proximal metaphyses of tibia and, although to a lesser extent, in the spongiosa of lumbar vertebrae whereas no signs of osteoporosis were seen in the spongy matter of iliac bones. Osteoporosis in the spongy matter of the above bones developed largely due to the inhibition of bone neoformation, which was indicated by a decrease in the number and activity of osteoblasts. Increased bone resorption (as shown by a greater number and activity of osteoclasts) was observed only in the spongy matter of tibial metaphyses. It is emphasized that a reduction of the number of highly active osteoblasts in spongy bones is one of the early signs of inhibition of bone neoformation and development of osteoporosis.

What Happens to bone health during and after spaceflight?

NASA Technical Reports Server (NTRS)

Sibonga, Jean D.; Evans, Harlan J.; Spector, Elisabeth R.; Maddocks, Mary J.; Smith, Scott A.; Shackelford, Linda C.; LeBlanc, Adrian D.

2006-01-01

Weightless conditions of space flight accelerate bone loss. There are no reports to date that address whether the bone that is lost during spaceflight could ever be recovered. Spaceinduced bone loss in astronauts is evaluated at the Johnson Space Center (JSC) by measurement of bone mineral density (BMD) by Dual-energy x-ray absorptiometry (DXA) scans. Astronauts are routinely scanned preflight and at various time points postflight (greater than or equal to Return+2 days). Two sets of BMD data were used to model spaceflight-induced loss and skeletal recovery in crewmembers following long-duration spaceflight missions (4-6 months). Group I was from astronauts (n=7) who were systematically scanned at multiple time points during the postflight period as part of a research protocol to investigate skeletal recovery. Group II came from a total of 49 sets of preflight and postflight data obtained by different protocols. These data were from 39 different crewmembers some of whom served on multiple flights. Changes in BMD (between pre- and postflight BMD) were plotted as a function of time (days-after-landing); plotted data were fitted to an exponential equation which enabled estimations of i) BMD change at day 0 after landing and ii) the number of days by which 50% of the lost bone is recovered (half-life). These fits were performed for BMD of the lumbar spine, trochanter, pelvis, femoral neck and calcaneus. There was consistency between the models for BMD recovery. Based upon the exponential model of BMD restoration, recovery following long-duration missions appears to be substantially complete in crewmembers within 36 months following return to Earth.

Effects of O-methylated (-)-epigallocatechin gallate (EGCG) on LPS-induced osteoclastogenesis, bone resorption, and alveolar bone loss in mice.

PubMed

Tominari, Tsukasa; Ichimaru, Ryota; Yoshinouchi, Shosei; Matsumoto, Chiho; Watanabe, Kenta; Hirata, Michiko; Grundler, Florian M W; Inada, Masaki; Miyaura, Chisato

2017-12-01

(-)-Epigallocatechin-3- O -gallate (EGCG), present in green tea, exhibits antioxidant and antiallergy effects. EGCG3″Me, a 3- O -methylated derivative of EGCG, has been reported to show similar biological functions; the inhibitory activity of EGCG3″Me in a mouse allergy model was more potent than that of EGCG, probably due to the efficiency of absorption from the intestine. However, the functional potency of these EGCGs is controversial in each disease model. We previously observed that EGCG suppressed inflammatory bone resorption and prevented alveolar bone loss in a mouse model of periodontosis. In this study, we examined the role of EGCG3″Me in bone resorption using a mouse model of periodontitis. Lipopolysaccharide (LPS)-induced osteoclast formation was suppressed by adding EGCG3″Me to cocultures of osteoblasts and bone marrow cells, and LPS-induced bone resorption was also inhibited by EGCG3″Me in calvarial organ cultures. EGCG3″Me acted on osteoblasts and suppressed prostaglandin E (PGE) production, which is critical for inflammatory bone resorption, by inhibiting the expression of COX-2 and mPGES-1, key enzymes for PGE synthesis. In osteoclast precursor macrophages, EGCG3″Me suppressed RANKL-dependent differentiation into mature osteoclasts. In a mouse model of periodontitis, LPS-induced bone resorption was suppressed by EGCG3″Me in organ culture of mouse alveolar bone, and the alveolar bone loss was further attenuated by the treatment of EGCG3″Me in the lower gingiva in vivo . EGCG3″Me may be a potential natural compound for the protection of inflammatory bone loss in periodontitis.

Astronaut activity in weightlessness and unsupported space

NASA Technical Reports Server (NTRS)

Ivanov, Y. A.; Popov, V. A.; Kachaturyants, L. S.

1975-01-01

For the purpose of study of the performance ability of a human operator in prolonged weightless conditions was studied by the following methods: (1) psychophysiological analysis of certain operations; (2) the dynamic characteristics of a man, included in a model control system, with direct and delayed feedback; (3) evaluation of the singularities of analysis and quality of the working memory, in working with outlines of patterned and random lines; and (4) biomechanical analysis of spatial orientation and motor activity in unsupported space.

Microgravity and bone cell mechanosensitivity: FLOW experiment during the DELTA mission

NASA Astrophysics Data System (ADS)

Bacabac, Rommel G.; Van Loon, Jack J. W. A.; de Blieck-Hogervorst, Jolanda M. A.; Semeins, Cor M.; Zandieh-Doulabi, Behrouz; Helder, Marco N.; Smit, Theo H.; Klein-Nulend, Jenneke

2007-09-01

The catabolic effects of microgravity on mineral metabolism in bone organ cultures might be explained as resulting from an exceptional form of disuse. It is possible that the mechanosensitivity of bone cells is altered under near weightlessness conditions, which likely contributes to disturbed bone metabolism observed in astronauts. In the experiment "FLOW", we tested whether the production of early signaling molecules that are involved in the mechanical load-induced osteogenic response by bone cells is changed under microgravity conditions. FLOW was one of the Biological experiment entries to the Dutch Soyuz Mission "DELTA" (Dutch Expedition for Life Science, Technology and Atmospheric Research). FLOW was flown by the Soyuz craft, launched on April 19, 2004, on its way to the International Space Station. Primary osteocytes, osteoblasts, and periosteal fibroblasts were incubated in plunger boxes, developed by Centre for Concepts in Mechatronics, using plunger activation events for single pulse fluid shear stress stimulations. Due to unforeseen hardware complications, results from in-flight cultures are considered lost. Ground control experiments showed an accumulative increase of NO in medium for osteocytes (as well as for osteoblasts and periosteal fibroblasts). Data from the online-NO sensor showed that the NO produced in medium by osteocytes increased sharply after pulse shear stress stimulations. COX-2 mRNA expression revealed high levels in osteoblasts compared to the other cell types tested. In conclusion, preparations for the FLOW experiment and preliminary ground results indicate that the FLOW setup is viable for a future flight opportunity.

Biomedical study on combined effects of simulated weightlessness and emergent depressurization of spacecraft

NASA Astrophysics Data System (ADS)

Yang, T. D.; Zhang, R. G.; Wang, C. M.; Fu, H. W.; Zhang, B. L.; Zhang, J. X.

1999-01-01

Cabin emergent depressurization (CED) may occur in spacecraft during manned space flight. The purpose of this paper was to study the combined effects of simulated weightlessness (SW) and CED factors on humans and animals. It was found that the amplitude of T wave of human electrocardiograms (ECG) significantly decreased in bed rest and hypoxia compared with the control condition (P<0.05), and that suspension with pure O2 induced severer edema in the lungs of rats than that in only a pure O2 environment. SW and pure O2 caused middle ear congestion and decreased the barofunction during pressure changes. These results indicate that human response to CED factors become more serious under SW because of the blood redistribution.

Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

NASA Technical Reports Server (NTRS)

LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeffrey A.; Shapiro, Jay; Lang, Thomas F.; Smith, Scott M.; Shackelford, Linda C.; Sibonga, Jean; Evans, Harlan; Spector, Elisabeth;

Engineering bone tissue substitutes from human induced pluripotent stem cells.

PubMed

de Peppo, Giuseppe Maria; Marcos-Campos, Iván; Kahler, David John; Alsalman, Dana; Shang, Linshan; Vunjak-Novakovic, Gordana; Marolt, Darja

2013-05-21

Congenital defects, trauma, and disease can compromise the integrity and functionality of the skeletal system to the extent requiring implantation of bone grafts. Engineering of viable bone substitutes that can be personalized to meet specific clinical needs represents a promising therapeutic alternative. The aim of our study was to evaluate the utility of human-induced pluripotent stem cells (hiPSCs) for bone tissue engineering. We first induced three hiPSC lines with different tissue and reprogramming backgrounds into the mesenchymal lineages and used a combination of differentiation assays, surface antigen profiling, and global gene expression analysis to identify the lines exhibiting strong osteogenic differentiation potential. We then engineered functional bone substitutes by culturing hiPSC-derived mesenchymal progenitors on osteoconductive scaffolds in perfusion bioreactors and confirmed their phenotype stability in a subcutaneous implantation model for 12 wk. Molecular analysis confirmed that the maturation of bone substitutes in perfusion bioreactors results in global repression of cell proliferation and an increased expression of lineage-specific genes. These results pave the way for growing patient-specific bone substitutes for reconstructive treatments of the skeletal system and for constructing qualified experimental models of development and disease.

Studies of Intercellular Communication and Intracellular Metabolic Responses by Bone Cells to Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Doty, Stephen B.

1997-01-01

Spaceflight affects the weight bearing skeletal tissues by reducing the rate of new bone formation. This effect on the long bones of flown rats has been quantitated but the effect at the cellular level and the mechanism(s) involved are not understood. We are applying electron microscopy, coupled with histochemistry and immunocytochemistry to determine the cellular functions most affected by spaceflight. The emphasis for study of these samples from SLS-1, a 9-day mission, is on the histochemical and structural changes of the endosteal and perivascular osteoblasts found in diaphyseal bone of femur and tibia. Work is still in progress but some findings are described: (1) An expected decrease in alkaline phosphatase activity in osteoblasts from flight animals, but an increase in enzyme activity in the stromal stem cells adjacent to the osteoblast. (2) An increase in osteoclastic TRAP activity in the trabecular bone region in response to spaceflight. (3) A large increase in procollagen containing secretory granules in osteoblasts in the recovery group, and a significant decrease in granule numbers in the flight group.

Simulated weightlessness in fish and neurophysiological studies on memory storage

NASA Technical Reports Server (NTRS)

Vonbaumgarten, R. J.

1973-01-01

Simulated weightlessness was used to study the different types of gravity responses in blind fish. It was found that a shift in the direction of low magnitude acceleration in weightlessness causes a rapid 180 deg turn in the blind fish, while a shift in the direction of the applied acceleration in the earth's gravitational field is not significant because of a higher acceleration magnitude threshold than during the zero g condition. This increased responsiveness seems to be explained by a combination of directional sensitivity with a Weber-Fechner relationship of increased receptor sensitivity at diminished levels of background stimulation. Neurophysical studies of the statocyst nerve of the gastropod Mollusc Pleurobranchaea Californica were undertaken in order to understand how complex otolith systems operate. Information storage was investigated on relatively simple neuronal networks in the mollusc Aplysia. Intracellular electrical stimulation of isolated neurons show that a manipulation of autoditonous rhymicity is possible. It was also found that glycolysis and oxidative phosphorylation are involved in inherent rhymicity of Aplysis neurons.

Pharmacological activation of aldehyde dehydrogenase 2 promotes osteoblast differentiation via bone morphogenetic protein-2 and induces bone anabolic effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mittal, Monika; Pal, Subhashis; China, Shyamsundar

Aldehyde dehydrogenases (ALDHs) are a family of enzymes involved in detoxifying aldehydes. Previously, we reported that an ALDH inhibitor, disulfiram caused bone loss in rats and among ALDHs, osteoblast expressed only ALDH2. Loss-of-function mutation in ALDH2 gene is reported to cause bone loss in humans which suggested its importance in skeletal homeostasis. We thus studied whether activating ALDH2 by N-(1, 3-benzodioxol-5-ylmethyl)-2, 6-dichlorobenzamide (alda-1) had osteogenic effect. We found that alda-1 increased and acetaldehyde decreased the differentiation of rat primary osteoblasts and expressions of ALDH2 and bone morphogenetic protein-2 (BMP-2). Silencing ALDH2 in osteoblasts abolished the alda-1 effects. Further, alda-1 attenuatedmore » the acetaldehyde-induced lipid-peroxidation and oxidative stress. BMP-2 is essential for bone regeneration and alda-1 increased its expression in osteoblasts. We then showed that alda-1 (40 mg/kg dose) augmented bone regeneration at the fracture site with concomitant increase in BMP-2 protein compared with control. The osteogenic dose (40 mg/kg) of alda-1 attained a bone marrow concentration that was stimulatory for osteoblast differentiation, suggesting that the tissue concentration of alda-1 matched its pharmacologic effect. In addition, alda-1 promoted modeling-directed bone growth and peak bone mass achievement, and increased bone mass in adult rats which reiterated its osteogenic effect. In osteopenic ovariectomized (OVX) rats, alda-1 reversed trabecular osteopenia with attendant increase in serum osteogenic marker (procollagen type I N-terminal peptide) and decrease in oxidative stress. Alda-1 has no effect on liver and kidney function. We conclude that activating ALDH2 by alda-1 had an osteoanabolic effect involving increased osteoblastic BMP-2 production and decreased OVX-induced oxidative stress. - Highlights: • Alda-1 induced osteoblast differentiation that involved upregulation of ALDH2 and BMP-2 • Alda

Engineering 3D Models of Tumors and Bone to Understand Tumor-Induced Bone Disease and Improve Treatments.

PubMed

Kwakwa, Kristin A; Vanderburgh, Joseph P; Guelcher, Scott A; Sterling, Julie A

2017-08-01

Bone is a structurally unique microenvironment that presents many challenges for the development of 3D models for studying bone physiology and diseases, including cancer. As researchers continue to investigate the interactions within the bone microenvironment, the development of 3D models of bone has become critical. 3D models have been developed that replicate some properties of bone, but have not fully reproduced the complex structural and cellular composition of the bone microenvironment. This review will discuss 3D models including polyurethane, silk, and collagen scaffolds that have been developed to study tumor-induced bone disease. In addition, we discuss 3D printing techniques used to better replicate the structure of bone. 3D models that better replicate the bone microenvironment will help researchers better understand the dynamic interactions between tumors and the bone microenvironment, ultimately leading to better models for testing therapeutics and predicting patient outcomes.

Anabolic activity of ursolic acid in bone: Stimulating osteoblast differentiation in vitro and inducing new bone formation in vivo.

PubMed

Lee, Su-Ui; Park, Sang-Joon; Kwak, Han Bok; Oh, Jaemin; Min, Yong Ki; Kim, Seong Hwan

2008-01-01

In the field of osteoporosis, there has been growing interest in anabolic agents that enhance bone mass and improve bone architecture. In this study, we demonstrated that the ubiquitous plant triterpenoid, ursolic acid, enhances differentiation and mineralization of osteoblasts in vitro. We found that ursolic acid induced the expression of osteoblast-specific genes with the activation of mitogen-activated protein kinases, nuclear factor-kappaB, and activator protein-1. Additionally, noggin, an antagonist of bone morphogenetic proteins (BMPs), inhibited ursolic acid-induced osteoblast differentiation. Noggin also inhibited the activation of Smad and the induction of BMP-2 mRNA expression by ursolic acid in the late stage of osteoblast differentiation. Importantly, ursolic acid was shown to have bone-forming activity in vivo in a mouse calvarial bone formation model. A high proportion of positive immunostaining of BMP-2 was found in the nuclear region of woven bone formed by ursolic acid. These results suggested that ursolic acid has the anabolic potential to stimulate osteoblast differentiation and enhance new bone formation.

Role of Oxidative Damage in Radiation-Induced Bone Loss

NASA Technical Reports Server (NTRS)

Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

2014-01-01

used an array of countermeasures (Antioxidant diets and injections) to prevent the radiation-induced bone loss, although these did not prevent bone loss, analysis is ongoing to determine if these countermeasure protected radiation-induced damage to other tissues.

Effect of weightlessness and centrifugation on red cell survival in rats subjected to space flight

NASA Technical Reports Server (NTRS)

Leon, H. A.; Serova, L. V.; Landaw, S. A.

1980-01-01

Rats were flown aboard the Soviet biosatellite Cosmos 936 for 18.5 d during August, 1977. Five rats were subjected to near-weightless space flight, as with Cosmos 782, and five rats were subjected to a 1-G force via an on-board centrifuge. These rats and three control groups were injected with 2-(C-14) glycine 19 d preflight. The flight rats were recovered from orbit after 18.5 d of space flight. Erythrocyte hemolysis and lifespan were evaluated in the five groups of rats by quantitation of radioactive carbon monoxide exhaled in the breath which arises from the breakdown of the previously labeled hemoglobin. The results support the previous findings wherein hemolysis was found to increase as a result of weightless space flight. A comparison to the centrifuged animals indicates that artificial gravity attenuates the effect of weightlessness on hemolysis and appears to normalize the hemolytic rate in the early postflight period.

Influence of single hindlimb support during simulated weightlessness in the rat

NASA Technical Reports Server (NTRS)

Stump, Craig S.; Overton, J. Michael; Tipton, Charles M.

1990-01-01

A study was carried out to develop and evaluate a hindlimb suspension model, making it possible to differentiate the effects of non-weight bearing by hindlimbs per se from the systemic influence of simulated weightlessness. A support platform was designed which allowed the animal to maintain one hindlimb in a posture similar to the hindlimbs of the control animals at rest and to maintain one hindlimb in a posture similar to the hindlimbs of the control animals, providing a support for the animal to contract or stretch hindlimb muscles against at any time during suspension. The results of this study indicated that hindlimb support during head-down suspension will maintain muscle-mass/body-mass ratios, glycogen concentration, and blood flow. However, it will not prevent the loss in citrate synthase activity associated with conditions of simulated weightlessness.

Platinum nanoparticles reduce ovariectomy-induced bone loss by decreasing osteoclastogenesis

PubMed Central

Kim, Woon-Ki; Kim, Jin-Chun; Park, Hyun-Jung; Sul, Ok-Joo; Lee, Mi-Hyun; Kim, Ji-Soon

2012-01-01

Platinum nanoparticles (PtNP) exhibit remarkable antioxidant activity. There is growing evidence concerning a positive relationship between oxidative stress and bone loss, suggesting that PtNP could protect against bone loss by modulating oxidative stress. Intragastric administration of PtNP reduced ovariectomy (OVX)-induced bone loss with a decreased level of activity and number of osteoclast (OC) in vivo. PtNP inhibited OC formation by impairing the receptor activator of nuclear factor-κB ligand (RANKL) signaling. This impairment was due to a decreased activation of nuclear factor-κB and a reduced level of nuclear factor in activated T-cells, cytoplasmic 1 (NFAT2). PtNP lowered RANKL-induced long lasting reactive oxygen species as well as intracellular concentrations of Ca2+ oscillation. Our data clearly highlight the potential of PtNP for the amelioration of bone loss after estrogen deficiency by attenuated OC formation. PMID:22525805

Effects of simulated weightlessness on fish otolith growth: Clinostat versus Rotating-Wall Vessel

NASA Astrophysics Data System (ADS)

Brungs, Sonja; Hauslage, Jens; Hilbig, Reinhard; Hemmersbach, Ruth; Anken, Ralf

2011-09-01

Stimulus dependence is a general feature of developing sensory systems. It has been shown earlier that the growth of inner ear heavy stones (otoliths) of late-stage Cichlid fish ( Oreochromis mossambicus) and Zebrafish ( Danio rerio) is slowed down by hypergravity, whereas microgravity during space flight yields an opposite effect, i.e. larger than 1 g otoliths, in Swordtail ( Xiphophorus helleri) and in Cichlid fish late-stage embryos. These and related studies proposed that otolith growth is actively adjusted via a feedback mechanism to produce a test mass of the appropriate physical capacity. Using ground-based techniques to apply simulated weightlessness, long-term clinorotation (CR; exposure on a fast-rotating Clinostat with one axis of rotation) led to larger than 1 g otoliths in late-stage Cichlid fish. Larger than normal otoliths were also found in early-staged Zebrafish embryos after short-term Wall Vessel Rotation (WVR; also regarded as a method to simulate weightlessness). These results are basically in line with the results obtained on Swordtails from space flight. Thus, the growth of fish inner ear otoliths seems to be an appropriate parameter to assess the quality of "simulated weightlessness" provided by a particular simulation device. Since CR and WVR are in worldwide use to simulate weightlessness conditions on ground using small-sized specimens, we were prompted to directly compare the effects of CR and WVR on otolith growth using developing Cichlids as model organism. Animals were simultaneously subjected to CR and WVR from a point of time when otolith primordia had begun to calcify both within the utricle (gravity perception) and the saccule (hearing); the respective otoliths are the lapilli and the sagittae. Three such runs were subsequently carried out, using three different batches of fish. The runs were discontinued when the animals began to hatch. In the course of all three runs performed, CR led to larger than normal lapilli, whereas WVR

Lactation induces increases in the RANK/RANKL/OPG system in maxillary bone.

PubMed

Macari, Soraia; Sharma, Lavanya A; Wyatt, Amanda; da Silva, Janine Maíra; Dias, George J; Silva, Tarcília A; Szawka, Raphael E; Grattan, David R

2018-05-01

The underlying causes of maxillary bone loss during lactation remain poorly understood. We evaluated the impact of lactation on physiological and mechanically-induced alveolar bone remodeling. Nulliparous non-lactating (N-LAC) and 21-day lactating (LAC) mice underwent mechanically-induced bone remodeling by orthodontic tooth movement (OTM). Micro-computed tomography (microCT) was performed in the maxilla, femur and vertebra. Tartrate-resistant-acid phosphatase (TRAP) and Masson's trichrome labelling was performed in the maxillary bone and gene expression was determined in the periodontal ligament. The effect of prolactin on osteoclast (OCL) and osteoblast (OBL) differentiation was also investigated in N-LAC and LAC mice. Lactation increased alveolar bone loss in the maxilla, femur and vertebra, while OTM was enhanced. The number of OCL and OBL was higher in the maxilla of LAC mice. OTM increased OCL in both groups; while OBL was increased only in N-LAC but not in LAC mice, in which cell numbers were already elevated. The alveolar bone loss during lactation was associated with increased expression of receptor activator of nuclear factor-KappaB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) in the maxilla. OTM induced the same responses in N-LAC mice, whereas it had no further effect in LAC mice. Lactation enhanced differentiation of OCL and OBL from bone marrow cells, and prolactin recapitulated OCL differentiation in N-LAC mice. Thus, lactation increases physiological maxillary bone remodeling and OTM, and both require activation of RANK/RANKL/OPG system. These findings expand our knowledge of lactation-induced osteopenia and have possible impact on clinical practice regarding orthodontic treatments and dental implants in lactating women. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of raloxifene against letrozole-induced bone loss in chemically-induced model of menopause in mice.

PubMed

Kalam, Abul; Talegaonkar, Sushama; Vohora, Divya

2017-01-15

The deleterious effects of letrozole, an aromatase inhibitor, used in the adjuvant treatment of breast cancer in postmenopausal women, on bone are well-documented and represent a major drawback to its clinical use. Raloxifene, a selective estrogen receptor modulator and a clinically approved anti-osteoporotic drug, has been recently demonstrated to be efficacious in women with breast cancer. The present study evaluated the effects of preventive and curative treatment with raloxifene on letrozole-induced alterations of bone microarchitecture and turnover markers in a chemically-induced menopause model in mice. Swiss strain albino female mice were made menopausal by inducing ovotoxicity using vinyl cyclohexene di epoxide (VCD, 160 mg/kg for 15 days followed by 30 days drug-free period) confirmed by ovarian histology and serum estradiol levels. Effects on femoral and lumbar bones were evaluated by micro CT determination of bone volume, trabecular number, separation, thickness, connective density and trabecular pattern factor and bone turnover markers including ALP, TRAP5b, hydroxyproline and RANKL. In addition to these, markers of Wnt signaling (sclerostin and dickkopf-1) were also evaluated. To rule out the involvement of pharmacokinetic interaction, plasma levels of letrozole and raloxifene were measured following drugs alone and in combination. Though bone loss was observed in VCD treated mice (as indicated by micro CT measurements), it was further enhanced with letrozole administration (1 mg/kg) for one month particularly in epiphysis of femoral bones. Raloxifene (15 mg/kg), whether administered concurrently or post-letrozole was able to revert the structural alterations and changes in turnover markers caused by letrozole to varying degrees (p < 0.01 or p < 0.001). Further, estrogen deficiency following letrozole treatment in ovotoxic mice was associated with significant increase in sclerostin and dickkopf-1 in both lumbar and femur bones (p < 0

Protocadherin-7 induces bone metastasis of breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Ai-Min; Tian, Ai-Xian; Zhang, Rui-Xue

2013-07-05

Highlights: •PCDH7 is overexpression in high bone metastatic MDA-MB-231 cells. •PCDH7 is up-regulation in bone metastatic breast cancer tissues. •Suppression of PCDH7 inhibits cell proliferation, migration, and invasion in vitro. •PCDH7 induces breast cancer bone metastasis in vivo. -- Abstract: Breast cancer had a propensity to metastasize to bone, resulting in serious skeletal complications associated with poor outcome. Previous study showed that Protocadherin-7 (PCDH7) play an important role in brain metastatic breast cancer, however, the role of PCDH7 in bone metastatic breast cancer has never been explored. In the present study, we found that PCDH7 expression was up-regulation in bonemore » metastatic breast cancer tissues by real-time PCR and immunohistochemistry assays. Furthermore, suppression of PCDH7 inhibits breast cancer cell proliferation, migration, and invasion in vitro by MTT, scratch, and transwell assays. Most importantly, overexpression of PCDH7 promotes breast cancer cell proliferation and invasion in vitro, and formation of bone metastasis in vivo. These data provide an important insight into the role of PCDH7 in bone metastasis of breast cancer.« less

Role of glucocorticoid-induced leucine zipper (GILZ) in bone acquisition

USDA-ARS?s Scientific Manuscript database

Glucocorticoids (GCs) have both anabolic and catabolic effects on bone. However, no GC anabolic effect mediator has been identified to date. In this report, we provide the first evidence that glucocorticoid-induced leucine zipper (GILZ), a GC anti-inflammatory effect mediator, can enhance bone forma...

Engineering 3D Models of Tumors and Bone to Understand Tumor-Induced Bone Disease and Improve Treatments

PubMed Central

Kwakwa, Kristin A.; Vanderburgh, Joseph P.; Guelcher, Scott A.

2018-01-01

Purpose of Review Bone is a structurally unique microenvironment that presents many challenges for the development of 3D models for studying bone physiology and diseases, including cancer. As researchers continue to investigate the interactions within the bone microenvironment, the development of 3D models of bone has become critical. Recent Findings 3D models have been developed that replicate some properties of bone, but have not fully reproduced the complex structural and cellular composition of the bone microenvironment. This review will discuss 3D models including polyurethane, silk, and collagen scaffolds that have been developed to study tumor-induced bone disease. In addition, we discuss 3D printing techniques used to better replicate the structure of bone. Summary 3D models that better replicate the bone microenvironment will help researchers better understand the dynamic interactions between tumors and the bone microenvironment, ultimately leading to better models for testing therapeutics and predicting patient outcomes. PMID:28646444

Perception of Affordance during Short-Term Exposure to Weightlessness in Parabolic Flight

PubMed Central

Bourrelly, Aurore; McIntyre, Joseph; Morio, Cédric; Despretz, Pascal; Luyat, Marion

2016-01-01

We investigated the role of the visual eye-height (VEH) in the perception of affordance during short-term exposure to weightlessness. Sixteen participants were tested during parabolic flight (0g) and on the ground (1g). Participants looked at a laptop showing a room in which a doorway-like aperture was presented. They were asked to adjust the opening of the virtual doorway until it was perceived to be just wide enough to pass through (i.e., the critical aperture). We manipulated VEH by raising the level of the floor in the visual room by 25 cm. The results showed effects of VEH and of gravity on the perceived critical aperture. When VEH was reduced (i.e., when the floor was raised), the critical aperture diminished, suggesting that widths relative to the body were perceived to be larger. The critical aperture was also lower in 0g, for a given VEH, suggesting that participants perceived apertures to be wider or themselves to be smaller in weightlessness, as compared to normal gravity. However, weightlessness also had an effect on the subjective level of the eyes projected into the visual scene. Thus, setting the critical aperture as a fixed percentage of the subjective visual eye-height remains a viable hypothesis to explain how human observers judge visual scenes in terms of potential for action or “affordances”. PMID:27097218

Study of Histopathological and Molecular Changes of Rat Kidney under Simulated Weightlessness and Resistance Training Protective Effect

PubMed Central

Li, Zhili; Tian, Jijing; Abdelalim, Saed; Du, Fang; She, Ruiping; Wang, Desheng; Tan, Cheng; Wang, Huijuan; Chen, Wenjuan; Lv, Dongqiang; Chang, Lingling

2011-01-01

To explore the effects of long-term weightlessness on the renal tissue, we used the two months tail suspension model to simulate microgravity and investigated the simulated microgravity on the renal morphological damages and related molecular mechanisms. The microscopic examination of tissue structure and ultrastructure was carried out for histopathological changes of renal tissue morphology. The immunohistochemistry, real-time PCR and Western blot were performed to explore the molecular mechanisms associated the observations. Hematoxylin and eosin (HE) staining showed severe pathological kidney lesions including glomerular atrophy, degeneration and necrosis of renal tubular epithelial cells in two months tail-suspended rats. Ultrastructural studies of the renal tubular epithelial cells demonstrated that basal laminas of renal tubules were rough and incrassate with mitochondria swelling and vacuolation. Cell apoptosis in kidney monitored by the expression of Bax/Bcl-2 and caspase-3 accompanied these pathological damages caused by long-term microgravity. Analysis of the HSP70 protein expression illustrated that overexpression of HSP70 might play a crucial role in inducing those pathological damages. Glucose regulated protein 78 (GRP78), one of the endoplasmic reticulum (ER) chaperones, was up-regulated significantly in the kidney of tail suspension rat, which implied that ER-stress was associated with apoptosis. Furthermore, CHOP and caspase-12 pathways were activated in ER-stress induced apoptosis. Resistance training not only reduced kidney cell apoptosis and expression of HSP70 protein, it also can attenuate the kidney impairment imposed by weightlessness. The appropriate optimization might be needed for the long term application for space exploration. PMID:21625440

Weightlessness - A case history. [for Skylab 2 crewmen

NASA Technical Reports Server (NTRS)

Kerwin, J. P.

1975-01-01

A review of the average bodily systems functioning aboard Skylab II after 20 days of weightlessness is presented. Condition of eyes, ears, nose and throat, gastrointestinal tract, vestibular organs, cardiovascular system, musculoskeletal system, sleep, general appearance, skin, abdomen, and extremities is summarized. The general health of the crewmen is good, although there are some slight anomalies, such as weight loss, dry skin, nasal speech, and paresthesia of the soles of the feet.

Micropore-induced Capillarity Enhances Bone Distribution in vivo in Biphasic Calcium Phosphate Scaffolds

PubMed Central

Rustom, Laurence E.; Boudou, Thomas; Lou, Siyu; Pignot-Paintrand, Isabelle; Nemke, Brett W.; Lu, Yan; Markel, Mark D.; Picart, Catherine; Wagoner Johnson, Amy J.

2016-01-01

The increasing demand for bone repair solutions calls for the development of efficacious bone scaffolds. Biphasic calcium phosphate (BCP) scaffolds with both macropores and micropores (MP) have improved healing compared to those with macropores and no micropores (NMP), but the role of micropores is unclear. Here, we evaluate capillarity induced by micropores as a mechanism that can affect bone growth in vivo. Three groups of cylindrical scaffolds were implanted in pig mandibles for three weeks: MP were implanted either dry (MP-Dry), or after submersion in phosphate buffered saline, which fills pores with fluid and therefore suppresses micropore-induced capillarity (MP-Wet); NMP were implanted dry. The amount and distribution of bone in the scaffolds were quantified using micro-computed tomography. MP-Dry had a more homogeneous bone distribution than MP-Wet, although the average bone volume fraction, BVF¯, was not significantly different for these two groups (0.45±0.03 and 0.37±0.03, respectively). There was no significant difference in the radial bone distribution of NMP and MP-Wet, but the BVF¯ of NMP was significantly lower among the three groups (0.25±0.02). These results suggest that micropore-induced capillarity enhances bone regeneration by improving the homogeneity of bone distribution in BCP scaffolds. The explicit design and use of capillarity in bone scaffolds may lead to more effective treatments of large and complex bone defects. PMID:27544807

Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

NASA Technical Reports Server (NTRS)

Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

1995-01-01

Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p < 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

Potential Effects of Phytoestrogen Genistein in Modulating Acute Methotrexate Chemotherapy-Induced Osteoclastogenesis and Bone Damage in Rats

PubMed Central

King, Tristan J.; Shandala, Tetyana; Lee, Alice M.; Foster, Bruce K.; Chen, Ke-Ming; Howe, Peter R.; Xian, Cory J.

2015-01-01

Chemotherapy-induced bone damage is a frequent side effect which causes diminished bone mineral density and fracture in childhood cancer sufferers and survivors. The intensified use of anti-metabolite methotrexate (MTX) and other cytotoxic drugs has led to the need for a mechanistic understanding of chemotherapy-induced bone loss and for the development of protective treatments. Using a young rat MTX-induced bone loss model, we investigated potential bone protective effects of phytoestrogen genistein. Oral gavages of genistein (20 mg/kg) were administered daily, for seven days before, five days during, and three days after five once-daily injections (sc) of MTX (0.75 mg/kg). MTX treatment reduced body weight gain and tibial metaphyseal trabecular bone volume (p < 0.001), increased osteoclast density on the trabecular bone surface (p < 0.05), and increased the bone marrow adipocyte number in lower metaphyseal bone (p < 0.001). Genistein supplementation preserved body weight gain (p < 0.05) and inhibited ex vivo osteoclast formation of bone marrow cells from MTX-treated rats (p < 0.001). However, MTX-induced changes in bone volume, trabecular architecture, metaphyseal mRNA expression of pro-osteoclastogenic cytokines, and marrow adiposity were not significantly affected by the co-administration of genistein. This study suggests that genistein may suppress MTX-induced osteoclastogenesis; however, further studies are required to examine its potential in protecting against MTX chemotherapy-induced bone damage. PMID:26258775

New insights to the role of aryl hydrocarbon receptor in bone phenotype and in dioxin-induced modulation of bone microarchitecture and material properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herlin, Maria, E-mail: maria.herlin@ki.se; Finnilä, Mikko A.J., E-mail: mikko.finnila@oulu.fi; Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu

Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such as dioxins. Although bone morphology, mineral density and strength are sensitive endpoints of dioxin toxicity, less is known about effects on bone microarchitecture and material properties. This study characterizes TCDD-induced modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity and for normal bone phenotype. Six AHR-knockout (Ahr{sup −/−}) and wild-type (Ahr{sup +/+}) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200 μg/kg bw. Bones were examined with micro-computed tomography, nanoindentation and biomechanical testing. Serummore » levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr{sup +/+} mice, TCDD-exposure resulted in harder bone matrix, thinner and more porous cortical bone, and a more compact trabecular bone compartment. Bone remodeling markers and altered expression of a number of osteogenesis related genes indicated imbalanced bone remodeling. Untreated Ahr{sup −/−} mice displayed a slightly modified bone phenotype as compared with untreated Ahr{sup +/+} mice, while TCDD exposure caused only a few changes in bones of Ahr{sup −/−} mice. Part of the effects of both TCDD-exposure and AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker bones and most notably, increased trabecular bone volume fraction in Ahr{sup +/+} mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. - Highlights: • TCDD disrupts bone remodeling resulting in altered cortical and trabecular bone. • In trabecular bone an anabolic effect is observed. • Cortical bone is thinner, more porous, harder, stiffer and mechanically weaker. • AHR

Spatial orientation in weightlessness and readaptation to earth's gravity

NASA Technical Reports Server (NTRS)

Young, L. R.; Oman, C. M.; Lichtenberg, B. K.; Watt, D. G. D.; Money, K. E.

1984-01-01

Unusual vestibular responses to head movements in weightlessness may produce spatial orientation illusions and symptoms of space motion sickness. An integrated set of experiments was performed during Spacelab 1, as well as before and after the flight, to evaluate responses mediated by the otolith organs and semicircular canals. A variety of measurements were used, including eye movements, postural control, perception of orientation, and susceptibility to space sickness.

Anti-osteoporotic activity of harpagide by regulation of bone formation in osteoblast cell culture and ovariectomy-induced bone loss mouse models.

PubMed

Chung, Hwa-Jin; Kyung Kim, Won; Joo Park, Hyen; Cho, Lan; Kim, Me-Riong; Kim, Min Jeong; Shin, Joon-Shik; Ho Lee, Jin; Ha, In-Hyuk; Kook Lee, Sang

2016-02-17

Harpagide, an iridoid glucoside, is a constituent of the root of Harpagophytum procumbens var. sublobatum (Engl.) Stapf, Devil's claw which has been used in patients with osteoarthritis (OA). In the present study, we investigated the anti-osteoporotic potential of harpagide and its underlying mechanism of action in in vitro cell culture and in vivo bone loss animal models. Harpagide was obtained from the alkalic hydrolysis of harpagoside, a major constituent of H. procumbens var. sublobatum Analysis of biomarkers for bone formation in osteoblastic MC3T3-E1 cells and bone resorption in osteoclast cells derived from mouse bone marrow cells was performed to evaluate the mechanism of action. The protective activity of harpagide against bone loss was also evaluated in ovariectomized (OVX) mouse model. Harpagide improved bone properties by stimulating the process of differentiation and maturation of osteoblast cells and suppressing the process of RANKL-induced differentiation of osteoclast cells. In OVX-induced bone loss mouse model, oral administration of harpagide significantly improved recovery of bone mineral density, trabecular bone volume, and trabecular number in the femur. Harpagide also prevented increase of trabecular separation and structure model index induced by OVX. Harpagide effectively inhibited the serum levels of biochemical markers of bone loss, including alkaline phosphatase, osteocalcin, C-terminal telopeptide, and tartrate-resistant acid phosphatase. Taken together, the present study demonstrates that harpagide has a potential for prevention of bone loss in OVX mice by regulating the stimulation of osteoblast differentiation and the suppression of osteoclast formation. Therefore, these findings suggest that harpagide might serve as a bioactive compound derived from H. procumbens var. sublobatum for improvement of age-dependent bone destruction disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of chronic acceleration on body composition

NASA Technical Reports Server (NTRS)

Pitts, G. C.

1982-01-01

Studies of the centrifugation of adult rats showed an unexpected decrease in the mass of fat-free muscle and bone, in spite of the added load induced by centrifugation. It is suggested that the lower but constant fat-free body mass was probably regulated during centrifugation. Rats placed in weightless conditions for 18.5 days gave indirect but strong evidence that the muscle had increased in mass. Other changes in the rats placed in weightless conditions included a smaller fraction of skeletal mineral, a smaller fraction of water in the total fat-free body, and a net shift of fluid from skin to viscera. Adult rats centrifuged throughout the post-weaning growth period exhibited smaller masses of bone and central nervous system (probably attributable to slower growth of the total body), and a larger mass of skin than controls at 1 G. Efforts at simulating the effects of weightlessness or centrifugation on the body composition of rats by regimens at terrestrial gravity were inconclusive.

The validity of an animal model for experiments related to weightlessness

NASA Technical Reports Server (NTRS)

Musacchia, X. J.; Steffen, J. M.

1983-01-01

Animal evolution has witnessed morphological and physiological adaptations to gravitational forces. In the rat, hind limb muscles can be used to illustrate a range of load bearing functions: soleus - gastrocnemius = plantaris - extensor digitorum longus (EDL). A harness suspension apparatus is used to induce hypokinesia and hypodynamia (H&H) and to simulate responses comparable to those seen in weightlessness (i.e., COSMOS experiments). After one and two weeks of suspension H&H, there is muscle atrophy with a loss in muscle mass; the result of loss in muscle protein. Concommitantly, there is a decrease in RNA, but not in DNA content. The effects are greatest in the soleus and least in the EDL. These recent findings, in concert with earlier reports of increased nitrogenous excretion, suggest that both decreased protein synthesis and increased protein catabolism are characteristic of muscle atrophy. Recovery is seen in terms of reversal of these effects after removal from suspension.

Genistein suppresses Prevotella intermedia lipopolysaccharide-induced inflammatory response in macrophages and attenuates alveolar bone loss in ligature-induced periodontitis.

PubMed

Choi, Eun-Young; Bae, Seung Han; Ha, Min Hee; Choe, So-Hui; Hyeon, Jin-Yi; Choi, Jeom-Il; Choi, In Soon; Kim, Sung-Jo

2016-02-01

Genistein is a major isoflavone subclass of flavonoids found in soybean and a potent tyrosine kinase inhibitor. The present study aimed to assess the effect of genistein on the production of proinflammatory mediators in murine macrophages stimulated with lipopolysaccharide (LPS) isolated from Prevotella intermedia, a pathogen associated with different forms of periodontal disease, and to evaluate its possible influence on alveolar bone loss in ligature-induced periodontitis using micro-computed tomography (micro-CT) analysis as well. LPS was isolated from P. intermedia ATCC 25611 by using the standard hot phenol-water method. Culture supernatants were analyzed for nitric oxide (NO) and interleukin-6 (IL-6). Inducible NO synthase (iNOS) protein expression was evaluated by immunoblot analysis. Real-time PCR was carried out to measure iNOS and IL-6 mRNA expression. In addition, effect of genistein on alveolar bone loss was evaluated in a rat model of experimental periodontitis using micro-CT analysis. Genistein significantly attenuated P. intermedia LPS-induced production of iNOS-derived NO and IL-6 with attendant decrease in their mRNA expression in RAW264.7 cells. In addition, when genistein was administered to rats, decreases in alveolar bone height and bone volume fraction induced by ligature placement were significantly inhibited. Genistein administration also prevented ligature-induced alterations in the microstructural parameters of trabecular bone, including trabecular thickness, trabecular separation, bone mineral density and structure model index. While additional studies are required, we suggest that genistein could be utilized for the therapy of human periodontitis in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

Electrical potentials in bone induced by ultrasound irradiation in the megahertz range

NASA Astrophysics Data System (ADS)

Okino, M.; Coutelou, S.; Mizuno, K.; Yanagitani, T.; Matsukawa, M.

2013-09-01

Low frequency mechanical studies have reported the contribution of stress-induced electrical potentials to bone metabolism. However, the healing mechanism of bone fractures by low intensity ultrasound is not yet clear. We demonstrate that bone can generate electrical potentials by ultrasound irradiation in the MHz range. Electrical potentials were obtained from the output of bovine cortical bone transducers. In the range of 0.7-2.5 MHz, sensitivities of bone transducers were around 1/1000 of a poly (vinylidene fluoride) ultrasonic transducer and did not depend on magnitude and alignment of hydroxyapatite crystallites in bone.

GEMINI-TITAN (GT)-8 - TRAINING - PILOT IN WEIGHTLESSNESS USING EXPERIMENT TOOL - FL

NASA Image and Video Library

1966-02-18

S66-24410 (18 Feb. 1966) --- Astronaut David R. Scott performs a maintenance and repair experiment with a battery-powered tool during a state of weightlessness while in extravehicular activity (EVA) training on a KC-135. Photo credit: NASA

Weightlessness and the human skeleton: A new perspective

NASA Technical Reports Server (NTRS)

Holick, Michael F.

1994-01-01

It is now clear after more than two decades of space exploration that one of the major short- and long-term effects of microgravity on the human body is the loss of bone. The purpose of this presentation will be to review the data regarding the impact of microgravity and bed rest on calcium and bone metabolism. The author takes the position in this Socratic debate that the effect of microgravity on bone metabolism can be either reversed or mitigated. As we begins to contemplate long-duration space flight and habitation of Space Station Freedom and the moon, one of the issues that needs to be addressed is whether humans need to maintain a skeleton that has been adapted for the one-g force on earth. Clearly, in the foreseeable future, a healthy and structurally sound skeleton will be required for astronauts to shuttle back and forth from earth to the moon, space station, and Mars. Based on most available data from bed-rest studies and the short- and long-duration microgravity experiences by astronauts and cosmonauts, bone loss is a fact of life in this environment. With the rapid advances in understanding of bone physiology it is now possible to contemplate measures that can prevent or mitigate microgravity-induced bone loss. Will the new therapeutic approaches for enhancing bone mineralization be useful for preventing significant bone loss during long-term space flight? Are there other approaches such as exercise and electrical stimulation that can be used to mitigate the impact of microgravity on the skeleton? A recent study that evaluated the effect of microgravity on bone modeling in developing chick embryos may perhaps provide a new perspective about the impact of microgravity on bone metabolism.

Can the adult skeleton recover lost bone?

NASA Technical Reports Server (NTRS)

Leblanc, Adrian; Schneider, Victor

1991-01-01

The loss of bone mineral with aging and subsequent development of osteoporosis is a common problem in elderly women, and as life expectancy increases, in elderly men as well. Space flight also causes bone loss and could be a limiting factor for long duration missions, such as, a Mars expedition or extended occupation of a Space Station. Before effective countermeasures can be devised, a thorough knowledge of the extent, location, and rate of bone loss during weightlessness is needed from actual space flight data or ground-based disuse models. In addition, the rate and extent that these losses are reversed after return from space flight are of primary importance. Although the mechanisms are not likely to be the same in aging and space flight, there are common elements. For example, strategies developed to prevent disuse bone loss or to enhance the rate of recovery following space flight might have direct applicability to clinical medicine. For various reasons, little attention has been given to recovery of bone mass following space flight. As a prelude to the design of strategies to enhance recovery of bone, this paper reviews published literature related to bone recovery in the adult. We conclude that recovery can be expected, but the rate and extent will be individual and bone site dependent. The development of strategies to encourage or enhance bone formation following space flight may be as important as implementing countermeasures during flight.

Automated potentiometric electrolyte analysis system. [for use in weightlessness

NASA Technical Reports Server (NTRS)

1973-01-01

The feasibility is demonstrated of utilizing chemical sensing electrode technology as the basis for an automatically-controlled system for blood gas and electrolyte analyses under weightlessness conditions. The specific measurements required were pH, pCO2, sodium, chloride, potassium ions, and ionized calcium. The general electrode theory, and ion activity measurements are described along with the fluid transport package, electronics unit, and controller for the automated potentiometric analysis system.

Suppression of NADPH oxidases prevents chronic ethanol-induced bone loss

USDA-ARS?s Scientific Manuscript database

Since the molecular mechanisms through which chronic excessive alcohol consumption induces osteopenia and osteoporosis are largely unknown, potential treatments for prevention of alcohol-induced bone loss remain unclear. We have previously demonstrated that, chronic ethanol (EtOH) treatment leads to...

Role of Prostaglandin Pathway and Alendronate-Based Carriers to Enhance Statin-induced Bone

PubMed Central

Lee, Yeonju; Liu, Xinming; Nawshad, Ali; Marx, David B.; Wang, Dong; Reinhardt, Richard A.

2011-01-01

Objective This study investigated the role of the prostaglandin (PG) pathway in locally-applied, simvastatin-induced oral bone growth. The possibility of enhancing long-term bone augmentation with an alendronate-based carrier was initiated. Methods Mandibles of 44 mature female rats were treated bilaterally with the following combinations: 2 mg simvastatin in ethanol (SIM-EtOH), EtOH, 2 mg simvastatin acid complexed with alendronate-beta-cyclodextrin conjugate (SIM/ALN-CD), ALN-CD, or ALN. Bone wash technology (injection of PBS and recollection by suction) was used to sample injection sites at baseline (day 0), and 3, 7, 14 and 21 days post-treatment. After 21-24 or 48 days, histomorphometric analysis was done. The amount of PGE2 in bone wash fluid was measured by ELISA, normalized by total protein, and compared between high and low bone growth groups (ANOVA) and correlated with subsequent bone histology at 21 days (Spearman). SIM-stimulated PGE2 synthase and EP4 receptor mRNA in murine osteoblast and fibroblast cell lines were evaluated with real-time PCR. Results Single injections of 2 mg SIM-EtOH induced significantly more new bone than control side after 21 days. PGE2/protein ratios peaked at day 7 and were correlated with the subsequent 21-day new bone width. The correlations at day 14 between PGE2 and new bone width changed to a negative relationship in the test group. SIM-stimulated osteoblasts expressed increased mRNA levels of PGE receptor EP4, while SIM activated PGE synthesis in fibroblasts. SIM/ALN-CD tended to preserve bone long-term. Conclusion Findings suggest that PGE pathway activation and higher levels of PGE2 during the first week following SIM-induced bone growth are desirable, and alendronate-beta-cyclodextrin conjugates not only act as tissue-specific carriers, but preserve new bone. PMID:21438610

Postural equilibrium following exposure to weightless space flight

NASA Technical Reports Server (NTRS)

Homick, J. L.; Reschke, M. F.

1977-01-01

Postural equilibrium performance by Skylab crewmen following exposure to weightlessness of 28, 59, and 84 days respectively was evaluated using a modified version of a quantitative ataxia test developed by Graybiel and Fregly (1966). Performance for this test was measured under two sets of conditions. In the first, the crewman was required to maintain postural equilibrium on narrow metal rails (or floor) with his eyes open. In the second condition, he attempted to balance with his eyes closed. A comparison of the preflight and postflight data indicated moderate postflight decrements in postural equilibrium in three of the crewmen during the eyes open test condition. In the eyes-closed condition, a considerable decrease in ability to maintain balance on the rails was observed postflight for all crewmen tested. The magnitude of the change was most pronounced during the first postflight test day. Improvement was slow; however, on the basis of data obtained, recovery of preflight baseline levels of performance was evidently complete at the end of approximately two weeks for all crewmen. The findings are explained in terms of functional alterations in the kinesthetic, touch, vestibular and neuromuscular sensory mechanisms induced by the prolonged absence of a normal 1-G gravitational environment.

The effects of orbital spaceflight on bone histomorphometry and messenger ribonucleic acid levels for bone matrix proteins and skeletal signaling peptides in ovariectomized growing rats

NASA Technical Reports Server (NTRS)

Cavolina, J. M.; Evans, G. L.; Harris, S. A.; Zhang, M.; Westerlind, K. C.; Turner, R. T.

1997-01-01

A 14-day orbital spaceflight was performed using ovariectomized Fisher 344 rats to determine the combined effects of estrogen deficiency and near weightlessness on tibia radial bone growth and cancellous bone turnover. Twelve ovariectomized rats with established cancellous osteopenia were flown aboard the space shuttle Columbia (STS-62). Thirty ovariectomized rats were housed on earth as ground controls: 12 in animal enclosure modules, 12 in vivarium cages, and 6 killed the day of launch for baseline measurements. An additional 18 ovary-intact rats were housed in vivarium cages as ground controls: 8 rats were killed as baseline controls and the remaining 10 rats were killed 14 days later. Ovariectomy increased periosteal bone formation at the tibia-fibula synostosis; cancellous bone resorption and formation in the secondary spongiosa of the proximal tibial metaphysis; and messenger RNA (mRNA) levels for the prepro-alpha2(1) subunit of type 1 collagen, osteocalcin, transforming growth factor-beta, and insulin-like growth factor I in the contralateral proximal tibial metaphysis and for the collagen subunit in periosteum pooled from tibiae and femora and decreased cancellous bone area. Compared to ovariectomized weight-bearing rats, the flight group experienced decreases in periosteal bone formation, collagen subunit mRNA levels, and cancellous bone area. The flight rats had a small decrease in the cancellous mineral apposition rate, but no change in the calculated bone formation rate. Also, spaceflight had no effect on cancellous osteoblast and osteoclast perimeters or on mRNA levels for bone matrix proteins and signaling peptides. On the other hand, spaceflight resulted in an increase in bone resorption, as ascertained from the diminished retention of a preflight fluorochrome label. This latter finding suggests that osteoclast activity was increased. In a follow-up ground-based experiment, unilateral sciatic neurotomy of ovariectomized rats resulted in cancellous

High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo.

PubMed

Zara, Janette N; Siu, Ronald K; Zhang, Xinli; Shen, Jia; Ngo, Richard; Lee, Min; Li, Weiming; Chiang, Michael; Chung, Jonguk; Kwak, Jinny; Wu, Benjamin M; Ting, Kang; Soo, Chia

2011-05-01

The major Food and Drug Association-approved osteoinductive factors in wide clinical use are bone morphogenetic proteins (BMPs). Although BMPs can promote robust bone formation, they also induce adverse clinical effects, including cyst-like bone formation and significant soft tissue swelling. In this study, we evaluated multiple BMP2 doses in a rat femoral segmental defect model and in a minimally traumatic rat femoral onlay model to determine its dose-dependent effects. Results of our femoral segmental defect model established a low BMP2 concentration range (5 and 10 μg/mL, total dose 0.375 and 0.75 μg in 75 μg total volume) unable to induce defect fusion, a mid-range BMP2 concentration range able to fuse the defect without adverse effects (30 μg/mL, total dose 2.25 μg in 75 μg total volume), and a high BMP2 concentration range (150, 300, and 600 μg/mL, total dose 11.25, 22.5, and 45 μg in 75 μg total volume) able to fuse the defect, but with formation of cyst-like bony shells filled with histologically confirmed adipose tissue. In addition, compared to control, 4 mg/mL BMP2 also induced significant tissue inflammatory infiltrates and exudates in the femoral onlay model that was accompanied by increased numbers of osteoclast-like cells at 3, 7, and 14 days. Overall, we consistently reproduced BMP2 side effects of cyst-like bone and soft tissue swelling using high BMP2 concentration approaching the typical human 1500 μg/mL.

High Doses of Bone Morphogenetic Protein 2 Induce Structurally Abnormal Bone and Inflammation In Vivo

PubMed Central

Zara, Janette N.; Siu, Ronald K.; Zhang, Xinli; Shen, Jia; Ngo, Richard; Lee, Min; Li, Weiming; Chiang, Michael; Chung, Jonguk; Kwak, Jinny; Wu, Benjamin M.; Ting, Kang

2011-01-01

The major Food and Drug Association–approved osteoinductive factors in wide clinical use are bone morphogenetic proteins (BMPs). Although BMPs can promote robust bone formation, they also induce adverse clinical effects, including cyst-like bone formation and significant soft tissue swelling. In this study, we evaluated multiple BMP2 doses in a rat femoral segmental defect model and in a minimally traumatic rat femoral onlay model to determine its dose-dependent effects. Results of our femoral segmental defect model established a low BMP2 concentration range (5 and 10 μg/mL, total dose 0.375 and 0.75 μg in 75 μg total volume) unable to induce defect fusion, a mid-range BMP2 concentration range able to fuse the defect without adverse effects (30 μg/mL, total dose 2.25 μg in 75 μg total volume), and a high BMP2 concentration range (150, 300, and 600 μg/mL, total dose 11.25, 22.5, and 45 μg in 75 μg total volume) able to fuse the defect, but with formation of cyst-like bony shells filled with histologically confirmed adipose tissue. In addition, compared to control, 4 mg/mL BMP2 also induced significant tissue inflammatory infiltrates and exudates in the femoral onlay model that was accompanied by increased numbers of osteoclast-like cells at 3, 7, and 14 days. Overall, we consistently reproduced BMP2 side effects of cyst-like bone and soft tissue swelling using high BMP2 concentration approaching the typical human 1500 μg/mL. PMID:21247344

Focused Assessment with Sonography for Trauma in weightlessness: a feasibility study

NASA Technical Reports Server (NTRS)

Kirkpatrick, Andrew W.; Hamilton, Douglas R.; Nicolaou, Savvas; Sargsyan, Ashot E.; Campbell, Mark R.; Feiveson, Alan; Dulchavsky, Scott A.; Melton, Shannon; Beck, George; Dawson, David L.

2003-01-01

BACKGROUND: The Focused Assessment with Sonography for Trauma (FAST) examines for fluid in gravitationally dependent regions. There is no prior experience with this technique in weightlessness, such as on the International Space Station, where sonography is currently the only diagnostic imaging tool. STUDY DESIGN: A ground-based (1 g) porcine model for sonography was developed. We examined both the feasibility and the comparative performance of the FAST examination in parabolic flight. Sonographic detection and fluid behavior were evaluated in four animals during alternating weightlessness (0 g) and hypergravity (1.8 g) periods. During flight, boluses of fluid were incrementally introduced into the peritoneal cavity. Standardized sonographic windows were recorded. Postflight, the video recordings were divided into 169 20-second segments for subsequent interpretation by 12 blinded ultrasonography experts. Reviewers first decided whether a video segment was of sufficient diagnostic quality to analyze (determinate). Determinate segments were then analyzed as containing or not containing fluid. A probit regression model compared the probability of a positive fluid diagnosis to actual fluid levels (0 to 500 mL) under both 0-g and 1.8-g conditions. RESULTS: The in-flight sonographers found real-time scanning and interpretation technically similar to that of terrestrial conditions, as long as restraint was maintained. On blinded review, 80% of the recorded ultrasound segments were considered determinate. The best sensitivity for diagnosis in 0 g was found to be from the subhepatic space, with probability of a positive fluid diagnosis ranging from 9% (no fluid) to 51% (500 mL fluid). CONCLUSIONS: The FAST examination is technically feasible in weightlessness, and merits operational consideration for clinical contingencies in space.

Suppression of asparaginyl endopeptidase attenuates breast cancer-induced bone pain through inhibition of neurotrophin receptors.

PubMed

Yao, Peng; Ding, Yuanyuan; Han, Zhenkai; Mu, Ying; Hong, Tao; Zhu, Yongqiang; Li, Hongxi

2017-01-01

Objective Cancer-induced bone pain is a common clinical problem in breast cancer patients with bone metastasis. However, the mechanisms driving cancer-induced bone pain are poorly known. Recent studies show that a novel protease, asparaginyl endopeptidase (AEP) plays crucial roles in breast cancer metastasis and progression. We aim to determine the functions and targeted suppress of AEP in a mouse model of breast cancer-induced bone pain. Methods Breast cancer cells with AEP knocked-down or overexpression were constructed and implanted into the intramedullary space of the femur to induce pain-like behavior in mice. AEP-specific inhibitors or purified AEP proteins were further used in animal model. The histological characters of femur and pain ethological changes were measured. The expressions of AEP and neurotrophin receptors (p75NTR and TrkA) in dorsal root ganglion and spinal cord were examined. Results Femur radiographs and histological analysis revealed that cells with AEP knocked-down reduced bone destruction and pain behaviors. However, cells with AEP overexpression elevated bone damage and pain behaviors. Further, Western blot results found that the expressions of p75NTR and TrkA in dorsal root ganglions and spinal cords were reduced in mice inoculated with AEP knocked-down cells. Targeted suppression of AEP with specific small compounds significantly reduced the bone pain while purified recombinant AEP proteins increased bone pain. Conclusions AEP aggravate the development of breast cancer bone metastasis and bone pain by increasing the expression of neurotrophin receptors. AEP might be an effective target for treatment of breast cancerinduced bone pain.

Prostaglandin E2 Prevents Ovariectomy-Induced Cancellous Bone Loss in Rats

NASA Technical Reports Server (NTRS)

Ke, Hua Zhu; Li, Mei; Jee, Webster S. S.

1992-01-01

The object of this study was to determine whether prostaglandin E2, (PGE2) can prevent ovariectomy induced cancellous bone loss. Thirty-five 3-month-old female Sprague-Dawley rats were divided into two groups. The rats in the first group were ovariectomized (OVX) while the others received sham operation (sham-OVX). The OVX group was further divided into three treatment groups. The daily doses for the three groups were 0,1 and 6 mg PGE2/kg for 90 days. Bone histomorphometric analyses were performed on double-fluorescent-labeled undecalcified proximal tibial metaphysis (PTM). We confirmed that OVX induces massive cancellous bone loss (-80%) and a higher bone turnover (+143%). The new findings from the present study demonstrate that bone loss due to ovarian hormone deficiency can be prevented by a low-dose (1 mg) daily administration of PGE2. Furthermore, a higher-dose (6 mg) daily administration of PGE2 not only prevents bone loss but also adds extra bone to the proximal tibial metaphyses. PGE, at the 1-mg dose level significantly increased trabecular bone area, trabecular width, trabecular node density, density of node to node, ratio of node to free end, and thus significantly decreased trabecular separation from OVX controls. At this dose level, these same parameters did not differ significantly from sham-OVX controls. However, at the 6-mg dose level PGE2, there were significant increases in trabecular bone area, trabecular width, trabecular node density, density of node to node, and ratio of node to free end, while there was significant decrease in trabecular separation from both OVX and sham-operated controls. The changes in indices of trabecular bone microanatomical structure indicated that PGE2 prevented bone loss as well as the disconnection of existing trabeculae. In summary, PGE2, administration to OVX rats decreased bone turnover and increased bone formation parameters resulting in a positive bone balance that prevented bone loss (in both lower and higher

Multiscale alterations in bone matrix quality increased fragility in steroid induced osteoporosis

PubMed Central

Karunaratne, A.; Xi, L.; Bentley, L.; Sykes, D.; Boyde, A.; Esapa, C.T.; Terrill, N.J.; Brown, S.D.M.; Cox, R.D.; Thakker, R.V.; Gupta, H.S.

2016-01-01

A serious adverse clinical effect of glucocorticoid steroid treatment is secondary osteoporosis, enhancing fracture risk in bone. This rapid increase in bone fracture risk is largely independent of bone loss (quantity), and must therefore arise from degradation of the quality of the bone matrix at the micro- and nanoscale. However, we lack an understanding of both the specific alterations in bone quality n steroid-induced osteoporosis as well as the mechanistic effects of these changes. Here we demonstrate alterations in the nanostructural parameters of the mineralized fibrillar collagen matrix, which affect bone quality, and develop a model linking these to increased fracture risk in glucocorticoid induced osteoporosis. Using a mouse model with an N-ethyl-N-nitrosourea (ENU)-induced corticotrophin releasing hormone promoter mutation (Crh− 120/+) that developed hypercorticosteronaemia and osteoporosis, we utilized in situ mechanical testing with small angle X-ray diffraction, synchrotron micro-computed tomography and quantitative backscattered electron imaging to link altered nano- and microscale deformation mechanisms in the bone matrix to abnormal macroscopic mechanics. We measure the deformation of the mineralized collagen fibrils, and the nano-mechanical parameters including effective fibril modulus and fibril to tissue strain ratio. A significant reduction (51%) of fibril modulus was found in Crh− 120/+ mice. We also find a much larger fibril strain/tissue strain ratio in Crh− 120/+ mice (~ 1.5) compared to the wild-type mice (~ 0.5), indicative of a lowered mechanical competence at the nanoscale. Synchrotron microCT show a disruption of intracortical architecture, possibly linked to osteocytic osteolysis. These findings provide a clear quantitative demonstration of how bone quality changes increase macroscopic fragility in secondary osteoporosis. PMID:26657825

A systems analysis of the erythropoietic responses to weightlessness. Volume 1: Mathematical model simulations of the erythropoietic responses to weightlessness

NASA Technical Reports Server (NTRS)

Leonard, J. I.

1985-01-01

Theoretical responses to weightlessness are summarized. The studies include development and validation of a model of erythropoiesis regulation, analysis of the behavior of erythropoiesis under a variety of conditions, simulations of bed rest and space flight, and an evaluation of ground-based animal studies which were conducted as analogs of zero-g. A review of all relevant space flight findings and a set of testable hypotheses which attempt to explain how red cell mass decreases in space flight are presented. An additional document describes details of the mathematical model used in these studies.

Network Analysis Implicates Alpha-Synuclein (Snca) in the Regulation of Ovariectomy-Induced Bone Loss

PubMed Central

Calabrese, Gina; Mesner, Larry D.; Foley, Patricia L.; Rosen, Clifford J.; Farber, Charles R.

2016-01-01

The postmenopausal period in women is associated with decreased circulating estrogen levels, which accelerate bone loss and increase the risk of fracture. Here, we gained novel insight into the molecular mechanisms mediating bone loss in ovariectomized (OVX) mice, a model of human menopause, using co-expression network analysis. Specifically, we generated a co-expression network consisting of 53 gene modules using expression profiles from intact and OVX mice from a panel of inbred strains. The expression of four modules was altered by OVX, including module 23 whose expression was decreased by OVX across all strains. Module 23 was enriched for genes involved in the response to oxidative stress, a process known to be involved in OVX-induced bone loss. Additionally, module 23 homologs were co-expressed in human bone marrow. Alpha synuclein (Snca) was one of the most highly connected “hub” genes in module 23. We characterized mice deficient in Snca and observed a 40% reduction in OVX-induced bone loss. Furthermore, protection was associated with the altered expression of specific network modules, including module 23. In summary, the results of this study suggest that Snca regulates bone network homeostasis and ovariectomy-induced bone loss. PMID:27378017

Nanostructured thick 3D nanofibrous scaffold can induce bone.

PubMed

Eap, Sandy; Morand, David; Clauss, François; Huck, Olivier; Stoltz, Jean-François; Lutz, Jean-Christophe; Gottenberg, Jacques-Eric; Benkirane-Jessel, Nadia; Keller, Laetitia; Fioretti, Florence

2015-01-01

Designing unique nanostructured biomimetic materials is a new challenge in modern regenerative medicine. In order to develop functional substitutes for damaged organs or tissues, several methods have been used to create implants able to regenerate robust and durable bone. Electrospinning produces nonwoven scaffolds based on polymer nanofibers mimicking the fibrillar organization of bone extracellular matrix. Here, we describe a biomimetic 3D thick nanofibrous scaffold obtained by electrospinning of the biodegradable, bioresorbable and FDA-approved polymer, poly(ε-caprolactone). Such scaffold presents a thickness reaching one centimeter. We report here the demonstration that the designed nanostructured implant is able to induce in vivo bone regeneration.

Repression of Osteoblast Maturation by ERRα Accounts for Bone Loss Induced by Estrogen Deficiency

PubMed Central

Gallet, Marlène; Saïdi, Soraya; Haÿ, Eric; Photsavang, Johann; Marty, Caroline; Sailland, Juliette; Carnesecchi, Julie; Tribollet, Violaine; Barenton, Bruno; Forcet, Christelle; Birling, Marie-Christine; Sorg, Tania; Chassande, Olivier; Cohen-Solal, Martine; Vanacker, Jean-Marc

2013-01-01

ERRα is an orphan member of the nuclear receptor family, the complete inactivation of which confers resistance to bone loss induced by ageing and estrogen withdrawal to female mice in correlation with increased bone formation in vivo. Furthermore ERRα negatively regulates the commitment of mesenchymal cells to the osteoblast lineage ex vivo as well as later steps of osteoblast maturation. We searched to determine whether the activities of ERRα on osteoblast maturation are responsible for one or both types of in vivo induced bone loss. To this end we have generated conditional knock out mice in which the receptor is normally present during early osteoblast differentiation but inactivated upon osteoblast maturation. Bone ageing in these animals was similar to that observed for control animals. In contrast conditional ERRαKO mice were completely resistant to bone loss induced by ovariectomy. We conclude that the late (maturation), but not early (commitment), negative effects of ERRα on the osteoblast lineage contribute to the reduced bone mineral density observed upon estrogen deficiency. PMID:23359549

Repression of osteoblast maturation by ERRα accounts for bone loss induced by estrogen deficiency.

PubMed

Gallet, Marlène; Saïdi, Soraya; Haÿ, Eric; Photsavang, Johann; Marty, Caroline; Sailland, Juliette; Carnesecchi, Julie; Tribollet, Violaine; Barenton, Bruno; Forcet, Christelle; Birling, Marie-Christine; Sorg, Tania; Chassande, Olivier; Cohen-Solal, Martine; Vanacker, Jean-Marc

2013-01-01

ERRα is an orphan member of the nuclear receptor family, the complete inactivation of which confers resistance to bone loss induced by ageing and estrogen withdrawal to female mice in correlation with increased bone formation in vivo. Furthermore ERRα negatively regulates the commitment of mesenchymal cells to the osteoblast lineage ex vivo as well as later steps of osteoblast maturation. We searched to determine whether the activities of ERRα on osteoblast maturation are responsible for one or both types of in vivo induced bone loss. To this end we have generated conditional knock out mice in which the receptor is normally present during early osteoblast differentiation but inactivated upon osteoblast maturation. Bone ageing in these animals was similar to that observed for control animals. In contrast conditional ERRαKO mice were completely resistant to bone loss induced by ovariectomy. We conclude that the late (maturation), but not early (commitment), negative effects of ERRα on the osteoblast lineage contribute to the reduced bone mineral density observed upon estrogen deficiency.

Weightless Environment Training Facility (WETF) materials coating evaluation, volume 2

NASA Technical Reports Server (NTRS)

1995-01-01

This volume consists of Appendices A and B to the report on the Weightless Environment Training Facility Materials Coating Evaluation project. The project selected 10 coating systems to be evaluated in six separate exposure environments, and subject to three tests for physical properties. Appendix A holds the coating system, surface preparation, and application data. Appendix B holds the coating material infrared spectra.

Distributed automatic control of technological processes in conditions of weightlessness

NASA Technical Reports Server (NTRS)

Kukhtenko, A. I.; Merkulov, V. I.; Samoylenko, Y. I.; Ladikov-Royev, Y. P.

1986-01-01

Some problems associated with the automatic control of liquid metal and plasma systems under conditions of weightlessness are examined, with particular reference to the problem of stability of liquid equilibrium configurations. The theoretical fundamentals of automatic control of processes in electrically conducting continuous media are outlined, and means of using electromagnetic fields for simulating technological processes in a space environment are discussed.

The salutary effect of dietary calcium on bone mass in a rat model of simulated weightlessness

NASA Technical Reports Server (NTRS)

Bikle, D. D.; Globus, R.; Halloran, B. P.; Morey-Holton, E.

1985-01-01

Whether supplementation of dietary calcium reduces the differences in bone mass of unweighed limbs and normally weighted limbs, and whether parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH)2D) respond differently to dietary calcium in unweighted animals in comparison with pair-fed controls was studied. The hind limbs of rats were unweighted by a tail suspension method and diets containing 0.1% to 2.4% calcium. After 2 weeks serum calcium, phosphorus, PTH and 1,25(OH)2D intestinal calcium transport were determined and bone mass, ash weight, and calcium in the tibia, L-1 vertebra, and humerus were measured. No significant differences in body weights were observed among the various groups. Suspended rats maintained constant levels of serum calcium and phosphate over the wide range of dietary calcium. Serum PTH and 1,25(OH)2D and intestinal calcium transport fell as dietary calcium was increased. Bone calcium in the tibia and vertebra from suspended rats remained less than that from pair-fed control. It is suggested that although no striking difference between suspended and control animals was observed in response to dieteary calcium, increasing dietary calcium may reduce the negative impact of unloading on the calcium content of the unweighted bones. The salutary effect of high dietary calcium appears to be due to inhibition of bone resorption rather than to stimulation of bone formation.

Endoscopic surgery in weightlessness: the investigation of basic principles for surgery in space.

PubMed

Campbell, M R; Kirkpatrick, A W; Billica, R D; Johnston, S L; Jennings, R; Short, D; Hamilton, D; Dulchavsky, S A

2001-12-01

Performing a surgical procedure in weightlessness, also called 0-gravity (0-g), has been shown to be no more difficult than in a 1-g environment if the requirements for the restraint of the patient, operator, surgical hardware, are observed. The performance of laparoscopic and thorascopic procedures in weightlessness, if feasible, would offer several advantages over the performance of an open operation. Concerns about the feasibility of performing minimally invasive procedures in weightlessness have included impaired visualization from the absence of gravitational retraction of the bowel (laparoscopy) or thoracic organs (thoracoscopy) as well as obstruction and interference from floating debris such as blood, pus, and irrigation fluid. The purpose of this study was to determine the feasibility of performing laparoscopic and thorascopic procedures and the degree of impaired surgical endoscopic visualization in weightlessness. From 1993 to 2000, laparoscopic and thorascopic procedures were performed on 10 anesthetized adult pigs weighing approximately 50 kg in the National Aeronautics and Space Administration (NASA) Microgravity Program using a modified KC-135 airplane. The parabolic simulation system for advanced life support was used in this project, and 20 to 40 parabolas were used for laparoscopic or thorascopic investigation, each containing approximately 30 s of 0-g alternating with 2-g pullouts. The animal model was restrained in the supine position on a floor-level Crew Medical Restraint System, and the abdominal cavity was insufflated with carbon dioxide. The intraabdominal and intrathoracic anatomy was visualized in the 1-g, 0-g, and 2-g periods of parabolic flight. Bleeding was created in the animals, and the behavior of the blood in the abdominal and thoracic cavities was observed. In the thoracic cavity, gas insufflation and mechanical retraction was used at times unilaterally to decrease pulmonary ventilation enough to increase the thoracic domain

Exercise prevents high fat diet-induced bone loss, marrow adiposity and dysbiosis in male mice.

PubMed

McCabe, Laura R; Irwin, Regina; Tekalur, Arjun; Evans, Christian; Schepper, Jonathan D; Parameswaran, Narayanan; Ciancio, Mae

2018-03-29

High fat diets can have detrimental effects on the skeleton as well as cause intestinal dysbiosis. Exercise prevents high fat (HF) diet-induced obesity and also improves bone density and prevents the intestinal dysbiosis that promotes energy storage. Previous studies indicate a link between intestinal microbial balance and bone health. Therefore, we examined whether exercise could prevent HF-induced bone pathology in male mice and determined whether benefits correlate to changes in host intestinal microbiota. Male C57Bl/6 mice were fed either a low fat diet (LF; 10 kcal% fat) or a HF diet (60 kcal% fat) and put under sedentary or voluntary exercise conditions for 14 weeks. Our results indicated that HF diet reduced trabecular bone volume, when corrected for differences in body weight, of both the tibia (40% reduction) and vertebrae (25% reduction) as well and increased marrow adiposity (44% increase). More importantly, these effects were prevented by exercise. Exercise also had a significant effect on several cortical bone parameters and enhanced bone mechanical properties in LF but not HF fed mice. Microbiome analyses indicated that exercise altered the HF induced changes in microbial composition by reducing the Firmicutes/Bacteriodetes ratio. This ratio negatively correlated with bone volume as did levels of Clostridia and Lachnospiraceae. In contrast, the abundance of several Actinobacteria phylum members (i.e., Bifidobacteriaceae) were positively correlated with bone volume. Taken together, exercise can prevent many of the negative effects of a high fat diet on male skeletal health. Exercise induced changes in microbiota composition could represent a novel mechanism that contributes to exercise induced benefits to bone health. Copyright © 2018 Elsevier Inc. All rights reserved.

High glucose induces bone marrow-derived mesenchymal stem cell senescence by upregulating autophagy.

PubMed

Chang, Tzu-Ching; Hsu, Min-Fen; Wu, Kenneth K

2015-01-01

Hyperglycemia was reported to cause bone marrow hematopoietic niche dysfunction, and high glucose (HG) in the cultured medium induces MSC senescence. The underlying mechanism is unclear. Here, we investigated the role of HG-induced autophagy in bone-marrow-derived mesenchymal stem cell (BMSC) senescence. HG (25 mM) increased expression of Beclin-1, Atg 5, 7 and 12, generation of LC3-II and autophagosome formation which was correlated with development of cell senescence. Pretreatment of HG-MSC with 3-methyladenine (3-MA) prevented senescence but increased apoptosis. N-acetylcysteine (NAC) was effective in abrogating HG-induced autophagy accompanied by prevention of senescence. Diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase, blocked autophagy and senescence in a manner comparable to NAC. 3-MA, NAC and DPI inhibited HG-induced interleukin-6 production in BMSCs. These results suggest that hyperglycemia induces MSC senescence and local inflammation via a novel oxidant-mediated autophagy which contributes to bone marrow niche dysfunction and hematopoietic impairment.

Niclosamide suppresses RANKL-induced osteoclastogenesis and prevents LPS-induced bone loss

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheon, Yoon-Hee; Kim, Ju-Young; Baek, Jong Min

Niclosamide (5-chloro-salicyl-(2-chloro-4-nitro) anilide) is an oral anthelmintic drug used for treating intestinal infection of most tapeworms. Recently, niclosamide was shown to have considerable efficacy against some tumor cell lines, including colorectal, prostate, and breast cancers, and acute myelogenous leukemia. Specifically, the drug was identified as a potent inhibitor of signal transducer and activator of transcription 3 (STAT3), which is associated with osteoclast differentiation and function. In this study, we assessed the effect of niclosamide on osteoclastogenesis in vitro and in vivo. Our in vitro study showed that receptor activator of nuclear factor-kappaB ligand (RANKL)-induced osteoclast differentiation was inhibited by niclosamide, due to inhibitionmore » of serine–threonine protein kinase (Akt) phosphorylation, inhibitor of nuclear factor-kappaB (IκB), and STAT3 serine{sup 727}. Niclosamide decreased the expression of the major transcription factors c-Fos and NFATc1, and thereafter abrogated the mRNA expression of osteoclast-specific genes, including TRAP, OSCAR, αv/β3 integrin (integrin αv, integrin β3), and cathepsin K (CtsK). In an in vivo model, niclosamide prevented lipopolysaccharide-induced bone loss by diminishing osteoclast activity. Taken together, our results show that niclosamide is effective in suppressing osteoclastogenesis and may be considered as a new and safe therapeutic candidate for the clinical treatment of osteoclast-related diseases such as osteoporosis. - Highlights: • We first investigated the anti-osteoclastogenic effects of niclosamide in vitro and in vivo. • Niclosamide impairs the activation of the Akt-IκB-STAT3 ser{sup 727} signaling axis. • Niclosamide acts a negative regulator of actin ring formation during osteoclast differentiation. • Niclosamide suppresses LPS-induced bone loss in vivo. • Niclosamide deserves new evaluation as a potential treatment target in various bone diseases.« less

Acupuncture for Cancer-Induced Bone Pain?

PubMed Central

Paley, Carole A.; Bennett, Michael I.; Johnson, Mark I.

2011-01-01

Bone pain is the most common type of pain in cancer. Bony metastases are common in advanced cancers, particularly in multiple myeloma, breast, prostate or lung cancer. Current pain-relieving strategies include the use of opioid-based analgesia, bisphosphonates and radiotherapy. Although patients experience some pain relief, these interventions may produce unacceptable side-effects which inevitably affect the quality of life. Acupuncture may represent a potentially valuable adjunct to existing strategies for pain relief and it is known to be relatively free of harmful side-effects. Although acupuncture is used in palliative care settings for all types of cancer pain the evidence-base is sparse and inconclusive and there is very little evidence to show its effectiveness in relieving cancer-induced bone pain (CIBP). The aim of this critical review is to consider the known physiological effects of acupuncture and discuss these in the context of the pathophysiology of malignant bone pain. The aim of future research should be to produce an effective protocol for treating CIBP with acupuncture based on a sound, evidence-based rationale. The physiological mechanisms presented in this review suggest that this is a realistic objective. PMID:21799687

Role of subchondral bone properties and changes in development of load-induced osteoarthritis in mice.

PubMed

Adebayo, O O; Ko, F C; Wan, P T; Goldring, S R; Goldring, M B; Wright, T M; van der Meulen, M C H

2017-12-01

Animal models recapitulating post-traumatic osteoarthritis (OA) suggest that subchondral bone (SCB) properties and remodeling may play major roles in disease initiation and progression. Thus, we investigated the role of SCB properties and its effects on load-induced OA progression by applying a tibial loading model on two distinct mouse strains treated with alendronate (ALN). Cyclic compression was applied to the left tibia of 26-week-old male C57Bl/6 (B6, low bone mass) and FVB (high bone mass) mice. Mice were treated with ALN (26 μg/kg/day) or vehicle (VEH) for loading durations of 1, 2, or 6 weeks. Changes in articular cartilage and subchondral and epiphyseal cancellous bone were analyzed using histology and microcomputed tomography. FVB mice exhibited thicker cartilage, a thicker SCB plate, and higher epiphyseal cancellous bone mass and tissue mineral density than B6 mice. Loading induced cartilage pathology, osteophyte formation, and SCB changes; however, lower initial SCB mass and stiffness in B6 mice did not attenuate load-induced OA severity compared to FVB mice. By contrast, FVB mice exhibited less cartilage damage, and slower-growing and less mature osteophytes. In B6 mice, inhibiting bone remodeling via ALN treatment exacerbated cartilage pathology after 6 weeks of loading, while in FVB mice, inhibiting bone remodeling protected limbs from load-induced cartilage loss. Intrinsically lower SCB properties were not associated with attenuated load-induced cartilage loss. However, inhibiting bone remodeling produced differential patterns of OA pathology in animals with low compared to high SCB properties, indicating that these factors do influence load-induced OA progression. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

2014 Summer Series - Josh Alwood - To the Bone: Spaceflight and the Skeletal System

NASA Image and Video Library

2014-08-05

During spaceflight, astronauts experience weightlessness and are exposed to novel types of radiation. These environmental conditions may contribute to bone loss and reduction of structural integrity of the skeleton, which have negative implications for long-duration missions. The aim of this talk is to provide an overview of skeletal changes observed both in astronauts and in ground-based models of spaceflight, focusing on the fundamental biology and the prevention of deleterious skeletal changes.

Prediction of femoral neck and spine bone mineral content from the BMC of the radius or ulna and the relationship between bone strength and BMC

NASA Technical Reports Server (NTRS)

Wilson, C. R.

1974-01-01

The bone mineral content (BMC) is extensively used to provide information about the status of an entire skeleton. Changes in BMC are employed to evaluate the effect of various drugs, disease states, weightlessness, exercise, renal dialysis and others on the skeleton. Clinical and functional information is discussed that may be derived from the BMC of a limited region of the skeleton. In particular there is a fairly high degree of correlation between the BMC of the radius or ulna and that of the femoral neck, r about 0.85 and a somewhat lower relationship between the BMC of the radius or ulna and the thoracic vertebrae, r about 0.65. Also the BMC is highly related to the strength of bone at that scan site.

Effects of microstructure and water on the electrical potentials in bone induced by ultrasound irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsuneda, H.; Matsukawa, S.; Takayanagi, S.

The healing mechanism of bone fractures by low intensity pulse ultrasound is yet to be fully understood. There have been many discussions regarding how the high frequency dynamic stress can stimulate numerous cell types through various pathways. As one possible initial process of this mechanism, we focus on the piezoelectricity of bone and demonstrate that bone can generate electrical potentials by ultrasound irradiation in the MHz range. We have fabricated ultrasonic bone transducers using bovine cortical bone as the piezoelectric device. The ultrasonically induced electrical potentials in the transducers change as a function of time during immersed ultrasonic pulse measurementsmore » and become stable when the bone is fully wet. In addition, the magnitude of the induced electrical potentials changes owing to the microstructure in the cortical bone. The potentials of transducers with haversian structure bone are higher than those of plexiform structure bone, which informs about the effects of bone microstructure on the piezoelectricity.« less

Effects of microstructure and water on the electrical potentials in bone induced by ultrasound irradiation

NASA Astrophysics Data System (ADS)

Tsuneda, H.; Matsukawa, S.; Takayanagi, S.; Mizuno, K.; Yanagitani, T.; Matsukawa, M.

2015-02-01

The healing mechanism of bone fractures by low intensity pulse ultrasound is yet to be fully understood. There have been many discussions regarding how the high frequency dynamic stress can stimulate numerous cell types through various pathways. As one possible initial process of this mechanism, we focus on the piezoelectricity of bone and demonstrate that bone can generate electrical potentials by ultrasound irradiation in the MHz range. We have fabricated ultrasonic bone transducers using bovine cortical bone as the piezoelectric device. The ultrasonically induced electrical potentials in the transducers change as a function of time during immersed ultrasonic pulse measurements and become stable when the bone is fully wet. In addition, the magnitude of the induced electrical potentials changes owing to the microstructure in the cortical bone. The potentials of transducers with haversian structure bone are higher than those of plexiform structure bone, which informs about the effects of bone microstructure on the piezoelectricity.

Ablation of the pro-apoptotic protein Bax protects mice from glucocorticoid-induced bone growth impairment.

PubMed

Zaman, Farasat; Chrysis, Dionisios; Huntjens, Kirsten; Fadeel, Bengt; Sävendahl, Lars

2012-01-01

Dexamethasone (Dexa) is a widely used glucocorticoid to treat inflammatory diseases; however, a multitude of undesired effects have been reported to arise from this treatment including osteoporosis, obesity, and in children decreased longitudinal bone growth. We and others have previously shown that glucocorticoids induce apoptosis in growth plate chondrocytes. Here, we hypothesized that Bax, a pro-apoptotic member of the Bcl-2 family, plays a key role in Dexa-induced chondrocyte apoptosis and bone growth impairment. Indeed, experiments in the human HCS-2/8 chondrocytic cell line demonstrated that silencing of Bax expression using small-interfering (si) RNA efficiently blocked Dexa-induced apoptosis. Furthermore, ablation of Bax in female mice protected against Dexa-induced bone growth impairment. Finally, Bax activation by Dexa was confirmed in human growth plate cartilage specimens cultured ex vivo. Our findings could therefore open the door for new therapeutic approaches to prevent glucocorticoid-induced bone growth impairment through specific targeting of Bax.

Hydromechanics and heat and mass exchange in weightlessness (Russian book): Table of contents

NASA Technical Reports Server (NTRS)

Avduyevskiy, V. S.; Poleshayev, V. I.

1983-01-01

The table of contents is given for a book on hydromechanics and heat and mass exchange in weightlessness. The book covers such subjects as hydromechanics, convection and heat and mass exchange, and technological experiments and complicated systems.

A systems approach to the physiology of weightlessness

NASA Technical Reports Server (NTRS)

White, Ronald J.; Leonard, Joel I.; Rummel, John A.; Leach, Carolyn S.

1991-01-01

A general systems approach to conducting and analyzing research on the human adaptation to weightlessness is presented. The research is aimed at clarifying the role that each of the major components of the human system plays following the transition to and from space. The approach utilizes a variety of mathematical models in order to pose and test alternative hypotheses concerned with the adaptation process. Certain aspects of the problem of fluid and electrolyte shifts in weightlessnes are considered, and an integrated hypothesis based on numerical simulation studies and experimental data is presented.

Gravity, Calcium, and Bone: Update, 1989

NASA Technical Reports Server (NTRS)

Arnaud, Sara B.; Morey-Holton, Emily

1991-01-01

Some of the results of recent short-term flights and ground-based experiments that have contributed new insights into skeletal adaptation, calcium metabolism, and growth processes in 0 g, are highlighted. After 6 months in space, bone demineralization, invariably involving the os calcis, was found not to extend to the lumbar spine in 4 exercising cosmonauts. A flight experiment in the Space Shuttle crew has documented the early events in the calcium endocrine system during spaceflight. On the ground, brief and long-term bed rest studies of healthy volunteers in the head-down tile (HDT) model of weightlessness were completed. The skeleton of the adult male responds more rapidly to unloading than previously recognized. Regional changes in bone density can be quantified in only 30 days, are highly individual, and follow the direction of gravitational forces in the HDT model during inactivity. Bone biopsy results in healthy volunteers after bed rest differ from results in paraplegics from the same sampling site. Flight experiments in growing rats reveal changes in the composition of bone mineral and matrix in the femur postflight that were found to be highly regional and suggestive of an effect of gravity on mineral distribution. These observations may be relevant to the results from an earlier Cosmos flight where artificial gravity in space was found to maintain bone strength, but not to correct the radial growth deficit.

Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

NASA Technical Reports Server (NTRS)

LeBlanc, A.; Matsumoto, T.; Jones, J.; Shapiro, J.; Lang, T.; Shackelford, L.; Smith, S.; Evans, H.; Spector, E.; Ploutz-Snyder, R.;

Synergistic Effects of Vascular Endothelial Growth Factor on Bone Morphogenetic Proteins Induced Bone Formation In Vivo: Influencing Factors and Future Research Directions

PubMed Central

Li, Bo; Wang, Hai; Qiu, Guixing; Su, Xinlin

2016-01-01

Vascular endothelial growth factor (VEGF) and bone morphogenetic proteins (BMPs), as key mediators in angiogenesis and osteogenesis, are used in a combined delivery manner as a novel strategy in bone tissue engineering. VEGF has the potential to enhance BMPs induced bone formation. Both gene delivery and material-based delivery systems were incorporated in previous studies to investigate the synergistic effects of VEGF and BMPs. However, their results were controversial due to variation of methods incorporated in different studies. Factors influencing the synergistic effects of VEGF on BMPs induced bone formation were identified and analyzed in this review to reduce confusion on this issue. The potential mechanisms and directions of future studies were also proposed here. Further investigating mechanisms of the synergistic effects and optimizing these influencing factors will help to generate more effective bone regeneration. PMID:28070506

Selected contribution: redistribution of pulmonary perfusion during weightlessness and increased gravity

NASA Technical Reports Server (NTRS)

Glenny, R. W.; Lamm, W. J.; Bernard, S. L.; An, D.; Chornuk, M.; Pool, S. L.; Wagner, W. W. Jr; Hlastala, M. P.; Robertson, H. T.

2000-01-01

To compare the relative contributions of gravity and vascular structure to the distribution of pulmonary blood flow, we flew with pigs on the National Aeronautics and Space Administration KC-135 aircraft. A series of parabolas created alternating weightlessness and 1.8-G conditions. Fluorescent microspheres of varying colors were injected into the pulmonary circulation to mark regional blood flow during different postural and gravitational conditions. The lungs were subsequently removed, air dried, and sectioned into approximately 2 cm(3) pieces. Flow to each piece was determined for the different conditions. Perfusion heterogeneity did not change significantly during weightlessness compared with normal and increased gravitational forces. Regional blood flow to each lung piece changed little despite alterations in posture and gravitational forces. With the use of multiple stepwise linear regression, the contributions of gravity and vascular structure to regional perfusion were separated. We conclude that both gravity and the geometry of the pulmonary vascular tree influence regional pulmonary blood flow. However, the structure of the vascular tree is the primary determinant of regional perfusion in these animals.

Changes in markers of bone formation and resorption in a bed rest model of weightlessness

NASA Technical Reports Server (NTRS)

Lueken, S. A.; Arnaud, S. B.; Taylor, A. K.; Baylink, D. J.

1993-01-01

To study the mechanism of bone loss in physical unloading, we examined indices of bone formation and bone resorption in the serum and urine of eight healthy men during a 7 day -6 degrees head-down tilt bed rest. Prompt increases in markers of resorption--pyridinoline (PD), deoxypyridinoline (DPD), and hydroxyproline (Hyp)/g creatinine--during the first few days of inactivity were paralleled by tartrate-resistant acid phosphatase (TRAP) with significant increases in all these markers by day 4 of bed rest. An index of formation, skeletal alkaline phosphatase (SALP), did not change during bed rest and showed a moderate 15% increase 1 week after reambulation. In contrast to SALP, serum osteocalcin (OC) began increasing the day preceding the increase in Hyp, remained elevated for the duration of the bed rest, and returned to pre-bed rest values within 5 days of reambulation. Similarly, DPD increased significantly at the onset of bed rest, remained elevated for the duration of bed rest, and returned to pre-bed rest levels upon reambulation. On the other hand, the other three indices of resorption, Hyp, PD, and TRAP, remained elevated for 2 weeks after reambulation. The most sensitive indices of the levels of physical activity proved to be the noncollagenous protein, OC, and the collagen crosslinker, DPD. The bed rest values of both these markers were significantly elevated compared to both the pre-bed rest values and the post-bed rest values. The sequence of changes in the circulating markers of bone metabolism indicated that increases in serum OC are the earliest responses of bone to head-down tilt bed rest.

Intake of Fish and Omega-3 (N-3) Fatty Acid: Effect on Humans during Actual and Simulated Weightlessness

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Mehta, Satish K.; Pierson, Duane L.; Zwart, Sara R.

2009-01-01

Space flight has many negative effects on human physiology, including bone and muscle loss. These are some of the systems on which intakes of fish and n-3 fatty acids have positive effects. These effects are likely to occur through inhibition of inflammatory cytokines (such as TNFalpha) and thus inhibition of downstream NF-KB activation. We documented this effect in a 3D cell culture model, where NF-KB activation in osteoclasts was inhibited by eicosapentaenoic acid, an n-3 fatty acid. We have extended these studies and report here (a) NF-KB expression in peripheral blood mononuclear cells of Space Shuttle crews on 2-wk missions, (b) the effects of n-3 fatty acid intake after 60 d of bed rest (a weightlessness analog), and (c) the effects of fish intake in astronauts after 4 to 6 mo on the International Space Station. After Shuttle flights of 2 wk, NFKB p65 expression at landing was increased (P less than 0.001). After 60 d of bed rest, higher intake of n-3 fatty acids was associated with less N-telopeptide excretion (Pearson r = -0.62, P less than 0.05). Higher consumption of fish during flight was associated with higher bone mineral density (Pearson r = -0.46, P less than 0.05). Together with our earlier findings, these data provide mechanistic cellular and preliminary human evidence of the potential for n-3 fatty acids to counteract bone loss associated with spaceflight. This study was supported by the NASA Human Research Program.

Effects of weightlessness on human fluid and electrolyte physiology

NASA Technical Reports Server (NTRS)

Leach, Carolyn S.; Johnson, Philip C., Jr.

1991-01-01

Skylab and Spacelab data on changes occurring in human fluid and electrolyte physiology during the acute and adaptive phases of adaptation to spaceflight are summarized. The combined results for all three Spacelab studies show that hyponatremia developed within 20 h after the onset of weightlessness and continued throughout the flights, and hypokalemia developed by 40 h. Antidiuretic hormone was increased in plasma throughout the flights. Aldosterone decreased by 40 h, but after 7 days it had reached preflight levels.

Acoustical levitation for space processing. [weightless molten material manipulation

NASA Technical Reports Server (NTRS)

Wang, T. G.; Saffren, M. M.; Elleman, D. D.

1974-01-01

It is pointed out that many space-manufacturing processes will require the manipulation of weightless molten material within a container in such a way that the material does not touch the container wall. A description is given of an acoustical method which can be used for the positioning and shaping of any molten material including nonconductors such as glasses. The new approach makes use of an acoustical standing wave which is excited within an enclosure or resonator.

Bone loss and human adaptation to lunar gravity

NASA Technical Reports Server (NTRS)

Keller, T. S.; Strauss, A. M.

1992-01-01

Long-duration space missions and establishment of permanently manned bases on the Moon and Mars are currently being planned. The weightless environment of space and the low-gravity environments of the Moon and Mars pose an unknown challenge to human habitability and survivability. Of particular concern in the medical research community today is the effect of less than Earth gravity on the human skeleton, since the limits, if any, of human endurance in low-gravity environments are unknown. This paper provides theoretical predictions on bone loss and skeletal adaptation to lunar and other nonterrestrial-gravity environments based upon the experimentally derived relationship, density approximately (mass x gravity)(exp 1/8). The predictions are compared to skeletal changes reported during bed rest, immobilization, certrifugation, and spaceflight. Countermeasures to reduce bone losses in fractional gravity are also discussed.

Adaptations of young adult rat cortical bone to 14 days of spaceflight

NASA Technical Reports Server (NTRS)

Vailas, A. C.; Vanderby, R., Jr.; Martinez, D. A.; Ashman, R. B.; Ulm, M. J.; Grindeland, R. E.; Durnova, G. N.; Kaplanskii, A.

1992-01-01

To determine whether mature humeral cortical bone would be modified significantly by an acute exposure to weightlessness, adult rats (110 days old) were subjected to 14 days of microgravity on the COSMOS 2044 biosatellite. There were no significant changes in peak force, stiffness, energy to failure, and displacement at failure in the flight rats compared with ground-based controls. Concentrations and contents of hydroxyproline, calcium, and mature stable hydroxylysylpyridinoline and lysylpyridinoline collagen cross-links remained unchanged after spaceflight. Bone lengths, cortical and endosteal areas, and regionl thicknesses showed no significant differences between flight animals and ground controls. The findings suggest that responsiveness of cortical bone to microgravity is less pronounced in adult rats than in previous spaceflight experiments in which young growing animals were used. It is hypothesized that 14 days of spaceflight may not be sufficient to impact the biochemical and biomechanical properties of cortical bone in the mature rat skeleton.

Glucocorticoids Induce Bone and Muscle Atrophy by Tissue-Specific Mechanisms Upstream of E3 Ubiquitin Ligases

PubMed Central

Sato, Amy Y.; Richardson, Danielle; Cregor, Meloney; Davis, Hannah M.; Au, Ernie D.; McAndrews, Kevin; Zimmers, Teresa A.; Organ, Jason M.; Peacock, Munro; Plotkin, Lilian I.

2017-01-01

Glucocorticoid excess, either endogenous with diseases of the adrenal gland, stress, or aging or when administered for immunosuppression, induces bone and muscle loss, leading to osteopenia and sarcopenia. Muscle weakness increases the propensity for falling, which, combined with the lower bone mass, increases the fracture risk. The mechanisms underlying glucocorticoid-induced bone and muscle atrophy are not completely understood. We have demonstrated that the loss of bone and muscle mass, decreased bone formation, and reduced muscle strength, hallmarks of glucocorticoid excess, are accompanied by upregulation in both tissues in vivo of the atrophy-related genes atrogin1, MuRF1, and MUSA1. These are E3 ubiquitin ligases traditionally considered muscle-specific. Glucocorticoids also upregulated atrophy genes in cultured osteoblastic/osteocytic cells, in ex vivo bone organ cultures, and in muscle organ cultures and C2C12 myoblasts/myotubes. Furthermore, glucocorticoids markedly increased the expression of components of the Notch signaling pathway in muscle in vivo, ex vivo, and in vitro. In contrast, glucocorticoids did not increase Notch signaling in bone or bone cells. Moreover, the increased expression of atrophy-related genes in muscle, but not in bone, and the decreased myotube diameter induced by glucocorticoids were prevented by inhibiting Notch signaling. Thus, glucocorticoids activate different mechanisms in bone and muscle that upregulate atrophy-related genes. However, the role of these genes in the effects of glucocorticoids in bone is unknown. Nevertheless, these findings advance our knowledge of the mechanism of action of glucocorticoids in the musculoskeletal system and provide the basis for novel therapies to prevent glucocorticoid-induced atrophy of bone and muscle. PMID:28359087

Inertial torque during reaching directly impacts grip-force adaptation to weightless objects.

PubMed

Giard, T; Crevecoeur, F; McIntyre, J; Thonnard, J-L; Lefèvre, P

2015-11-01

A hallmark of movement control expressed by healthy humans is the ability to gradually improve motor performance through learning. In the context of object manipulation, previous work has shown that the presence of a torque load has a direct impact on grip-force control, characterized by a significantly slower grip-force adjustment across lifting movements. The origin of this slower adaptation rate remains unclear. On the one hand, information about tangential constraints during stationary holding may be difficult to extract in the presence of a torque. On the other hand, inertial torque experienced during movement may also potentially disrupt the grip-force adjustments, as the dynamical constraints clearly differ from the situation when no torque load is present. To address the influence of inertial torque loads, we instructed healthy adults to perform visually guided reaching movements in weightlessness while holding an unbalanced object relative to the grip axis. Weightlessness offered the possibility to remove gravitational constraints and isolate the effect of movement-related feedback on grip force adjustments. Grip-force adaptation rates were compared with a control group who manipulated a balanced object without any torque load and also in weightlessness. Our results clearly show that grip-force adaptation in the presence of a torque load is significantly slower, which suggests that the presence of torque loads experienced during movement may alter our internal estimates of how much force is required to hold an unbalanced object stable. This observation may explain why grasping objects around the expected location of the center of mass is such an important component of planning and control of manipulation tasks.

Fucoidan-induced osteogenic differentiation promotes angiogenesis by inducing vascular endothelial growth factor secretion and accelerates bone repair.

PubMed

Kim, Beom-Su; Yang, Sun-Sik; You, Hyung-Keun; Shin, Hong-In; Lee, Jun

2018-03-01

Osteogenesis and angiogenesis, including cell-cell communication between blood vessel cells and bone cells, are essential for bone repair. Fucoidan is a chemical compound that has a variety of biological activities. It stimulates osteoblast differentiation in human mesenchymal stem cells (MSCs), which in turn induces angiogenesis. However, the mechanism by which this communication between osteoblasts and endothelial cells is mediated remains unclear. Thus, the aim of this study was to clarify the relationship between fucoidan-induced osteoblastic differentiation in MSCs and angiogenesis in endothelial cells. First, the effect was confirmed of fucoidan on osteoblast differentiation in MSCs and obtained conditioned media from these cells (Fucoidan-MSC-CM). Next, the angiogenic activity of Fucoidan-MSC-CM was investigated and it was found that it stimulated angiogenesis, demonstrated by proliferation, tube formation, migration and sprout capillary formation in human umbilical vein endothelial cells. Messenger ribonucleic acid expression and protein secretion of vascular endothelial growth factor (VEGF) were dramatically increased during fucoidan-induced osteoblast differentiation and that its angiogenic activities were reduced by a VEGF/VEGF receptor-specific binding inhibitor. Furthermore, Fucoidan-MSC-CM increased the phosphorylation of mitogen-activated protein kinase and PI3K/AKT/eNOS signalling pathway, and that its angiogenic effects were markedly suppressed by SB203580 and AKT 1/2 inhibitor. Finally, an in vivo study was conducted and it was found that fucoidan accelerated new blood vessel formation and partially promoted bone formation in a rabbit model of a calvarial bone defect. This is the first study to investigate the angiogenic effect of fucoidan-induced osteoblastic differentiation through VEGF secretion, suggesting the therapeutic potential of fucoidan for enhancing bone repair. Copyright © 2017 John Wiley & Sons, Ltd.

Functionalization of PCL-3D Electrospun Nanofibrous Scaffolds for Improved BMP2-Induced Bone Formation.

PubMed

Miszuk, Jacob M; Xu, Tao; Yao, Qingqing; Fang, Fang; Childs, Josh D; Hong, Zhongkui; Tao, Jianning; Fong, Hao; Sun, Hongli

2018-03-01

Bone morphogenic protein 2 (BMP2) is a key growth factor for bone regeneration, possessing FDA approval for orthopedic applications. BMP2 is often required in supratherapeutic doses clinically, yielding adverse side effects and substantial treatment costs. Considering the crucial role of materials for BMPs delivery and cell osteogenic differentiation, we devote to engineering an innovative bone-matrix mimicking niche to improve low dose of BMP2-induced bone formation. Our previous work describes a novel technique, named thermally induced nanofiber self-agglomeration (TISA), for generating 3D electrospun nanofibrous (NF) polycaprolactone (PCL) scaffolds. TISA process could readily blend PCL with PLA, leading to increased osteogenic capabilities in vitro , however, these bio-inert synthetic polymers produced limited BMP2-induced bone formation in vivo. We therefore hypothesize that functionalization of NF 3D PCL scaffolds with bone-like hydroxyapatite (HA) and BMP2 signaling activator phenamil will provide a favorable osteogenic niche for bone formation at low doses of BMP2. Compared to PCL-3D scaffolds, PCL/HA-3D scaffolds demonstrated synergistically enhanced osteogenic differentiation capabilities of C2C12 cells with phenamil. Importantly, in vivo studies showed this synergism was able to generate significantly increased new bone in an ectopic mouse model, suggesting PCL/HA-3D scaffolds act as a favorable synthetic extracellular matrix for bone regeneration.

Endoscopic surgery in weightlessness: the investigation of basic principles for surgery in space

NASA Technical Reports Server (NTRS)

Campbell, M. R.; Kirkpatrick, A. W.; Billica, R. D.; Johnston, S. L.; Jennings, R.; Short, D.; Hamilton, D.; Dulchavsky, S. A.

2001-01-01

BACKGROUND: Performing a surgical procedure in weightlessness, also called 0-gravity (0-g), has been shown to be no more difficult than in a 1-g environment if the requirements for the restraint of the patient, operator, surgical hardware, are observed. The performance of laparoscopic and thorascopic procedures in weightlessness, if feasible, would offer several advantages over the performance of an open operation. Concerns about the feasibility of performing minimally invasive procedures in weightlessness have included impaired visualization from the absence of gravitational retraction of the bowel (laparoscopy) or thoracic organs (thoracoscopy) as well as obstruction and interference from floating debris such as blood, pus, and irrigation fluid. The purpose of this study was to determine the feasibility of performing laparoscopic and thorascopic procedures and the degree of impaired surgical endoscopic visualization in weightlessness. METHODS: From 1993 to 2000, laparoscopic and thorascopic procedures were performed on 10 anesthetized adult pigs weighing approximately 50 kg in the National Aeronautics and Space Administration (NASA) Microgravity Program using a modified KC-135 airplane. The parabolic simulation system for advanced life support was used in this project, and 20 to 40 parabolas were used for laparoscopic or thorascopic investigation, each containing approximately 30 s of 0-g alternating with 2-g pullouts. The animal model was restrained in the supine position on a floor-level Crew Medical Restraint System, and the abdominal cavity was insufflated with carbon dioxide. The intraabdominal and intrathoracic anatomy was visualized in the 1-g, 0-g, and 2-g periods of parabolic flight. Bleeding was created in the animals, and the behavior of the blood in the abdominal and thoracic cavities was observed. In the thoracic cavity, gas insufflation and mechanical retraction was used at times unilaterally to decrease pulmonary ventilation enough to increase the

Optimizing tamoxifen-inducible Cre/loxp system to reduce tamoxifen effect on bone turnover in long bones of young mice.

PubMed

Zhong, Zhendong A; Sun, Weihua; Chen, Haiyan; Zhang, Hongliang; Lay, Yu-An E; Lane, Nancy E; Yao, Wei

2015-12-01

For tamoxifen-dependent Cre recombinase, also known as CreER recombinase, tamoxifen (TAM) is used to activate the Cre to generate time- and tissue-specific mouse mutants. TAM is a potent CreER system inducer; however, TAM is also an active selective estrogen receptor modulator (SERM) that can influence bone homeostasis. The purpose of this study was to optimize the TAM dose for Cre recombinase activation while minimizing the effects of TAM on bone turnover in young growing mice. To evaluate the effects of TAM on bone turnover and bone mass, 1-month-old wild-type male and female mice were intraperitoneally injected with TAM at 0, 1, 10 or 100mg/kg/day for four consecutive days, or 100, 300 mg/kg/day for one day. The distal femurs were analyzed one month after the last TAM injection by microCT, mechanical test, and surface-based bone histomorphometry. Similar doses of TAM were used in Col1 (2.3 kb)-CreERT2; mT/mG reporter male mice to evaluate the dose-dependent efficacy of Cre-ER activation in bone tissue. A TAM dose of 100 mg/kg × 4 days significantly increased trabecular bone volume/total volume (BV/TV) of the distal femur, femur length, bone strength, and serum bone turnover markers compared to the 0mg control group. In contrast, TAM doses ≤ 10 mg/kg did not significantly change any of these parameters compared to the 0mg group, although a higher bone strength was observed in the 10mg group. Surface-based histomorphometry revealed that the 100mg/kg dose of TAM dose significantly increased trabecular bone formation and decreased periosteal bone formation at 1-week post-TAM treatment. Using the reporter mouse model Col1-CreERT2; mT/mG, we found that 10mg/kg TAM induced Col1-CreERT2 activity in bone at a comparable level to the 100mg/kg dose. TAM treatment at 100mg/kg/day × 4 days significantly affects bone homeostasis, resulting in an anabolic bone effect on trabecular bone in 1-month-old male mice. However, a lower dose of TAM at 10 mg/kg/day × 4 days can

Effects of a metabolic syndrome induced by a fructose-rich diet on bone metabolism in rats.

PubMed

Felice, Juan Ignacio; Gangoiti, María Virginia; Molinuevo, María Silvina; McCarthy, Antonio Desmond; Cortizo, Ana María

2014-02-01

The aims of this study were: first, to evaluate the possible effects of a fructose rich diet (FRD)-induced metabolic syndrome (MS) on different aspects of long bone histomorphometry in young male rats; second, to investigate the effects of this diet on bone tissue regeneration; and third, to correlate these morphometric alterations with changes in the osteogenic/adipogenic potential and expression of specific transcription factors, of marrow stromal cells (MSC) isolated from rats with fructose-induced MS. MS was induced in rats by treatment with a FRD for 28 days. Halfway through treatment, a parietal wound was made and bone healing was evaluated 14 days later. After treatments, histomorphometric analysis was performed in dissected femoral and parietal bones. MSC were isolated from the femora of control or fructose-treated rats and differentiated either to osteoblasts (evaluated by type 1 collagen, Alkaline phosphatase and extracellular nodule mineralization) or to adipocytes (evaluated by intracellular triglyceride accumulation). Expression of Runx2 and PPARγ was assessed by Western blot. Fructose-induced MS induced deleterious effects on femoral metaphysis microarchitecture and impaired bone regeneration. Fructose treatment decreased the osteogenic potential of MSC and Runx2 expression. In addition, it increased the adipogenic commitment of MSC and PPARγ expression. Fructose-induced MS is associated with deleterious effects on bone microarchitecture and with a decrease in bone repair. These alterations could be due to a deviation in the adipogenic/osteogenic commitment of MSC, probably by modulation of the Runx2/PPARγ ratio. Copyright © 2014 Elsevier Inc. All rights reserved.

Inhibitory effects of melatonin on titanium particle-induced inflammatory bone resorption and osteoclastogenesis via suppression of NF-κB signaling.

PubMed

Ping, Zichuan; Wang, Zhirong; Shi, Jiawei; Wang, Liangliang; Guo, Xiaobin; Zhou, Wei; Hu, Xuanyang; Wu, Xiexing; Liu, Yu; Zhang, Wen; Yang, Huilin; Xu, Yaozeng; Gu, Ye; Geng, Dechun

2017-10-15

Wear debris-induced peri-implant osteolysis challenges the longevity of implants. The host response to wear debris causes chronic inflammation, promotes bone resorption, and impairs bone formation. We previously demonstrated that melatonin enhances bone formation and attenuates wear debris-induced bone loss in vivo. However, whether melatonin inhibits chronic inflammation and bone resorption at sites of wear debris-induced osteolysis remains unclear. In this study, we examined the potential inhibitory effects of melatonin on titanium particle-induced inflammatory osteolysis in a murine calvarial model and on RANKL-induced osteoclastic formation in bone marrow-derived macrophages. We found that the exogenous administration of melatonin significantly inhibited wear debris-induced bone resorption and the expression of inflammatory cytokines in vivo. Additionally, melatonin inhibited RANKL-induced osteoclast differentiation, F-actin ring formation, and osteoclastic resorption in a concentration-dependent manner in vitro. We also showed that melatonin blocked the phosphorylation of IκB-α and p65, but not IKKα, and significantly inhibited the expression of NFATc1 and c-Fos. However, melatonin had no effect on MAPK or PI3K/AKT signaling pathways. These results provide novel mechanistic insight into the anti-inflammatory and anti-bone resorptive effects of melatonin on wear debris-induced bone loss and provide an evidence-based rationale for the protective effects of melatonin as a treatment for peri-implant osteolysis. Wear debris-induced chronic inflammation, osteoclastic activation and osteoblastic inhibition have been identified as critical factors of peri-implant bone loss. We previously demonstrated that melatonin, a bioactive indolamine secreted mainly by the pineal gland, activates Wnt/β-catenin signaling pathway and enhances bone regeneration at osteolytic site in vivo. In the current study, we further demonstrated that melatonin significantly suppresses wear

Physiological responses to environmental factors related to space flight. [hemodynamic and metabolic responses to weightlessness

NASA Technical Reports Server (NTRS)

Pace, N.

1973-01-01

Physiological base line data are established, and physiological procedures and instrumentation necessary for the automatic measurement of hemodynamic and metabolic parameters during prolonged periods of weightlessness are developed.

Zoledronate induces apoptosis in cells from fibro-cellular membrane of unicameral bone cyst (UBC).

PubMed

Yu, John; Chang, Seong-Sil; Suratwala, Sanjeev; Chung, Woo-Sik; Abdelmessieh, Peter; Lee, Hahn-Jun; Yang, Jay; Lee, Francis Young-In

2005-09-01

Unicameral bone cyst (UBC) is a benign cystic lesion in children which is prone to fracture. Various treatments are available, but recurrence after different types of percutaneous injection therapy can cause bone destruction and pathologic fracture. The potential therapeutic effects of anti-resorptive agents, such as bisphosphonates, have not been investigated for UBC. The objective of this study was to characterize the cells from the fibro-cellular membrane of unicameral bone cyst (UBC cells) and to determine whether zoledronate, a nitrogen-containing bisphosphonate, could induce apoptosis in UBC cells. Flow cytometry and immunoblotting were performed in order to determine whether zoledronate induced apoptosis. Cells derived from normal human trabecular bones were used as controls against UBC cells to compare the effect of zoledronate in inducing apoptosis. Immunohisto/cytochemistry (IHC/ICC) and mini-array analyses were performed on tissues and cultured cells. Isolated peripheral blood mononuclear cells were incubated with conditioned media from the UBC cells to determine whether they are capable of inducing osteoclastogenesis. UBC membrane is composed of cells staining positively with CD68, SDF-1, STRO-1 and RANKL, but in vitro cells showed no staining with antibodies to CD68 and STRO-1, suggesting that there was a clonal selection of stromal cells during cell culture. UBC cells also express RUNX2 (runt-related transcription factor-2, core binding factor-1), a key transcription factor for osteoblastic differentiation. In addition, media collected from UBC cells induced a generation of multi-nucleated osteoclast-like cells of peripheral blood mononuclear cells. Zoledronate induced apoptosis of UBC cells in a dose-dependent manner. Apoptosis was evidenced by induction of the active cleaved form of caspase-3. The baseline apoptotic fractions were similar in UBC cells and trabecular bone cells. However, in the overall apoptotic fractions in this study, trabecular

Urea, sugar, nonesterified fatty acid and cholesterol content of the blood in prolonged weightlessness

NASA Technical Reports Server (NTRS)

Balakhovskiy, I. S.; Orlova, T. A.

1975-01-01

Biochemical blood composition studies on astronauts during weightlessness flight simulation tests and during actual space flights showed some disturbances of metabolic processes. Increases in blood sugar, fatty acid and cholesterol, and urea content are noted.

Deregulation of arginase induces bone complications in high-fat/high-sucrose diet diabetic mouse model

PubMed Central

Bhatta, Anil; Sangani, Rajnikumar; Kolhe, Ravindra; Toque, Haroldo A.; Cain, Michael; Wong, Abby; Howie, Nicole; Shinde, Rahul; Elsalanty, Mohammed; Yao, Lin; Chutkan, Norman; Hunter, Monty; Caldwell, Ruth B.; Isales, Carlos; Caldwell, R. William; Fulzele, Sadanand

2016-01-01

A balanced diet is crucial for healthy development and prevention of musculoskeletal related diseases. Diets high in fat content are known to cause obesity, diabetes and a number of other disease states. Our group and others have previously reported that activity of the urea cycle enzyme arginase is involved in diabetes-induced dysregulation of vascular function due to decreases in nitric oxide formation. We hypothesized that diabetes may also elevate arginase activity in bone and bone marrow, which could lead to bone-related complications. To test this we determined the effects of diabetes on expression and activity of arginase, in bone and bone marrow stromal cells (BMSCs). We demonstrated that arginase 1 is abundantly present in the bone and BMSCs. We also demonstrated that arginase activity and expression in bone and bone marrow is up-regulated in models of diabetes induced by HFHS diet and streptozotocin (STZ). HFHS diet down-regulated expression of healthy bone metabolism markers (BMP2, COL-1, ALP, and RUNX2) and reduced bone mineral density, bone volume and trabecular thickness. However, treatment with an arginase inhibitor (ABH) prevented these bone-related complications of diabetes. In-vitro study of BMSCs showed that high glucose treatment increased arginase activity and decreased nitric oxide production. These effects were reversed by treatment with an arginase inhibitor (ABH). Our study provides evidence that deregulation of L-arginine metabolism plays a vital role in HFHS diet-induced diabetic complications and that these complications can be prevented by treatment with arginase inhibitors. The modulation of L-arginine metabolism in disease could offer a novel therapeutic approach for osteoporosis and other musculoskeletal related diseases. PMID:26704078

Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats

PubMed Central

Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung

2016-01-01

Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model. PMID:27997588

Protective Effects of Vildagliptin against Pioglitazone-Induced Bone Loss in Type 2 Diabetic Rats.

PubMed

Eom, Young Sil; Gwon, A-Ryeong; Kwak, Kyung Min; Kim, Ju-Young; Yu, Seung Hee; Lee, Sihoon; Kim, Yeun Sun; Park, Ie Byung; Kim, Kwang-Won; Lee, Kiyoung; Kim, Byung-Joon

2016-01-01

Long-term use of thiazolidinediones (TZDs) is associated with bone loss and an increased risk of fracture in patients with type 2 diabetes (T2DM). Incretin-based drugs (glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors) have several benefits in many systems in addition to glycemic control. In a previous study, we reported that exendin-4 might increase bone mineral density (BMD) by decreasing the expression of SOST/sclerostin in osteocytes in a T2DM animal model. In this study, we investigated the effects of a DPP-4 inhibitor on TZD-induced bone loss in a T2DM animal model. We randomly divided 12-week-old male Zucker Diabetic Fatty (ZDF) rats into four groups; control, vildagliptin, pioglitazone, and vildagliptin and pioglitazone combination. Animals in each group received the respective treatments for 5 weeks. We performed an intraperitoneal glucose tolerance test (IPGTT) before and after treatment. BMD and the trabecular micro-architecture were measured by DEXA and micro CT, respectively, at the end of the treatment. The circulating levels of active GLP-1, bone turnover markers, and sclerostin were assayed. Vildagliptin treatment significantly increased BMD and trabecular bone volume. The combination therapy restored BMD, trabecular bone volume, and trabecular bone thickness that were decreased by pioglitazone. The levels of the bone formation marker, osteocalcin, decreased and that of the bone resorption marker, tartrate-resistant acid phosphatase (TRAP) 5b increased in the pioglitazone group. These biomarkers were ameliorated and the pioglitazone-induced increase in sclerostin level was lowered to control values by the addition of vildagliptin. In conclusion, our results indicate that orally administered vildagliptin demonstrated a protective effect on pioglitazone-induced bone loss in a type 2 diabetic rat model.

R-Spondin 1 promotes vibration-induced bone formation in mouse models of osteoporosis

PubMed Central

Wang, Haitao; Brennan, Tracy A.; Russell, Elizabeth; Kim, Jung-Hoon; Egan, Kevin P.; Chen, Qijun; Israelite, Craig; Schultz, David C.; Johnson, Frederick B.; Pignolo, Robert J.

2013-01-01

Bone tissue adapts to its functional environment by optimizing its morphology for mechanical demand. Among the mechanosensitive cells that recognize and respond to forces in the skeleton are osteocytes, osteoblasts, and mesenchymal progenitor cells (MPCs). Therefore, the ability to use mechanical signals to improve bone health through exercise and devices that deliver mechanical signals is an attractive approach to age-related bone loss; however, the extracellular or circulating mediators of such signals are largely unknown. Using SDS-PAGE separation of proteins secreted by MPCs in response to low magnitude mechanical signals and in-gel trypsin digestion followed by HPLC and mass spectroscopy, we identified secreted proteins up-regulated by vibratory stimulation. We exploited a cell senescence-associated secretory phenotype screen, and reasoned that a subset of vibration-induced proteins with diminished secretion by senescent MPCs will have the capacity to promote bone formation in vivo. We identified one such vibration-induced bone-enhancing (vibe) gene as R-Spondin 1, a Wnt pathway modulator, and demonstrated that it has the capacity to promote bone formation in three mouse models of age-related bone loss. By virtue of their secretory status, some vibe proteins may be candidates for pre-clinical development as anabolic agents for the treatment of osteoporosis. PMID:23974989

Delineating the Impact of Weightlessness on Human Physiology Using Computational Models

NASA Technical Reports Server (NTRS)

Kassemi, Mohammad

2015-01-01

Microgravity environment has profound effects on several important human physiological systems. The impact of weightlessness is usually indirect as mediated by changes in the biological fluid flow and transport and alterations in the deformation and stress fields of the compliant tissues. In this context, Fluid-Structural and Fluid-Solid Interaction models provide a valuable tool in delineating the physical origins of the physiological changes so that systematic countermeasures can be devised to reduce their adverse effects. In this presentation, impact of gravity on three human physiological systems will be considered. The first case involves prediction of cardiac shape change and altered stress distributions in weightlessness. The second, presents a fluid-structural-interaction (FSI) analysis and assessment of the vestibular system and explores the reasons behind the unexpected microgravity caloric stimulation test results performed aboard the Skylab. The last case investigates renal stone development in microgravity and the possible impact of re-entry into partial gravity on the development and transport of nucleating, growing, and agglomerating renal calculi in the nephron. Finally, the need for model validation and verification and application of the FSI models to assess the effects of Artificial Gravity (AG) are also briefly discussed.

Role of carbonic anhydrase in bone resorption induced by prostaglandin E2 in vitro

NASA Technical Reports Server (NTRS)

Hall, G. E.; Kenny, A. D.

1985-01-01

The possible role of carbonic anhydrase in bone resorption induced by prostaglandin E2 (PGE2) was studied using an in vitro neonatal mouse calvarial culture system. PGE2 (10 to the -6th M) was effective in stimulating resorption, as assessed by calcium release into culture media. This enhanced resorption was accompanied by significant increases in calvarial carbonic anhydrase activity over control values at 48 and 96 h. At 48 h, bones treated with PGE2 had 20 percent more carbonic anhydrase activity than controls. By 96 h, treated bones contained 79 percent more carbonic anhydrase activity than controls. PGE2-induced bone resorption was inhibited by the carbonic anhydrase inhibitor acetazolamide in a dose-dependent fashion from 10 to the -5th to 10 to the -4th M with 77 percent inhibition observed at 10 to the -4th M. The acetazolamide analogue CL 13,850 (N-t-butylacetazolamide), which does not inhibit carbonic anhydrase, failed to inhibit PGE2-induced resorption. These results are consistent with the hypothesis that carbonic anhydrase is a necessary component of the osteoclastic bone resorptive mechanism.

M.I.T./Canadian vestibular experiments on the Spacelab-1 mission. I - Sensory adaptation to weightlessness and readaptation to one-g: An overview

NASA Technical Reports Server (NTRS)

Young, L. R.; Oman, C. M.; Lichtenberg, B. K.; Watt, D. G. D.; Money, K. E.

1986-01-01

Human sensory/motor adaptation to weightlessness and readaptation to earth's gravity are assessed. Preflight and postflight vestibular and visual responses for the crew on the Spacelab-1 mission are studied; the effect of the abnormal pattern of otolith afferent signals caused by weightlessness on the pitch and roll perception and postural adjustments of the subjects are examined. It is observed that body position and postural reactions change due to weightlessness in order to utilize the varied sensory inputs in a manner suited to microgravity conditions. The aspects of reinterpretation include: (1) tilt acceleration reinterpretation, (2) reduced postural response to z-axis linear acceleration, and (3) increased attention to visual cues.

Co-registration of multi-modality imaging allows for comprehensive analysis of tumor-induced bone disease

PubMed Central

Seeley, Erin H.; Wilson, Kevin J.; Yankeelov, Thomas E.; Johnson, Rachelle W.; Gore, John C.; Caprioli, Richard M.; Matrisian, Lynn M.; Sterling, Julie A.

2014-01-01

Bone metastases are a clinically significant problem that arises in approximately 70% of metastatic breast cancer patients. Once established in bone, tumor cells induce changes in the bone microenvironment that lead to bone destruction, pain, and significant morbidity. While much is known about the later stages of bone disease, less is known about the earlier stages or the changes in protein expression in the tumor micro-environment. Due to promising results of combining magnetic resonance imaging (MRI) and Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry (MALDI IMS) ion images in the brain, we developed methods for applying these modalities to models of tumor-induced bone disease in order to better understand the changes in protein expression that occur within the tumor-bone microenvironment. Specifically, we integrated three dimensional-volume reconstructions of spatially resolved MALDI IMS with high-resolution anatomical and diffusion weighted MRI data and histology in an intratibial model of breast tumor-induced bone disease. This approach enables us to analyze proteomic profiles from MALDI IMS data with corresponding in vivo imaging and ex vivo histology data. To the best of our knowledge, this is the first time these three modalities have been rigorously registered in the bone. The MALDI mass-to-charge ratio peaks indicate differential expression of calcyclin, ubiquitin, and other proteins within the tumor cells, while peaks corresponding to hemoglobin A and calgranulin A provided molecular information that aided in the identification of areas rich in red and white blood cells, respectively. This multimodality approach will allow us to comprehensively understand the bone-tumor microenvironment and thus may allow us to better develop and test approaches for inhibiting bone metastases. PMID:24487126

Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ming, Wei, E-mail: weiming@xiyi.edu.cn; Department of Pharmacology, Xi’an Medical University, Xi’an 710021; Lu, Gan, E-mail: leonming99@163.com

Therapeutic targeting bone loss has been the focus of the study in osteoporosis. The present study is intended to evaluate whether MOTS-c, a novel mitochondria related 16 aa peptide, can protect mice from ovariectomy-induced osteoporosis. After ovary removal, the mice were injected with MOTS-c at a dose of 5 mg/kg once a day for 12 weeks. Our results showed that MOTS-c treatment significantly alleviated bone loss, as determined by micro-CT examination. Mechanistically, we found that the receptor activator of nuclear factor-κB ligand (RANKL) induced osteoclast differentiation was remarkably inhibited by MOTS-c. Moreover, MOTS-c increased phosphorylated AMPK levels, and compound C, anmore » AMPK inhibitor, could partially abrogate the effects of the MOTS-c on osteoclastogenesis. Thus, our findings provide evidence that MOTS-c may exert as an inhibitor of osteoporosis via AMPK dependent inhibition of osteoclastogenesis. -- Highlights: •MOTS-c decreases OVX-induced bone loss in vivo. •MOTS-c inhibits RANKL-induced osteoclast formation. •MOTS-c inhibits RANKL-induced osteoclast-specific gene expression. •MOTS-c represses osteoclast differentiation via the activation of AMPK.« less

A new synthetic granular calcium phosphate compound induces new bone in a sinus lift rabbit model.

PubMed

Trbakovic, Amela; Hedenqvist, Patricia; Mellgren, Torbjörn; Ley, Cecilia; Hilborn, Jöns; Ossipov, Dmitri; Ekman, Stina; Johansson, Carina B; Jensen-Waern, Marianne; Thor, Andreas

2018-03-01

The aim of this study was to investigate if a synthetic granular calcium phosphate compound (CPC) and a composite bisphosphonate-linked hyaluronic acid-calcium phosphate hydrogel (HABP·CaP) induced similar or more amount of bone as bovine mineral in a modified sinus lift rabbit model. Eighteen adult male New Zeeland White rabbits, received randomly one of the two test materials on a random side of the face, and bovine mineral as control on the contralateral side. In a sinus lift, the sinus mucosa was elevated and a titanium mini-implant was placed in the alveolar bone. Augmentation material (CPC, HABP·CaP or bovine bone) was applied in the space around the implant. The rabbits were euthanized three months after surgery and qualitative and histomorphometric evaluation were conducted. Histomorphometric evaluation included three different regions of interest (ROIs) and the bone to implant contact on each installed implant. Qualitative assessment (p = <.05), histomorphometric evaluations (p = < .01), and implant incorporation (p = <.05) showed that CPC and bovine mineral induced similar amount of bone and more than the HABP·CaP hydrogel. CPC induced similar amount of bone as bovine mineral and both materials induced more bone than HABP·CaP hydrogel. The CPC is suggested as a synthetic alternative for augmentations in the maxillofacial area. Copyright © 2017 Elsevier Ltd. All rights reserved.

Knee-ligament loading properties as influenced by gravity. I - Junction with bone of 3-G rodents

NASA Technical Reports Server (NTRS)

Wunder, C. C.; Matthes, R. D.; Tipton, C. M.

1982-01-01

The effect of 3-G conditions on the bone-to-ligament junctions of the knee is studied in rats. Results following chronic 3-G centrifugation of rats show that their bone-to-ligament junctions exhibited a force-sustaining capacity (F) which was 95 + or - 12% of the value for the control group. However, F was actually 29 + or - 5% greater for centrifuged rats than for control rats of comparable size, as the experimental animals grew to smaller body mass. It is concluded that gravity determines part of the magnitude of F, and therefore this value will probably be weaker after development in a weightless environment.

Physiological responses of women to simulated weightlessness: A review of the first female bed-rest study

NASA Technical Reports Server (NTRS)

Sandler, H.; Winter, D. L.

1978-01-01

Subjects were exposed to centrifugation, to lower body negative pressure (LBNP), and to exericse stress both before and after bed rest. Areas studied were centrifugation tolerance, fluid electrolyte changes and hematology, tolerance to LBNP, physical working capacity, biochemistries, blood fibrinolytic activity, female metabolic and hormonal responses, circadian alterations, and gynecology. Results were compared with the responses observed in similarly bed-rested male subjects. The bed-rested females showed deconditioning responses similar to those of the males, although with some differences. Results indicate that women are capable of coping with exposure to weightlessness and, moreover, that they may be more sensitive subjects for evaluating countermeasures to weightlessness and developing criteria for assessing applicants for shuttle voyages.

Biological effects of weightlessness and clinostatic conditions registered in cells of root meristem and cap of higher plants

NASA Astrophysics Data System (ADS)

Sytnik, K. M.; Kordyum, E. L.; Belyavskaya, N. A.; Nedukha, E. M.; Tarasenko, V. A.

Research in cellular reproduction, differentiation and vital activity, i.e. processes underlying the development and functioning of organisms, plants included, is essential for solving fundamental and applied problems of space biology. Detailed anatomical analysis of roots of higher plants grown on board the Salyut 6 orbital research station show that under conditions of weightlessness for defined duration mitosis, cytokinesis and tissue differentiation in plant vegetative organs occur essentially normally. At the same time, certain rearrangements in the structural organization of cellular organelles - mainly the plastid apparatus, mitochondria, Golgi apparatus and nucleus - are established in the root meristem and cap of the experimental plants. This is evidence for considerable changes in cellular metabolism. The structural changes in the subcellular level arising under spaceflight conditions are partially absent in clinostat experiments designed to simulate weightlessness. Various clinostatic conditions have different influences on the cell structural and functional organization than does space flight. It is suggested that alterations of cellular metabolism under weightlessness and clinostatic conditions occur within existing genetic programs.

Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss

NASA Technical Reports Server (NTRS)

LeBlanc, Adrian; Matsumoto, Toshio; Jones, Jeff; Shapiro, Jay; Lang, Tom; Smith, Scott M.; Shackelford, Linda C.; Sibonga, Jean; Evans, Harlan; Spector, Elisabeth;

Regeneration of bone and periodontal ligament induced by recombinant amelogenin after periodontitis.

PubMed

Haze, Amir; Taylor, Angela L; Haegewald, Stefan; Leiser, Yoav; Shay, Boaz; Rosenfeld, Eli; Gruenbaum-Cohen, Yael; Dafni, Leah; Zimmermann, Bernd; Heikinheimo, Kristiina; Gibson, Carolyn W; Fisher, Larry W; Young, Marian F; Blumenfeld, Anat; Bernimoulin, Jean P; Deutsch, Dan

2009-06-01

Regeneration of mineralized tissues affected by chronic diseases comprises a major scientific and clinical challenge. Periodontitis, one such prevalent disease, involves destruction of the tooth-supporting tissues, alveolar bone, periodontal-ligament and cementum, often leading to tooth loss. In 1997, it became clear that, in addition to their function in enamel formation, the hydrophobic ectodermal enamel matrix proteins (EMPs) play a role in the regeneration of these periodontal tissues. The epithelial EMPs are a heterogeneous mixture of polypeptides encoded by several genes. It was not clear, however, which of these many EMPs induces the regeneration and what mechanisms are involved. Here we show that a single recombinant human amelogenin protein (rHAM(+)), induced in vivo regeneration of all tooth-supporting tissues after creation of experimental periodontitis in a dog model. To further understand the regeneration process, amelogenin expression was detected in normal and regenerating cells of the alveolar bone (osteocytes, osteoblasts and osteoclasts), periodontal ligament, cementum and in bone marrow stromal cells. Amelogenin expression was highest in areas of high bone turnover and activity. Further studies showed that during the first 2 weeks after application, rHAM(+) induced, directly or indirectly, significant recruitment of mesenchymal progenitor cells, which later differentiated to form the regenerated periodontal tissues. The ability of a single protein to bring about regeneration of all periodontal tissues, in the correct spatio-temporal order, through recruitment of mesenchymal progenitor cells, could pave the way for development of new therapeutic devices for treatment of periodontal, bone and ligament diseases based on rHAM(+).

Some results from studies on the effects of weightlessness on the growth of epiphytic orchids

NASA Technical Reports Server (NTRS)

Cherevchenko, T. M.; Mayko, T. K.

1983-01-01

Epidendrum orchids were placed in a Malakhit-2 micro-greenhouse aboard the Soyuz-36-Salyut-6 space station to test their growth under weightless conditions. Growth occurred but was less than in control plants left on Earth; cells were smaller and parenchymal development slowed in all tissues. Stems, roots, and leaves were smaller. The number of stomas on the leaves was about the same as in the controls, but, because of the smaller leaf size, there were more per unit area. A modeling experiment using a clinostat revealed a large decrease in gibberellin activity and auxin activity. It was assumed that weightlessness primarily affects gibberellin biosynthesis, inhibiting cell growth. Reestablishment of growth compound activity upon return of the plants to Earth was indicated by the fact that the orchids resumed growth thereafter.

Cancer treatment-induced bone loss in premenopausal women: a need for therapeutic intervention?

PubMed

Hadji, P; Gnant, M; Body, J J; Bundred, N J; Brufsky, A; Coleman, R E; Guise, T A; Lipton, A; Aapro, M S

2012-10-01

Current clinical treatment guidelines recommend cytotoxic chemotherapy, endocrine therapy, or both (with targeted therapy if indicated) for premenopausal women with early-stage breast cancer, depending on the biologic characteristics of the primary tumor. Some of these therapies can induce premature menopause or are specifically designed to suppress ovarian function and reduce circulating estrogen levels. In addition to bone loss associated with low estrogen levels, cytotoxic chemotherapy may have a direct negative effect on bone metabolism. As a result, cancer treatment-induced bone loss poses a significant threat to bone health in premenopausal women with breast cancer. Clinical trials of antiresorptive therapies, such as bisphosphonates, have demonstrated the ability to slow or prevent bone loss in this setting. Current fracture risk assessment tools are based on data from healthy postmenopausal women and do not adequately address the risks associated with breast cancer therapy, especially in younger premenopausal women. We therefore recommend that all premenopausal women with breast cancer be informed about the potential risk of bone loss prior to beginning anticancer therapy. Women who experience amenorrhea should have bone mineral density assessed by dual-energy X-ray absorptiometry and receive regular follow-up to monitor bone health. Regular exercise and daily calcium and vitamin D supplementation are recommended. Women with a Z-score <-2.0 or Z-score ≤-1.0 and/or a 5-10% annual decrease in bone mineral density should be considered for bisphosphonate therapy in addition to calcium and vitamin D supplements. Copyright © 2012 Elsevier Ltd. All rights reserved.

Maintenance of exercise-induced benefits in physical functioning and bone among elderly women.

PubMed

Karinkanta, S; Heinonen, A; Sievänen, H; Uusi-Rasi, K; Fogelholm, M; Kannus, P

2009-04-01

This study showed that about a half of the exercise-induced gain in dynamic balance and bone strength was maintained one year after cessation of the supervised high-intensity training of home-dwelling elderly women. However, to maintain exercise-induced gains in lower limb muscle force and physical functioning, continued training seems necessary. Maintenance of exercise-induced benefits in physical functioning and bone structure was assessed one year after cessation of 12-month randomized controlled exercise intervention. Originally 149 healthy women 70-78 years of age participated in the 12-month exercise RCT and 120 (81%) of them completed the follow-up study. Self-rated physical functioning, dynamic balance, leg extensor force, and bone structure were assessed. During the intervention, exercise increased dynamic balance by 7% in the combination resistance and balance-jumping training group (COMB). At the follow-up, a 4% (95% CI: 1-8%) gain compared with the controls was still seen, while the exercise-induced isometric leg extension force and self-rated physical functioning benefits had disappeared. During the intervention, at least twice a week trained COMB subjects obtained a significant 2% benefit in tibial shaft bone strength index compared to the controls. A half of this benefit seemed to be maintained at the follow-up. Exercise-induced benefits in dynamic balance and rigidity in the tibial shaft may partly be maintained one year after cessation of a supervised 12-month multi-component training in initially healthy elderly women. However, to maintain the achieved gains in muscle force and physical functioning, continued training seems necessary.

Salmon DNA Accelerates Bone Regeneration by Inducing Osteoblast Migration

PubMed Central

Sato, Ayako; Kajiya, Hiroshi; Mori, Nana; Sato, Hironobu; Fukushima, Tadao; Kido, Hirofumi

2017-01-01

The initial step of bone regeneration requires the migration of osteogenic cells to defective sites. Our previous studies suggest that a salmon DNA-based scaffold can promote the bone regeneration of calvarial defects in rats. We speculate that the salmon DNA may possess osteoinductive properties, including the homing of migrating osteogenic cells. In the present study, we investigated the influence of the salmon DNA on osteoblastic differentiation and induction of osteoblast migration using MG63 cells (human preosteoblasts) in vitro. Moreover, we analyzed the bone regeneration of a critical-sized in vivo calvarial bone defect (CSD) model in rats. The salmon DNA enhanced both mRNA and protein expression of the osteogenesis-related factors, runt-related transcription factor 2 (Runx2), alkaline phosphatase, and osterix (OSX) in the MG63 cells, compared with the cultivation using osteogenic induction medium alone. From the histochemical and immunohistochemical assays using frozen sections of the bone defects from animals that were implanted with DNA disks, many cells were found to express aldehyde dehydrogenase 1, one of the markers for mesenchymal stem cells. In addition, OSX was observed in the replaced connective tissue of the bone defects. These findings indicate that the DNA induced the migration and accumulation of osteogenic cells to the regenerative tissue. Furthermore, an in vitro transwell migration assay showed that the addition of DNA enhanced an induction of osteoblast migration, compared with the medium alone. The implantation of the DNA disks promoted bone regeneration in the CSD of rats, compared with that of collagen disks. These results indicate that the salmon DNA enhanced osteoblastic differentiation and induction of migration, resulting in the facilitation of bone regeneration. PMID:28060874

Glucocorticoid-Induced Avascular Bone Necrosis: Diagnosis and Management

PubMed Central

Chan, KL; Mok, CC

2012-01-01

Glucocorticoid use is one of the most important causes of avascular bone necrosis (AVN). The pathogenesis of glucocorticoid-induced AVN is not fully understood but postulated mechanisms include fat hypertrophy, fat emboli and intravascular coagulation that cause impedance of blood supply to the bones. Data regarding the relationship between AVN and dosage, route of administration and treatment duration of glucocorticoids are conflicting, with some studies demonstrating the cumulative dose of glucocorticoid being the most important determining factor. Early recognition of this complication is essential as the prognosis is affected by the stage of the disease. Currently, there is no consensus on whether universal screening of asymptomatic AVN should be performed for long-term glucocorticoid users. A high index of suspicion should be exhibited for bone and joint pain at typical sites. Magnetic resonance imaging (MRI) or bone scintigraphy is more sensitive than plain radiograph for diagnosing early-stage AVN. Conservative management of AVN includes rest and reduction of weight bearing. Minimization of glucocorticoid dose or a complete withdrawal of the drug should be considered if the underlying conditions allow. The efficacy of bisphosphonates in reducing the rate of collapse of femoral head in AVN is controversial. Surgical therapy of AVN includes core decompression, osteotomy, bone grafting and joint replacement. Recent advances in the treatment of AVN include the use of tantalum rod and the development of more wear resistant bearing surface in hip arthroplasty. PMID:23115605

Glucocorticoid-induced avascular bone necrosis: diagnosis and management.

PubMed

Chan, K L; Mok, C C

2012-01-01

Glucocorticoid use is one of the most important causes of avascular bone necrosis (AVN). The pathogenesis of glucocorticoid-induced AVN is not fully understood but postulated mechanisms include fat hypertrophy, fat emboli and intravascular coagulation that cause impedance of blood supply to the bones. Data regarding the relationship between AVN and dosage, route of administration and treatment duration of glucocorticoids are conflicting, with some studies demonstrating the cumulative dose of glucocorticoid being the most important determining factor. Early recognition of this complication is essential as the prognosis is affected by the stage of the disease. Currently, there is no consensus on whether universal screening of asymptomatic AVN should be performed for long-term glucocorticoid users. A high index of suspicion should be exhibited for bone and joint pain at typical sites. Magnetic resonance imaging (MRI) or bone scintigraphy is more sensitive than plain radiograph for diagnosing early-stage AVN. Conservative management of AVN includes rest and reduction of weight bearing. Minimization of glucocorticoid dose or a complete withdrawal of the drug should be considered if the underlying conditions allow. The efficacy of bisphosphonates in reducing the rate of collapse of femoral head in AVN is controversial. Surgical therapy of AVN includes core decompression, osteotomy, bone grafting and joint replacement. Recent advances in the treatment of AVN include the use of tantalum rod and the development of more wear resistant bearing surface in hip arthroplasty.

[The development OF THE vestibular apparatus under conditions of weightlessness].

PubMed

Vinikov, Ia A; Gazenko, O G; Titovo, L K; Bornshteĭn, A A; Govardovskiĭ, V I

1976-01-01

The spawn of the aquarium fish Brachydanio rerio was developing during 5--6 days under conditions of weightlessness (first on board the spaceship "Sojuz-16", then in the space station "Salut-4") in special aquariums "EMKON", in thermostable installations. Electron microscopically the embryos were found to have a well developed labyrinth in early developmental histologically and cytologically differentiated receptory structures of the macula utriculi and macula saccili. In contrast to controls, the experimental animals showed certain alterations in the otolite organization. In similar experiments the embryos of clawed frog Xenopus laevis in the stage of the tail bud were also placed in special containers "EMKON" and thermostable apparatus "Biotherm-4" and by the spaceship "Sojuz-17" were brought to the space station "Salut-4", where it stayed for 16 days. The initial embryos had already had a well developed acoustic vesicle with macula communis. Inspite of the preliminary load by start acceleration and staying under conditions of weightlessness, they reached the general development fairly similar to controls. As it was shown electron microscopically their labyrinth had highly histologically and cytologically differentiated structures. However, a disturbance of the development of the otolithic membrane and otoconia should be noted. The alterations observed in the otolithic membrane organization in experimental fishes and frogs may be explained by general disorders in calcium metabolism.

Novel Wnt Regulator NEL-Like Molecule-1 Antagonizes Adipogenesis and Augments Osteogenesis Induced by Bone Morphogenetic Protein 2

PubMed Central

Shen, Jia; James, Aaron W.; Zhang, Xinli; Pang, Shen; Zara, Janette N.; Asatrian, Greg; Chiang, Michael; Lee, Min; Khadarian, Kevork; Nguyen, Alan; Lee, Kevin S.; Siu, Ronald K.; Tetradis, Sotirios; Ting, Kang; Soo, Chia

2017-01-01

The differentiation factor NEL-like molecule-1 (NELL-1) has been reported as osteoinductive in multiple in vivo preclinical models. Bone morphogenetic protein (BMP)-2 is used clinically for skeletal repair, but in vivo administration can induce abnormal, adipose-filled, poor-quality bone. We demonstrate that NELL-1 combined with BMP2 significantly optimizes osteogenesis in a rodent femoral segmental defect model by minimizing the formation of BMP2-induced adipose-filled cystlike bone. In vitro studies using the mouse bone marrow stromal cell line M2-10B4 and human primary bone marrow stromal cells have confirmed that NELL-1 enhances BMP2-induced osteogenesis and inhibits BMP2-induced adipogenesis. Importantly, the ability of NELL-1 to direct BMP2-treated cells toward osteogenesis and away from adipogenesis requires intact canonical Wnt signaling. Overall, these studies establish the feasibility of combining NELL-1 with BMP2 to improve clinical bone regeneration and provide mechanistic insight into canonical Wnt pathway activity during NELL-1 and BMP2 osteogenesis. The novel abilities of NELL-1 to stimulate Wnt signaling and to repress adipogenesis may highlight new treatment approaches for bone loss in osteoporosis. PMID:26772960

Amodiaquine induced agranulocytosis: inhibition of colony growth in bone marrow by antimalarial agents.

PubMed Central

Rhodes, E G; Ball, J; Franklin, I M

1986-01-01

Bone marrow was cultured in vitro for colonies of granulocytes and macrophages five months after a patient had recovered from amodiaquine induced agranulocytosis. The addition of amodiaquine, chloroquine, and sulfadoxine to the culture was followed by a dose dependent inhibition of colony growth in the patient's marrow but not in normal control bone marrow. Colony growth was, however, unaffected by proguanil, pyrimethamine, and quinine. These findings show that in vitro marrow culture may have important predictive value in some cases of drug induced agranulocytosis. PMID:3082409

Calcium-containing scaffolds induce bone regeneration by regulating mesenchymal stem cell differentiation and migration.

PubMed

Aquino-Martínez, Rubén; Angelo, Alcira P; Pujol, Francesc Ventura

2017-11-16

Osteoinduction and subsequent bone formation rely on efficient mesenchymal stem cell (MSC) recruitment. It is also known that migration is induced by gradients of growth factors and cytokines. Degradation of Ca 2+ -containing biomaterials mimics the bone remodeling compartment producing a localized calcium-rich osteoinductive microenvironment. The aim of our study was to determine the effect of calcium sulfate (CaSO 4 ) on MSC migration. In addition, to evaluate the influence of CaSO 4 on MSC differentiation and the potential molecular mechanisms involved. A circular calvarial bone defect (5 mm diameter) was created in the parietal bone of 35 Balb-C mice. We prepared and implanted a cell-free agarose/gelatin scaffold alone or in combination with different CaSO 4 concentrations into the bone defects. After 7 weeks, we determined the new bone regenerated by micro-CT and histological analysis. In vitro, we evaluated the CaSO 4 effects on MSC migration by both wound healing and agarose spot assays. Osteoblastic gene expression after BMP-2 and CaSO 4 treatment was also evaluated by qPCR. CaSO 4 increased MSC migration and bone formation in a concentration-dependent manner. Micro-CT analysis showed that the addition of CaSO 4 significantly enhanced bone regeneration compared to the scaffold alone. The histological evaluation confirmed an increased number of endogenous cells recruited into the cell-free CaSO 4 -containing scaffolds. Furthermore, MSC migration in vitro and active AKT levels were attenuated when CaSO 4 and BMP-2 were in combination. Addition of LY294002 and Wortmannin abrogated the CaSO 4 effects on MSC migration. Specific CaSO 4 concentrations induce bone regeneration of calvarial defects in part by acting on the host's undifferentiated MSCs and promoting their migration. Progenitor cell recruitment is followed by a gradual increment in osteoblast gene expression. Moreover, CaSO 4 regulates BMP-2-induced MSC migration by differentially activating the PI3

Weightless Environment Training Facility (WETF) materials coating evaluation, volume 3

NASA Technical Reports Server (NTRS)

1995-01-01

This volume consists of Appendices C, D, E, and F to the report on the Weightless Environment Training Facility Materials Coating Evaluation project. The project selected 10 coating systems to be evaluated in six separate exposure environments, and subject to three tests for physical properties. Appendix C is the photographic appendix of the test panels. Appendix D details methods and procedures. Appendix E lists application equipment costs. Appendix F is a compilation of the solicitation of the candidate coating systems.

Axial jet mixing of ethanol in cylindrical containers during weightlessness

NASA Technical Reports Server (NTRS)

Aydelott, J. C.

1979-01-01

An experimental program was conducted to examine the liquid flow patterns that result from the axial jet mixing of ethanol in 10-centimeter-diameter cylindrical tanks in weightlessness. A convex hemispherically ended tank and two Centaur liquid-hydrogen-tank models were used for the study. Four distinct liquid flow patterns were observed to be a function of the tank geometry, the liquid-jet velocity, the volume of liquid in the tank, and the location of the tube from which the liquid jet exited.

Relationships between orientation, movement and posture in weightlessness: Preliminary ethological observations

NASA Astrophysics Data System (ADS)

Tafforin, Carole

Weightlessness in man induces changes in astronaut orientations and consequently in his patterns of movements and postures. An ethological method has been used to describe the "overall" spontaneous behaviour of astronauts as seen from video recordings made during Space Flights. The work has consisted in analysing the relationships between orientation, movement and posture as an indication of a motor adaptative reorganization in such a situation. The results obtained lead us to consider three different aspects: (1) Orientation references. The astronaut orientates himself with reference to the Space Shuttle's internal structure; the increase of visual activity confirms the choice of the retinal vertical as frame of reference. (2) Motor coordination. The main data reveals a decrease in motor stereotypies by the diversity of motor acts observed and the importance of the link between orientation and posture described as follows: slightly inclined forward position, with legs flexed at about 135°. (3) Cognitive references. There appears to be a new organization of the cognitive image of the body scheme, the missing vestibular information being supplied by peripheral vision instead which could play a role in the astronaut's perception of his own movement.

Effects of Polymethoxyflavonoids on Bone Loss Induced by Estrogen Deficiency and by LPS-Dependent Inflammation in Mice.

PubMed

Matsumoto, Shigeru; Tominari, Tsukasa; Matsumoto, Chiho; Yoshinouchi, Shosei; Ichimaru, Ryota; Watanabe, Kenta; Hirata, Michiko; Grundler, Florian M W; Miyaura, Chisato; Inada, Masaki

2018-01-20

Polymethoxyflavonoids (PMFs) are a family of the natural compounds that mainly compise nobiletin, tangeretin, heptamethoxyflavone (HMF), and tetramethoxyflavone (TMF) in citrus fruits. PMFs have shown various biological functions, including anti-oxidative effects. We previously showed that nobiletin, tangeretin, and HMF all inhibited interleukin (IL)-1-mediated osteoclast differentiation via the inhibition of prostaglandin E2 synthesis. In this study, we created an original mixture of PMFs (nobiletin, tangeretin, HMF, and TMF) and examined whether or not PMFs exhibit co-operative inhibitory effects on osteoclastogenesis and bone resorption. In a coculture of bone marrow cells and osteoblasts, PMFs dose-dependently inhibited IL-1-induced osteoclast differentiation and bone resorption. The optimum concentration of PMFs was lower than that of nobiletin alone in the suppression of osteoclast differentiation, suggesting that the potency of PMFs was stronger than that of nobiletin in vitro. The oral administration of PMFs recovered the femoral bone loss induced by estrogen deficiency in ovariectomized mice. We further tested the effects of PMFs on lipopolysaccharide-induced bone resorption in mouse alveolar bone. In an ex vivo experimental model for periodontitis, PMFs significantly suppressed the bone-resorbing activity in organ cultures of mouse alveolar bone. These results indicate that a mixture of purified nobiletin, tangeretin, HMF, and TMF exhibits a co-operative inhibitory effect for the protection against bone loss in a mouse model of bone disease, suggesting that PMFs may be potential candidates for the prevention of bone resorption diseases, such as osteoporosis and periodontitis.

Comparison of naturally occurring and ligature-induced peri-implantitis bone defects in humans and dogs.

PubMed

Schwarz, Frank; Herten, Monika; Sager, Martin; Bieling, Katrin; Sculean, Anton; Becker, Jürgen

2007-04-01

The aim of the present study was to evaluate and compare naturally occuring and ligature-induced peri-implantitis bone defects in humans and dogs. Twenty-four partially and fully edentulous patients undergoing peri-implant bone augmentation procedures due to advanced peri-implant infections were included in this study (n=40 implants). Furthermore, peri-implantitis was induced by ligature placement and plaque accumulation in five beagle dogs for three months following implant insertion (n=15 implants). The ligatures were removed when about 30% of the initial bone was lost. During open flap surgery, configuration and defect characteristics of the peri-implant bone loss were recorded in both humans and dogs. Open flap surgery generally revealed two different classes of peri-implant bone defects. While Class I defects featured well-defined intrabony components, Class II defects were characterized by consistent horizontal bone loss. The allocation of intrabony components of Class I defects regarding the implant body allowed a subdivision of five different configurations (Classes Ia-e). In particular, human defects were most frequently Class Ie (55.3%), followed by Ib (15.8%), Ic (13.3%), Id (10.2%), and Ia (5.4%). Similarly, bone defects in dogs were also most frequently Class Ie (86.6%), while merely two out of 15 defects were Classes Ia and Ic (6.7%, respectively). Within the limits of the present study, it might be concluded that configurations and sizes of ligature-induced peri-implantitis bone defects in dogs seemed to resemble naturally occurring lesions in humans.

Phage nanofibers induce vascularized osteogenesis in 3D printed bone scaffolds.

PubMed

Wang, Jianglin; Yang, Mingying; Zhu, Ye; Wang, Lin; Tomsia, Antoni P; Mao, Chuanbin

2014-08-06

A virus-activated matrix is developed to overcome the challenge of forming vascularized bone tissue. It is generated by filling a 3D printed bioceramic scaffold with phage nanofibers displaying high-density RGD peptide. After it is seeded with mesenchymal stem cells (MSCs) and implanted into a bone defect, the phage nanofibers induce osteogenesis and angiogenesis by activating endothelialization and osteogenic differentiation of MSCs. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Randomized Trial on the Effect of Bone Tissue on Vibration-induced Muscle Strength Gain and Vibration-induced Reflex Muscle Activity

PubMed Central

Cidem, Muharrem; Karacan, İlhan; Diraçoğlu, Demirhan; Yıldız, Aysel; Küçük, Suat Hayri; Uludağ, Murat; Gün, Kerem; Özkaya, Murat; Karamehmetoğlu, Şafak Sahir

2014-01-01

Background: Whole-body vibration (WBV) induces reflex muscle activity and leads to increased muscle strength. However, little is known about the physiological mechanisms underlying the effects of whole-body vibration on muscular performance. Tonic vibration reflex is the most commonly cited mechanism to explain the effects of whole-body vibration on muscular performance, although there is no conclusive evidence that tonic vibration reflex occurs. The bone myoregulation reflex is another neurological mechanism used to explain the effects of vibration on muscular performance. Bone myoregulation reflex is defined as a reflex mechanism in which osteocytes exposed to cyclic mechanical loading induce muscle activity. Aims: The aim of this study was to assess whether bone tissue affected vibration-induced reflex muscle activity and vibration-induced muscle strength gain. Study Design: A prospective, randomised, controlled, double-blind, parallel-group clinical trial. Methods: Thirty-four participants were randomised into two groups. High-magnitude whole-body vibration was applied in the exercise group, whereas low-magnitude whole-body vibration exercises were applied in the control group throughout 20 sessions. Hip bone mineral density, isokinetic muscle strength, and plasma sclerostin levels were measured. The surface electromyography data were processed to obtain the Root Mean Squares, which were normalised by maximal voluntarily contraction. Results: In the exercise group, muscle strength increased in the right and left knee flexors (23.9%, p=0.004 and 27.5%, p<0.0001, respectively). However, no significant change was observed in the knee extensor muscle strength. There was no significant change in the knee muscle strength in the control group. The vibration-induced corrected Root Mean Squares of the semitendinosus muscle was decreased by 2.8 times (p=0.005) in the exercise group, whereas there was no change in the control group. Sclerostin index was decreased by 15

A Randomized Trial on the Effect of Bone Tissue on Vibration-induced Muscle Strength Gain and Vibration-induced Reflex Muscle Activity.

PubMed

Cidem, Muharrem; Karacan, Ilhan; Diraçoğlu, Demirhan; Yıldız, Aysel; Küçük, Suat Hayri; Uludağ, Murat; Gün, Kerem; Ozkaya, Murat; Karamehmetoğlu, Safak Sahir

2014-03-01

Whole-body vibration (WBV) induces reflex muscle activity and leads to increased muscle strength. However, little is known about the physiological mechanisms underlying the effects of whole-body vibration on muscular performance. Tonic vibration reflex is the most commonly cited mechanism to explain the effects of whole-body vibration on muscular performance, although there is no conclusive evidence that tonic vibration reflex occurs. The bone myoregulation reflex is another neurological mechanism used to explain the effects of vibration on muscular performance. Bone myoregulation reflex is defined as a reflex mechanism in which osteocytes exposed to cyclic mechanical loading induce muscle activity. The aim of this study was to assess whether bone tissue affected vibration-induced reflex muscle activity and vibration-induced muscle strength gain. A prospective, randomised, controlled, double-blind, parallel-group clinical trial. Thirty-four participants were randomised into two groups. High-magnitude whole-body vibration was applied in the exercise group, whereas low-magnitude whole-body vibration exercises were applied in the control group throughout 20 sessions. Hip bone mineral density, isokinetic muscle strength, and plasma sclerostin levels were measured. The surface electromyography data were processed to obtain the Root Mean Squares, which were normalised by maximal voluntarily contraction. In the exercise group, muscle strength increased in the right and left knee flexors (23.9%, p=0.004 and 27.5%, p<0.0001, respectively). However, no significant change was observed in the knee extensor muscle strength. There was no significant change in the knee muscle strength in the control group. The vibration-induced corrected Root Mean Squares of the semitendinosus muscle was decreased by 2.8 times (p=0.005) in the exercise group, whereas there was no change in the control group. Sclerostin index was decreased by 15.2% (p=0.031) in the exercise group and increased by

Does the centre of mass remain stable during complex human postural equilibrium tasks in weightlessness?

NASA Astrophysics Data System (ADS)

Stapley, Paul; Pozzo, Thierry

In normal gravity conditions the execution of voluntary movement involves the displacement of body segments as well as the maintenance of a stable reference value for equilibrium control. It has been suggested that centre of mass (CM) projection within the supporting base (BS) is the stabilised reference for voluntary action, and is conserved in weightlessness. The purpose of this study was to determine if the CM is stabilised during whole body reaching movements executed in weightlessness. The reaching task was conducted by two cosmonauts aboard the Russian orbital station MIR, during the Franco-Russian mission ALTAIR, 1993. Movements of reflective markers were recorded using a videocamera, successive images being reconstructed by computer every 40ms. The position of the CM, ankle joint torques and shank and thigh angles were computed for each subject pre- in- and post-flight using a 7-link mathematical model. Results showed that both cosmonauts adopted a backward leaning posture prior to reaching movements. Inflight, the CM was displaced throughout values in the horizontal axis three times those of pre-flight measures. In addition, ankle dorsi flexor torques inflight increased to values double those of pre- and post-flight tests. This study concluded that CM displacements do not remain stable during complex postural equilibrium tasks executed in weightlessness. Furthermore, in the absence of gravity, subjects changed their strategy for producing ankle torque during spaceflight from a forward to a backward leaning posture.

[Effects of simulated weightlessness on pressure-volume relationships of femoral vein of New Zealand Rabbits].

PubMed

Yue, Yong; Yao, Yong-jie; Xie, Xiao-ping; Wang, Bing; Zhu, Qing-sheng; Wu, Xing-yu

2002-12-01

Objective. To observe the changes of pressure-volume relationships of rabbit femoral veins and their structural changes caused by simulated weightlessness. Method. Head-Down Tilt (HDT) -20 degrees rabbit model was used to simulate weightlessness. Twenty four healthy male New Zealand Rabbits were randomly divided into 21 d HDT group,10 d HDT group and control group, (8 in each group). Pressure-volume (P-V) relationship of rabbits femoral veins was measured and the microstructure of the veins was observed. Result. The femoral vein P-V relationship curves of HDT groups showed a larger volume change ratio than that of control group. This change was that 21 d HDT group was even more obvious than that of HDT-10 d group. B1 and B2 in quadratic equations of 21 d HDT group were significantly higher than the values of both 10 d HDT group and control group during expansion (inflow) and collapse (outflow) (P<0.01). The result of histological examination showed that the contents and structure of femoral vein wall of HDT-rabbits changed significantly. Endothelial cells of femoral vein became short and columnar or cubic, some of which fell off. Smooth muscle layer became thinner. Conclusion. Femoral venous compliance increased after weightlessness-simulation and the femoral venous compliance in 21 d-HDT rabbits increased more obviously than that in 10 d-HDT rabbits. The structure of femoral vein wall had changed obviously.

Biotechnology

NASA Image and Video Library

2002-07-31

This diagram shows the normal pathways of calcium movement in the body and indicates changes (green arrows) seen during preliminary space flight experiments. Calcium plays a central role because 1) it gives strength and structure to bone and 2) all types of cells require it to function normally. To better understand how and why weightlessness induces bone loss, astronauts have participated in a study of calcium kinetics -- that is, the movement of calcium through the body, including absorption from food, and its role in the formation and breakdown of bone.

Diagram of Calcium Movement in the Human Body

NASA Technical Reports Server (NTRS)

2002-01-01

This diagram shows the normal pathways of calcium movement in the body and indicates changes (green arrows) seen during preliminary space flight experiments. Calcium plays a central role because 1) it gives strength and structure to bone and 2) all types of cells require it to function normally. To better understand how and why weightlessness induces bone loss, astronauts have participated in a study of calcium kinetics -- that is, the movement of calcium through the body, including absorption from food, and its role in the formation and breakdown of bone.

Low Doses of Simvastatin Potentiate the Effect of Sodium Alendronate in Inhibiting Bone Resorption and Restore Microstructural and Mechanical Bone Properties in Glucocorticoid-Induced Osteoporosis.

PubMed

Sequetto, Priscila L; Gonçalves, Reggiani V; Pinto, Aloísio S; Oliveira, Maria G A; Maldonado, Izabel R S C; Oliveira, Tânia T; Novaes, Rômulo D

2017-10-01

By using an experimental model of dexamethasone-induced osteoporosis we investigated the effects of different therapeutic schemes combining sodium alendronate (SA) and simvastatin on bone mineral and protein composition, microstructural and mechanical remodeling. Wistar rats were randomized into eight groups: G1: non-osteoporotic; G2: osteoporotic; G3, G4, and G5: osteoporotic+SA (0.2, 0.4, and 0.8 mg/kg, respectively); G6, G7, and G8: osteoporotic+SA (0.2, 0.4, and 0.8 mg/kg, respectively)+simvastatin (0.4, 0.6, and 1 mg/kg, respectively). Osteoporosis was induced by dexamethasone (7 mg/kg, i.m.) once a week for 5 weeks. All treatments were administered for 8 weeks. Dexamethasone increased serum levels of alkaline phosphatase, calcium, phosphorus, and urea, especially in non-treated animals, which showed severe osteoporosis. Dexamethasone also induced bone microstructural fragility and reduced mechanical resistance, which were associated with a marked depletion in mineral mass, collagenous and non-collagenous protein levels in cortical and cancellous bone. Although SA has attenuated osteoporosis severity, the effectiveness of drug therapy was enhanced combining alendronate and simvastatin. The restoration in serum parameters, organic and inorganic bone mass, and mechanical behavior showed a dose-dependent effect that was potentially related to the complementary mechanisms by which each drug acts to induce bone anabolism, accelerating tissue repair.

The effect of changing gravity and weightlessness of vasopressin control systems

NASA Technical Reports Server (NTRS)

Moran, W. H.

1972-01-01

An immunoassay to determine the effects of changing gravity and weightlessness on vasopressin control system is discussed. Seven extracts from persons known to have inappropriate ADH syndrome secondary to pulmonary oat cell cancer were examined. The extracts had previously been subject to bioassay in rats. The intent of the examination was to determine if the vasopressin content could be confirmed immunologically. The results compared favorably with the values obtained by biological assay.

Treatment of Radix Dipsaci extract prevents long bone loss induced by modeled microgravity in hindlimb unloading rats.

PubMed

Niu, Yinbo; Li, Chenrui; Pan, Yalei; Li, Yuhua; Kong, Xianghe; Wang, Shuo; Zhai, YuanKun; Wu, Xianglong; Fan, Wutu; Mei, Qibing

2015-01-01

Radix Dipsaci is a kidney tonifying herbal medicine with a long history of safe use for treatment of bone fractures and joint diseases in China. Previous studies have shown that Radix Dipsaci extract (RDE) could prevent bone loss in ovariectomized rats. This study investigates the effect of RDE against bone loss induced by simulated microgravity. A hindlimb unloading rat model was established to determine the effect of RDE on bone mineral density and bone microarchitecture. Twenty-four male Sprague-Dawley rats were divided into four groups (n = 6 per group): control (CON), hindlimb unloading with vehicle (HLU), hindlimb unloading treated with alendronate (HLU-ALN, 2.0 mg/kg/d), and hindlimb unloading treated with RDE (HLU-RDE, 500 mg/kg/d). RDE or ALN was administrated orally for 4 weeks. Treatment with RDE had a positive effect on mechanical strength, BMD, BMC, bone turnover markers, and the changes in urinary calcium and phosphorus excretion. MicroCT analysis showed that RDE significantly prevented the reduction of the bone volume fraction, connectivity density, trabecular number, thickness, tissue mineral density, and tissue mineral content as well as improved the trabecular separation and structure model index. RDE was demonstrated to prevent the loss of bone mass induced by HLU treatment, which suggests the potential application of RDE in the treatment of microgravity-induced bone loss.

Characterization of blood drawn rapidly for use in blood volume expansion studies: An animal model for simulated weightlessness

NASA Technical Reports Server (NTRS)

Chenault, V. Michelle; Lynch, Colleen D.; Morris, Mariana; Clodfelter, Jill; Hutchins, Phillip M.

1990-01-01

It was demonstrated that up to 8ml of blood can be drawn from donar rats without significantly increasing volume and stress sensitive hormones, and thus can be used for volume expansion studies. Infusion of whole blood allows more physiological changes that can be seen with volume expansion by saline or other ionic solutions. The infusion of whole blood to induce hypervolemia may provide an improved model to study the fluid balance and control mechanisms operative in weightlessness. Blood samples were drawn as quickly as possible from femoral artery catheters chronically implanted in Sprague Dawley rats and analyzed for hematocrit, plasma sodium, potassium, osmolality, corticosterone, epinepherine, norepinephrine, and vasopressin. The levels were found to be comparable to those of normal rats.

Axial jet mixing of ethanol in spherical containers during weightlessness

NASA Technical Reports Server (NTRS)

Audelott, J. C.

1976-01-01

An experimental program was conducted to examine the liquid flow patterns that result from the axial jet mixing of ethanol in 10-centimeter-diameter spherical containers in weightlessness. Complete liquid circulation flow patterns were easily established in containers that were less than half full of liquid, while for higher liquid fill conditions, vapor was drawn into the inlet of the simulated mixer unit. Increasing the liquid-jet or lowering the position at which the liquid jet entered the container caused increasing turbulence and bubble formation.

Stem cell niches and other factors that influence the sensitivity of bone marrow to radiation-induced bone cancer and leukaemia in children and adults

PubMed Central

Richardson, Richard B

2011-01-01

Purpose: This paper reviews and reassesses the internationally accepted niches or ‘targets’ in bone marrow that are sensitive to the induction of leukaemia and primary bone cancer by radiation. Conclusions: The hypoxic conditions of the 10 μm thick endosteal/osteoblastic niche where preleukemic stem cells and hematopoietic stem cells (HSC) reside provides a radioprotective microenvironment that is 2-to 3-fold less radiosensitive than vascular niches. This supports partitioning the whole marrow target between the low haematological cancer risk of irradiating HSC in the endosteum and the vascular niches within central marrow. There is a greater risk of induced bone cancer when irradiating a 50 μm thick peripheral marrow adjacent to the remodelling/reforming portion of the trabecular bone surface, rather than marrow next to the quiescent bone surface. This choice of partitioned bone cancer target is substantiated by the greater radiosensitivity of: (i) Bone with high remodelling rates, (ii) the young, (iii) individuals with hypermetabolic benign diseases of bone, and (iv) the epidemiology of alpha-emitting exposures. Evidence is given to show that the absence of excess bone-cancer in atomic-bomb survivors may be partially related to the extremely low prevalence among Japanese of Paget's disease of bone. Radiation-induced fibrosis and the wound healing response may be implicated in not only radiogenic bone cancers but also leukaemia. A novel biological mechanism for adaptive response, and possibility of dynamic targets, is advocated whereby stem cells migrate from vascular niches to stress-mitigated, hypoxic niches. PMID:21204614

Bone-induced c-kit expression in prostate cancer: a driver of intraosseous tumor growth

PubMed Central

Mainetti, Leandro E.; Zhe, Xiaoning; Diedrich, Jonathan; Saliganan, Allen D.; Cho, Won Jin; Cher, Michael L.; Heath, Elisabeth; Fridman, Rafael; Kim, Hyeong-Reh Choi; Bonfil, R. Daniel

2014-01-01

Loss of BRCA2 function stimulates prostate cancer (PCa) cell invasion and is associated with more aggressive and metastatic tumors in PCa patients. Concurrently, the receptor tyrosine kinase c-kit is highly expressed in skeletal metastases of PCa patients and induced in PCa cells placed into the bone microenvironment in experimental models. However, the precise requirement of c-kit for intraosseous growth of PCa and its relation to BRCA2 expression remain unexplored. Here, we show that c-kit expression promotes migration and invasion of PCa cells. Alongside, we found that c-kit expression in PCa cells parallels BRCA2 downregulation. Gene rescue experiments with human BRCA2 transgene in c-kit-transfected PCa cells resulted in reduction of c-kit protein expression and migration and invasion, suggesting a functional significance of BRCA2 downregulation by c-kit. The inverse association between c-kit and BRCA2 gene expressions in PCa cells was confirmed using laser capture microdissection in experimental intraosseous tumors and bone metastases of PCa patients. Inhibition of bone-induced c-kit expression in PCa cells transduced with lentiviral short hairpin RNA reduced intraosseous tumor incidence and growth. Overall, our results provide evidence of a novel pathway that links bone-induced c-kit expression in PCa cells to BRCA2 downregulation and supports bone metastasis. PMID:24798488

Oral administration of vitamin C prevents alveolar bone resorption induced by high dietary cholesterol in rats.

PubMed

Sanbe, Toshihiro; Tomofuji, Takaaki; Ekuni, Daisuke; Azuma, Tetsuji; Tamaki, Naofumi; Yamamoto, Tatsuo

2007-11-01

A high-cholesterol diet stimulates alveolar bone resorption, which may be induced via tissue oxidative damage. Vitamin C reduces tissue oxidative damage by neutralizing free radicals and scavenging hydroxyl radicals, and its antioxidant effect may offer the clinical benefit of preventing alveolar bone resorption in cases of hyperlipidemia. We examined whether vitamin C could suppress alveolar bone resorption in rats fed a high-cholesterol diet. In this 12-week study, rats were divided into four groups: a control group (fed a regular diet) and three experimental groups (fed a high-cholesterol diet supplemented with 0, 1, or 2 g/l vitamin C). Vitamin C was provided by adding it to the drinking water. The bone mineral density of the alveolar bone was analyzed by microcomputerized tomography. As an index of tissue oxidative damage, the 8-hydroxydeoxyguanosine level in the periodontal tissue was determined using a competitive enzyme-linked immunosorbent assay. Hyperlipidemia, induced by a high-cholesterol diet, decreased rat alveolar bone density and increased the number of tartrate-resistant acid phosphatase-positive osteoclasts. The expression of 8-hydroxydeoxyguanosine was upregulated in the periodontal tissues. Intake of vitamin C reduced the effect of a high-cholesterol diet on alveolar bone density and osteoclast differentiation and decreased periodontal 8-hydroxydeoxyguanosine expression. In the rat model, vitamin C suppressed alveolar bone resorption, induced by high dietary cholesterol, by decreasing the oxidative damage of periodontal tissue.

Ground experiments for finding principles and working out methods for preventing adverse effects of weightlessness on the human organism

NASA Technical Reports Server (NTRS)

Kakurin, L. I.; Gregoryev, A. I.; Mikhailov, V. M.; Tishler, V. A.

1980-01-01

A comparative assessment of the effectiveness of different prophylactic procedures to prevent the adverse effects of weightlessness is presented. It is concluded that: physical training is most effective but no single method by itself produces the full effect, and an adjustment of regimes to one another enhances the effect. The approved complex of prophylactic procedures affected basic changes occurring in hypokinesia: deficit of muscular activity, no or reduced BP hydrostatic component, reduced volume of blood circulation, reduced hydration level, and the application of various prophylactic complexes during 49 day antiorthostatic hypodynamia eliminated or reduced the adverse effects of weightlessness in simulation.

Bone Formation Rate in Experimental Disuse Osteoporosis in Monkeys

NASA Technical Reports Server (NTRS)

Cann, Christopher; Young, Donald R.

1976-01-01

Specific mechanisms underlying weightless and hypodynamic bone loss are obscure. A principal relationship which must be affected is the balance between bone formation and bone resorption rates. In order to better define the influence of those parameters on bone loss, and also to develop measurements in other species as a useful adjunct to human research, studies were undertaken with experimental monkeys. Tests were conducted with a total of 6 adult male monkeys, weighing 10-13 kg, and approximately 10-12 yrs. of age to evaluate specifically bone formation rate during the development of disuse osteoporosis and osteopenia. Three animals were restrained in a semi-recumbent position for six months; three animals served as normal caged controls. Food intake (Purina) was held relatively constant at 200g/day for each animal. Using a Norland Bone Mineral Analyzer, bone mineral losses of 3.5 to 6% were seen in the mid-shaft of the tibia and in the distal radius. Bone loss was confirmed radiographically, with observation of thinning of the proximal tibial cortex and trabeculae in the calcaneus. Bone formation rate was determined using standard Ca-47 kinetics under metabolic balance conditions. After six months of restraint, accretion was 7.2-13.2 mg Ca/kg/day, compared to 3.2-4.1 mg Ca/kg/day in caged controls and 3-8 mg Ca/kg/day in normal adult humans. Fecal and urine calcium was 25-40% higher in restrained animals than in controls. Dietary calcium absorption decreases during restraint, and calcium turnover increases, implying a rise in bone resorption rate concommitant with the observed rise in bone accretion rate. Further studies dealing specifically with bone resorption are underway to define this more fully.

Glucocorticoid-induced bone loss can be reversed by the actions of PTH and Risedronate on different pathways for bone formation and mineralization

PubMed Central

Yao, Wei; Cheng, Zhiqiang; Pham, Aaron; Busse, Cheryl; Zimmermann, Elizabeth A.; Ritchie, Robert O.; Lane, Nancy E.

2008-01-01

Glucocorticoid (GC) excess decreases bone mineralization and microarchitecture and lead to reduced bone strength. Both anabolic (PTH) and anti-resorptive agents are used to prevent and treat GC-induced bone loss, yet these bone active agents alter bone turnover by very different mechanisms. Our study objective was to determine how PTH and risedronate (Ris) alter bone quality following GC excess. Five-month-old Swiss-Webster male mice were treated with the glucocorticoid (GC) prednisolone (5 mg/kg 60-day slow-release pellet) or placebo (PL)]. At day 28−56, two groups of GC-treated animals had either PTH (5μg/kg, 5x/wk) or Ris (5μg/kg, 5x/wk) intervention. Bone quality and quantity measurements include x-ray tomography microscopy (XTM) for the degree of bone mineralization (DBM), microCT for bone microarchitecture, compression testing for trabecular bone strength, biochemistry and histomorphometry for bone turnover. In addition, real-time PCR and immunohistochemistry were performed to monitor the expression of several key genes regulating Wnt signaling (bone formation) and mineralization. Results Compared to the placebo treated mice, GC treatment decreased trabecular bone volume (BV/TV) and serum osteocalcin, but increased serum CTX and osteoclast surface with a peak at day 28. GC+PTH increased and GC+Ris restored BV/TV to the PL levels after a 28 day treatment period. Average DBM was lowered after GC treatment (−27%), and it was restored to PL level with GC+Ris and GC+PTH. At day 56, RT-PCR revealed that continuous exposure to GC and GC+PTH increased, while GC+Ris decreased the expression of genes that inhibit bone mineralization (Dmp1 and Phex), compared to the PL group. Wnt signaling antagonists Dkk1, Sost and Wif1 were up-regulated by GC treatment but were down-regulated after GC+PTH treatment. Immunohistochemistry of bone sections found GC increased N terminal dmp-1 while PTH treatment increased both N and C terminal dmp-1 staining around osteocytes

DNA survival and physical and histological properties of heat-induced alterations in burnt bones.

PubMed

Imaizumi, K; Taniguchi, K; Ogawa, Y

2014-05-01

During forensic casework, it is vital to be able to obtain valuable information from burnt bone fragments to ascertain the identity of the victim. Here, we report the findings of an experimental study on burnt bovine compact bone segments. Compact bones were cut to size and heated in an electric furnace at a temperature range of 100–1,100 °C with 100 °C increments. Heat-induced alterations to the bone color,weight, volume, and density were monitored using gross morphology and micro-focus X-ray computed tomography.We found that the increase in temperature caused the color of the compact bones to change in order of yellow, brown, gray,and white. In contrast to the weight reduction that occurred immediately after burning, we measured no significant reduction in volume even at 600 °C; however, volume reduced drastically once the temperature reached 700 °C. Light microscopic histological observations of burnt bone revealed heat induced alterations such as cracking and separation of the osteons at higher temperatures. In addition to these findings,we sought to examine the survival of DNA in the burnt bones using polymerase chain reaction of mitochondrial DNA. No amplification was found in the specimens burnt at 250 °C or higher, indicating the likely difficulty in testing the DNA of burnt bones from forensic casework. The results of this study will enable an estimation of the burning temperatures of burnt bones found in forensic cases and will provide an important framework with which to interpret data obtained during anthropological testing and DNA typing.

Vitamin K catabolite inhibition of ovariectomy-induced bone loss: structure-activity relationship considerations.

PubMed

Soper, Robin J; Oguz, Cenk; Emery, Roger; Pitsillides, Andrew A; Hodges, Stephen J

2014-08-01

The potential benefit of vitamin K as a therapeutic in osteoporosis is controversial and the vitamin K regimen being used clinically (45 mg/day) employs doses that are many times higher than required to ensure maximal gamma-carboxylation of the vitamin K-dependent bone proteins. We therefore tested the hypothesis that vitamin K catabolites, 5-carbon (CAN5C) and 7-carbon carboxylic acid (CAN7C) aliphatic side-chain derivatives of the naphthoquinone moiety exert an osteotrophic role consistent with the treatment of osteoporosis. Osteoblast-like MG63 cell cultures were challenged with lipopolysaccharide and the levels of interleukin-6, an osteoclastogenic cytokine, measured with and without catabolites; low concentrations of CAN7C significantly inhibited interleukin-6 release, but CAN5C did not. In models of bone loss induced by ovariectomy or sciatic neurectomy in C57BL/6 mice, we found that the rarer CAN7C catabolite markedly restricted ovariectomy-induced bone loss and possibly limited sciatic neurectomy-induced bone loss. CAN7C activity depends on a free carboxylic acid and its particular side-chain structure. These in vivo data indicate for the first time that the clinical utility of vitamin K for osteoporosis may reside in an unusual catabolite. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hybrid water immersion simulation of manual IVA performance in weightlessness

NASA Technical Reports Server (NTRS)

Loats, H. L., Jr.; Mattingly, G. S.

1971-01-01

A description is given of the development, tests, and analysis of a manual simulator. The simulator was developed to test mass handling and translation under weightlessness conditions by a test subject. The system is composed of a hybrid simulator with a combination of water immersion and mechanical, Peter Pan, simulation. The concept operates on the equivalence principle, with the subject and the cargo remaining quasi-stationary. Movement is effected through a moving device controlled through force by the subject. Motion response is determined through computations of the inertial movement under such conditions.

The Development of the Vestibular Apparatus Under Conditions of Weightlessness

NASA Technical Reports Server (NTRS)

Vinnikov, Y. A.; Gazenko, O. G.; Lychakov, D. V.; Palmbakh, L. R.

1984-01-01

A series of experiments has been carried out on the effect of space flight conditions on morphogenesis and the structure of the vestibular apparatus in amphibian and fish larvae. Larval development proceeded in weightlessness without serious morphological defects. The vestibular apparatus developed; its organization in the experimental animals did not differ qualitatively from that in the controls. The specific external stimulus (gravitation) appears not to be a necessary condition for the development of a gravitation receptor in ontogenesis although the appearance of the vestibular apparatus in phylogenesis was apparently related to this stimulus.

Results of intravehicular manned cargo-transfer studies in simulated weightlessness

NASA Technical Reports Server (NTRS)

Spady, A. A., Jr.; Beasley, G. P.; Yenni, K. R.; Eisele, D. F.

1972-01-01

A parametric investigation was conducted in a water immersion simulator to determine the effect of package mass, moment of inertia, and size on the ability of man to transfer cargo in simulated weightlessness. Results from this study indicate that packages with masses of at least 744 kg and moments of inertia of at least 386 kg-m2 can be manually handled and transferred satisfactorily under intravehicular conditions using either one- or two-rail motion aids. Data leading to the conclusions and discussions of test procedures and equipment are presented.

[The role of Smads and related transcription factors in the signal transduction of bone morphogenetic protein inducing bone formation].

PubMed

Xu, Xiao-liang; Dai, Ke-rong; Tang, Ting-ting

2003-09-01

To clarify the mechanisms of the signal transduction of bone morphogenetic proteins (BMPs) inducing bone formation and to provide theoretical basis for basic and applying research of BMPs. We looked up the literature of the role of Smads and related transcription factors in the signal transduction of BMPs inducing bone formation. The signal transduction processes of BMPs included: 1. BMPs combined with type II and type I receptors; 2. the type I receptor phosphorylated Smads; and 3. Smads entered the cell nucleus, interacted with transcription factors and influenced the transcription of related proteins. Smads could be divided into receptor-regulated Smads (R-Smads: Smad1, Smad2, Smad3, Smad5, Smad8 and Smad9), common-mediator Smad (co-Smad: Smad4), and inhibitory Smads (I-Smads: Smad6 and Smad7). Smad1, Smad5, Smad8, and probable Smad9 were involved in the signal transduction of BMPs. Multiple kinases, such as focal adhesion kinase (FAK), Ras-extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), and Akt serine/threonine kinase were related to Smads signal transduction. Smad1 and Smad5 related with transcription factors included core binding factor A1 (CBFA1), smad-interacting protein 1 (SIP1), ornithine decarboxylase antizyme (OAZ), activating protein-1 (AP-1), xenopus ventralizing homeobox protein-2 (Xvent-2), sandostatin (Ski), antiproliferative proteins (Tob), and homeodomain-containing transcriptian factor-8 (Hoxc-8), et al. CBFA1 could interact with Smad1, Smad2, Smad3, and Smad5, so it was involved in TGF-beta and BMP-2 signal transduction, and played an important role in the bone formation. Cleidocranial dysplasia (CCD) was thought to be caused by heterozygous mutations in CBFA1. The CBFA1 knockout mice showed no osteogenesis and had maturational disturbance of chondrocytes. Smads and related transcription factors, especially Smad1, Smad5, Smad8 and CBFA1, play an important role in the signal transduction of BMPs inducing bone

Disruption of collagen/apatite alignment impairs bone mechanical function in osteoblastic metastasis induced by prostate cancer.

PubMed

Sekita, Aiko; Matsugaki, Aira; Nakano, Takayoshi

2017-04-01

Prostate cancer (PCa) frequently metastasizes to the bone, generally inducing osteoblastic alterations that increase bone brittleness. Although there is growing interest in the management of the physical capability of patients with bone metastasis, the mechanism underlying the impairment of bone mechanical function remains unclear. The alignment of both collagen fibrils and biological apatite (BAp) c-axis, together with bone mineral density, is one of the strongest contributors to bone mechanical function. In this study, we analyzed the bone microstructure of the mouse femurs with and without PCa cell inoculation. Histological assessment revealed that the bone-forming pattern in the PCa-bearing bone was non-directional, resulting in a spongious structure, whereas that in the control bone was unidirectional and layer-by-layer, resulting in a compact lamellar structure. The degree of preferential alignment of collagen fibrils and BAp, which was evaluated by quantitative polarized microscopy and microbeam X-ray diffraction, respectively, were significantly lower in the PCa-bearing bone than in the control bone. Material parameters including Young's modulus and toughness, measured by the three-point bending test, were simultaneously decreased in the PCa-bearing bone. Specifically, there was a significant positive correlation between the degree of BAp c-axis orientation and Young's modulus. In conclusion, the impairment of mechanical function in the PCa-bearing bone is attributable to disruption of the anisotropic microstructure of bone in multiple phases. This is the first report demonstrating that cancer bone metastasis induces disruption of the collagen/BAp alignment in long bones, thereby impairing their mechanical function. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim

Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulatedmore » with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. �

Measurement of Bone: Diagnosis of SCI-Induced Osteoporosis and Fracture Risk Prediction.

PubMed

Troy, Karen L; Morse, Leslie R

2015-01-01

Spinal cord injury (SCI) is associated with a rapid loss of bone mass, resulting in severe osteoporosis and a 5- to 23-fold increase in fracture risk. Despite the seriousness of fractures in SCI, there are multiple barriers to osteoporosis diagnosis and wide variations in treatment practices for SCI-induced osteoporosis. We review the biological and structural changes that are known to occur in bone after SCI in the context of promoting future research to prevent or reduce risk of fracture in this population. We also review the most commonly used methods for assessing bone after SCI and discuss the strengths, limitations, and clinical applications of each method. Although dual-energy x-ray absorptiometry assessments of bone mineral density may be used clinically to detect changes in bone after SCI, 3-dimensional methods such as quantitative CT analysis are recommended for research applications and are explained in detail.

Reconstruction of Long Bone Infections Using the Induced Membrane Technique: Tips and Tricks.

PubMed

Mauffrey, Cyril; Hake, Mark E; Chadayammuri, Vivek; Masquelet, Alain-Charles

2016-06-01

The management of posttraumatic long bone osteomyelitis remains a challenging clinical problem. A systematic approach is necessary, beginning with eradication of the infected bone and soft tissue. There are a number of options for reconstruction of the remaining bone defect, including the induced membrane technique developed by Masquelet. We describe our technique for the 2-stage treatment of long bone osteomyelitis. The first stage involves a radical debridement, stabilization of the bone with either external fixation or an antibiotic-coated intramedullary nail, and placement of a polymethylmethacrylate spacer. The second stage includes excision of the spacer and placement of autologous bone graft. Various resection methods, fixation strategies, antibiotic additives, and types of bone grafts or substitutes can be used. The purpose of our technical article is to share our personal experience and describe several nuances that are critical for the success of this treatment strategy. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The role of weightlessness in the genetic damage from preflight gamma-irradiation of organisms in experiments aboard the Salyut 6 orbital station

NASA Astrophysics Data System (ADS)

Vaulina, E. N.; Anikeeva, I. D.; Kostina, L. N.; Kogan, I. G.; Palmbakh, L. R.; Mashinsky, A. L.

The effect of weightlessness on chromosomal aberration frequency in preflight irradiated Crepis capillaris seeds, on the viability, fertility and mutation frequency in Arabidopsis thaliana, and on the frequency of nondisjunction and loss of X chromosomes in preflight irradiated Drosophila melanogaster gametes was studied aboard the Salyut 6 orbital station. The following effects were observed: a flight-time dependent amplification of the effects of preflight ?-irradiation in A. thaliana with respect to all the parameters studied; unequal effects in seeds and seedlings of Crepis capillaris; and a significant increase in the frequency of nondisjunction and loss of chromosomes during meiosis in Drosophila females. These observations are discussed in terms of the data of ground-based model experiments and flight experiments with a different time of exposure of objects to weightlessness. An attempt is made to elucidate the role of weightlessness in the modification of ionizing radiation effects.

Benzene-induced myelotoxicity: application of flow cytofluorometry for the evaluation of early proliferative change in bone marrow.

PubMed Central

Irons, R D

1981-01-01

A detailed description of flow cytofluorometric DNA cell cycle analysis is presented. A number of studies by the author and other investigators are reviewed in which a method is developed for the analysis of cell cycle phase in bone marrow of experimental animals. Bone marrow cell cycle analysis is a sensitive indicator of changes in bone marrow proliferative activity occurring early in chemically-induced myelotoxicity. Cell cycle analysis, used together with other hematologic methods, has revealed benzene-induced toxicity in proliferating bone marrow cells to be cycle specific, appearing to affect a population in late S phase which then accumulate in G2/M. PMID:7016521

Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss

DTIC Science & Technology

2012-07-01

Mesenchymal stem cell (MSC) differentiation towards the bone forming osteoblastic lineage decreases as a function of age and may contribute to age-related...problem of age-related reduced availability of MSC we propose to examine the bone anabolic potential of induced pluripotent stem cell (iPS) derived MSC

Effect of avocado/soybean unsaponifiables on ligature-induced bone loss and bone repair after ligature removal in rats.

PubMed

Oliveira, G J P L; Paula, L G F; Souza, J A C; Spin-Neto, R; Stavropoulos, A; Marcantonio, R A C

2016-06-01

The aim of this study was to evaluate the effects of administration of avocado/soybean unsaponifiable (ASU), a drug that is commonly used in the treatment of rheumatoid arthritis, on ligature-induced bone loss and bone repair after ligature removal in rats. Eighty-four rats were randomly assigned to four groups of equal size and received a daily gavage of either sterile saline [control (CTR)] or ASU (0.6 mg/kg), starting 7 d before (ASU/-7), on the day of (ASU/0) or 7 d after (ASU/+7) periodontitis induction. Periodontitis was induced by placing silk ligatures into the gingival sulcus of the second maxillary molars for 7 d; after 7 d, the ligatures were removed. Seven rats from each group were sacrificed, 7, 15 or 30 d after ligature removal. Bone resorption was evaluated by histomorphometry and micro-computed tomography (micro-CT). Immunohistochemistry was used to evaluate the expression of TRAP, RANKL and alkaline phosphatase (ALP), and quantitative PCR (qPCR) was used to evaluate the levels of interleukin-1beta (Il1β), tumor necrosis factor alpha (Tnfα), interleukin-6 (Il-6), Rankl and Alp. Statistical analysis was performed using the Shapiro-Wilk test, ANOVA and Tukey's test for normal data, and using the Kruskall-Wallis and Dunnet's tests for non-normal data (p < 0.05). Histomorphometry and micro-CT analysis showed greater bone resorption in the CTR group than in the ASU/0 (15 d) and ASU/+7 (7 and 15 d) groups. The CTR group also presented with a higher expression of TRAP (15 and 30 d) and RANKL (7 and 15 d) compared with ASU/0 and ASU/+7 groups. Similarly, qPCR analysis showed higher levels of Rankl and Il1β mRNAs, and lower levels of Alp mRNA, in the CTR group compared with all other groups (for all periods). ASU exhibited a positive effect on bone repair following ligature-induced periodontitis in rats. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Early arthritis induces disturbances at bone nanostructural level reflected in decreased tissue hardness in an animal model of arthritis

PubMed Central

Cascão, Rita; Finnilä, Mikko A. J.; Lopes, Inês P.; Saarakkala, Simo; Zioupos, Peter; Canhão, Helena; Fonseca, João E.

2018-01-01

Introduction Arthritis induces joint erosions and skeletal bone fragility. Objectives The main goal of this work was to analyze the early arthritis induced events at bone architecture and mechanical properties at tissue level. Methods Eighty-eight Wistar rats were randomly housed in experimental groups, as follows: adjuvant induced arthritis (AIA) (N = 47) and a control healthy group (N = 41). Rats were monitored during 22 days for the inflammatory score, ankle perimeter and body weight and sacrificed at different time points (11 and 22 days post disease induction). Bone samples were collected for histology, micro computed tomography (micro-CT), 3-point bending and nanoindentation. Blood samples were also collected for bone turnover markers and systemic cytokine quantification. Results At bone tissue level, measured by nanoindentation, there was a reduction of hardness in the arthritic group, associated with an increase of the ratio of bone concentric to parallel lamellae and of the area of the osteocyte lacuna. In addition, increased bone turnover and changes in the microstructure and mechanical properties were observed in arthritic animals, since the early phase of arthritis, when compared with healthy controls. Conclusion We have shown in an AIA rat model that arthritis induces very early changes at bone turnover, structural degradation and mechanical weakness. Bone tissue level is also affected since the early phase of arthritis, characterized by decreased tissue hardness associated with changes in bone lamella organization and osteocyte lacuna surface. These observations highlight the pertinence of immediate control of inflammation in the initial stages of arthritis. PMID:29315314

[Compensatory-adaptive reactions of regional hemodynamics to weightlessness during a long space flight].

PubMed

Iarullin, Kh Kh; Vasil'eva, T D; Turchaninova, V F; Sokolova, I V; Vikharev, N D

1984-01-01

This paper discusses regional hemodynamics and vascular regulation during and after space flights of over 3 months in duration. Mechanisms of cardiovascular adaptation to weightlessness are described. The postflight differences in the recovery of regional hemodynamics seem to depend on the individual characteristics, age-related changes of the cardiovascular system, as well as the countermeasures and rehabilitation measures performed during and after flight.

Canola and hydrogenated soybean oils accelerate ectopic bone formation induced by implantation of bone morphogenetic protein in mice.

PubMed

Hashimoto, Yoko; Mori, Mayumi; Kobayashi, Shuichiro; Hanya, Akira; Watanabe, Shin-Ichi; Ohara, Naoki; Noguchi, Toshihide; Kawai, Tatsushi; Okuyama, Harumi

2014-01-01

Canola oil (Can) and hydrogenated soybean oil (H2-Soy) are commonly used edible oils. However, in contrast to soybean oil (Soy), they shorten the survival of stroke-prone spontaneously hypertensive (SHRSP) rats. It has been proposed that the adverse effects of these oils on the kidney and testis are caused at least in part by dihydro-vitamin K (VK) 1 in H2-Soy and unidentified component(s) in Can. Increased intake of dihydro-VK1 is associated with decreased tissue VK2 levels and bone mineral density in rats and humans, respectively. The aim of the present study was to determine the effects of these oils on bone morphogenetic protein (BMP)-induced ectopic bone formation, which is promoted by VK2 deficiency, in relation to the role of VK in the γ-carboxylation of osteocalcin and matrix Gla protein. A crude extract of BMPs was implanted into a gap in the fascia of the femoral muscle in 5-week-old mice maintained on a Soy, Can, or H2-Soy diet. Newly formed bone volume, assessed by three-dimensional X-ray micro-computed tomography and three-dimensional reconstruction imaging for bone, was 4-fold greater in the Can and H2-Soy groups than in the Soy group. The plasma carboxylated osteocalcin (Gla-OC) and total OC (Gla-OC plus undercarboxylated osteocalcin [Glu-OC]) levels were significantly lower in the Can group than in the Soy group ( p < 0.05). However, these levels did not significantly differ between the H2-Soy and Soy groups. The plasma Gla-OC/Glu-OC ratio in the Can and H2-Soy groups was significantly lower (in Can; p = 0.044) or was almost significantly lower (in H2-Soy; p = 0.053) than that in the Soy group. In conclusion, Can and H2-Soy accelerated BMP-induced bone formation in mice to a greater extent than Soy. Further research is required to evaluate whether the difference in accelerated ectopic bone formation is associated with altered levels of VK2 and VK-dependent protein(s) among the three dietary groups.

Bone and hormonal changes induced by skeletal unloading in the mature male rat

NASA Technical Reports Server (NTRS)

Dehority, W.; Halloran, B. P.; Bikle, D. D.; Curren, T.; Kostenuik, P. J.; Wronski, T. J.; Shen, Y.; Rabkin, B.; Bouraoui, A.; Morey-Holton, E.

1999-01-01

To determine whether the rat hindlimb elevation model can be used to study the effects of spaceflight and loss of gravitational loading on bone in the adult animal, and to examine the effects of age on bone responsiveness to mechanical loading, we studied 6-mo-old rats subjected to hindlimb elevation for up to 5 wk. Loss of weight bearing in the adult induced a mild hypercalcemia, diminished serum 1,25-dihydroxyvitamin D, decreased vertebral bone mass, and blunted the otherwise normal increase in femoral mass associated with bone maturation. Unloading decreased osteoblast numbers and reduced periosteal and cancellous bone formation but had no effect on bone resorption. Mineralizing surface, mineral apposition rate, and bone formation rate decreased during unloading. Our results demonstrate the utility of the adult rat hindlimb elevation model as a means of simulating the loss of gravitational loading on the skeleton, and they show that the effects of nonweight bearing are prolonged and have a greater relative effect on bone formation in the adult than in the young growing animal.

Effect of methylprednisolone on bone mineral density in rats with ovariectomy-induced bone loss and suppressed endogenous adrenaline levels by metyrosine

PubMed Central

Yilmaz, Mehmet; Isaoglu, Unal; Uslu, Turan; Yildirim, Kadir; Seven, Bedri; Akcay, Fatih; Hacimuftuoglu, Ahmet

2013-01-01

Objectives: In this study, effect of methylprednisolone on bone mineral density (BMD) was investigated in rats with overiectomy induced bone lose and suppressed endogenous adrenalin levels, and compared to alendronate. Materials and Methods: Severity of bone loss in the examined material (femur bones) was evaluated by BMD measurement. Results: The group with the highest BMD value was metyrosinemetyrosine + methylprednisolone combination (0.151 g/cm2), while that with the lowest BMD was methylprednisolone (0.123 g/cm2). Alendronate was effective only when used alone in ovariectomized rats (0.144 g/cm2), but not when used in combination with methylprednisolone (0.124 g/cm2). In the ovariectomized rat group which received only metyrosine, BMD value was statistically indifferent from ovariectomized control group. Conclusions: Methylprednisolone protected bone loss in rats with suppressed adrenaline levels because of metyrosinemetyrosine. PMID:24014908

Nutlin-3 Treatment Spares Cisplatin-Induced Inhibition of Bone Healing While Maintaining Osteosarcoma Toxicity

PubMed Central

Stine, Kimo C.; Wahl, Elizabeth C.; Liu, Lichu; Skinner, Robert A.; VanderSchilden, Jaclyn; Bunn, Robert C.; Montgomery, Corey O.; Aronson, James; Becton, David L.; Nicholas, Richard W.; Swearingen, Christopher J.; Suva, Larry J.; Lumpkin, Charles K.

2017-01-01

The majority of Osteosarcoma (OS) patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. These protocols include distraction osteogenesis (DO), which is characterized by direct new bone formation. Cisplatin (CDP) is extensively used for OS chemotherapy and recent studies, using a mouse DO model, have demonstrated that CDP has profound negative effects on bone repair. Recent oncological therapeutic strategies are based on the use of standard cytotoxic drugs plus an assortment of biologic agents. Here we demonstrate that the previously reported CDP-associated inhibition of bone repair can be modulated by the administration of a small molecule p53 inducer (nutlin-3). The effects of nutlin-3 on CDP osteotoxicity were studied using both pre- and post-operative treatment models. In both cases the addition of nutlin-3, bracketing CDP exposure, demonstrated robust and significant bone sparing activity (p < 0.01–0.001). In addition the combination of nutlin-3 and CDP induced equivalent OS tumor killing in a xenograft model. Collectively, these results demonstrate that the induction of p53 peri-operatively protects bone healing from the toxic effects of CDP, while maintaining OS toxicity. PMID:26867804

Novel Resorbable and Osteoconductive Calcium Silicophosphate Scaffold Induced Bone Formation

PubMed Central

Ros-Tárraga, Patricia; Mazón, Patricia; Rodríguez, Miguel A.; Meseguer-Olmo, Luis; De Aza, Piedad N.

2016-01-01

This aim of this research was to develop a novel ceramic scaffold to evaluate the response of bone after ceramic implantation in New Zealand (NZ) rabbits. Ceramics were prepared by the polymer replication method and inserted into NZ rabbits. Macroporous scaffolds with interconnected round-shaped pores (0.5–1.5 mm = were prepared). The scaffold acted as a physical support where cells with osteoblastic capability were found to migrate, develop processes, and newly immature and mature bone tissue colonized on the surface (initially) and in the material’s interior. The new ceramic induced about 62.18% ± 2.28% of new bone and almost complete degradation after six healing months. An elemental analysis showed that the gradual diffusion of Ca and Si ions from scaffolds into newly formed bone formed part of the biomaterial’s resorption process. Histological and radiological studies demonstrated that this porous ceramic scaffold showed biocompatibility and excellent osteointegration and osteoinductive capacity, with no interposition of fibrous tissue between the implanted material and the hematopoietic bone marrow interphase, nor any immune response after six months of implantation. No histological changes were observed in the various organs studied (para-aortic lymph nodes, liver, kidney and lung) as a result of degradation products being released. PMID:28773906

Bone growth and bone development in the presence of implants or after induced leg-lengthening studied using the Oxford Scanning Proton Microprobe

NASA Astrophysics Data System (ADS)

Pålsgård, Eva; Johansson, Carina; Li, Gang; Grime, Geoff W.; Triffitt, J. T.

1997-07-01

To respond to varying environmental demands the bone tissue in the body is under continual reconstruction throughout life. It is known that metallic elements are important for maintaining normal bone structure, but their roles are not well understood. More information about the effects of metal excess or deficiency is needed to help in the development of metallic bone implants and to improve the treatment of bone fractures and defects. The Oxford Scanning Proton Microprobe (SPM) is being applied in two studies involving metal ions in bone: (1) bone regrowth and bonding to titanium bone implants may be influenced by diffusion of Ti ions into the bone. We are using microPIXE to determine the metal ion content of bone developing in contact with implants of pure Nb, Ti and Ti alloys. (2) Bone lengthening as a surgical procedure is induced by fracturing the bone and allowing it to heal with a small gap between the fractured ends created by the use of external fixators. The gap can be slowly increased during the healing process to stimulate the production of new bone. The enzymes and other constituents of the developing bone need certain metals for their function. Using experimental animals we have studied the concentrations of the metals and whether a deficiency of trace metals limits the optimum rate of bone lengthening.

Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling

PubMed Central

Accardi, Fabrizio; Toscani, Denise; Dalla Palma, Benedetta; Aversa, Franco; Giuliani, Nicola

2015-01-01

Multiple myeloma (MM) is characterized by a high capacity to induce alterations in the bone remodeling process. The increase in osteoclastogenesis and the suppression of osteoblast formation are both involved in the pathophysiology of the bone lesions in MM. The proteasome inhibitor (PI) bortezomib is the first drug designed and approved for the treatment of MM patients by targeting the proteasome. However, recently novel PIs have been developed to overcome bortezomib resistance. Interestingly, several preclinical data indicate that the proteasome complex is involved in both osteoclast and osteoblast formation. It is also evident that bortezomib either inhibits osteoclast differentiation induced by the receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) or stimulates the osteoblast differentiation. Similarly, the new PIs including carfilzomib and ixazomib can inhibit bone resorption and stimulate the osteoblast differentiation. In a clinical setting, PIs restore the abnormal bone remodeling by normalizing the levels of bone turnover markers. In addition, a bone anabolic effect was described in responding MM patients treated with PIs, as demonstrated by the increase in the osteoblast number. This review summarizes the preclinical and clinical evidence on the effects of bortezomib and other new PIs on myeloma bone disease. PMID:26579531

Absence of ERRα in Female Mice Confers Resistance to Bone Loss Induced by Age or Estrogen-Deficiency

PubMed Central

Rabier, Bénédicte; Monfoulet, Laurent; Dine, Julien; Macari, Claire; Espallergues, Julie; Horard, Béatrice; Giguère, Vincent; Cohen-Solal, Martine; Chassande, Olivier; Vanacker, Jean-Marc

2009-01-01

Background ERRα is an orphan member of the nuclear hormone receptor superfamily, which acts as a transcription factor and is involved in various metabolic processes. ERRα is also highly expressed in ossification zones during mouse development as well as in human bones and cell lines. Previous data have shown that this receptor up-modulates the expression of osteopontin, which acts as an inhibitor of bone mineralization and whose absence results in resistance to ovariectomy-induced bone loss. Altogether this suggests that ERRα may negatively regulate bone mass and could impact on bone fragility that occurs in the absence of estrogens. Methods/Principal Findings In this report, we have determined the in vivo effect of ERRα on bone, using knock-out mice. Relative to wild type animals, female ERRαKO bones do not age and are resistant to bone loss induced by estrogen-withdrawal. Strikingly male ERRαKO mice are indistinguishable from their wild type counterparts, both at the unchallenged or gonadectomized state. Using primary cell cultures originating from ERRαKO bone marrow, we also show that ERRα acts as an inhibitor of osteoblast differentiation. Conclusion/Significance Down-regulating ERRα could thus be beneficial against osteoporosis. PMID:19936213

Synergistic Phytochemicals Fail to Protect Against Ovariectomy Induced Bone Loss in Rats.

PubMed

Ambati, Suresh; Miller, Colette N; Bass, Erica F; Hohos, Natalie M; Hartzell, Diane L; Kelso, Emily W; Trunnell, Emily R; Yang, Jeong-Yeh; Della-Fera, Mary Anne; Baile, Clifton A; Rayalam, Srujana

2018-05-24

Menopause induces a loss of bone as a result of estrogen deficiency. Despite pharmaceutical options for the treatment of osteopenia and osteoporosis, many aging women use dietary supplements with estrogenic activity to prevent bone loss and other menopausal-related symptoms. Such supplements are yet to be tested for efficacy against a Food and Drug Administration (FDA) approved medication for menopausal bone loss such as zoledronic acid (ZA). The postmenopausal rat model was used to investigate the efficacy of various synergistic phytochemical blends mixed into the diet for 16 weeks. Retired-breeder, Fischer 344 rats were randomly assigned to sham or ovariectomy surgery and 4 treatment groups: ZA; genistein supplementation; and a low dose and high dose blend of genistein, resveratrol, and quercetin. Ovariectomy resulted in a loss of both trabecular and cortical bone which was prevented with ZA. The phytochemical blends tested were unable to reverse these losses. Despite the lack of effectiveness in preventing bone loss, a significant dose-response trend was observed in the phytochemical-rich diets in bone adipocyte number compared to ovariectomized control rats. Data from this study indicate that estrogenic phytochemicals are not as efficacious as ZA in preventing menopausal-related bone loss but may have beneficial effects on bone marrow adiposity in rats.

Measurement of Bone: Diagnosis of SCI-Induced Osteoporosis and Fracture Risk Prediction

PubMed Central

Morse, Leslie R.

2015-01-01

Background: Spinal cord injury (SCI) is associated with a rapid loss of bone mass, resulting in severe osteoporosis and a 5- to 23-fold increase in fracture risk. Despite the seriousness of fractures in SCI, there are multiple barriers to osteoporosis diagnosis and wide variations in treatment practices for SCI-induced osteoporosis. Methods: We review the biological and structural changes that are known to occur in bone after SCI in the context of promoting future research to prevent or reduce risk of fracture in this population. We also review the most commonly used methods for assessing bone after SCI and discuss the strengths, limitations, and clinical applications of each method. Conclusions: Although dual-energy x-ray absorptiometry assessments of bone mineral density may be used clinically to detect changes in bone after SCI, 3-dimensional methods such as quantitative CT analysis are recommended for research applications and are explained in detail. PMID:26689691

Secreted Wnt Signaling Inhibitors in Disuse-Induced Bone Loss

DTIC Science & Technology

2011-05-01

decreased mechanical loading environment (e.g., as occurs in soldiers after spinal cord  injury ) leads to rapid bone loss via enhanced local...induced paralysis of the quadriceps,  hamstrings , and soleus) in one hindlimb of a series of mice  with mutations in Wnt modulators (Sost‐/‐, Dkk1...treatment strategies for overcoming the disuse‐associated bone loss that accompanies spinal cord  injury , and other battlefield‐related  injuries

High-Dose α-Tocopherol Supplementation Does Not Induce Bone Loss in Normal Rats

PubMed Central

Kasai, Shunji; Ito, Akemi; Shindo, Kaori; Toyoshi, Tohru; Bando, Masahiro

2015-01-01

Oxidative stress affects bone turnover. Preventative effects of antioxidants such as vitamin E on reduced bone mineral density and fractures associated with aging, osteoporosis, and smoking have been examined in animals and humans. The effects of vitamin E (α-tocopherol; αT) on bone health have yielded conflicting and inconclusive results from animal studies. In this study, to determine the bone effects of αT, we investigated the in vivo effects of αT on the bone mineral density, bone mass, bone microstructure, bone resorption, and osteogenesis through peripheral quantitative computed tomography (pQCT) measurements, micro-computed tomography (micro-CT) analyses, and bone histomorphometry of lumbar vertebrae and femurs in normal female Wistar rats fed diets containing αT in different quantities (0, 30, 120, or 600 mg/kg diet) for 8 weeks. To validate our hypotheses regarding bone changes, we examined ovariectomized rats as an osteoporosis model and control sham-operated rats in parallel. As expected, ovariectomized rats had reduced bone mineral density in lumbar vertebrae and the distal metaphyses of their femurs, reduced bone mass and deteriorated microstructure of cancellous bones in the vertebral body and distal femur metaphyses, and reduced bone mass due to resorption-dominant enhanced bone turnover in secondary cancellous bones in these sites. In comparison, αT administered to normal rats, even at the highest dose, did not induce reduced bone mineral density of lumbar vertebrae and femurs or a reduced bone mass or fragile microstructure of cancellous bones of the vertebral body and distal femur metaphyses. Instead, αT-fed rats showed a tendency for an osteogenesis-dominant bone mass increase in secondary cancellous bones in the vertebral body, in which active bone remodeling occurs. Thus, αT consumption may have beneficial effects on bone health. PMID:26147575

Bone marrow transplantation in a patient with drug-induced aplastic anemia.

PubMed

Banerjee, T K; Band, P R; Pabst, H; Goldsand, G; Armstrong, W D; Brown, J; Hill, J R; Dossetor, J B

1972-09-09

A 23-year-old woman gravely ill with Pseudomonas septicemia secondary to presumed drug-induced bone marrow aplasia received marrow transplantation from two male HL-A identical sibling donors. She had a successful engraftment with excellent but temporary clinical improvement. Subsequently she succumbed to graft-versus-host disease manifested by Pseudomonas and Candida albicans septicemia, cytomegalovirus pneumonitis, three phases of dermatitis, nausea, vomiting, dysphagia, diarrhea, fever, edema and bone pain, with gradual but complete graft suppression by the 74th day after the transplantation. A second marrow transplant on the 70th day was unsuccessful.

High dietary calcium intake does not counteract disuse-induced bone loss

NASA Astrophysics Data System (ADS)

Baecker, N.; Boese, A.; Smith, S. M.; Heer, M.

Reduction of mechanical stress on bone inhibits osteoblast-mediated bone formation, increases osteoclast-mediated bone resorption, and leads to what has been called disuse osteoporosis. Prolonged therapeutic bed rest, immobilization and space flight are common causes of disuse osteoporosis. There are sufficient data supporting the use of calcium in combination with vitamin D in the prevention and treatment of postmenopausal osteoporosis. In our study we examined the potential of high dietary calcium intake as a nutrition therapy for disuse-induced bone loss during head-down bed rest in healthy young men. In 2 identical metabolic ward, head-down bed rest (HDBR) experiments (crossover design), we studied the effect of high dietary calcium intake (2000 mg/d) in comparison to the recommended calcium intake of 1000 mg/d on markers of bone turnover. Experiment A (EA) was a 6-day randomized, controlled HDBR study. Experiment B (EB) was a 14-day randomized, controlled HDBR study. In both experiments, the test subjects stayed under well-controlled environmental conditions in our metabolic ward. Subjects' diets in the relevant study phases (HDBR versus Ambulatory Control) of EA and EB were identical except for the calcium intake. The subjects obtained 2000 mg/d Calcium in EA and 2000 mg/d in EB. Blood was drawn at baseline, before entering the relevant intervention period, on day 5 in study EA, and on days 6, 11 and 14 in study EB. Serum calcium, bone formation markers - Procollagen-I-C-Propeptide (PICP) and bone alkaline phosphatase (bAP) were analyzed in serum. 24h-urine was collected throughout the studies for determination of the excretion of calcium (UCaV) and a bone resorption marker, C-terminal telopeptide of collagen type I (UCTX). In both studies, serum calcium levels were unchanged. PICP tended to decrease in EA (p=0.08). In EB PICP decreased significantly over time (p=0.003) in both the control and HDBR periods, and tended to further decrease in the HDBR period (p

[Morphofunctional properties of the peripheral blood and bone marrow cells of rats following a flight on board the Kosmos-936 biosatellite].

PubMed

Kozinets, G I; Korol'kov, V I; Britvan, I I; Bykova, I A; Spitsyna, N E

1983-01-01

Morphofunctional properties of peripheral blood cells of Cosmos-936 rats were examined, using morphological, interferometric and electron microscopic techniques. As follows from the morphological data, immediately after recovery the weightless rats showed symptoms of a stress reaction which disappeared by R+3. The centrifuged rats exhibited less expressed symptoms of this sort. The percentage of bone marrow cell distribution was shifted towards enhanced myelopoiesis and diminished erythropoiesis. By the end of the readaptation period the ratio of bone marrow cell composition returned to normal. Interferometric and electron microscopic examinations did not reveal any irreversible changes in the structure and function of cells that may be caused by zero-g.

Formononetin prevents ovariectomy-induced bone loss in rats.

PubMed

Ha, Hyekyung; Lee, Ho Young; Lee, Je-Hyun; Jung, Dayoung; Choi, Jiyoon; Song, Kye-Yong; Jung, Hee Jin; Choi, Jae Sue; Chang, Soo-Ik; Kim, Chungsook

2010-04-01

The major risk factor of postmenopausal osteoporosis is estrogen deficiency. Hormone replacement therapy is efficacious against osteoporosis, but it induces several significant adverse effects. In this study, therefore, we compared therapeutic potencies of three phytoestrogens: genistein, daidzein, and formononetin. Our result showed that in Saos-2 cells, formononetin and genistein (5 x 10(-7) M) treatment increased alkaline phosphatase activity by 33.0 +/- 5.8% and 21.1 +/- 4.0%. Genistein inhibited osteoclast formation in a dose-dependent manner. In OVX rats, formononetin-treated groups given 1 and 10 mg/kg/day displayed increased trabecular bone areas (TBAs) within the tibia. Genistein- and daidzein-treated groups also displayed increased tibial TBAs. TBAs of the lumbar vertebrae were higher in all treated groups than in the control group. In conclusion, formononetin as well as other isoflavones, such as daidzein and genistein, inhibited bone loss caused by estrogen-deficiency.

Toll-Like Receptor 2 Stimulation of Osteoblasts Mediates Staphylococcus Aureus Induced Bone Resorption and Osteoclastogenesis through Enhanced RANKL

PubMed Central

Kassem, Ali; Lindholm, Catharina; Lerner, Ulf H

2016-01-01

Severe Staphylococcus aureus (S. aureus) infections pose an immense threat to population health and constitute a great burden for the health care worldwide. Inter alia, S. aureus septic arthritis is a disease with high mortality and morbidity caused by destruction of the infected joints and systemic bone loss, osteoporosis. Toll-Like receptors (TLRs) are innate immune cell receptors recognizing a variety of microbial molecules and structures. S. aureus recognition via TLR2 initiates a signaling cascade resulting in production of various cytokines, but the mechanisms by which S. aureus causes rapid and excessive bone loss are still unclear. We, therefore, investigated how S. aureus regulates periosteal/endosteal osteoclast formation and bone resorption. S. aureus stimulation of neonatal mouse parietal bone induced ex vivo bone resorption and osteoclastic gene expression. This effect was associated with increased mRNA and protein expression of receptor activator of NF-kB ligand (RANKL) without significant change in osteoprotegerin (OPG) expression. Bone resorption induced by S. aureus was abolished by OPG. S. aureus increased the expression of osteoclastogenic cytokines and prostaglandins in the parietal bones but the stimulatory effect of S. aureus on bone resorption and Tnfsf11 mRNA expression was independent of these cytokines and prostaglandins. Stimulation of isolated periosteal osteoblasts with S. aureus also resulted in increased expression of Tnfsf11 mRNA, an effect lost in osteoblasts from Tlr2 knockout mice. S. aureus stimulated osteoclastogenesis in isolated periosteal cells without affecting RANKL-stimulated resorption. In contrast, S. aureus inhibited RANKL-induced osteoclast formation in bone marrow macrophages. These data show that S. aureus enhances bone resorption and periosteal osteoclast formation by increasing osteoblast RANKL production through TLR2. Our study indicates the importance of using different in vitro approaches for studies of how S

The impact of microgravity on bone metabolism in vitro and in vivo.

PubMed

Loomer, P M

2001-01-01

Exposure to microgravity has been associated with several physiological changes in astronauts and cosmonauts, including an osteoporosis-like loss of bone mass. In-flight measures used to counteract this, including intensive daily exercise regimens, have been only partially successful in reducing the bone loss and in the process have consumed valuable work time. If this bone loss is to be minimized or, preferably, prevented, more effective treatment strategies are required. This, however, requires a greater understanding of the mechanisms through which bone metabolism is affected by microgravity. Various research strategies have been used to examine this problem, including in vitro studies using bone cells and in vivo studies on humans and rats. These have been conducted both in flight and on the ground, by strategies that produce weightlessness to mimic the effects of microgravity. Overall, the majority of the studies have found that marked decreases in gravitation loading result in the loss of bone mass. The processes of bone formation and bone resorption become uncoupled, with an initial transitory increase in resorption accompanied by a prolonged decrease in formation. Loss of bone mass is not uniform throughout the skeleton, but varies at different sites depending on the type of bone and on the mechanical load received. It appears that the skeletal response is a physiologic adaptation to the space environment which, after long space flights or repeated shorter ones, could eventually lead to significant reductions in the ability of the skeletal tissues to withstand the forces of gravity and increased susceptibility to fracture.

Radiation and mechanical unloading effects on mouse vertebral bone: Ground-based models of the spaceflight environment

NASA Astrophysics Data System (ADS)

Alwood, Joshua Stewart

Astronauts on long-duration space missions experience increased ionizing radiation background levels and occasional acute doses of ionizing radiation from solar particle events, in addition to biological challenges introduced by weightlessness. Previous research indicates that cancer radiotherapy damages bone marrow cell populations and reduces mechanical strength of bone. However, the cumulative doses in radiotherapy are an order of magnitude or greater than dose predictions for long-duration space missions. Further detriments to the skeletal system are the disuse and mechanical unloading experienced during weightlessness, which causes osteopenia in weight-bearing cancellous bone (a sponge-like bony network of rods, plates and voids) and cortical bone (dense, compact bone). Studies of radiation exposure utilizing spaceflight-relevant types and doses, and in combination with mechanical unloading, have received little attention. Motivated by the future human exploration of the solar system, the effects of acute and increased background radiation on astronaut skeletal health are important areas of study in order to prevent osteopenic deterioration and, ultimately, skeletal fracture. This dissertation addresses how spaceflight-relevant radiation affects bone microarchitecture and mechanical properties in the cancellous-rich vertebrae and compares results to that of mechanical unloading. In addition, a period of re-ambulation is used to test whether animals recover skeletal tissue after irradiation. Whether radiation exposure displays synergism with mechanical unloading is further investigated. Finite element structural and statistical analyses are used to investigate how changes in architecture affect mechanical stress within the vertebra and to interpret the mechanical testing results. In this dissertation, ground-based models provide evidence that ionizing radiation, both highly energetic gamma-rays and charged iron ions, resulted in a persistent loss of cancellous

Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring.

PubMed

Azuma, Kagaku; Ogura, Minori; Kondo, Hiroko; Suzuki, Ayumi; Hayashi, Sakurako; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

2017-01-01

Chronic psychological stress is a risk factor for osteoporosis. Maternal active mastication during prenatal stress attenuates stress response. The aim of this study is to test the hypothesis that maternal active mastication influences the effect of prenatal stress on bone mass and bone microstructure in adult offspring. Pregnant ddY mice were randomly divided into control, stress, and stress/chewing groups. Mice in the stress and stress/chewing groups were placed in a ventilated restraint tube for 45 minutes, 3 times a day, and was initiated on day 12 of gestation and continued until delivery. Mice in the stress/chewing group were allowed to chew a wooden stick during the restraint stress period. The bone response of 5-month-old male offspring was evaluated using quantitative micro-CT, bone histomorphometry, and biochemical markers. Prenatal stress resulted in significant decrease of trabecular bone mass in both vertebra and distal femur of the offspring. Maternal active mastication during prenatal stress attenuated the reduced bone formation and increased bone resorption, improved the lower trabecular bone volume and bone microstructural deterioration induced by prenatal stress in the offspring. These findings indicate that maternal active mastication during prenatal stress can ameliorate prenatal stress-induced lower bone mass of the vertebra and femur in adult offspring. Active mastication during prenatal stress in dams could be an effective coping strategy to prevent lower bone mass in their offspring.

Using Natural Stable Calcium Isotopes to Rapidly Assess Changes in Bone Mineral Balance Using a Bed Rest Model to Induce Bone Loss

NASA Technical Reports Server (NTRS)

Morgan, J. L. L.; Skulan, J. L.; Gordon, G. E.; Smith, Scott M.; Romaniello, S. J.; Anbar, A. D.

2012-01-01

Metabolic bone diseases like osteoporosis result from the disruption of normal bone mineral balance (BMB) resulting in bone loss. During spaceflight astronauts lose substantial bone. Bed rest provides an analog to simulate some of the effects of spaceflight; including bone and calcium loss and provides the opportunity to evaluate new methods to monitor BMB in healthy individuals undergoing environmentally induced-bone loss. Previous research showed that natural variations in the Ca isotope ratio occur because bone formation depletes soft tissue of light Ca isotopes while bone resorption releases that isotopically light Ca back into soft tissue (Skulan et al, 2007). Using a bed rest model, we demonstrate that the Ca isotope ratio of urine shifts in a direction consistent with bone loss after just 7 days of bed rest, long before detectable changes in bone mineral density (BMD) occur. The Ca isotope variations tracks changes observed in urinary N-teleopeptide, a bone resorption biomarker. Bone specific alkaline phosphatase, a bone formation biomarker, is unchanged. The established relationship between Ca isotopes and BMB can be used to quantitatively translate the changes in the Ca isotope ratio to changes in BMD using a simple mathematical model. This model predicts that subjects lost 0.25 0.07% ( SD) of their bone mass from day 7 to day 30 of bed rest. Given the rapid signal observed using Ca isotope measurements and the potential to quantitatively assess bone loss; this technique is well suited to study the short-term dynamics of bone metabolism.

Apoptosis-induced CXCL5 accelerates inflammation and growth of prostate tumor metastases in bone.

PubMed

Roca, Hernan; Jones, Jacqueline D; Purica, Marta C; Weidner, Savannah; Koh, Amy J; Kuo, Robert; Wilkinson, John E; Wang, Yugang; Daignault-Newton, Stephanie; Pienta, Kenneth J; Morgan, Todd M; Keller, Evan T; Nör, Jacques E; Shea, Lonnie D; McCauley, Laurie K

2018-01-02

During tumor progression, immune system phagocytes continually clear apoptotic cancer cells in a process known as efferocytosis. However, the impact of efferocytosis in metastatic tumor growth is unknown. In this study, we observed that macrophage-driven efferocytosis of prostate cancer cells in vitro induced the expression of proinflammatory cytokines such as CXCL5 by activating Stat3 and NF-κB(p65) signaling. Administration of a dimerizer ligand (AP20187) triggered apoptosis in 2 in vivo syngeneic models of bone tumor growth in which apoptosis-inducible prostate cancer cells were either coimplanted with vertebral bodies, or inoculated in the tibiae of immunocompetent mice. Induction of 2 pulses of apoptosis correlated with increased infiltration of inflammatory cells and accelerated tumor growth in the bone. Apoptosis-induced tumors displayed elevated expression of the proinflammatory cytokine CXCL5. Likewise, CXCL5-deficient mice had reduced tumor progression. Peripheral blood monocytes isolated from patients with bone metastasis of prostate cancer were more efferocytic compared with normal controls, and CXCL5 serum levels were higher in metastatic prostate cancer patients relative to patients with localized prostate cancer or controls. Altogether, these findings suggest that the myeloid phagocytic clearance of apoptotic cancer cells accelerates CXCL5-mediated inflammation and tumor growth in bone, pointing to CXCL5 as a potential target for cancer therapeutics.

Maternal Perinatal Diet Induces Developmental Programming of Bone Architecture

PubMed Central

Devlin, MJ; Grasemann, C; Cloutier, AM; Louis, L; Alm, C; Palmert, MR; Bouxsein, ML

2013-01-01

Maternal high fat diet can alter offspring metabolism via perinatal developmental programming. This study tests the hypothesis that maternal high fat diet also induces perinatal programming of offspring bone mass and strength. We compared skeletal acquisition in pups from C57Bl/6J mice fed high fat or normal diet from preconception through lactation. Three-week-old male and female pups from high fat (HF-N) and normal mothers (N-N) were weaned onto normal diet. Outcomes at 14 and 26 wks of age included body mass, body composition, whole body bone mineral content via pDXA, femoral cortical and trabecular architecture via μCT, and glucose tolerance. Female HF-N had normal body mass and glucose tolerance, with lower %body fat but higher serum leptin at 14 wks vs. N-N (p<0.05 for both). Whole body bone mineral content was 12% lower at 14 wks and 5% lower at 26 wks, but trabecular bone volume fraction was 20% higher at 14 wks in female HF-N vs. N-N (p<0.05 for all). Male HF-N had normal body mass and mildly impaired glucose tolerance, with lower %body fat at 14 wks and lower serum leptin at 26 wks vs. N-N (p<0.05 for both). Serum insulin was higher at 14 wks and lower at 26 wks in HF-N vs. N-N (p<0.05). Trabecular BV/TV was 34% higher and cortical bone area was 6% higher at 14 wks vs. N-N (p<0.05 for both). These data suggest maternal high fat diet has complex effects on offspring bone, supporting the hypothesis that maternal diet alters postnatal skeletal homeostasis. PMID:23503967

Fcγ receptor-mediated influx of S100A8/A9-producing neutrophils as inducer of bone erosion during antigen-induced arthritis.

PubMed

Di Ceglie, Irene; Ascone, Giuliana; Cremers, Niels A J; Sloetjes, Annet W; Walgreen, Birgitte; Vogl, Thomas; Roth, Johannes; Verbeek, J Sjef; van de Loo, Fons A J; Koenders, Marije I; van der Kraan, Peter M; Blom, Arjen B; van den Bosch, Martijn H J; van Lent, Peter L E M

2018-05-02

Osteoclast-mediated bone erosion is a central feature of rheumatoid arthritis (RA). Immune complexes, present in a large percentage of patients, bind to Fcγ receptors (FcγRs), thereby modulating the activity of immune cells. In this study, we investigated the contribution of FcγRs, and FcγRIV in particular, during antigen-induced arthritis (AIA). AIA was induced in knee joints of wild-type (WT), FcγRI,II,III -/- , and FcγRI,II,III,IV -/- mice. Bone destruction, numbers of tartrate-resistant acid phosphatase-positive (TRAP + ) osteoclasts, and inflammation were evaluated using histology; expression of the macrophage marker F4/80, neutrophil marker NIMPR14, and alarmin S100A8 was evaluated using immunohistochemistry. The percentage of osteoclast precursors in the bone marrow was determined using flow cytometry. In vitro osteoclastogenesis was evaluated with TRAP staining, and gene expression was assessed using real-time PCR. FcγRI,II,III,IV -/- mice showed decreased bone erosion compared with WT mice during AIA, whereas both the humoral and cellular immune responses against methylated bovine serum albumin were not impaired in FcγRI,II,III,IV -/- mice. The percentage of osteoclast precursors in the bone marrow of arthritic mice and their ability to differentiate into osteoclasts in vitro were comparable between FcγRI,II,III,IV -/- and WT mice. In line with these observations, numbers of TRAP + osteoclasts on the bone surface during AIA were comparable between the two groups. Inflammation, a process that strongly activates osteoclast activity, was reduced in FcγRI,II,III,IV -/- mice, and of note, mainly decreased numbers of neutrophils were present in the joint. In contrast to FcγRI,II,III,IV -/- mice, AIA induction in knee joints of FcγRI,II,III -/- mice resulted in increased bone erosion, inflammation, and numbers of neutrophils, suggesting a crucial role for FcγRIV in the joint pathology by the recruitment of neutrophils. Finally, significant

Possibility of long-distance heat transport in weightlessness using supercritical fluids

NASA Astrophysics Data System (ADS)

Beysens, D.; Chatain, D.; Nikolayev, V. S.; Ouazzani, J.; Garrabos, Y.

2010-12-01

Heat transport over large distances is classically performed with gravity or capillarity driven heat pipes. We investigate here whether the “piston effect,” a thermalization process that is very efficient in weightlessness in compressible fluids, could also be used to perform long-distance heat transfer. Experiments are performed in a modeling heat pipe (16.5 mm long, 3 mm inner diameter closed cylinder), with nearly adiabatic polymethylmethacrylate walls and two copper base plates. The cell is filled with H2 near its gas-liquid critical point (critical temperature: 33 K). Weightlessness is achieved by submitting the fluid to a magnetic force that compensates gravity. Initially the fluid is isothermal. Then heat is sent to one of the bases with an electrical resistance. The instantaneous amount of heat transported by the fluid is measured at the other end. The data are analyzed and compared with a two-dimensional numerical simulation that allows an extrapolation to be made to other fluids (e.g., CO2 , with critical temperature of 300 K). The major result is concerned with the existence of a very fast response at early times that is only limited by the thermal properties of the cell materials. The yield in terms of ratio, injected or transported heat power, does not exceed 10-30% and is limited by the heat capacity of the pipe. These results are valid in a large temperature domain around the critical temperature.

Bone Regeneration Using Bone Morphogenetic Proteins and Various Biomaterial Carriers

PubMed Central

Sheikh, Zeeshan; Javaid, Mohammad Ahmad; Hamdan, Nader; Hashmi, Raheel

2015-01-01

Trauma and disease frequently result in fractures or critical sized bone defects and their management at times necessitates bone grafting. The process of bone healing or regeneration involves intricate network of molecules including bone morphogenetic proteins (BMPs). BMPs belong to a larger superfamily of proteins and are very promising and intensively studied for in the enhancement of bone healing. More than 20 types of BMPs have been identified but only a subset of BMPs can induce de novo bone formation. Many research groups have shown that BMPs can induce differentiation of mesenchymal stem cells and stem cells into osteogenic cells which are capable of producing bone. This review introduces BMPs and discusses current advances in preclinical and clinical application of utilizing various biomaterial carriers for local delivery of BMPs to enhance bone regeneration. PMID:28788032

Use of Animal Models in Understanding Cancer-induced Bone Pain

PubMed Central

Slosky, Lauren M; Largent-Milnes, Tally M; Vanderah, Todd W

2015-01-01

Many common cancers have a propensity to metastasize to bone. Although malignancies often go undetected in their native tissues, bone metastases produce excruciating pain that severely compromises patient quality of life. Cancer-induced bone pain (CIBP) is poorly managed with existing medications, and its multifaceted etiology remains to be fully elucidated. Novel analgesic targets arise as more is learned about this complex and distinct pain state. Over the past two decades, multiple animal models have been developed to study CIBP’s unique pathology and identify therapeutic targets. Here, we review animal models of CIBP and the mechanistic insights gained as these models evolve. Findings from immunocompromised and immunocompetent host systems are discussed separately to highlight the effect of model choice on outcome. Gaining an understanding of the unique neuromolecular profile of cancer pain through the use of appropriate animal models will aid in the development of more effective therapeutics for CIBP. PMID:26339191

Protective effect of zinc supplementation against cadmium-induced oxidative stress and the RANK/RANKL/OPG system imbalance in the bone tissue of rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brzóska, Malgorzata M., E-mail: Malgorzata.Brzoska@umb.edu.pl; Rogalska, Joanna

It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-κΒ (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/antioxidative status, and Cd and Zn were determined in the distal femur of the rats administered Zn (30 and 60 mg/l) or/and Cd (5 and 50 mg/l) for 6 months. Soluble RANKL (sRANKL) and OPG were measured in the bone and serum. Zn supplementation importantly protected from Cd-induced oxidative stress preventing protein, DNA, and lipid oxidation in the bone.more » Moreover, Zn protected from the Cd-induced increase in sRANKL concentration and the sRANKL/OPG ratio, and decrease in OPG concentration in the bone and serum. Numerous correlations were noted between indices of the oxidative/antioxidative bone status, concentrations of sRANKL and OPG in the bone and serum, as well as the bone concentrations of Zn and Cd, and previously reported by us in these animals (Brzóska et al., 2007) indices of bone turnover and bone mineral density. The results allow us to conclude that the ability of Zn to prevent from oxidative stress and the RANK/RANKL/OPG system imbalance may be implicated in the mechanisms of its protective impact against Cd-induced bone damage. This paper is the first report from an in vivo study providing evidence that beneficial Zn impact on the skeleton under exposure to Cd is related to the improvement of the bone tissue oxidative/antioxidative status and mediating the RANK/RANKL/OPG system. - Highlights: • Cd induces oxidative stress in the bone tissue. • Cd disturbs bone metabolism via disorder of the RANK/RANKL/OPG system balance. • Zn supplementation protects from Cd-induced oxidative stress in the bone tissue. • Zn protects from the RANK/RANKL/OPG system imbalance caused by Cd in the bone tissue. • Enhanced Zn intake protects

Bone Markers, Calcium Metabolism, and Calcium Kinetics During Extended-Duration Space Flight on the Mir Space Station

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Wastney, Meryl E.; O'Brien, Kimberly O.; Morukov, Boris V.; Larina, Irina M.; Abrams, Steven A.; Davis-Street, Janis E.; Oganov, Victor; Shackelford, Linda C.

2005-01-01

Bone loss is a current limitation for long-term space exploration. Bone markers, calcitropic hormones, and calcium kinetics of crew members on space missions of 4-6 months were evaluated. Spaceflight-induced bone loss was associated with increased bone resorption and decreased calcium absorption. INTRODUCTION: Bone loss is a significant concern for the health of astronauts on long-duration missions. Defining the time course and mechanism of these changes will aid in developing means to counteract these losses during space flight and will have relevance for other clinical situations that impair weight-bearing activity. MATERIALS AND METHODS: We report here results from two studies conducted during the Shuttle-Mir Science Program. Study 1 was an evaluation of bone and calcium biochemical markers of 13 subjects before and after long-duration (4-6 months) space missions. In study 2, stable calcium isotopes were used to evaluate calcium metabolism in six subjects before, during, and after flight. Relationships between measures of bone turnover, biochemical markers, and calcium kinetics were examined. RESULTS: Pre- and postflight study results confirmed that, after landing, bone resorption was increased, as indicated by increases in urinary calcium (p < 0.05) and collagen cross-links (N-telopeptide, pyridinoline, and deoxypyridinoline were all increased >55% above preflight levels, p < 0.001). Parathyroid hormone and vitamin D metabolites were unchanged at landing. Biochemical markers of bone formation were unchanged at landing, but 2-3 weeks later, both bone-specific alkaline phosphatase and osteocalcin were significantly (p < 0.01) increased above preflight levels. In studies conducted during flight, bone resorption markers were also significantly higher than before flight. The calcium kinetic data also validated that bone resorption was increased during flight compared with preflight values (668 +/- 130 versus 427 +/- 153 mg/day; p < 0.001) and clearly documented that

IL-17A GENE TRANSFER INDUCES BONE LOSS AND EPIDERMAL HYPERPLASIA ASSOCIATED WITH PSORIATIC ARTHRITIS

PubMed Central

ADAMOPOULOS, IANNIS E.; SUZUKI, ERIKA; CHAO, CHENG-CHI; GORMAN, DAN; ADDA, SARVESH; MAVERAKIS, EMANUAL; ZARBALIS, KONSTANTINOS; GEISSLER, RICHARD; ASIO, AGELIO; BLUMENSCHEIN, WENDY M; McCLANAHAN, TERRILL; DE WAAL MALEFYT, RENE; GERSHWIN, M. ERIC; BOWMAN, EDWARD P.

2014-01-01

Background Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by clinical features that include bone loss and epidermal hyperplasia. Aberrant cytokine expression has been linked to joint and skin pathology; however, it is unclear which cytokines are critical for disease initiation. IL-17A participates in many pathologic immune responses; however, its role in PsA has not been fully elucidated. Objective To determine the role of IL-17A in epidermal hyperplasia and bone destruction associated with psoriatic arthritis. Design An in vivo gene transfer approach was used to investigate the role of IL-17A in animal models of inflammatory (Collagen-induced arthritis) and non-inflammatory (RANKL-gene transfer) bone loss. Results IL-17A gene transfer induced the expansion of IL-17RA+CD11b+Gr1low osteoclast precursors and a concomitant elevation of biomarkers indicative of bone resorption. This occurred at a time preceding noticeable joint inflammation suggesting that IL-17A is critical for the induction of pathological bone resorption through direct activation of osteoclast precursors. Moreover, IL-17A induced a second myeloid population CD11b+Gr1high neutrophil-like cells which was associated with cutaneous pathology including epidermal hyperplasia, parakeratosis, and Munro’s microabscesses formation. Conclusion Collectively, these data support that IL-17A can play a key role in the pathogenesis of inflammation-associated arthritis and/or skin disease, as observed in PsA. PMID:24567524

Murine bone cell lines as models for spaceflight induced effects on differentiation and gene expression

NASA Astrophysics Data System (ADS)

Lau, P.; Hellweg, C. E.; Baumstark-Khan, C.; Reitz, G.

Critical health factors for space crews especially on long-term missions are radiation exposure and the absence of gravity DNA double strand breaks DSB are presumed to be the most deleterious DNA lesions after radiation as they disrupt both DNA strands in close proximity Besides radiation risk the absence of gravity influences the complex skeletal apparatus concerning muscle and especially bone remodelling which results from mechanical forces exerting on the body Bone is a dynamic tissue which is life-long remodelled by cells from the osteoblast and osteoclast lineage Any imbalance of this system leads to pathological conditions such as osteoporosis or osteopetrosis Osteoblastic cells play a crucial role in bone matrix synthesis and differentiate either into bone-lining cells or into osteocytes Premature terminal differentiation has been reported to be induced by a number of DNA damaging or cell stress inducing agents including ionising and ultraviolet radiation as well as treatment with mitomycin C In the present study we compare the effects of sequential differentiation by adding osteoinductive substances ss -glycerophosphate and ascorbic acid Radiation-induced premature differentiation was investigated regarding the biosynthesis of specific osteogenic marker molecules and the differentiation dependent expression of marker genes The bone cell model established in our laboratory consists of the osteocyte cell line MLO-Y4 the osteoblast cell line OCT-1 and the subclones 4 and 24 of the osteoblast cell line MC3T3-E1 expressing several

Effect of radioactive iodine-induced hypothyroidism on longitudinal bone growth during puberty in immature female rats.

PubMed

Choi, Hyeonhae; Ryu, Ki-Young; Roh, Jaesook; Bae, Jaeman

2018-05-22

Thyroid cancer in children, the most common endocrine malignancy, shows aggressive behavior and has a high recurrence rate after surgical ablation. Radioactive iodine (RAI) treatment is the most effective primary modality for medical ablation of juvenile thyroid cancer, and leads to intentional hypothyroidism. Although several negative impacts of hypothyroidism have been reported in children in response to other antithyroid agents, the combined effects of RAI exposure and hypothyroidism, on growing bones specifically, are unknown. In this study, we investigated the effect of RAI-induced hypothyroidism on the long bones during the pubertal growth spurt using immature female rats. Female Sprague-Dawley rats were randomly divided into a control group, and an RAI-treated group fed with RAI (0.37 MBq/g body weight) twice via gavage. After 4 weeks, we observed a significantly-reduced serum free thyroxine level in the RAI group. The latter group also displayed decreased body weight gain compared to the control. In addition, the lengths of long bones, such as the leg bones and vertebral column, as well as bone mineral content, were reduced in the RAI-treated animals. Our results confirm the negative impacts of RAI-induced thyroid deficiency during puberty on longitudinal bone growth and bone mineralization.

Eccentric and concentric muscle performance following 7 days of simulated weightlessness

NASA Technical Reports Server (NTRS)

Hayes, Judith C.; Roper, Mary L.; Mazzocca, Augustus D.; Mcbrine, John J.; Barrows, Linda H.; Harris, Bernard A.; Siconolfi, Steven F.

1992-01-01

Changes in skeletal muscle strength occur in response to chronic disuse or insufficient functional loading. The purpose of this study was to examine changes in muscle performance of the lower extremity and torso prior to and immediately after 7 days of simulated weightlessness (horizontal bed rest). A Biodex was used to determine concentric and eccentric peak torque and angle at peak torque for the back, abdomen, quadriceps, hamstring, soleus, and tibialis anterior. A reference angle of 0 degrees was set at full extension. Data were analyzed by ANOVA.

BMI-1 Mediates Estrogen-Deficiency-Induced Bone Loss by Inhibiting Reactive Oxygen Species Accumulation and T Cell Activation.

PubMed

Li, Jinbo; Wang, Qian; Yang, Renlei; Zhang, Jiaqi; Li, Xing; Zhou, Xichao; Miao, Dengshun

2017-05-01

Previous studies have shown that estrogen regulates bone homeostasis through regulatory effects on oxidative stress. However, it is unclear how estrogen deficiency triggers reactive oxygen species (ROS) accumulation. Recent studies provide evidence that the B lymphoma Mo-MLV insertion region 1 (BMI-1) plays a critical role in protection against oxidative stress and that this gene is directly regulated by estrogen via estrogen receptor (ER) at the transcriptional level. In this study, ovariectomized mice were given drinking water with/without antioxidant N-acetyl-cysteine (NAC, 1 mg/mL) supplementation, and compared with each other and with sham mice. Results showed that ovariectomy resulted in bone loss with increased osteoclast surface, increased ROS levels, T cell activation, and increased TNF and RANKL levels in serum and in CD4 T cells; NAC supplementation largely prevented these alterations. BMI-1 expression levels were dramatically downregulated in CD4 T cells from ovariectomized mice. We supplemented drinking water to BMI-1-deficient mice with/without NAC and compared them with each other and with wild-type (WT) mice. We found that BMI-1 deficiency mimicked alterations observed in ovariectomy whereas NAC supplementation reversed all alterations induced by BMI-1 deficiency. Because T cells are critical in mediating ovariectomy-induced bone loss, we further assessed whether BMI-1 overexpression in lymphocytes can protect against estrogen deficiency-induced osteoclastogenesis and bone loss by inhibiting oxidative stress, T cell activation, and RANKL production. When WT and Eμ-BMI-1 transgenic mice with BMI-1 specifically overexpressed in lymphocytes were ovariectomized and compared with each other and with WT sham mice, we found that BMI-1 overexpression in lymphocytes clearly reversed all alterations induced by ovariectomy. Results from this study indicate that estrogen deficiency downregulates BMI-1 and subsequently increases ROS, T cell activation, and

Whole-body vibration of mice induces articular cartilage degeneration with minimal changes in subchondral bone.

PubMed

McCann, M R; Yeung, C; Pest, M A; Ratneswaran, A; Pollmann, S I; Holdsworth, D W; Beier, F; Dixon, S J; Séguin, C A

2017-05-01

Low-amplitude, high-frequency whole-body vibration (WBV) has been adopted for the treatment of musculoskeletal diseases including osteoarthritis (OA); however, there is limited knowledge of the direct effects of vibration on joint tissues. Our recent studies revealed striking damage to the knee joint following exposure of mice to WBV. The current study examined the effects of WBV on specific compartments of the murine tibiofemoral joint over 8 weeks, including microarchitecture of the tibia, to understand the mechanisms associated with WBV-induced joint damage. Ten-week-old male CD-1 mice were exposed to WBV (45 Hz, 0.3 g peak acceleration; 30 min/day, 5 days/week) for 4 weeks, 8 weeks, or 4 weeks WBV followed by 4 weeks recovery. The knee joint was evaluated histologically for tissue damage. Architecture of the subchondral bone plate, subchondral trabecular bone, primary and secondary spongiosa of the tibia was assessed using micro-CT. Meniscal tears and focal articular cartilage damage were induced by WBV; the extent of damage increased between 4 and 8-week exposures to WBV. WBV did not alter the subchondral bone plate, or trabecular bone of the tibial spongiosa; however, a transient increase was detected in the subchondral trabecular bone volume and density. The lack of WBV-induced changes in the underlying subchondral bone suggests that damage to the articular cartilage may be secondary to the meniscal injury we detected. Our findings underscore the need for further studies to assess the safety of WBV in the human population to avoid long-term joint damage. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

[Remodeling simulation of human femur under bed rest and spaceflight circumstances based on three dimensional finite element analysis].

PubMed

Yang, Wenting; Wang, Dongmei; Lei, Zhoujixin; Wang, Chunhui; Chen, Shanguang

2017-12-01

Astronauts who are exposed to weightless environment in long-term spaceflight might encounter bone density and mass loss for the mechanical stimulus is smaller than normal value. This study built a three dimensional model of human femur to simulate the remodeling process of human femur during bed rest experiment based on finite element analysis (FEA). The remodeling parameters of this finite element model was validated after comparing experimental and numerical results. Then, the remodeling process of human femur in weightless environment was simulated, and the remodeling function of time was derived. The loading magnitude and loading cycle on human femur during weightless environment were increased to simulate the exercise against bone loss. Simulation results showed that increasing loading magnitude is more effective in diminishing bone loss than increasing loading cycles, which demonstrated that exercise of certain intensity could help resist bone loss during long-term spaceflight. At the end, this study simulated the bone recovery process after spaceflight. It was found that the bone absorption rate is larger than bone formation rate. We advise that astronauts should take exercise during spaceflight to resist bone loss.

PTH [1-34]-induced alterations of the subchondral bone provoke early osteoarthritis.

PubMed

Orth, P; Cucchiarini, M; Wagenpfeil, S; Menger, M D; Madry, H

2014-06-01

To test the hypothesis that changes in the subchondral bone induced by parathyroid hormone (PTH [1-34]) reciprocally affect the integrity of the articular cartilage within a naïve osteochondral unit in vivo. Daily subcutaneous injections of 10 μg PTH [1-34]/kg were given to adult rabbits for 6 weeks, controls received saline. Blood samples were continuously collected to monitor renal function. The subchondral bone plate and subarticular spongiosa of the femoral heads were separately assessed by micro-computed tomography. Articular cartilage was evaluated by macroscopic and histological osteoarthritis scoring, polarized light microscopy, and immunohistochemical determination of type-I, type-II, type-X collagen contents, PTH [1-34] receptor and caspase-3 expression. Absolute and relative extents of hyaline and calcified articular cartilage layers were measured histomorphometrically. The correlation between PTH-induced changes in subchondral bone and articular cartilage was determined. PTH [1-34] enhanced volume, mineral density, and trabecular thickness within the subarticular spongiosa, and increased thickness of the calcified cartilage layer (all P < 0.05). Moreover, PTH [1-34] led to cartilage surface irregularities and reduced matrix staining (both P < 0.03). These early osteoarthritic changes correlated with and were ascribed to the increased thickness of the calcified cartilage layer (P = 0.026) and enhanced mineral density of the subarticular spongiosa (P = 0.001). Modifications of the subarticular spongiosa by PTH [1-34] cause broadening of the calcified cartilage layer, resulting in osteoarthritic cartilage degeneration. These findings identify a mechanism by which PTH-induced alterations of the normal subchondral bone microarchitecture may provoke early osteoarthritis. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Maternal Active Mastication during Prenatal Stress Ameliorates Prenatal Stress-Induced Lower Bone Mass in Adult Mouse Offspring