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Sample records for weightlessness induces bone

  1. Sensitivity of bone cell populations to weightlessness and simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Roberts, W. E.; Morey-Holton, E. R.; Gonsalves, M. R.

    1984-01-01

    A rat suspension model for simulating certain aspects of weightlessness is discussed. Perturbations in physiological systems induced by this head down suspension model are verified by flight data. Findings of a suppression of osteoblast differentiation help explain the inhibition of bone formation inflight and during Earth-bound simulations. Since the anatomical site for these studies was in the maxilla, which is gravity loaded but non weightbearing in ground-based simulations, the similarity of bone cell kinetic changes, both inflight and in the ground-based model, suggest that fluid shifts rather than unloading may play an important role in bone alterations, at least at this sampling site.

  2. Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss.

    PubMed

    Aguirre, J Ignacio; Plotkin, Lilian I; Stewart, Scott A; Weinstein, Robert S; Parfitt, A Michael; Manolagas, Stavros C; Bellido, Teresita

    2006-04-01

    Mechanical stimulation of cultured osteocytic cells attenuates their apoptosis. We report here that, conversely, reduced mechanical forces in the murine model of unloading by tail suspension increases the prevalence of osteocyte apoptosis, followed by bone resorption and loss of mineral and strength. Mechanical loading is critical for the maintenance of bone mass; weightlessness, as with reduced physical activity in old age, bed rest, or space flight, invariably leads to bone loss. However, the cellular and molecular mechanisms responsible for these phenomena are poorly understood. Based on our earlier findings that physiologic levels of mechanical strain prevent apoptosis of osteocytic cells in vitro, we examined here whether, conversely, reduced mechanical forces increase the prevalence of osteocyte apoptosis in vivo and whether this event is linked to bone loss. Swiss Webster mice or OG2-11beta-hydroxysteroid dehydrogenase type 2 (OG2-11beta-HSD2) transgenic mice and wildtype littermates were tail-suspended or kept under ambulatory conditions. Static and dynamic histomorphometry and osteocyte and osteoblast apoptosis by in situ end-labeling (ISEL) were assessed in lumbar vertebra; spinal BMD was measured by DXA; and bone strength was measured by vertebral compression. We show that within 3 days of tail suspension, mice exhibited an increased incidence of osteocyte apoptosis in both trabecular and cortical bone. This change was followed 2 weeks later by increased osteoclast number and cortical porosity, reduced trabecular and cortical width, and decreased spinal BMD and vertebral strength. Importantly, whereas in ambulatory animals, apoptotic osteocytes were randomly distributed, in unloaded mice, apoptotic osteocytes were preferentially sequestered in endosteal cortical bone--the site that was subsequently resorbed. The effect of unloading on osteocyte apoptosis and bone resorption was reproduced in transgenic mice in which osteocytes are refractory to

  3. Weightlessness and bone loss in man

    NASA Technical Reports Server (NTRS)

    Rambaut, P. C.

    1983-01-01

    A review is presented of data whicih has been accumulated on the calcium and skeletal changes occurring in humans subjected to various periods of weightlessness. These data reveal that spaceflight induces an overall loss of calcium which continues unabated for at least three months. Urinary calcium levels reach a constant level within approximately four weeks while fecal calcium losses continue to increase throughout the flight period. A decline in the mineral density of weight-bearing bones accompanies these changes. Available data support the contention that the demineralization affects primarily the weight bearing bones. The rates of loss and recovery of calcium and bone mineral density are approximately equal to those observed during and following bedrest of comparable duration. No measure to wholly prevent these losses has yet been devised.

  4. Comparative study on measured variables and sensitivity to bone microstructural changes induced by weightlessness between in vivo and ex vivo micro-CT scans.

    PubMed

    Sun, Lian Wen; Wang, Chao; Pu, Fang; Li, De Yu; Niu, Hai Jun; Fan, Yu Bo

    2011-01-01

    Depending on the experimental design, micro-CT can be used to examine bones either in vivo or ex vivo (excised fresh or formalin-fixed). In this study we investigated if differences exist in the variables measured by micro-CT between in vivo and ex vivo scans and which kind of scan is more sensitive to the changes of bone microstructure induced by simulated weightlessness. Rat tail suspension was used to simulate the weightless condition. The same bone from either normal or tail-suspended rats was scanned by micro-CT both in vivo and ex vivo (fresh and fixed by formalin). Then, bone mineral density (BMD) and microstructural characteristics were analyzed. The results showed that no significant differences existed in the microstructural parameters of trabecular bone among in vivo, fresh, and formalin-fixed bone scans from both femurs and tibias, although BMD exhibited differences. On the other hand, most parameters of the tail-suspended rats measured by micro-CT deteriorated compared with controls. Ex vivo scanning appeared to be more sensitive to bone microstructural changes induced by tail suspension than in vivo scanning. In general, the results indicate that values obtained in vivo and ex vivo (fresh and fixed) are comparable, thus allowing for meaningful comparison of experimental results from different studies irrespective of the type of scans. In addition, this study suggests that it is better to use ex vivo scanning when evaluating bone microstructure under weightlessness. However, researchers can select any type of scan depending upon the objective and the demands of the experiment.

  5. Effects of simulated weightlessness on the kinase activity of MEK1 induced by bone morphogenetic protein-2 in rat osteosarcoma cells

    NASA Astrophysics Data System (ADS)

    Zhang, S.; Wang, B.; Cao, X. S.; Yang, Z.

    Objective The mRNA expression of alpha 1 chain of type I collagen COL-I alpha 1 in rat osteosarcoma ROS17 2 8 cells induced by bone morphogenetic protein-2 BMP-2 was reduced under simulated microgravity The protein kinase MEK1 of MAPK signal pathway plays an important role in the expression of COL-I alpha 1 mRNA The purpose of this study is to investigate the effects of simulated weightlessness on the activity of MEK1 induced by BMP-2 in ROS17 2 8 cells Methods ROS17 2 8 cells were cultured in 1G control and rotating clinostat simulated weightlessness for 24 h 48 h and 72 h BMP-2 500 ng ml was added into the medium 1 h before the culture ended There was a control group in which ROS17 2 8 cells were cultured in 1G condition without BMP-2 Then the total protein of cells was extracted and the expression of phosphated-ERK1 2 p-ERK1 2 protein was detected by means of Western Blotting to show the kinase activity of MEK1 Results There were no significant differences in the expression of total ERK1 2 among all groups The expression of p-ERK1 2 was unconspicuous in the control group without BMP-2 but increased significantly when BMP-2 was added P 0 01 The level of p-ERK1 2 in simulated weightlessness group was much more lower than that in 1G group in every time point P 0 01 The expression of p-ERK1 2 gradually decreased along with the time of weightlessness simulation P 0 01 Conclusions The kinase activity of MEK1 induced by BMP-2 in rat osteosarcoma cells was reduced under simulated weightlessness

  6. Evaluation of Treadmill Exercise in a Lower Body Negative Pressure Chamber as a Countermeasure for Weightlessness-Induced Bone Loss: a Bed Rest Study with Identical Twins

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Davis-Street, Janis E.; Fesperman, J. Vernell; Calkins, D. S.; Bawa, Maneesh; Macias, Brandon R.; Meyer, R. Scott; Hargens, Alan R.

    2003-01-01

    Counteracting bone loss is required for future space exploration. We evaluated the ability of treadmill exercise in a LBNP chamber to counteract bone loss in a 30-day bed rest study. Eight pairs of identical twins were randomly assigned to sedentary control or exercise groups. Exercise within LBNP decreased the bone resorption caused by bed rest and may provide a countermeasure for spaceflight. INTRODUCTION: Bone loss is one of the greatest physiological challenges for extended-duration space missions. The ability of exercise to counteract weightlessness-induced bone loss has been studied extensively, but to date, it has proven ineffective. We evaluated the effectiveness of a combination of two countermeasures-treadmill exercise while inside a lower body negative pressure (LBNP) chamber-on bone loss during a 30-day bed rest study. MATERIALS AND METHODS: Eight pairs of identical twins were randomized into sedentary (SED) or exercise/LBNP (EX/LBNP) groups. Blood and urine samples were collected before, several times during, and after the 30-day bed rest period. These samples were analyzed for markers of bone and calcium metabolism. Repeated measures ANOVA was used to determine statistical significance. Because identical twins were used, both time and group were treated as repeated variables. RESULTS: Markers of bone resorption were increased during bed rest in samples from sedentary subjects, including the collagen cross-links and serum and urinary calcium concentrations. For N-telopeptide and deoxypyridinoline, there were significant (p < 0.05) interactions between group (SED versus EX/LBNP) and phase of the study (sample collection point). Pyridinium cross-links were increased above pre-bed rest levels in both groups, but the EX/LBNP group had a smaller increase than the SED group. Markers of bone formation were unchanged by bed rest in both groups. CONCLUSIONS: These data show that this weight-bearing exercise combined with LBNP ameliorates some of the negative

  7. Evaluation of treadmill exercise in a lower body negative pressure chamber as a countermeasure for weightlessness-induced bone loss: a bed rest study with identical twins.

    PubMed

    Smith, Scott M; Davis-Street, Janis E; Fesperman, J Vernell; Calkins, D S; Bawa, Maneesh; Macias, Brandon R; Meyer, R Scott; Hargens, Alan R

    2003-12-01

    Counteracting bone loss is required for future space exploration. We evaluated the ability of treadmill exercise in a LBNP chamber to counteract bone loss in a 30-day bed rest study. Eight pairs of identical twins were randomly assigned to sedentary control or exercise groups. Exercise within LBNP decreased the bone resorption caused by bed rest and may provide a countermeasure for spaceflight. Bone loss is one of the greatest physiological challenges for extended-duration space missions. The ability of exercise to counteract weightlessness-induced bone loss has been studied extensively, but to date, it has proven ineffective. We evaluated the effectiveness of a combination of two countermeasures-treadmill exercise while inside a lower body negative pressure (LBNP) chamber-on bone loss during a 30-day bed rest study. Eight pairs of identical twins were randomized into sedentary (SED) or exercise/LBNP (EX/LBNP) groups. Blood and urine samples were collected before, several times during, and after the 30-day bed rest period. These samples were analyzed for markers of bone and calcium metabolism. Repeated measures ANOVA was used to determine statistical significance. Because identical twins were used, both time and group were treated as repeated variables. Markers of bone resorption were increased during bed rest in samples from sedentary subjects, including the collagen cross-links and serum and urinary calcium concentrations. For N-telopeptide and deoxypyridinoline, there were significant (p < 0.05) interactions between group (SED versus EX/LBNP) and phase of the study (sample collection point). Pyridinium cross-links were increased above pre-bed rest levels in both groups, but the EX/LBNP group had a smaller increase than the SED group. Markers of bone formation were unchanged by bed rest in both groups. These data show that this weight-bearing exercise combined with LBNP ameliorates some of the negative effects of simulated weightlessness on bone metabolism. This

  8. Evaluation of Treadmill Exercise in a Lower Body Negative Pressure Chamber as a Countermeasure for Weightlessness-Induced Bone Loss: a Bed Rest Study with Identical Twins

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Davis-Street, Janis E.; Fesperman, J. Vernell; Calkins, D. S.; Bawa, Maneesh; Macias, Brandon R.; Meyer, R. Scott; Hargens, Alan R.

    2003-01-01

    Counteracting bone loss is required for future space exploration. We evaluated the ability of treadmill exercise in a LBNP chamber to counteract bone loss in a 30-day bed rest study. Eight pairs of identical twins were randomly assigned to sedentary control or exercise groups. Exercise within LBNP decreased the bone resorption caused by bed rest and may provide a countermeasure for spaceflight. INTRODUCTION: Bone loss is one of the greatest physiological challenges for extended-duration space missions. The ability of exercise to counteract weightlessness-induced bone loss has been studied extensively, but to date, it has proven ineffective. We evaluated the effectiveness of a combination of two countermeasures-treadmill exercise while inside a lower body negative pressure (LBNP) chamber-on bone loss during a 30-day bed rest study. MATERIALS AND METHODS: Eight pairs of identical twins were randomized into sedentary (SED) or exercise/LBNP (EX/LBNP) groups. Blood and urine samples were collected before, several times during, and after the 30-day bed rest period. These samples were analyzed for markers of bone and calcium metabolism. Repeated measures ANOVA was used to determine statistical significance. Because identical twins were used, both time and group were treated as repeated variables. RESULTS: Markers of bone resorption were increased during bed rest in samples from sedentary subjects, including the collagen cross-links and serum and urinary calcium concentrations. For N-telopeptide and deoxypyridinoline, there were significant (p < 0.05) interactions between group (SED versus EX/LBNP) and phase of the study (sample collection point). Pyridinium cross-links were increased above pre-bed rest levels in both groups, but the EX/LBNP group had a smaller increase than the SED group. Markers of bone formation were unchanged by bed rest in both groups. CONCLUSIONS: These data show that this weight-bearing exercise combined with LBNP ameliorates some of the negative

  9. Simulated Space Radiation and Weightlessness: Vascular-Bone Coupling Mechanisms to Preserve Skeletal Health

    NASA Technical Reports Server (NTRS)

    Alwood, J. S.; Limoli, C. L.; Delp, M. D.; Castillo, A. B.; Globus, R. K.

    2012-01-01

    Weightlessness causes a cephalad fluid shift and reduction in mechanical stimulation, adversely affecting both cortical and trabecular bone tissue in astronauts. In rodent models of weightlessness, the onset of bone loss correlates with reduced skeletal perfusion, reduced and rarified vasculature and lessened vasodilation, which resembles blood-bone symbiotic events that can occur with fracture repair and aging. These are especially serious risks for long term, exploration class missions when astronauts will face the challenge of increased exposure to space radiation and abrupt transitions between different gravity environments upon arrival and return. Previously, we found using the mouse hindlimb unloading model and exposure to heavy ion radiation, both disuse and irradiation cause an acute bone loss that was associated with a reduced capacity to produce bone-forming osteoblasts from the bone marrow. Together, these findings led us to hypothesize that exposure to space radiation exacerbates weightlessness-induced bone loss and impairs recovery upon return, and that treatment with anti-oxidants may mitigate these effects. The specific aims of this recently awarded grant are to: AIM 1 Determine the functional and structural consequences of prolonged weightlessness and space radiation (simulated spaceflight) for bone and skeletal vasculature in the context of bone cell function and oxidative stress. AIM 2 Determine the extent to which an anti-oxidant protects against weightlessness and space radiation-induced bone loss and vascular dysfunction. AIM 3 Determine how space radiation influences later skeletal and vasculature recovery from prolonged weightlessness and the potential of anti-oxidants to preserve adaptive remodeling.

  10. Weightlessness

    NASA Technical Reports Server (NTRS)

    Pestov, I. D.; Gerathewohl, S. J.

    1975-01-01

    Significance of gravitation forces in regulating homeostasis is discussed, along with weightlessness effects on humans and a state of reduced weight (subgravity), such as on the moon. Biomedical effects of weightlessness adaptation to zero G and readaptation to terrestrial gravitation are described for the nervous system, cardiovascular system, metabolism, and musculoskeletal system. Reactions caused primarly by: (1) changes in the afferent nervous system, (2) lack of hydrostatic blood pressure, (3) lack of weight on the musculoskeletal system, and (4) exposure limits derived from the effects of prolonged weightlessness on humans are reviewed. Protection of humans from adverse effects of weightlessness is considered; Skylab missions are also summarized.

  11. Effects of simulated weightlessness on bone mineral metabolism

    NASA Technical Reports Server (NTRS)

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

    1984-01-01

    It is pointed out that prolonged space flight, bedrest, and immobilization are three factors which can produce a negative calcium balance, osteopenia, and an inhibition of bone formation. It is not known whether the effects of gravity on bone mineral metabolism are mediated by systemic endocrine factors which affect all bones simultaneously, or by local factors which affect each bone individually. The present investigation has the objective to test the relative importance of local vs. systemic factors in regulating the bone mineral response to conditions simulating weightlessness. Experiments were conducted with male Sprague-Dawley rats. The test conditions made it possible to compare the data from weighted and unweighted bones in the same animal. The obtained findings indicate that a decrease in bone mass relative to control value occurs rapidly under conditions which simulate certain aspects of weightlessness. However, this decrease reaches a plateau after 10 days.

  12. Capacity of omega-3 fatty acids or eicosapentaenoic acid to counteract weightlessness-induced bone loss by inhibiting NF-kappaB activation: from cells to bed rest to astronauts.

    PubMed

    Zwart, Sara R; Pierson, Duane; Mehta, Satish; Gonda, Steve; Smith, Scott M

    2010-05-01

    NF-kappaB is a transcriptional activator of many genes, including some that lead to muscle atrophy and bone resorption-significant concerns for astronauts. NF-kappaB activation is inhibited by eicosapentaenoic acid (EPA), but the influence of this omega-3 fatty acid on the effects of weightlessness are unknown. We report here cellular, ground analogue, and spaceflight findings. We investigated the effects of EPA on differentiation of RAW264.7 monocyte/macrophage cells induced by receptor activator of NF-kappaB ligand (RANKL) and on activation of NF-kappaB by tumor necrosis factor alpha (TNF-alpha) or exposure to modeled weightlessness. EPA (50 microM for 24 hours) inhibited RANKL-induced differentiation and decreased activation of NF-kappaB induced by 0.2 microg/mL of TNF-alpha for 30 minutes or by modeled weightlessness for 24 hours (p < .05). In human studies, we evaluated whether NF-kappaB activation was altered after short-duration spaceflight and determined the relationship between intake of omega-3 fatty acids and markers of bone resorption during bed rest and the relationship between fish intake and bone mineral density after long-duration spaceflight. NF-kappaB was elevated in crew members after short-duration spaceflight, and higher consumption of fish (a rich source of omega-3 fatty acids) was associated with reduced loss of bone mineral density after flight (p < .05). Also supporting the cell study findings, a higher intake of omega-3 fatty acids was associated with less N-telopeptide excretion during bed rest (Pearson r = -0.62, p < .05). Together these data provide mechanistic cellular and preliminary human evidence of the potential for EPA to counteract bone loss associated with spaceflight. (c) 2010 American Society for Bone and Mineral Research.

  13. Actual and Simulated Weightlessness Inhibit Osteogenesis in Long Bone Metaphysis by Different Mechanisms

    NASA Technical Reports Server (NTRS)

    Roberts, W. E.

    1985-01-01

    Weightlessness and simulated weightlessness inhibit the rate of periosteal bone formation in long bones. Formation of preosteoblasts is suppressed in periodontal ligament (PDL) of maxillary molars, which suggests a generalized block in osteoblast histogenesis. Growth in length of long bones is decreased by simulated weightlessness, but there are no reliable data on the influence of actual weightlessness on metaphyseal growth. The nuclear size assay for assessing relative numbers of osteoblast precursor cells was utilized in the primary spongiosa of growing long bones subjected to actual and simulated weightlessness. It is found that: (1) Actual weightlessness decreases total number of osteogenic cells and inhibits differentiation of osteoblast precursor cells, (2) Simulated weightlessness suppresses only osteoblast differentation; and (3) The nuclear morphometric assay is an effective means of assessing osteogenic activity in the growing metaphysis or long bones.

  14. Actual and Simulated Weightlessness Inhibit Osteogenesis in Long Bone Metaphysis by Different Mechanisms

    NASA Technical Reports Server (NTRS)

    Roberts, W. E.

    1985-01-01

    Weightlessness and simulated weightlessness inhibit the rate of periosteal bone formation in long bones. Formation of preosteoblasts is suppressed in periodontal ligament (PDL) of maxillary molars, which suggests a generalized block in osteoblast histogenesis. Growth in length of long bones is decreased by simulated weightlessness, but there are no reliable data on the influence of actual weightlessness on metaphyseal growth. The nuclear size assay for assessing relative numbers of osteoblast precursor cells was utilized in the primary spongiosa of growing long bones subjected to actual and simulated weightlessness. It is found that: (1) Actual weightlessness decreases total number of osteogenic cells and inhibits differentiation of osteoblast precursor cells, (2) Simulated weightlessness suppresses only osteoblast differentation; and (3) The nuclear morphometric assay is an effective means of assessing osteogenic activity in the growing metaphysis or long bones.

  15. Effect of simulated weightlessness and chronic 1,25-dihydroxyvitamin D administration on bone metabolism

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Bikle, D. D.; Globus, R. K.; Levens, M. J.; Wronski, T. J.; Morey-Holton, E.

    1985-01-01

    Weightlessness, as experienced during space flight, and simulated weightlessness induce osteopenia. Using the suspended rat model to simulate weightlessness, a reduction in total tibia Ca and bone formation rate at the tibiofibular junction as well as an inhibition of Ca-45 and H-3-proline uptake by bone within 5-7 days of skeletal unloading was observed. Between days 7 and 15 of unloading, uptake of Ca-45 and H-3-proline, and bone formation rate return to normal, although total bone Ca remains abnormally low. To examine the relationship between these characteristic changes in bone metabolism induced by skeletal unloading and vitamin D metabolism, the serum concentrations of 25-hydroxyvitamin D (25-OH-D), 24, 25-dihydroxyvitamin D (24,25(OH)2D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) at various times after skeletal unloading were measured. The effect of chronic infusion of 1,25(OH)2D3 on the bone changes associated with unloading was also determined.

  16. Effect of simulated weightlessness and chronic 1,25-dihydroxyvitamin D administration on bone metabolism

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Bikle, D. D.; Globus, R. K.; Levens, M. J.; Wronski, T. J.; Morey-Holton, E.

    1985-01-01

    Weightlessness, as experienced during space flight, and simulated weightlessness induce osteopenia. Using the suspended rat model to simulate weightlessness, a reduction in total tibia Ca and bone formation rate at the tibiofibular junction as well as an inhibition of Ca-45 and H-3-proline uptake by bone within 5-7 days of skeletal unloading was observed. Between days 7 and 15 of unloading, uptake of Ca-45 and H-3-proline, and bone formation rate return to normal, although total bone Ca remains abnormally low. To examine the relationship between these characteristic changes in bone metabolism induced by skeletal unloading and vitamin D metabolism, the serum concentrations of 25-hydroxyvitamin D (25-OH-D), 24, 25-dihydroxyvitamin D (24,25(OH)2D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) at various times after skeletal unloading were measured. The effect of chronic infusion of 1,25(OH)2D3 on the bone changes associated with unloading was also determined.

  17. Weightlessness

    NASA Astrophysics Data System (ADS)

    Shiells, Robin

    1981-01-01

    The phenomenon of weightlessness is clearly demonstrated if the ball is thrown. A diagram shows an astronaut as he would be seen by an observer inside a ship. With his left arm he is throwing a ball horizontally and with his right arm he is throwing a ball diagonally upwards. In space the ball thrown horizontally does not fall but maintains its level flight, and similarly the ball thrown diagonally upwards continues in a straight line. On the ground the familiar parabolic curves resulting from the action of gravity are seen. At low speeds the condition of weightlessness can be reproduced using simple, small scale apparatus. The spaceship is replaced by a large, open sided, wooden box, the arm of the astronaut by a small catapult, the ball by an ordinary marble (1.27 cm diameter) and the observer by a camera. The success of the experiment depends upon the efficient working of the catapult. The box is allowed to fall from the ceiling of an attic in a cottage, on to a mattress on the floor, to reproduce conditions of weightlessness.

  18. Effects of simulated weightlessness on rat osteocalcin and bone calcium

    NASA Technical Reports Server (NTRS)

    Patterson-Buckendhal, Patricia; Globus, Ruth K.; Bikle, Daniel D.; Cann, Christopher E.; Morey-Holton, Emily

    1989-01-01

    The effect of weightlessness on the serum content of the mineral-binding protein osteocalcin (OC), bone OC, and bone Ca were investigated in rats subjected for periods from 2 to 28 days to a hindlimb unweighting procedure simulating weightlessness. It was found that serum OC decreased by 25 percent (consistent with a decreased rate of bone growth), during the first week of hindlimb suspension, but returned to normal levels after 15 days. The third lumbar vertebra (L3) and femur (analyzed in this study) lost 20 percent of weight after 10-28 days of suspension. Analysis of OC and Ca concentrations and content in L3 and femur suggest a temporal divergence of the metabolism of these two bone components. The OC and Ca concentrations were found to vary not only with respect to the duration of unweighting but also to differ from each other in the magnitude of their response. The data showed that unweighting affects the formation and deposition of OC and Ca differently, depending on the bone location and the duration of unweighting.

  19. [Vertebral, femoral and radial bone density in simulation of prolonged weightlessness. Experience with healthy volunteers].

    PubMed

    Pouilles, J M; Ribot, C; Trémollières, F; Guell, A

    1992-02-01

    Disturbances in bone tissue induced by weightlessness in man are incompletely known. All we possess are indirect data which show negativation of the calcium-phosphate balance and bone density measurements mainly in peripheral bones (calcaneum and radius bones). Staying in supine position with the head down (the so-called anti-orthostatic position) is a means of simulating on earth the effects of weightlessness in space flights. We studied the changes in vertebral, femoral and radial bone densities that might occur in 7 healthy volunteers subjected to two 1-month period of bed rest with strict (-6 degrees) anti-orthostatic position. No significant variation was recorded at the end of each period. When the two periods were added the mean vertebral bone loss was -0.9 percent per month. This figure was comparable to that found in similar studies performed in the USA with longer periods of bed rest. The bone loss in such experiments was 4 to 8 times less than that reported for pathological immobilization. Further simulation studies are needed to evaluate the bone loss kinetics and to test the effectiveness of the preventive measures used in spatial flights.

  20. Effects of simulated weightlessness on bone metabolism in rats at different ages.

    PubMed

    Tan, Xiong-Jin; Wang, Qian; Zheng, Lei; Sun, Yong-Jian

    2002-07-01

    To compare the effects of simulated weightlessness on age-related bone metabolism and on the mechanical parameters of the weight-bearing bones of rats at different ages. Two-month-old and 6-month-old rats (8 in each group) were both subjected to tail suspension test for up to 4 weeks, with 2 groups of rats of corresponding ages (n=8) serving as control. The bone metabolism markers, biomechanical parameters of the femurs, along with the growth and mineral contents of the tibia, were respectively measured and compared with those of the controls. The bone formation markers, alkaline phosphatase and osteocalcin levels, dropped drastically in both groups of rats undergoing tail suspension test (P<0.01), which also induced significant hypocalcaemia (P<0.01). Bone material loss of the tibia occurred in both groups of rats receiving the test (P<0.01) whose effect on the volume and mass of fresh tibia was age-related (P<0.05), but the degree of mineral loss was not consistent with calcium loss in rats at different ages. Except for elastic deformation (P>0.05), both structural and biomechanical properties altered significantly after tail suspension test (P<0.01), and the changes of maximum deformation and maximum load were related to the age of the rats (P<0.05). The result is an age-related difference in the response of bone metabolism to simulated weightlessness.

  1. [Effect of Chinese herb medicine compound on bone loss in rats under 3 weeks simulated weightlessness: preliminary study].

    PubMed

    Zhou, Peng; Hu, Su-min; Tong, Hai-ying; Fu, Qian; Yang, Jia; Gao, Xue-min; Zhang, Jian-jun

    2008-09-01

    To investigate the effect of Chinese herb medicine compound on bone lose in rats under 3 weeks simulated weightlessness, and to observe the synergistic action of other ingredients in the compound on calcium. Thirty male Wistar rats were divided into 3 groups: control group, tail-suspend group, tail-suspend and medicine group which took Chinese herb medicine compound (contains Radix Rehmanniae Praeparata, Radix Achyranthis Bidentatae, Radix Astragali, Radix Angelicae Sinensis, Concha Ostreae prepared by acetic acid) by gastric administration. After 3 weeks simulated weightlessness, serum calcium (Ca), phosphorus (P), bone mineral density (BMD) and content (BMC), bone mechanical properties (MEC) were observed. At the end of the experiment, serum Ca and P increased significantly (P<0.01), BMD and BMC of posterior body decreased significantly (P< 0.01) in tail suspend rats, compared with in the control group. In rats of tail suspended and medicine group, the increase degree of serum Ca and P were smaller, BMD and BMC of posterior body increased significantly (P<0.01 or 0.05), and MEC also tend to increase. Bone mass of posterior body lose significantly, with mechanical property significantly decrease in rats after 3 weeks simulated weightlessness. Chinese herb medicine compound is effective to prevent the change of bone. Simple calcium supplement can not prevent simulated weightlessness induced bone loss, therefore other ingredients in the compound may perform synergistic action to calcium (Concha Ostreae prepared by acetic acid).

  2. Bone density in limb-immobilized beagles: An animal model for bone loss in weightlessness

    NASA Technical Reports Server (NTRS)

    Wolinsky, Ira

    1987-01-01

    Prolonged weightlessness is man in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. In order to seek and test preventative measures an appropriate ground based animal model simulating weightlessness is necessary. Use of the mature Beagle in limb immobilization has been documented as an excellent model for orthopedic research since this animal most closely simulates the phenomenom of bone loss with regards to growth, remodeling, structure, chemistry and mineralization. The purpose of this project is to develop a research protocol for the study of bone loss in Beagles during and after cast immobilization of a hindleg; research will then be initiated.

  3. [Effects of weightlessness on phosphorus and calcium metabolism and bone remodeling].

    PubMed

    Alexandre, C; Chappard, D; Vico, L; Minaire, P; Riffat, G

    1986-05-17

    Weightlessness results in negative calcium balance which can only reflect a redistribution of calcium in the body: the loss of calcium in the faeces and/or urine is constant, but an increase in urinary hydroxyproline indicating bone collagen destruction is not always detectable; moreover, a slowing down of collagen maturation may be suspected. Bone analysis by histomorphometry in animals and by indirect, non-invasive methods in man shows a decrease in bone mass. However, this bone tissue atrophy might only reflect excessive ageing of the bone during weightlessness, as suggested by slow bone formation and lack of variation in bone resorption. Since the experimental results obtained in men and animals during simulated weightlessness on earth are not strictly identical with those observed in space- flights, their validity may be questioned. Additional studies (notably histomorphometric studies) are therefore required for a better knowledge, as well as prevention, of the problems raised by human life in space.

  4. [Effects on rats' bone mineral density and bone biomechanics by suspensory simulated weightlessness and removing suspension].

    PubMed

    Tong, Hai-ying; Hu, Su-min; Zhou, Peng; Fu, Qian; Li, Jin; Gao, Xue-min; Zhang, Jian-jun

    2008-04-01

    To study the effects on rats' bone mineral density and bone biomechanics by suspensory simulated weightlessness and removing suspension. Twenty Wistar rats were divided into two groups randomly as control group and model group. Suspend the model group rats for 14 days, then remove suspension and continue to feed for another 14 days. Feed control group rats for 28 days. Detect the bone mineral density (BMD) in vivo of cranial bone, second thoracic vertebra, fourth lumbar vertebra, pelvis, right radioulna and right femoral bone of each group at the 14th day. At the 28th day,execute all the rats and take out of right femoral bone and fourth lumbar vertebra for detecting BMD and the intensity of biomechanics. At the 14th day in experiment, being compared with control group,the BMD of femoral bone, pelvis and lumbar vertebra in model group decreased significantly (P < 0.001, P < 0.001, P < 0.01) and the change of BMD of cranial bone, thoracic vertebra and radioulna in model group was not remarkable (P > 0.05). At the 28th day in experiment, the BMD of femoral bone and lumbar vertebra, the maximal load of femoral bone decreased significantly in model group as compared with control group (P < 0.01, P < 0.001, P < 0.01). BMD in vive body showed that suspensory simulated weightlessness for 14 days could cause disorder of bone metabolism and remarkable mineral loss of weight bearing bone, even BMD and biomechanical intensity of weight bearing bone decrease obviously when removing suspension for 14 days. The results suggest that the disorder of bone metabolism could not be recovered in short time.

  5. Bone loss during simulated weightlessness: a biomechanical and mineralization study in the rat model.

    PubMed

    Garber, M A; McDowell, D L; Hutton, W C

    2000-06-01

    Astronauts exposed to weightlessness for extended periods experience significant decreases in bone mineral density. The clinical implications of this demineralization are not entirely clear, and the biomechanics involved are not completely understood. Local (rather than global) measurements of geometry and calcium concentration effectively predict femur strength in adult rats exposed to a hind-limb suspension model of weightlessness. Female Fischer rats (6-mo-old) were divided into groups of control and hind-limb-suspended animals. Animals were sacrificed after 2 or 4 wk of hind-limb suspension, and both femurs removed from each animal. The 3-point bending strength and total bone mineralization were determined for one femur from each animal, and the mid-shaft cross-sectional geometrical properties and distribution of calcium were determined for the contralateral femur. Although suspension led to significant decreases in total bone mineralization, the concentration of calcium at the anterior periosteal surface was unaffected. Total bone percent mineralization was not well correlated with structural properties, but bone geometrical properties (particularly cross-sectional moment of inertia and length) correlated strongly with ultimate bending strength (r2 = 0.81). Differences in bone geometry due to suspension were consistent with a distribution of bone material closer to the axis of the femur. Structural properties of bone are predicted well by bone geometry and poorly by total bone percent mineralization. Decreased bone mechanical strength in this model of weightlessness is primarily due to a distribution of bone material nearer the axis of the bone.

  6. 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.

  7. 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.

  8. Spaceflight and bone turnover - Correlation with a new rat model of weightlessness

    NASA Technical Reports Server (NTRS)

    Morey, E. R.

    1979-01-01

    Earlier manned spaceflight studies have revealed that the near-weightless environment of orbital flight produce certain biological effects in humans, including abnormalities in mineral metabolism. The data collected were compatible with bone mineral loss. Cosmos 782 and 936 experiments have shown a decrease in rat bone formation rate. In this paper, a rat model of weightlessness is described, which is unique in that the animal is free to move about a 360-deg arc. The model meets the requirements for an acceptable system. Data from the model and spaceflight are presented. Many of the responses noted in suspended animals indicate that the model closely mimics results from rats and man exposed to near-weightlessness during orbital spaceflight.

  9. Effects of Zoledronate and Mechanical Loading during Simulated Weightlessness on Bone Structure and Mechanical Properties

    NASA Technical Reports Server (NTRS)

    Scott, R. T.; Nalavadi, M. O.; Shirazi-Fard, Y.; Castillo, A. B.; Alwood, J. S.

    2016-01-01

    Space flight modulates bone remodeling to favor bone resorption. Current countermeasures include an anti-resorptive drug class, bisphosphonates (BP), and high-force loading regimens. Does the combination of anti-resorptives and high-force exercise during weightlessness have negative effects on the mechanical and structural properties of bone? In this study, we implemented an integrated model to mimic mechanical strain of exercise via cyclical loading (CL) in mice treated with the BP Zoledronate (ZOL) combined with hindlimb unloading (HU). Our working hypothesis is that CL combined with ZOL in the HU model induces additive structural and mechanical changes. Thirty-two C57BL6 mice (male,16 weeks old, n8group) were exposed to 3 weeks of either HU or normal ambulation (NA). Cohorts of mice received one subcutaneous injection of ZOL (45gkg), or saline vehicle, prior to experiment. The right tibia was axially loaded in vivo, 60xday to 9N in compression, repeated 3xweek during HU. During the application of compression, secant stiffness (SEC), a linear estimate of slope of the force displacement curve from rest (0.5N) to max load (9.0N), was calculated for each cycle once per week. Ex vivo CT was conducted on all subjects. For ex vivo mechanical properties, non-CL left femurs underwent 3-point bending. In the proximal tibial metaphysis, HU decreased, CL increased, and ZOL increased the cancellous bone volume to total volume ratio by -26, +21, and +33, respectively. Similar trends held for trabecular thickness and number. Ex vivo left femur mechanical properties revealed HU decreased stiffness (-37),and ZOL mitigated the HU stiffness losses (+78). Data on the ex vivo Ultimate Force followed similar trends. After 3 weeks, HU decreased in vivo SEC (-16). The combination of CL+HU appeared additive in bone structure and mechanical properties. However, when HU + CL + ZOL were combined, ZOL had no additional effect (p0.05) on in vivo SEC. Structural data followed this trend with

  10. [Effects of Chinese Bushen Zhuanggu medicine on bone loss in female rats after simulated weightlessness].

    PubMed

    Sun, Ping; Huang, Zhen; Cai, De-Hong; He, Lei

    2007-02-01

    To study the effect of Bushen Zhuanggu, the traditional Chinese medicine for reinforcing kidney and strengthening bone, on bone loss in female rats after simulated weightlessness. Thirty-six female SD rats were randomly divided into 3 groups, namely normal control group (group A) and two groups of weightlessness simulated by tail suspension (groups B and C). Group C were treated with the Chinese medicine, while groups A and B were given the same dose of normal saline. The experiment lasted 28 days, and all rats were allowed to drink water freely. In the rats of group B, serum bone Gla protein (BGP), alkaline phosphatase (ALP), estradiol (E(2)) and P content and femur bone mineral content (BMD) were significantly lower than those in group A (P<0.01, P<0.05), whereas serum calcium concentration was markedly higher than that in group A (P<0.01). In rats of group C, serum BGP, ALP, E2 and P content and femur BMD were significantly higher than those in group B (P<0.01, P<0.05), but serum calcium concentration was markedly lower (P<0.01). This Chinese prescription can stimulate bone formation and reduce bone loss in female rats subjected to simulated weightlessness.

  11. Bone Proteomics experiment (BOP): the first proteomics analysis of mammalian cells cultivated in weightlessness conditions

    NASA Astrophysics Data System (ADS)

    Costessi, A.; Vascotto, C.; Pines, A.; Romanello, M.; Schonenborg, R.; Schiller, P.; Moro, L.; Tell, G.

    Bone mass loss is a major consequence of extended periods of weightlessness Many studies have been performed on astronauts and animal models establishing that a decrease of the maturation process and of the bone synthesising activity of osteoblast cells play a key role in microgravity-dependent bone mass loss Several experiments on single cells and tissues showed that weightlessness can also influence cells cultivated in vitro Many molecular mechanisms are affected among which the cytoskeleton and intracellular signal transduction cascades However the underlying mechanisms of these changes and their molecular consequences are far from being fully understood and the cellular gravisensing machinery is still unknown In contrast to weightlessness dynamic mechanical loading increases bone density and strength and promotes osteoblast proliferation differentiation and matrix production by acting at the gene expression level However the molecular mechanisms by which mechanical forces are converted into biochemical signalling in bone are also poorly understood A growing body of evidence points to extracellular nucleotides i e ATP and UTP as soluble factors that are released by several cell types in response to mechanical stimulation and that eventually trigger an intracellular signal We have recently demonstrated in the HOBIT osteoblast cell line that ATP and UTP treatments can activate two fundamental transcription factors that promote osteoblast differentiation and physiology Runx2 and Egr-1 as well as their target genes galectin-3 and

  12. Changes in bone structure and metabolism during simulated weightlessness: Endocrine and dietary factors

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Wronski, T. J.

    1985-01-01

    The role of vitamin D, PTH and corticosterone in the skeletal alterations induced by simulated weightlessness was examined. The first objective was to determine if changes in the serum concentrations of Ca, P sub i, osteocalcin, 25-OH-D, 24,25(OH)2D or 1,25(OH)2D also occur following acute skeletal unloading. Animals were either suspended or pair fed for 2, 5, 7, 10, 12 and 15 days and the serum concentrations of Ca, P sub i, osteocalcin and the vitamin D metabolites measured. Bone histology was examined at day 5 after suspension. Acute skeletal unloading produced a transient hypercalcemia, a significant fall in serum osteocalcin and serum 1,25(OH)2D, a slight rise in serum 24,25(OH)2D, but did not affect the serum concentrations of P sub i or 25-OH-D. At the nadir in serum 1,25(OH)2D serum osteocalcin was reduced by 22%, osteoblast surface by 32% and longitudinal bone growth by 21%.

  13. 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.

  14. 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.

  15. 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.

  16. Selection of an appropriate animal model for study of bone loss in weightlessness

    NASA Technical Reports Server (NTRS)

    Wolinsky, I.

    1986-01-01

    Prolonged weightlessness in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. A number of preventative measures have been suggested, i.e., exercise during flight, dietary calcium supplements, use of specific prophylactic drugs. In order to facilitate research in these areas it is necessary to develop appropriate ground-based animal models that simulate the human condition of osteoporsis. An appropriate animal model would permit bone density studies, calcium balance studies, biochemical analyses, ground-based simulation models of weightlessness (bed rest, restraint, immobilization) and the planning of inflight experiments. Several animal models have been proposed in the biomedical research literature, but have inherent deficiencies. The purpose of this project was to evaluate models in the literature and determine which of these most closely simulates the phenomenon of bone loss in humans with regard to growth, bone remodeling, structural, chemical and mineralization similarities to human. This was accomplished by a comprehensive computer assisted literature search and report. Three animal models were examined closely for their relative suitability: the albino rat, monkey, and Beagle.

  17. Selection of an appropriate animal model for study of bone loss in weightlessness

    NASA Technical Reports Server (NTRS)

    Wolinsky, I.

    1986-01-01

    Prolonged weightlessness in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. A number of preventative measures have been suggested, i.e., exercise during flight, dietary calcium supplements, use of specific prophylactic drugs. In order to facilitate research in these areas it is necessary to develop appropriate ground-based animal models that simulate the human condition of osteoporsis. An appropriate animal model would permit bone density studies, calcium balance studies, biochemical analyses, ground-based simulation models of weightlessness (bed rest, restraint, immobilization) and the planning of inflight experiments. Several animal models have been proposed in the biomedical research literature, but have inherent deficiencies. The purpose of this project was to evaluate models in the literature and determine which of these most closely simulates the phenomenon of bone loss in humans with regard to growth, bone remodeling, structural, chemical and mineralization similarities to human. This was accomplished by a comprehensive computer assisted literature search and report. Three animal models were examined closely for their relative suitability: the albino rat, monkey, and Beagle.

  18. 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.

  19. 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.

  20. 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.

  1. Simulated weightlessness and synbiotic diet effects on rat bone mechanical strength

    NASA Astrophysics Data System (ADS)

    Sarper, Hüseyin; Blanton, Cynthia; DePalma, Jude; Melnykov, Igor V.; Gabaldón, Annette M.

    2014-10-01

    This paper reports results on exposure to simulated weightlessness that leads to a rapid decrease in bone mineral density known as spaceflight osteopenia by evaluating the effectiveness of dietary supplementation with synbiotics to counteract the effects of skeletal unloading. Forty adult male rats were studied under four different conditions in a 2 × 2 factorial design with main effects of diet (synbiotic and control) and weight condition (unloaded and control). Hindlimb unloading was performed at all times for 14 days followed by 14 days of recovery (reambulation). The synbiotic diet contained probiotic strains Lactobacillus acidophilus and Lactococcus lactis lactis and prebiotic fructooligosaccharide. This paper also reports on the development of a desktop three-point bending device to measure the mechanical strength of bones from rats subjected to simulated weightlessness. The importance of quantifying bone resistance to breakage is critical when examining the effectiveness of interventions against osteopenia resulting from skeletal unloading, such as astronauts experience, disuse or disease. Mechanical strength indices provide information beyond measures of bone density and microarchitecture that enhance the overall assessment of a treatment's potency. In this study we used a newly constructed three-point bending device to measure the mechanical strength of femur and tibia bones from hindlimb-unloaded rats fed an experimental synbiotic diet enriched with probiotics and fermentable fiber. Two calculated outputs for each sample were Young's modulus of elasticity and fracture stress. Bone major elements (calcium, magnesium, and phosphorous) were quantified using ICP-MS analysis. Hindlimb unloading was associated with a significant loss of strength in the femur, and with significant reductions in major bone elements. The synbiotic diet did not protect against these unloading effects. Tibia strength and major elements were not reduced by hindlimb unloading, as was

  2. 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.

  3. 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.

  4. Calcium transport from the intestine and into bone in a rat model simulating weightlessness

    NASA Technical Reports Server (NTRS)

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

    1982-01-01

    The objective of this study was to determine whether a defect in transport of calcium in the duodenum was related to decreased bone formation in the suspended rat. Rats were suspended by the tail at a 40 deg angle for up to 15 days. Ca-45 was injected into the ligated duodenum in situ 15 minutes prior to sacrific. Blood, tibia, vertebra and humerus were obtained for total calcium and Ca-45 analyses. Intestinal calcium transport did not appear to be significantly altered by suspension. However, by 5 days of suspension a significant decrease in accumulation of Ca-45 into tibia and vertebra was observed. A trend of decreasing bone mineral and mass was established in tibia and vertebra by the fifth day of suspension. The humerus failed to demonstrate a significant weight decrease or change in Ca-45 accumulation after 15 days of suspension. Results from this simulated weightlessness model suggest that transport of calcium from intestine into bone is decreased within 5 days of suspension. This deficiency appears to be associated with a progressive decrease in total mass of non-weightbearing bones.

  5. [Effects of simulated weightlessness on biological activity of human NK cells induced by IL-2].

    PubMed

    Liu, Wenli; Zhu, Xia; Zhao, Li; Yang, Xiling; Cao, Fei; Huang, Yong; Mu, Peihong

    2015-10-01

    To investigate the effects of simulated weightlessness on the activity of human natural killer (NK) cells induced by interleukin 2 (IL-2). Primary human NK cells were cultured under simulated weightlessness condition. The viability of NK cells was determined by CCK-8 assay; cell apoptosis was analyzed by flow cytometry combined with annexin V-FITC/PI staining; the level of interferon γ (IFN-γ) was examined by ELISA; the mRNA levels of IL-12 receptor genes were detected by reverse transcription PCR. Compared with control cells cultured in normal gravity, IL-2-induced cell proliferation rate of NK cells cultured in simulated weightlessness decreased by 13.6% and 31% at 24 and 48 hours, respectively; the cell apoptotic rate increased by 8% and 19%; IL-2-induced IFN-γ production was inhibited by 25.2% and 47.8%; the cytotoxicity of NK cells induced by IL-2 was reduced by 7% and 18%; IL-12-induced IFN-γ production was suppressed by 21.8% and 58.8% in IL-2 pretreated cells at 24 and 48 hours, respectively. In addition, the mRNA levels of IL-12 β1 and β2 receptor genes were significantly down-regulated in the cells cultured in simulated weightlessness. Simulated weightlessness can inhibit the proliferation of NK cells induced by IL-2, promote NK cell apoptosis, impair IL-2-induced IFN-γ production and cytotoxicity in NK cells, and inhibit IL-12-induced IFN-γ production through down-regulating IL-12 receptor gene expression in NK cells.

  6. [Relationship between simulated weightlessness-induced muscle spindle change and muscle atrophy].

    PubMed

    Zhao, Xue-Hong; Fan, Xiao-Li

    2013-02-25

    One of the most important and urgent issues in the field of space medicine is to reveal the potential mechanism underlying the disused muscle atrophy during the weightlessness or microgravity environment. It will conduce to find out effective methods for the prevention and treatment of muscle atrophy during a long-term space flight. Increasing data show that muscle spindle discharges are significantly altered following the hindlimb unloading, suggesting a vital role in the progress of muscle atrophy. In the last decades, we have made a series of studies on changes in the morphological structure and function of muscle spindle following simulated weightlessness. This review will discuss our main results and related researches for understanding of muscle spindle activities during microgravity environment, which may provide a theoretic basis for effective prevention and treatment of muscle atrophy induced by weightlessness.

  7. Influences of traditional Chinese medicine intervention on the bone growth and metabolism of rats with simulated weightlessness.

    PubMed

    Zhu, Jun

    2013-03-01

    To probe into the influences of Chinese herbal compound on the growth and metabolism of weight-bearing bones of tail-suspended rats. Twenty-four male SD rats were randomly divided into blank control group (eight), tail-suspended control group (eight) and Chinese medicine treatment group (eight) according to their weights. No treatment was done for the blank control group. Double distilled water lavage was performed daily for the tail-suspended control group. On the basis of the tail-suspended rat model, the rats were given Chinese herbal compound lavage every day in Chinese medicine treatment group. This compound includes mulberry, Poria cocos and barbary wolfberry, etc. The test cycle was four weeks. The rats were killed after the experiment. The right femoral bone was taken out for the physical measurements, and the left femoral bone was for the three-point bending test. The influences of Chinese herbal compound on femoral bone growth and biomechanical properties of simulated weightlessness rats were observed. (1) After simulated weightlessness (tail-suspension), compared with the blank control group, all the physiological indexes of rat femoral bone decreased in tail-suspended group and Chinese medicine treatment group (P<0.05). The strength and rigidity of rat femoral bone decreased in tail-suspended group (P<0.01). The maximum load and rigidity coefficient also decreased with the increasing toughness coefficient in the control group (P<0.01). (2) After the countermeasure of Chinese herbal compound, each biomechanical indexes showed the tendency of increasing in Chinese medicine treatment group, and theses indexes were close to those of the blank control group (P<0.05), which indicated that the bone loss caused by simulated weightlessness was improved. Chinese herbal compound for tonifying kidney could effectively prevent the bone loss and have some enhancements on the bone biomechanical properties. Copyright © 2013 Hainan Medical College. Published by

  8. [Mechanism of cardiac atrophy under weightlessness/simulated weightlessness].

    PubMed

    Zhong, Guo-Hui; Ling, Shu-Kuan; Li, Ying-Xian

    2016-04-25

    Cardiac remodeling is the heart's response to external or internal stimuli. Weightlessness/simulated weightlessness leads to cardiac atrophy and heart function declining. Understanding the mechanism of cardiac atrophy under weightlessness is important to help astronaut recover from unloading-induced cardiovascular changes after spaceflight. Unloading-induced changes of hemodynamics, metabolic demands and neurohumoral regulation contribute to cardiac atrophy and function declining. During this process, Ca(2+)-related signaling, NF-κB signaling, ERK signaling, ubiquitin-proteasome pathway and autophagy are involved in weightlessness-induced cardiac atrophy. This article reviews the underlying mechanism of cardiac atrophy under weightlessness/simulated weightlessness.

  9. Simulated weightlessness aggravates hypergravity-induced impairment of learning and memory and neuronal apoptosis in rats.

    PubMed

    Sun, Xi-Qing; Xu, Zhi-Peng; Zhang, Shu; Cao, Xin-Sheng; Liu, Ting-Song

    2009-05-16

    It has been demonstrated that altered gravity may lead to impairments in cognitive functions. However, the effect of a combination of hypergravity and weightlessness on cognitive functions is not well understood. In the present study, we report the effects of high sustained hypergravity after 7 days' simulated weightlessness on learning and memory abilities and neuronal apoptosis in rats. In the Y-maze tests, hypergravity (HG) or simulated weightlessness (SW) significantly decreases accuracy, and increases reaction time of rats compared to that of controls. On the contrary, in the passive avoidance test, HG or SW treatment significantly shortens latency and prolongs total time compared to those of controls. In addition, TUNEL staining shows a few apoptotic cells in cortex and hippocampus in the HG, SW and HG+SW groups, and the number of TUNEL positive cells was found to be the most in the HG+SW group. Furthermore, rats with combined HG and SW treatment reveal a synergistic effect in both the Y-maze and the passive avoidance tests, as well as increased neuronal cell death. These findings suggest that simulated weightlessness may exacerbate hypergravity-induced impairment of learning and memory, likely caused by neuronal cell death in rats.

  10. Skeletal response to short-term weightlessness

    NASA Technical Reports Server (NTRS)

    Wronski, T. J.; Morey-Holton, E. R.

    1986-01-01

    Male Sprague Dawley rats were placed in orbit for 7 days aboard the space shuttle. Bone histomorphometry was performed in the long bones and lumbar vertebrae of flight rats and compared to data derived from ground based control rats. Trabecular bone mass was not altered during the first week of weightlessness. Strong trends were observed in flight rats for decreased periosteal bone formation in the tibial diaphysis, reduced osteoblast size in the proximal tibia, and decreased osteoblast surface and number in the lumbar vertebra. Histologic indices of bone resorption was relatively normal in flight rats. The results indicate that 7 day of weightlessness are not of sufficient duration to induce histologicaly detectable loss of trabecular bone in rats. However, cortical and trabecular bone formation appear to be diminished during the first week of space flight.

  11. Role of muscle spindle in weightlessness-induced amyotrophia and muscle pain.

    PubMed

    Ali, Umar; Fan, Xiao-Li; You, Hao-Jun

    2009-10-01

    To date, the medium and long-term space flight is urgent in need and has become a major task of our manned space flight program. There is no doubt that medium and long-term space flight has serious damaging impact upon human physiological systems. For instance, atrophy of the lower limb anti-gravity muscle can be induced during the space flight. Muscle atrophy significantly affects the flight of astronauts in space. Most importantly, it influences the precise manipulation of the astronauts and their response capacity to emergencies on returning to the atmosphere from space. Muscle atrophy caused by weightlessness may also seriously disrupt the normal life and work of the astronauts during the re-adaptation period. Here we summarize the corresponding research concentrating on weightlessness-induced changes of muscular structure and function. By combining research on muscle pain, which is a common clinical pain disease, we further provide a hypothesis concerning a dynamic feedback model of "weightlessness condition right triple arrow muscular atrophy <--> muscle pain". This may be useful to explore the neural mechanisms underlying the occurrence and development of muscular atrophy and muscle pain, through the key study of muscle spindle, and furthermore provide more effective therapy for clinical treatment.

  12. 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.

  13. 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.

  14. 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.

  15. Cardiovascular Effects Of Weightlessness

    NASA Technical Reports Server (NTRS)

    Sandler, Harold

    1992-01-01

    NASA technical memorandum presents study of effects of weightlessness and simulations upon cardiovascular systems of humans and animals. Reviews research up to year 1987 in United States and Soviet space programs on such topics as physiological changes induced by weightlessness in outer space and by subsequent return to Earth gravity and also reviews deconditioning effects of prolonged bed rest on ground.

  16. Experiment K305: Quantitative analysis of selected bone parameters. Supplement 1: Effects of weightlessness on osteoblast differentiation in rat molar periodontium

    NASA Technical Reports Server (NTRS)

    Roberts, W. E.; Mozsary, P. G.; Morey-Holton, E.

    1981-01-01

    The morphometric analysis of periodontal ligament (PDL), the osteogenic interface between tooth and bone, is described. Immediately post-flight, PDL width and total cell number were decreased. Frequency distributions of nuclear volume revealed that presumptive preosteoblasts were particularly depressed. Depleted numbers of preosteoblasts may be an important factor in the mechanism of inhibited bone formation during weightlessness.

  17. Experiment K305: Quantitative analysis of selected bone parameters. Supplement 1: Effects of weightlessness on osteoblast differentiation in rat molar periodontium

    NASA Technical Reports Server (NTRS)

    Roberts, W. E.; Mozsary, P. G.; Morey-Holton, E.

    1981-01-01

    The morphometric analysis of periodontal ligament (PDL), the osteogenic interface between tooth and bone, is described. Immediately post-flight, PDL width and total cell number were decreased. Frequency distributions of nuclear volume revealed that presumptive preosteoblasts were particularly depressed. Depleted numbers of preosteoblasts may be an important factor in the mechanism of inhibited bone formation during weightlessness.

  18. [Effects of Chinese herbal medicine for supplementing Shen and strengthening the bone on rat distal femur cancellous bone in simulated weightlessness: an observation with scanning electron microscope].

    PubMed

    Sun, Ping; Huang, Zhen; Cai, De-hong; He, Lei; Wu, Chang-xing

    2007-09-01

    To observe the effect of Chinese herbal medicine for supplementing Shen and strengthening the bone on distal femoral trabecular ultrastructure of male rats subjected to simulated weightlessness. Fifteen male SD rats were randomized equally into 3 groups, including a control group (group A, in which the rats were allowed free movement) and two simulated weightlessness (via tail suspension) groups (group B and C). The rats in group C were treated with the commercially available Chinese herbal preparation, and those in the other two groups received normal saline at the same dose, for a treatment course of 28 days. Observation of trabeculae was performed with scanning electron microscopy. In group B, the trabeculae of the femur became thinner, fragile, discontinuous with reduced quantity as compared with those in group A. The rats in group C had greater number of the trabeculae than those in group B. Resorption surface decreased and the collagenous fiber were much more regular in group B. The Chinese herbal medicine may produce beneficial effect on bone microstructure of rats subjected to simulated weightlessness.

  19. [Counteracting effect of Chinese herbs on "insufficiency of spleen qi" induced by simulated weightlessness].

    PubMed

    Shi, H Z; Wang, B Z; Gao, J Y; Qian, J K; Fan, Q C

    1999-06-01

    Objective. To observe the counteracting effect of a Chinese herb-compound on "insufficiency of spleen qi" induced by simulated weightlessness. Methods. Animal and human experiment were carried out to the Chinese herb-compound (Dangshen, Baizhu, Fuling etc). Result. This compound protected the tail suspended rats from atrophy of spleen, thymus, soleus and gastrocnemius muscles, prevented excessive decrease of body weight effectively; at the same time it relieved the symptoms of the subjects greatly. Conclusion. It demonstrated that the compound decreased the "insufficiency of spleen qi" of both animals and human subjects.

  20. 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

  1. Mechanical factors and bone health: effects of weightlessness and neurologic injury.

    PubMed

    Amin, Shreyasee

    2010-06-01

    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.

  2. [Mechanisms of human osteopenia and some peculiarities of bone metabolism in weightlessness conditions].

    PubMed

    Oganov, V S; Grigor'ev, A I

    2012-03-01

    Systematically results and new analysis data on the investigation of human bone system in space flight, the orbital station Mir and International Space Station, are presented. The bone mineral density, bone mineral content, identified as bone mass and body composition using dual energy X-ray absorptiometry were measured. Theoretically, an expected bone mass loss in trabecular tissue of lower skeletal half may by described as a quickly developing but reversible osteopenia and considered as evidence of functional adaptation of bone tissue to the changing mechanical load. A hypothesis of main mechanisms of osteopenia in microgravity is presented. High individual variability of bone mass losses and stability of individual pattern of correlation between bone mass losses in different skeletal segments were found. It is not possible to identify the relationship between bone mass losses and duration of space missions. Therefore it is not a sufficient ground to calculate the probability of reaching the critical level of bone demineralization by prolonged space flight. The same relates to the probability of prognosis of bone quality changes. There is data about dual energy X-ray absorptiometry that is insufficient for this prognosis. The main direction of investigations is presented which might optimize the interplanetary mission from the point of view of skeletal mechanical functions preservation.

  3. 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.

  4. Is suppression of bone formation during simulated weightlessness related to glucocorticoid levels

    NASA Technical Reports Server (NTRS)

    Morey-Holton, E. R.; Bomalaski, M. D.; Enayati-Gordon, E.; Gonsalves, M. R.; Wronski, T. J.

    1982-01-01

    To investigate the hypothesis that suppression of bone formation in the suspended rat model was the result of increased levels of corticosterone, experiments were performed on young, growing, male rats exposed either to 4 C or suspended for two weeks. Rats suspended on the model system, designed to simulate certain aspects of spaceflight, gained weight at a rate at least equal to control animals but still showed a significant suppression of bone formation within 7 days. Cold-exposed rats gained less weight than their corresponding control group and did not demonstrate any suppression of bone formation. These findings suggest: (1) tail suspension is less stressful than previously used harness systems; (2) suspension in young, rapidly growing rats causes a significant suppression of cortical bone formation; (3) cold exposure does not alter bone formation rate in rats of a similar age and strain to those suspended in this study; and (4) suppression of bone formation provoked by unloading the rear limbs is not due solely to sustained stimulation of the pituitary-adrenal system.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. [Weightlessness or weightlessness simulation and vascular remodeling].

    PubMed

    Yue, Yong; Yao, Yong-jie; Sun, Xi-qing; Wu, Xing-yu

    2003-04-01

    Weightlessness is inavoidable during spaceflight. It brings profound physiological effects on human body. Vascular remodeling is one of the important changes of cardiovascular system caused by weightlessness or simulated weightlessness. The paper summarized the studies on the effects of weightlessness or weightlessness simulation on vascular remodeling in recent years. The emergence and development of the concept of vascular remodeling were briefly reviewed. The advances of study on vascular remodeling in recent years was briefly discussed with the points focused on the effects of weightlessness or weightlessness simulation on cardiovascular remodeling and its mechanism. It is proposed that cardiovascular remodeling might be important in studying the causes of orthostatic intolerance after spaceflight.

  13. A comparison of leaf epinasty induced by weightlessness or by clinostat rotation

    NASA Technical Reports Server (NTRS)

    Brown, A. H.; Chapman, D. K.; Liu, S. W. W.

    1974-01-01

    A space flight experiment to determine the effect of weightlessness on the liminal angle of leaves of pepper as compared to the angles of leaves of central plants that rotate horizontally on an earth-based clinostat is evaluated. Copies of the Biosatellite II pepper plant flight film and of the clinostat central film were obtained, and an objective analysis of the information on these films is presented. Results confirm that epinastic leaf movements are characteristic in both orbital and clinostated pepper plants. Claims that the rotation on the clinostat produce the same effect as weightlessness are not supported by the pepper plant experiment.

  14. [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.

  15. Antinatriuretic kidney response to weightlessness

    NASA Astrophysics Data System (ADS)

    Gerzer, R.; Drummer, C.; Heer, M.

    We have tested the effects of weightlessness on renal function in one subject who flew the recent week-long Russian-German MIR'92 space mission. Urine flow, renal sodium excretion, and the excretion of urodilatin were measured during the first and last days of the flight. Our results demonstrated, in contrast to expectations, that urine flow and sodium excretion during weightlessness were actually lower than the values obtained during preflight measurements. These results therefore are inconsistent with the commonly held hypothesis that weightlessness induces a diuresis and natriuresis in human subjects. It would seem that further studies are necessary to resolve this issue and to determine whether currently used ground-based models of weightlessness correctly predict physiological adaptations that occur during space flight.

  16. Effects of weightlessness on tissue proliferation

    NASA Technical Reports Server (NTRS)

    Crosby, W. H.; Tavassoli, M.

    1975-01-01

    The repair of bone marrow stroma following mechanical injury was studied to obtain baseline data for a proposed space experiment regarding the effect of weightlessness on marrow stroma and other proliferating cell systems.

  17. Microgravity induced fluid and electrolyte balance changes. [in astronauts during weightlessness

    NASA Technical Reports Server (NTRS)

    Phillips, R. W.

    1986-01-01

    The effect of reduced gravity on the fluid and electrolyte balance in astronauts is discussed. The acquired data indicate an early and marked sodium and potassium loss and a negative water balance. The conditions in astronauts may be likened to the syndrome of inappropriate secretion of antidiuretic hormone, but the mechanisms by which weightlessness causes a continued negative water and electrolyte balance, after the early shifts have occurred, are not clear. It is suggested that a transient increase in the release of the atrial naturetic factor and the altered gastrointestinal function may play a role in the initial and continued fluid and electrolyte changes, respectively.

  18. Effects of simulated weightlessness on intramuscular hypertonic saline induced muscle nociception and spinal Fos expression in rats.

    PubMed

    Lei, Jing; Pertovaara, Antti; You, Hao-Jun

    2015-01-12

    We assessed the effects of simulated weightlessness, hindlimb unloading (HU) by 7 days of tail suspension, on noxious mechanically and heat evoked spinal withdrawal reflexes and spinal Fos expression during muscle nociception elicited by intramuscular (i.m.) injection of hypertonic (HT; 5.8%) saline into gastrocnemius muscle in rats. In HU rats, i.m. HT saline-induced secondary mechanical hyperalgesia was enhanced, and secondary heat hypoalgesia was significantly delayed. After 7 days of HU, basal Fos expression in spinal L4-6 segments was bilaterally enhanced only in superficial (I-II) but not middle and deep laminae (III-VI) of the spinal dorsal horn, which finding was not influenced by tail denervation. Unilateral i.m. HT saline injection increased spinal Fos expression bilaterally in both the control rats and 7 days of HU rats. The HT saline-induced bilateral increase of spinal Fos occurred within 0.5h and reached its peak within 1h, after which it gradually returned to the control levels within 8h. Spatial patterns of spinal Fos expression differed between the control group and 7 days of HU group. In superficial laminae, the HT saline-induced increases in Fos expression were higher and in the middle and deep laminae V-VI lower in the 7 days of HU than control rats. It is suggested that supraspinal mechanisms presumably underlie the effects of HU on spinally-organized nociception. Simulated weightlessness may enhance descending facilitation and weaken descending inhibition of nociception. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Random root movements in weightlessness

    NASA Technical Reports Server (NTRS)

    Johnsson, A.; Karlsson, C.; Iversen, T. H.; Chapman, D. K.

    1996-01-01

    The dynamics of root growth was studied in weightlessness. In the absence of the gravitropic reference direction during weightlessness, root movements could be controlled by spontaneous growth processes, without any corrective growth induced by the gravitropic system. If truly random of nature, the bending behavior should follow so-called 'random walk' mathematics during weightlessness. Predictions from this hypothesis were critically tested. In a Spacelab ESA-experiment, denoted RANDOM and carried out during the IML-2 Shuttle flight in July 1994, the growth of garden cress (Lepidium sativum) roots was followed by time lapse photography at 1-h intervals. The growth pattern was recorded for about 20 h. Root growth was significantly smaller in weightlessness as compared to gravity (control) conditions. It was found that the roots performed spontaneous movements in weightlessness. The average direction of deviation of the plants consistently stayed equal to zero, despite these spontaneous movements. The average squared deviation increased linearly with time as predicted theoretically (but only for 8-10 h). Autocorrelation calculations showed that bendings of the roots, as determined from the 1-h photographs, were uncorrelated after about a 2-h interval. It is concluded that random processes play an important role in root growth. Predictions from a random walk hypothesis as to the growth dynamics could explain parts of the growth patterns recorded. This test of the hypothesis required microgravity conditions as provided for in a space experiment.

  20. Inducible models of bone loss.

    PubMed

    Doucette, Casey R; Rosen, Clifford J

    2014-12-11

    Bone is an essential organ that not only confers structural stability to the organism, but also serves as a reservoir for hematopoietic elements and is thought to affect systemic homeostasis through the release of endocrine factors as well as calcium. The loss of bone mass due to an uncoupling of bone formation and bone resorption leads to increased fragility that can result in devastating fractures. Further understanding of the effects of environmental stimuli on the development of bone disease in humans is needed, and they can be studied using animal models. Here, we present established and novel methods for the induction of bone loss in mice, including manipulation of diet and environment, administration of drugs, irradiation, and surgically induced hormone deficiency. All of these models are directly related to human cases, and thus, can be used to investigate the causes of bone loss resulting from these interventions. Copyright © 2014 John Wiley & Sons, Inc.

  1. Clinorotation-induced weightlessness influences the cytoskeleton of glial cells in culture.

    PubMed

    Uva, Bianca Maria; Masini, Maria Angela; Sturla, Maddalena; Prato, Paola; Passalacqua, Mario; Giuliani, Massimo; Tagliafierro, Grazia; Strollo, Felice

    2002-05-03

    During and after spaceflight astronauts experience neurophysiological alterations. To investigate if the impairment observed might be traced back to cytomorphology, we undertook a ground based research using a random positioning machine (clinostat) as a simulation method for microgravity. The outcome of the study was represented by cytoskeletal changes occurring in cultured glial cells (C(6) line) after 15 min, 30 min, 1 h, 20 h and 32 h under simulated microgravity. Glia is fundamental for brain function and it is essential for the normal health of the entire nervous system. Our data showed that after 30 min under simulated microgravity the cytoskeleton was damaged: microfilaments (F-actin) and intermediate filaments (Vimentin, Glial Fibrillary Acidic Proteins GFAP) were highly disorganised, microtubules (alpha-tubulin) lost their radial array, the overall cellular shape was deteriorated, and the nuclei showed altered chromatin condensations and DNA fragmentation. This feature got less dramatic after 20 h of simulated microgravity when glial cells appeared to reorganise their cytoskeleton and mitotic figures were present. The research was carried out by immunohistochemistry using antibodies to alpha-tubulin, vimentin and GFAP, and cytochemical labelling of F-actin (Phalloidin-TRIC). The nuclei were stained with propidium iodide or 4,6-diamidino-2-phenylindole dihydrochloride (DAPI). The cells were observed at the conventional and/or the confocal laser scanning microscope. Samples were also observed at the scanning electron microscope (SEM). Our data showed that in weightlessness alterations occur already visible at the scale of the single cell; if this may lead to the neurophysiological problems observed in flight is yet to be established.

  2. Thermoconvectional phenomena induced by vibrations in supercritical SF6 under weightlessness.

    PubMed

    Garrabos, Y; Beysens, D; Lecoutre, C; Dejoan, A; Polezhaev, V; Emelianov, V

    2007-05-01

    The effect of a linear harmonic vibration on heat propagation is investigated in near-critical SF6 under weightlessness conditions in space. Heat was issued from a pointlike source (thermistor), a situation representative of an industrial use of pressurized supercritical fluid storage. Two kinds of vibrations were used, large amplitude (64 mm) at 0.2 Hz and low amplitude (0.8 mm) at 1.6 Hz, with temperatures from 5 K to 20 mK from the critical temperature. The vibrations are seen to strongly affect the evolution and shape of the hot boundary layer (HBL), the heat exchange between the heat source and the fluid, and the bulk thermalization process by the adiabatic piston-effect process. The HBL is initially convected as symmetrical plumes over a distance that only depends on the vibration velocity and which corresponds to a Rayleigh-Bénard-like instability where the vibration acceleration acts as the earth gravity. Then the extremities of the plumes are convected perpendicularly to the direction of oscillation as two "pancakes," a process encountered in the vibrational Rayleigh-Bénard instability. When the vibration velocity is small, only one pancake centered at the hot source is observed. Temperature evolutions of the hot source and the fluid are studied in different locations. Convection flows and adiabatic piston effect compete to determine the thermal dynamics, with the latter being the most efficient near the critical point. The experimental results are compared with a two-dimensional numerical simulation that highlights the similarities and differences between the very compressible van der Waals gas and an ideal gas.

  3. Suppression of osteoblast differentiation during weightlessness

    NASA Technical Reports Server (NTRS)

    Roberts, W. E.; Mozsary, P. G.; Morey, E. R.

    1982-01-01

    It is pointed out that associated with weightlessness is a marked depression or arrest of bone formation. Although the mechanism of this effect is unknown, it probably involves a failure of osteogenic induction. The present study's objective is to determine if weightlessness alters osteoblast differentiation, as evidenced by a change in relative distribution of large to small nuclei in rat moral periodontal ligament of the maxilla. In conjunction with the U.S./USSR Biological Satellite Program, male Wistar rats were flown aboard a modified Soviet Vostok spacecraft (Cosmos 1129). The results of the study are discussed. Morphometric investigations suggest that depleted numbers of preosteoblasts may be an important factor in the inhibition of bone formation during weightlessness.

  4. Suppression of osteoblast differentiation during weightlessness

    NASA Technical Reports Server (NTRS)

    Roberts, W. E.; Mozsary, P. G.; Morey, E. R.

    1982-01-01

    It is pointed out that associated with weightlessness is a marked depression or arrest of bone formation. Although the mechanism of this effect is unknown, it probably involves a failure of osteogenic induction. The present study's objective is to determine if weightlessness alters osteoblast differentiation, as evidenced by a change in relative distribution of large to small nuclei in rat moral periodontal ligament of the maxilla. In conjunction with the U.S./USSR Biological Satellite Program, male Wistar rats were flown aboard a modified Soviet Vostok spacecraft (Cosmos 1129). The results of the study are discussed. Morphometric investigations suggest that depleted numbers of preosteoblasts may be an important factor in the inhibition of bone formation during weightlessness.

  5. Weightlessness and Microgravity.

    ERIC Educational Resources Information Center

    Chandler, David

    1991-01-01

    The term "microgravity" has begun to appear in science texts as a substitute for "weightlessness." Presents examples to clarify three common misconceptions about gravity and weightlessness. Further examines these and other examples with respect to microgravity to make distinctions between the terms and avoid additional…

  6. 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.

  7. [Preventive and therapeutic effect of strontium ranelate on osteoporosis in rats subjected to simulated weightlessness].

    PubMed

    Yang, Rui; Huang, Zhen; Cai, De-hong; Zhang, Hua; Lai, A-na; Zhang, Zhen; Sun, Ping; Chen, Hong

    2010-04-01

    To study the effects of strontium ranelate on osteoporosis induced by simulated weightlessness in male rats. Twenty-seven male SD rats were randomly divided into 3 groups, namely the normal control group (group A) and two groups of weightlessness simulated by tail suspension (groups B and C). The rats in group C were treated with strontium ranelate, and those in the other two groups were given the same dose of normal saline for 28 consecutive days. The rats in group B showed significantly lower levels of alkaline phosphatase (ALP), bone mineral density (BMD) and bone mineral content (BMC) than those in group A (P<0.05), but serum calcium and phosphonium concentrations underwent no significant changes in the 3 groups (P>0.05). In the rats of group B, the trabeculae of the femur became thinner, fragile, and discontinuous with reduced quantity as compared with those in group A. The rats in group C had greater number of the trabeculae than those in group B with decreased resorption surface and more regular arrangement of the collagen fibers. Strontium ranelate may produce beneficial effect on the bone microstructure, reduce bone loss and stimulate bone formation in male rats subjected to simulated weightlessness.

  8. 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.

  9. 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.

  10. Cardiovascular Effects of Weightlessness

    NASA Technical Reports Server (NTRS)

    Short, K.

    1985-01-01

    Physiological changes resulting from long term weightlessness are reviewed and activities conducted to study cardiovascular deconditioning at NASA Ames are discussed. Emphasis is on using monkeys in chair rest, water immersion, and tilt table studies to simulate space environment effects.

  11. The memory enhancement effect of Kai Xin San on cognitive deficit induced by simulated weightlessness in rats.

    PubMed

    Qiong, Wang; Yong-Liang, Zhang; Ying-Hui, Li; Shan-Guang, Chen; Jiang-Hui, Gao; Yi-Xi, Chen; Ning, Jiang; Xin-Min, Liu

    2016-07-01

    It is vital for astronauts to develop effective countermeasures to prevent their decline of cognitive performance in microgravity to make space-flight missions successful. The traditional Chinese herbal formula Kai Xin San (KXS) has been used to treat amnesia for thousands years. It is a traditional complex prescription comprising of ginseng (Panax ginseng C. A. Meyer), hoelen (Poria cocos (Schw.) Wolf), polygala (Polygala tenaifolia Willd), and acorus (Acorus tatarinowii Schott). Previous study showed KXS could improve CMS-induced memory impairment in rats. In this paper, a unique environmental factor-microgravity (weightlessness) was simulated as hindlimb suspension (HLS) by tail in rats for two weeks as the HLS animal model. The KXS at the doses of 0.3 or 0.6g/kg p.o. daily was administrated to HLS rats for two weeks at the same time of HLS, the memory behavior tests were investigated with Morris water maze (MWM) and Shuttle Box (SB) test. The levels of ROS, 8-OHdG and 3-nitrotyrosine (3-NT) in the serum, and AChE and ChAT activity in the brain of rats were determined by ELISA or biochemical analysis. After HLS for two weeks, the escape latency and the swimming distance were significantly increased in the MWM test in rats in the HLS group, compared with control group. The percent of swimming distance in target quadrant and the number of target crossing was significantly decreased in rats in the HLS group compared with the control group. Performance in the SB test showed, the numbers and the distance of active avoidance was decreased from day 4 to day 7, the time spent in electric area was increased in rats in the HLS group compared with the control group. Administration of KXS 0.3 or 0.6g/kg to the HLS rats for two weeks significantly reduced the escape latency and the swimming distance, increased the percentage of swimming distance in target quadrant and the number of target crossings (P<0.01, compared with the HLS group) in the MWM test. Similar treatment with

  12. Bed Rest and Immobilization: Risk Factors for Bone Loss

    MedlinePlus

    ... weightlessness and immobility can result in bone loss. Space travel has provided significant research data on the subject of weightlessness and bone loss. Astronauts exposed to the microgravity of space experience significant bone loss, leaving their bones weak ...

  13. 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.

  14. 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.

  15. 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.

  16. Oxidative stress and gamma radiation-induced cancellous bone loss with musculoskeletal disuse

    PubMed Central

    Kondo, Hisataka; Yumoto, Kenji; Alwood, Joshua S.; Mojarrab, Rose; Wang, Angela; Almeida, Eduardo A. C.; Searby, Nancy D.; Limoli, Charles L.

    2010-01-01

    Exposure of astronauts in space to radiation during weightlessness may contribute to subsequent bone loss. Gamma irradiation of postpubertal mice rapidly increases the number of bone-resorbing osteoclasts and causes bone loss in cancellous tissue; similar changes occur in skeletal diseases associated with oxidative stress. Therefore, we hypothesized that increased oxidative stress mediates radiation-induced bone loss and that musculoskeletal disuse changes the sensitivity of cancellous tissue to radiation exposure. Musculoskeletal disuse by hindlimb unloading (1 or 2 wk) or total body gamma irradiation (1 or 2 Gy of 137Cs) of 4-mo-old, male C57BL/6 mice each decreased cancellous bone volume fraction in the proximal tibiae and lumbar vertebrae. The extent of radiation-induced acute cancellous bone loss in tibiae and lumbar vertebrae was similar in normally loaded and hindlimb-unloaded mice. Similarly, osteoclast surface in the tibiae increased 46% as a result of irradiation, 47% as a result of hindlimb unloading, and 64% as a result of irradiation + hindlimb unloading compared with normally loaded mice. Irradiation, but not hindlimb unloading, reduced viability and increased apoptosis of marrow cells and caused oxidative damage to lipids within mineralized tissue. Irradiation also stimulated generation of reactive oxygen species in marrow cells. Furthermore, injection of α-lipoic acid, an antioxidant, mitigated the acute bone loss caused by irradiation. Together, these results showed that disuse and gamma irradiation, alone or in combination, caused a similar degree of acute cancellous bone loss and shared a common cellular mechanism of increased bone resorption. Furthermore, irradiation, but not disuse, may increase the number of osteoclasts and the extent of acute bone loss via increased reactive oxygen species production and ensuing oxidative damage, implying different molecular mechanisms. The finding that α-lipoic acid protected cancellous tissue from the

  17. The influence of weightlessness on pharmacokinetics.

    PubMed

    Gandia, Peggy; Saivin, Sylvie; Houin, Georges

    2005-12-01

    The primary hostile factor during a spaceflight is the lack of gravity, which can induce space motion sickness and act on bones, muscles and the cardiovascular system. These physiological effects may modify the pharmacokinetics of the drugs administered during the flight producing reduced pharmacological activity or appearance of adverse effects. Given the small number of spaceflights and the difficulties of conducting experiments during missions, pharmacokinetic data obtained in flight are insufficient to determine if drug monitoring is necessary for the drugs present in the onboard medical kit. Therefore, validated earthbound models like tail-suspension performed with animals and long-term bedrest performed with human volunteers are used to simulate weightlessness and to study the pharmacokinetic variations of either absorption, distribution, or elimination of drugs. As a result of these studies, it is possible to make some dosing recommendations but more information is necessary to predict with precision all of the pharmacokinetic variations occurring in spaceflight. To collect more pharmacokinetic information, head-down bedrest studies are still the best solution and as saliva is an appropriate substitution for plasma for some drugs, salivary sampling can be planned during flights.

  18. [Effects of weightlessness on osseous tissue of the rat after a space flight of 5 days (Cosmos 1514)].

    PubMed

    Vico, L; Chappard, D; Alexandre, C; Palle, S; Minaire, P; Riffat, G; Novikov, V E; Bakulin, A V

    1987-01-01

    Five pregnant female growing rats have been orbited for five days aboard the Cosmos 1514 soviet biological satellite. They were compared to five female rats kept in vivarium and five female conditioned rats in synchronised way. Histomorphometric studies were performed in order to investigate: 1. The early effects of weightlessness on the bone mass in loading (tibiae and femur) and unloading bones (thoracic and lumbar vertebrae). 2. The changes of osteoblastic and osteoclastic activities. A short exposure does not induce changes in the bone mass and the inner structure of loading and unloading bones. These results fit in well with human data available in the literature: they show that weightlessness doesn't change bone mass in the early phase of a spaceflight. However extrapolation of animal results to men is discussed. In unloading bones (vertebrae) osteoblastic activity was not measurable. Osteoclasts detected by histoenzymologic method don't change as far as their number per mm3 of trabecular bone is concerned. However the number per mm2 of trabecular area increases. It seems likely that an increase of the osteoclastic population occurs in trabecular bone. In loading bones, formation activity (appreciated by the measurement of osteoid seam thickness) and total osteoclastic resorption surfaces were not modified. These results are different from those of longer flights.

  19. Skeletal response to simulated weightlessness - A comparison of suspension techniques

    NASA Technical Reports Server (NTRS)

    Wronski, T. J.; Morey-Holton, E. R.

    1987-01-01

    Comparisons are made of the skeletal response of rats subjected to simulated weightlessness by back or tail suspension. In comparison to pair-fed control rats, back-suspended rats failed to gain weight whereas tail-suspended rats exhibited normal weight gain. Quantitative bone histomorphometry revealed marked skeletal abnormalities in the proximal tibial metaphysis of back-suspended rats. Loss of trabecular bone mass in these animals was due to a combination of depressed longitudinal bone growth, decreased bone formation, and increased bone resorption. In contrast, the proximal tibia of tail-suspended rats was relatively normal by these histologic criteria. However, a significant reduction trabecular bone volume occurred during 2 weeks of tail suspension, possibly due to a transient inhibition of bone formation. The findings indicate that tail suspension may be a more appropriate model for evaluating the effects of simulated weightlessness on skeletal homeostasis.

  20. [Changes of cerebral circulation during weightlessness or simulated weightlessness].

    PubMed

    Wu, D W; Shen, X Y

    2000-10-01

    The results about studies on changes of the cerebral circulation during weightlessness/simulated weightlessness were reviewed in this paper. The possible influencing mechanism of weightlessness on cerebral circulation and its physiological significance were summarized. It could be concluded that the changes of cerebral circulation were the results of self-regulation of the brain to maintain its normal function, and it might play an important role in the genesis of postflight orthostatic intolerance.

  1. 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.

  2. Bacterially induced bone destruction: mechanisms and misconceptions.

    PubMed Central

    Nair, S P; Meghji, S; Wilson, M; Reddi, K; White, P; Henderson, B

    1996-01-01

    Normal bone remodelling requires the coordinated regulation of the genesis and activity of osteoblast and osteoclast lineages. Any interference with these integrated cellular systems can result in dysregulation of remodelling with the consequent loss of bone matrix. Bacteria are important causes of bone pathology in common conditions such as periodontitis, dental cysts, bacterial arthritis, and osteomyelitis. It is now established that many of the bacteria implicated in bone diseases contain or produce molecules with potent effects on bone cells. Some of these molecules, such as components of the gram-positive cell walls (lipoteichoic acids), are weak stimulators of bone resorption in vitro, while others (PMT, cpn60) are as active as the most active mammalian osteolytic factors such as cytokines like IL-1 and TNF. The complexity of the integration of bone cell lineage development means that there are still question marks over the mechanism of action of many well-known bone-modulatory molecules such as parathyroid hormone. The key questions which must be asked of the now-recognized bacterial bone-modulatory molecules are as follows: (i) what cell population do they bind to, (ii) what is the nature of the receptor and postreceptor events, and (iii) is their action direct or dependent on the induction of secondary extracellular bone-modulating factors such as cytokines, eicosanoids, etc. In the case of LPS, this ubiquitous gram-negative polymer probably binds to osteoblasts or other cells in bone through the CD14 receptor and stimulates them to release cytokines and eicosanoids which then induce the recruitment and activation of osteoclasts. This explains the inhibitor effects of nonsteroidal and anticytokine agents on LPS-induced bone resorption. However, other bacterial factors such as the potent toxin PMT may act by blocking the normal maturation pathway of the osteoblast lineage, thus inducing dysregulation in the tightly regulated process of resorption and

  3. Novel Receptor-Based Countermeasures to Microgravity-Induced Bone Loss

    NASA Technical Reports Server (NTRS)

    OMalley, Bert W.

    1999-01-01

    The biological actions mediated by the estrogen receptor (ER), vitamin D receptor (VDR) and Ca(sup 2+) (sub o) -sensing receptor (CaR) play key roles in the normal control of bone growth and skeletal turnover that is necessary for skeletal health. These receptors act by controlling the differentiation and/or function of osteoblasts and osteoclasts, and other cell types within the bone and bone marrow microenvironment. The appropriate use of selective ER modulators (SERMS) which target bone, vitamin D analogs that favor bone formation relative to resorption, and CaR agonists may both stimulate osteoblastogenesis and inhibit osteoclastogenesis and the function of mature osteoclasts, should make it possible to prevent the reduction in bone formation and increase in bone resorption that normally contribute to the bone loss induced by weightlessness. Indeed, there may be synergistic interactions among these receptors that enhance the actions of any one used alone. Therefore, we proposed to: 1) assess the in vitro ability of novel ER, VDR and CaR agonists, alone or in combination, to modulate osteoblastogenesis and mature osteoblast function under conditions of 1g and simulated microgravity; 2) assess the in vitro ability of novel ER, VDR and CaR agonists, alone or in combination, to modulate osteoclastogenesis and bone resorption under conditions of lg and simulated microgravity; and 3) carry out baseline studies on the skeletal localization of the CaR in normal rat bone as well as the in vivo actions of our novel ER- and VDR-based therapeutics in the rat in preparation for their use, alone or in combination, in well-established ground-based models of microgravity and eventually in space flight.

  4. The use of suspension models and comparison with true weightlessness. [Animal Model Workshop on Gravitational Physiology

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.; Ellis, S.

    1985-01-01

    A resume is presented of various papers concerning the effect of weightlessness on particular physiological and biochemical phenomena in animal model systems. Findings from weightlessness experiments on earth using suspension models are compared with results of experiments in orbit. The biological phenomena considered include muscle atrophy, changes in the endocrine system, reduction in bone formation, and changes in the cardiovascular system.

  5. The use of suspension models and comparison with true weightlessness. [Animal Model Workshop on Gravitational Physiology

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.; Ellis, S.

    1985-01-01

    A resume is presented of various papers concerning the effect of weightlessness on particular physiological and biochemical phenomena in animal model systems. Findings from weightlessness experiments on earth using suspension models are compared with results of experiments in orbit. The biological phenomena considered include muscle atrophy, changes in the endocrine system, reduction in bone formation, and changes in the cardiovascular system.

  6. 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.

  7. Microgravity and bone cell mechanosensitivity

    NASA Astrophysics Data System (ADS)

    Klein-Nulend, J.; Bacabac, R. G.; Veldhuijzen, J. P.; Van Loon, J. J. W. A.

    2003-10-01

    The capacity of bone tissue to alter its mass and structure in response to mechanical demands has long been recognized but the cellular mechanisms involved remained poorly understood. Bone not only develops as a structure designed specifically for mechanical tasks, but it can adapt during life toward more efficient mechanical performance. Mechanical adaptation of bone is a cellular process and needs a biological system that senses the mechanical loading. The loading information must then be communicated to the effector cells that form new bone or destroy old bone. The in vivo operating cell stress derived from bone loading is likely the flow of interstitial fluid along the surface of osteocytes and lining cells. The response of bone cells in culture to fluid flow includes prostaglandin (PG) synthesis and expression of prostaglandin G/H synthase inducible cyclooxygenase (COX-2). Cultured bone cells also rapidly produce nitric oxide (NO) in response to fluid flow as a result of activation of endothelial nitric oxide synthase (ecNOS), which enzyme also mediates the adaptive response of bone tissue to mechanical loading. Earlier studies have shown that the disruption of the actin-cytoskeleton abolishes the response to stress, suggesting that the cytoskeleton is involved in cellular mechanotransduction. Microgravity, or better near weightlessness, is associated with the loss of bone in astronauts, and has catabolic effects on mineral metabolism in bone organ cultures. This might be explained as resulting from an exceptional form of disuse under near weightlessness conditions. However, under near weightlessness conditions the assembly of cytoskeletal elements may be altered since it has been shown that the direction of the gravity vector determines microtubular pattern formation in vivo. We found earlier that the transduction of mechanical signals in bone cells also involves the cytoskeleton and is related to PGEZ production. Therefore it is possible that the

  8. Animal models for simulating weightlessness

    NASA Technical Reports Server (NTRS)

    Morey-Holton, E.; Wronski, T. J.

    1982-01-01

    NASA has developed a rat model to simulate on earth some aspects of the weightlessness alterations experienced in space, i.e., unloading and fluid shifts. Comparison of data collected from space flight and from the head-down rat suspension model suggests that this model system reproduces many of the physiological alterations induced by space flight. Data from various versions of the rat model are virtually identical for the same parameters; thus, modifications of the model for acute, chronic, or metabolic studies do not alter the results as long as the critical components of the model are maintained, i.e., a cephalad shift of fluids and/or unloading of the rear limbs.

  9. Animal models for simulating weightlessness

    NASA Technical Reports Server (NTRS)

    Morey-Holton, E.; Wronski, T. J.

    1982-01-01

    NASA has developed a rat model to simulate on earth some aspects of the weightlessness alterations experienced in space, i.e., unloading and fluid shifts. Comparison of data collected from space flight and from the head-down rat suspension model suggests that this model system reproduces many of the physiological alterations induced by space flight. Data from various versions of the rat model are virtually identical for the same parameters; thus, modifications of the model for acute, chronic, or metabolic studies do not alter the results as long as the critical components of the model are maintained, i.e., a cephalad shift of fluids and/or unloading of the rear limbs.

  10. [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.

  11. Microgravity and Bone Cell Mechanosensitivity

    NASA Astrophysics Data System (ADS)

    Klein-Nulend, J.; Bacabac, R.; Veldhuijzen, J.; van Loon, J.

    The capacity of bone tissue to alter its mass and structure in response to mechanical demands has long been recognized but the cellular mechanisms involved remained poorly understood. Bone not only develops as a structure designed specifically for mechanical tasks, but it can adapt during life toward more efficient mechanical performance. Mechanical adaptation of bone is a cellular process and needs a biological system that senses the mechanical loading. The loading information must then be communicated to the effector cells that form new bone or destroy old bone.The in vivo operating cell stress derived from bone loading is likely flow of interstitial fluid along the surface of osteocytes and lining cells. The response of bone cells in culture to fluid flow includes prostaglandin (PG) synthesis and expression of prostaglandin G/H synthase inducible cyclooxygenase (COX-2). Cultured bone cells also rapidly produce nitric oxide (NO) in response to fluid flow as a result of activation of endothelial nitric oxide synthase (ecNOS), which enzyme also mediates the adaptive response of bone tissue to mechanical loading. Disruption of the actin-cytoskeleton abolishes the response to stress, suggesting that the cytoskeleton is involved in cellular mechanotransduction.Microgravity, or better near weightlessness, has catabolic effects on the skeleton of astronauts, and on mineral metabolism in bone organ cultures. This might be explained as resulting from an exceptional form of disuse under near weightlessness conditions. However, under near weightlessness conditions the assembly of cytoskeletal elements may be altered since it has been shown that the direction of the gravity vector determines microtubular pattern formation in vivo. We found that the transduction of mechanical signals in bone cells also involves the cytoskeleton and is related to PGE2 production. Therefore it is possible that the mechanosensitivity of bone cells is altered under near weightlessness conditions

  12. Bone loss in tail-suspended rats in restricted to the unweighted limbs

    NASA Technical Reports Server (NTRS)

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

    1984-01-01

    Space flight which results in certain characteristic changes in the skeleton and it was hypothesized that these abnormalities are a direct result of the weightless state. To determine the role of PTH and 1,25(OH)2D in the bone changes associated with weightlessness, we studied bone metabolism under various dietary conditions using an Earth based rat model system which simulates weightlessness. In this model, rats are suspended by their tails such that their rear limbs are completely unloaded while their fore limbs are normally loaded. It is suggested that skeletal unloading induces a localized defect in the unloaded bone which results in abnormal growth and mineralization. It is concluded that skeletal unloading may make the unloaded bone more or less sensitive to a systemic factor which in turn could account for a change in bone metabolism.

  13. 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.

  14. 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.

  15. Motor activity under weightless conditions

    NASA Technical Reports Server (NTRS)

    Kasyan, I. I.; Kopanev, V. I.; Cherepakhin, M. A.; Yuganov, Y. M.

    1975-01-01

    The material presented on the motor activity under weightless conditions (brief and long) leads to the conclusion that it is not significantly disrupted, if those being examined are secured at the workplaces. Some discoordination of movement, moderately expressed disruption of the precision of reproduction of assigned muscular forces, etc., were observed. Motor disorders decrease significantly in proportion to the length of stay under weightless conditions. This apparently takes place, as a consequence of formation of a new functional system, adequate to the conditions of weightlessness. Tests on intact and labyrinthectomized animals have demonstrated that signaling from the inner ear receptors is superfluous in weightlessness, since it promotes the onset of disruptions in the combined work of the position analyzers.

  16. Blood circulation under weightless conditions

    NASA Technical Reports Server (NTRS)

    Kasyan, I. I.; Kopanev, V. I.; Yazdovskiy, V. I.

    1975-01-01

    Biomedical data obtained on men and animals during weightlessness conditions establish instabilities in pulse rate and blood circulation that smooth out in proportion to adaptation to the weightless condition. The unusual slowness of recovery of pulse rate to initial values after space flight stress is attributed to biological simulation of hormonal shifts and discharge of humoral substances into the blood that prevent a rapid recovery of some biological indicators to initial values.

  17. Vaccination against strontium-90-induced bone tumors

    SciTech Connect

    Reif, A.E.; Triest, W.E.

    1983-09-01

    The thesis was tested that immunization against a murine osteosarcoma virus can reduce the incidence of bone tumors induced by /sup 90/Sr. C57BL/6J female mice (190) were divided into three sets of 2 groups. Each set consisted of a control group and an experimental group treated ip with 1.0 muCi /sup 90/Sr at 66 days of age. The three sets of groups received the following additional treatments: none (controls), 6 injections of Formalin-inactivated FBJ osteosarcoma virus (vaccinated group), or 6 injections of active FBJ virus (active virus controls). Only 1 bone tumor developed in a mouse not treated with /sup 90/Sr in the active virus controls. In /sup 90/Sr-treated mice, vaccination reduced bone tumor deaths during the first 600 days from 9 of 36 in controls to 1 of 33 in vaccinated mice (P less than .01), but bone tumor deaths during the entire life-span, 10 of 36 and 5 of 33, respectively, were not significantly different (P . .07). Thus the vaccination procedure delayed the development of bone tumors. In contrast, injection of active virus into /sup 90/Sr-treated mice increased the lifetime incidence of bone tumors from 10 of 36 in controls to 19 of 32 (P . .01).

  18. Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes and simulated weightlessness in rats

    NASA Technical Reports Server (NTRS)

    Pamnani, M. B.; Chen, S.; Haddy, F. J.; Yuan, C.; Mo, Z.

    1998-01-01

    We have examined the role of plasma Na+-K+ pump inhibitor (SPI) in the hypertension of streptozotocin induced insulin dependent diabetes (IDDM) in reduced renal mass rats. The increase in blood pressure (BP) was associated with an increase in extracellular fluid volume (ECFV), and SPI and a decrease in myocardial Na+,K+ATPase (NKA) activity, suggesting that increased SPI, which inhibits cardiovascular muscle (CVM) cell NKA activity, may be involved in the mechanism of IDDM-hypertension. In a second study, using prolonged suspension resulted in a decrease in cardiac NKA activity, suggesting that cardiovascular deconditioning following space flight might in part result from insufficient SPI.

  19. Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes and simulated weightlessness in rats

    NASA Technical Reports Server (NTRS)

    Pamnani, M. B.; Chen, S.; Haddy, F. J.; Yuan, C.; Mo, Z.

    1998-01-01

    We have examined the role of plasma Na+-K+ pump inhibitor (SPI) in the hypertension of streptozotocin induced insulin dependent diabetes (IDDM) in reduced renal mass rats. The increase in blood pressure (BP) was associated with an increase in extracellular fluid volume (ECFV), and SPI and a decrease in myocardial Na+,K+ATPase (NKA) activity, suggesting that increased SPI, which inhibits cardiovascular muscle (CVM) cell NKA activity, may be involved in the mechanism of IDDM-hypertension. In a second study, using prolonged suspension resulted in a decrease in cardiac NKA activity, suggesting that cardiovascular deconditioning following space flight might in part result from insufficient SPI.

  20. Plants and weightlessness

    NASA Technical Reports Server (NTRS)

    Karminskiy, V.; Tarkhanovskiy, V.

    1980-01-01

    The growth of two plants, wall cress and short-day red goosefoot, was traced for their entire lifetime in weightlessness. In the beginning both plants grew normally: the seeds sprouted in the normal periods, and the shoots did not differ in any way from the control plants. It is true that certain roots lost their normal orientation and did not go deeper into the nutrient medium, but rather crept over its surface. But then both the wall cress and the goosefoot slowed down their normal rate of growth, which became noticeable from the rate of formation of new leaves in the wall cress and stem development in the goosefoot. Although no disorders were successfully found in the morphology of the two plants, almost half of the experimental cress and goosefoot plants ceased growth completely, yellowed and died. The other part continued to develop normally and by the end of vegetation, differed from the control plants only in a lower height. Not all were fertile since certain experimental plants, after losing spatial orientation, became twisted and produced sterile flowers.

  1. Rescuing Loading Induced Bone Formation at Senescence

    PubMed Central

    Srinivasan, Sundar; Ausk, Brandon J.; Prasad, Jitendra; Threet, Dewayne; Bain, Steven D.; Richardson, Thomas S.; Gross, Ted S.

    2010-01-01

    The increasing incidence of osteoporosis worldwide requires anabolic treatments that are safe, effective, and, critically, inexpensive given the prevailing overburdened health care systems. While vigorous skeletal loading is anabolic and holds promise, deficits in mechanotransduction accrued with age markedly diminish the efficacy of readily complied, exercise-based strategies to combat osteoporosis in the elderly. Our approach to explore and counteract these age-related deficits was guided by cellular signaling patterns across hierarchical scales and by the insight that cell responses initiated during transient, rare events hold potential to exert high-fidelity control over temporally and spatially distant tissue adaptation. Here, we present an agent-based model of real-time Ca2+/NFAT signaling amongst bone cells that fully described periosteal bone formation induced by a wide variety of loading stimuli in young and aged animals. The model predicted age-related pathway alterations underlying the diminished bone formation at senescence, and hence identified critical deficits that were promising targets for therapy. Based upon model predictions, we implemented an in vivo intervention and show for the first time that supplementing mechanical stimuli with low-dose Cyclosporin A can completely rescue loading induced bone formation in the senescent skeleton. These pre-clinical data provide the rationale to consider this approved pharmaceutical alongside mild physical exercise as an inexpensive, yet potent therapy to augment bone mass in the elderly. Our analyses suggested that real-time cellular signaling strongly influences downstream bone adaptation to mechanical stimuli, and quantification of these otherwise inaccessible, transient events in silico yielded a novel intervention with clinical potential. PMID:20838577

  2. 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.

  3. Bovine bone morphogenetic protein-induced dentinogenesis.

    PubMed

    Lianjia, Y; Yuhao, G; White, F H

    1993-10-01

    Differentiation of odontoblasts is important for dentin formation in tooth germs and mature teeth. Although previous reports have indicated that there may be a kind of inductive agent that could induce mesenchymal cells in dental pulps to differentiate into odontoblasts, and secrete dentin matrix, the primary inductive factor of odontoblasts has not been found. Bone morphogenetic protein (BMP), which induces the formation of cartilage and bone when implanted in muscle tissue, is found in dentin matrix. The relationship between the differentiation of odontoblasts and BMP was observed by means of immunohistochemical staining with monoclonal antibody (MAb) against BMP in dental pulp tissue and cell culture; [3H]thymidine incorporation; and measurement of alkaline phosphatase activity. The conclusions are: (1) BMP exists in odontoblasts, ameloblasts, and dentin matrix (the positive reaction in ameloblasts appeared earlier and remained stronger); (2) BMP promotes incorporation of [3H]thymidine and increases the activity of alkaline phosphatase in cultured dental pulp cells; (3) BMP-induced dental pulp cells in dental pulp tissue cultures differentiate from mesenchymal to odontoblast-like cells; and (4) BMP induces formation of osteodentin and tubular dentin when used as a dental capping agent of dogs' teeth. Bone morphogenetic protein plays an important role in differentiation of odontoblasts and might be one of the inductive agents of odontoblasts. Further investigations of BMP as a biologic dental capping agent are warranted.

  4. 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

  5. [Effect of a Chinese herbal prescription on femur calcium deposition in rats under simulated weightlessness: by using (41)Ca tracing-accelerator mass spectrometry analysis].

    PubMed

    Hu, Sumin; Zhou, Peng; Jiang, Shan; He, Ming; Fu, Qian; Yang, Jiajia; Gao, Xuemin

    2009-05-01

    To study the effect of a Chinese herbal prescription on external calcium deposition to weight-bearing bone in simulated weightlessness rats. Twenty-one male Wistar rats were divided into 3 groups: control group, tail suspension group, tail suspension with Chinese medicine group which takes a Chinese herbal prescription extract (containing Radix Rehmanniae Preparata, Radix Acanthopanacis Bidentatae, Radix Astragali, Radix Angelicae Sinensis, Concha Ostreae prepared by acetic acid) by intragastric administration. After 1 week adaption, there start off 3 weeks simulated weightlessness by tail suspension. At the eleventh day of simulated weightlessness, every rat was given one equal dose of 41Ca tracer by intragastric administration. Right femurs were separated as experiment over, and the ratio of 41Ca to 40Ca (41Ca/40Ca) was measured by accelerator mass spectrometry (AMS), while total femur calcium was measured by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). Femur 41Ca deposition amount (DA) and femur 41Ca deposition ratio (DR) were calculated. The results showed that compared with control group, 41Ca/40Ca decreased significantly (P < 0.001) in tail suspension group, while in tail suspension with Chinese medicine group, it significantly increased (P < 0.05). DA and DR were both decreased significantly (P < 0.001) in tail suspension group, but no significant change in tail suspension with Chinese medicine group as compared with control group. Compared with tail suspension group, DA and DR increased significantly (P < 0.001) in tail suspension with Chinese medicine group. Simulated weightlessness by tail suspension can cause decreased deposition of external calcium to weight-bearing bone, and the Chinese herbal prescription in this trial is effective to prevent the decrease. Moreover, multiple mechanisms may contribute to weightlessness induced osteoporosis, besides calcium deposition disturbance.

  6. [Effects of weightlessness on baroreflex function].

    PubMed

    Shen, Xian-yun

    2002-12-01

    The declination of baroreceptor reflex function is one of the important factor causing orthostatic intolerance after space flight. The change of baroreceptor reflex function during weightlessness and simulated weightlessness is introduced, and the influence of elevatory upper body blood pressure and electrolyte changes caused by weightlessness on baroreflex function are analyzed.

  7. [Simulated weightlessness inhibits antitumor immunity of T lymphocytes in melanoma-bearing mice].

    PubMed

    Si, Shaoyan; Song, Shujun; Shi, Liang; Liu, Junli; Xu, Bingxin; Yi, Yong; Tan, Xiaoqing; Zhang, Jianzhong

    2013-02-01

    To investigate the effects of simulated weightlessness on antitumor immunity of T lymphocytes in mice. The malignant melanoma was xenografted by subcutaneous injection of B16 cells into the right hind limb of every mouse. The mice suspended by tail at a -15 degree to 20 degree head-down tilt were used as simulated weightlessness models. The effects of simulated weightlessness on tumor volume and survival time were observed. T the numbers of leucocytes, lymphocytes and T lymphocyte subsets in peripheral blood of tumor-bearing mice under simulated weightlessness were monitored by an automatic hemacytometer and a flow cytometer. The effects of simulated weightlessness on the production of IL-2, TNF-α and IFN-γ in T lymphocytes and the cytotoxicities of tumor-specific CTLs to tumor cells were analyzed by ELISA and LDH release. Compared with control group, the tumors grew faster, the survival times were shorter, the number of lymphocytes, the ratio of lymphocytes, CD3(+);, CD4(+);/CD3(+); and CD8(+);/CD3(+); T lymphocytes in peripheral blood dropped, and the proliferation of splenic T lymphocytes induced by mitogen was reduced (P<0.05 or P<0.01) in the simulated weightlessness group. The production of IL-2, TNF-α and IFN-γ induced by tumor cells and cytotoxicities of tumor-specific CTLs to tumor cells were inhibited in mice under simulated weightlessness (P<0.05 or P<0.01). Simulated weightlessness inhibits antitumor immunity of T lymphocytes.

  8. 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-

  9. [Mechanism of weightlessness osteoporosis and preventive and therapeutic effect of traditional Chinese medicine].

    PubMed

    Zhu, Bin; Guo, Hua; Hao, Xi-Juan; Fu, Qian; Hu, Su-Min

    2012-07-01

    Weightlessness environment can lead to the muscle atrophy and body fluid distribution upward,which can cause the bone calcium metabolism disorder and always accompanied by the loss of bone microstructure and increased rate of bone fracture. Under microgravity,the astronauts are much easier to decrease the Ca2+ ion in bone, which can cause serious osteoporosis. However the bone lost is not equilibrium, it is especially serious in the mechanism loading bone and the recovery process is more difficult. These are very different from the osteoporosis in older people and postmenopausal osteoporosis. It is necessary to find an optimal method to due with it. In traditional Chinese medicine theory,the kidney stores "Jing" and dominates the bone, thus a lot of bone related diseases can be treated through the kidney. A lot of clinical practices have also proved that the Chinese herbs used under the guidance of basic Chinese medicine theory are always good at the treatment of common osteoporosis. In simulated weightlessness experiment, people found that the kidney nourishment drugs do can prevent the decrease of BMD. So in this article we want to review the causes of weightlessness and the potentials applications of tradition Chinese medicine in the treatment of weightlessness osteoporosis.

  10. 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

  11. Prostaglandin E2 Prevents Disuse-Induced Cortical Bone Loss

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Akamine, T.; Ke, Hua Zhu; Li, Xiao Jian; Tang, L. Y.; Zeng, Q. Q.

    1992-01-01

    The object of this study was to determine whether prostaglandin E2 (PGE2) can prevent disuse (underloaded)-induced cortical bone loss as well as add extra bone to underloaded bones. Thirteen-month-old retired female Sprague-Dawley breeders served as controls or were subjected to simultaneous right hindlimb immobilization by bandaging and daily subcutaneous doses of 0, 1, 3, or 6 mg PGE2/kg/d for two and six weeks. Histomorphometric analyses were performed on double-fluorescent labeled undecalcified tibial shaft sections (proximal to the tibiofibular junction). Disuse-induced cortical bone loss occurred by enlarging the marrow cavity and increasing intracortical porosity. PGE2 treatment of disuse shafts further increased intracortical porosity above that in disuse alone controls. This bone loss was counteracted by enhancement of periosteal and corticoendosteal bone formation. Stimulation of periosteal and corticoendosteal bone formation slightly enlarged the total tissue (cross-sectional) area and inhibited marrow cavity enlargement. These PGE2-induced activities netted the same percentage of cortical bone with a different distribution than the beginning and age related controls. These findings indicate the PGE2-induced increase in bone formation compensated for the disuse and PGE2-induced bone loss, and thus prevented immobilization induced bone loss.

  12. Diet-induced Obesity Alters Bone Remodeling Leading to Decreased Femoral Trabecular Bone Mass in Mice

    USDA-ARS?s Scientific Manuscript database

    Body mass derived from an obesity condition may be detrimental to bone health but the mechanism is unknown. This study was to examine changes in bone structure and serum cytokines related to bone metabolism in obese mice induced by a high-fat diet(HFD). Mice fed the HFD were obese and had higher ser...

  13. Mechanical stimulation of bone marrow in situ induces bone formation in trabecular explants.

    PubMed

    Birmingham, E; Kreipke, T C; Dolan, E B; Coughlin, T R; Owens, P; McNamara, L M; Niebur, G L; McHugh, P E

    2015-04-01

    Low magnitude high frequency (LMHF) loading has been shown to have an anabolic effect on trabecular bone in vivo. However, the precise mechanical signal imposed on the bone marrow cells by LMHF loading, which induces a cellular response, remains unclear. This study investigates the influence of LMHF loading, applied using a custom designed bioreactor, on bone adaptation in an explanted trabecular bone model, which isolated the bone and marrow. Bone adaptation was investigated by performing micro CT scans pre and post experimental LMHF loading, using image registration techniques. Computational fluids dynamic models were generated using the pre-experiment scans to characterise the mechanical stimuli imposed by the loading regime prior to adaptation. Results here demonstrate a significant increase in bone formation in the LMHF loaded group compared to static controls and media flow groups. The calculated shear stress in the marrow was between 0.575 and 0.7 Pa, which is within the range of stimuli known to induce osteogenesis by bone marrow mesenchymal stem cells in vitro. Interestingly, a correlation was found between the bone formation balance (bone formation/resorption), trabecular number, trabecular spacing, mineral resorption rate, bone resorption rate and mean shear stresses. The results of this study suggest that the magnitude of the shear stresses generated due to LMHF loading in the explanted bone cores has a contributory role in the formation of trabecular bone and improvement in bone architecture parameters.

  14. Weightlessness and skeleton homeostasis.

    PubMed

    Ziambaras, Konstantinos; Civitelli, Roberto; Papavasiliou, Stathis S

    2005-01-01

    As human beings venture into space in the 21st century, they will be confronted with a "hypodynamic" and thus hostile environment for the bone homeostasis, that could potentially compromise their mobility in general and skeletal strength in particular after landing. From this point of view, space flight studies are especially interesting and intriguing models for scientists. Space studies, however, must not only overcome enormous technical problems but are also limited in size and frequency. Therefore, ground-based models have also been developed to evaluate the effects of skeletal unloading. The most popular model for human studies is prolonged bed rest with normal volunteers, although studies with paraplegics have also been undertaken. In animals, the hindlimb elevation (tail suspension) model simulates space flight models and is well tolerated by the animals with minimal evidence of stress. Although negative calcium balance and bone loss have been observed in all the aforementioned models of skeletal unloading, the exact mechanism(s) by which this occurs are still unknown and mainly speculative.

  15. Observation of the morphology and calcium content of vestibular otoconia in rats after simulated weightlessness

    PubMed Central

    Zhang, Jiangping; Peng, Zhenhui; Yang, Miaoli; Zhang, Xianghong; Wei, Junrong; Xu, Min; Zheng, Qing Yin

    2010-01-01

    Conclusions Reduction in bone formation may have been the main reason for the lower calcium content of the otoconia after simulated weightlessness in rats. The head-ward distribution of blood volume may explain the morphological changes observed in the middle and inner ears. Objective To observe morphological changes in the vestibular organs and measure the calcium content of otoconia in rats after simulated weightlessness. Material and methods We used a tail suspension model of simulated weightlessness and then investigated changes in the vestibular organs using scanning electron microscopy and X-ray microanalysis. Results In comparison to untreated rats, the vestibular otoconia of the rats subjected to simulated weightlessness were small, irregularly shaped or fissured, and were arranged loosely and out of order. In addition, the calcium content of the otoconia was markedly decreased. PMID:16298783

  16. Prolonged weightlessness and calcium loss in man

    NASA Technical Reports Server (NTRS)

    Rambaut, P. C.; Johnston, R. S.

    1979-01-01

    Data have been accumulated from a series of studies in which men have been subjected to weightlessness in orbital space flight for periods of up to 12 weeks. These data are used to predict the long term consequences of weightlessness upon the skeletal system. Space flight induced a loss of calcium which accelerated exponentially from about 50 mg/d at the end of 1 week to approx. 300 mg/d at the end of 12 weeks. The hypercalciuria reached a constant level within 4 weeks while fecal calcium losses continued to increase throughout the period of exposure. This apparent diminution of gastrointestinal absorptive efficiency was accompanied by a slight decline in the plasma level of parathyroid hormone and a slight elevation in the plasma level of calcium and phosphorus. Although losses in mineral from the calcaneus were closely correlated with the calcium imbalance, no changes were detected in the mineral mass of the ulna and radius. From the data presented it is concluded that the process of demineralization observed in space flight is more severe than would be predicted on the basis of observations in immobilized, bed rested, or paralyzed subjects. It is, moreover, suggested that the process may not be totally reversible.

  17. Health care during prolonged weightlessness in humans.

    PubMed

    Bonde-Petersen, F

    1994-01-01

    The demands for accumulation of knowledge about the human adaptation to weightlessness of long duration and the implications for the health and well-being of the astronaut have become increasingly important also for the international space programmes which are under development. The health care during long duration space-flights starts already with the selection where professional, psychological and medical criteria are considered. Space flights in low earth orbit have not been extended beyond 1 year, so the predictable value for long term space flights is limited, because e.g. Mission to Mars will last from 1.5 to 3 years, depending on the position of the planets, the space vehicle etc. The long duration and the enormous distance covered will induce very special and until now unknown effects on the human psychology which might be seen as the one single major factor which might be prohibitive for such long duration flights. The Moon base will bring further knowledge useful for long duration space flights in the field of medical care in general, but also with regard to the development of countermeasures against the adverse effects of weightlessness on the human body. The Moon's gravitational field of 0.16 G makes it possible to study this as a threshold in the adaptation processes.

  18. Prolonged weightlessness and calcium loss in man

    NASA Technical Reports Server (NTRS)

    Rambaut, P. C.; Johnston, R. S.

    1979-01-01

    Data have been accumulated from a series of studies in which men have been subjected to weightlessness in orbital space flight for periods of up to 12 weeks. These data are used to predict the long term consequences of weightlessness upon the skeletal system. Space flight induced a loss of calcium which accelerated exponentially from about 50 mg/d at the end of 1 week to approx. 300 mg/d at the end of 12 weeks. The hypercalciuria reached a constant level within 4 weeks while fecal calcium losses continued to increase throughout the period of exposure. This apparent diminution of gastrointestinal absorptive efficiency was accompanied by a slight decline in the plasma level of parathyroid hormone and a slight elevation in the plasma level of calcium and phosphorus. Although losses in mineral from the calcaneus were closely correlated with the calcium imbalance, no changes were detected in the mineral mass of the ulna and radius. From the data presented it is concluded that the process of demineralization observed in space flight is more severe than would be predicted on the basis of observations in immobilized, bed rested, or paralyzed subjects. It is, moreover, suggested that the process may not be totally reversible.

  19. Calcium influx through stretch-activated channels mediates microfilament reorganization in osteoblasts under simulated weightlessness

    NASA Astrophysics Data System (ADS)

    Luo, Mingzhi; Yang, Zhouqi; Li, Jingbao; Xu, Huiyun; Li, Shengsheng; Zhang, Wei; Qian, Airong; Shang, Peng

    2013-06-01

    We have explored the role of Ca2+ signaling in microfilament reorganization of osteoblasts induced by simulated weightlessness using a random positioning machine (RPM). The RPM-induced alterations of cell morphology, microfilament distribution, cell proliferation, cell migration, cytosol free calcium concentration ([Ca2+]i), and protein expression in MG63 osteoblasts were investigated. Simulated weightlessness reduced cell size, disrupted microfilament, inhibited cellular proliferation and migration, and induced an increase in [Ca2+]i in MG63 human osteosarcoma cells. Gadolinium chloride (Gd), an inhibitor for stretch-activated channels, attenuated the increase in [Ca2+]i and microfilament disruption. Further, the expression of calmodulin was significantly increased by simulated weightlessness, and an inhibitor of calmodulin, W-7, aggravated microfilament disruption. Our findings demonstrate that simulated weightlessness induces Ca2+ influx through stretch-activated channels, then results in microfilament disruption.

  20. Bioceramic Implant Induces Bone Healing of Cranial Defects.

    PubMed

    Engstrand, Thomas; Kihlström, Lars; Lundgren, Kalle; Trobos, Margarita; Engqvist, Håkan; Thomsen, Peter

    2015-08-01

    Autologous bone or inert alloplastic materials used in cranial reconstructions are techniques that are associated with resorption, infection, and implant exposure. As an alternative, a calcium phosphate-based implant was developed and previously shown to potentially stimulate bone growth. We here uncover evidence of induced bone formation in 2 patients. Histological examination 9 months postoperatively showed multinuclear cells in the central defect zone and bone ingrowth in the bone-implant border zone. An increased expression of bone-associated markers was detected. The other patient was investigated 50 months postoperatively. Histological examination revealed ceramic materials covered by vascularized compact bone. The bone regenerative effect induced by the implant may potentially improve long-term clinical outcome compared with conventional techniques, which needs to be verified in a clinical study.

  1. 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.

  2. 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.

  3. Bone ultrasonography in glucocorticoid-induced osteoporosis.

    PubMed

    Cepollaro, C; Gonnelli, S; Rottoli, P; Montagnani, A; Caffarelli, C; Bruni, D; Nikiforakis, N; Fossi, A; Rossi, S; Nuti, R

    2005-07-01

    Osteoporosis is one of the major complications of glucocorticoid (GC) therapy. Few data are available on the usefulness of quantitative ultrasound (QUS), a technique that could also theoretically provide information on bone structure, in the management of glucocorticoid-induced osteoporosis (GIO). This study aimed (1) to evaluate the ability of QUS in detecting bone impairment and in being associated with the prevalence of fragility fracture in GC patients; and (2) to assess whether QUS parameters, and particularly the graphic trace analysis of QUS signal at phalanges, show any peculiar pattern of GIO. We studied 192 patients (136 women and 56 men, mean age 56.7 +/- 14.2 years) on treatment with GCs for at least 6 months, and 192 sex- and age-matched controls. In all subjects, we measured bone mineral density (BMD) at lumbar spine and at femur by DXA, and ultrasound parameters at calcaneus and phalanges. All DXA and QUS parameters were significantly lower in GC patients than in controls and in fracture than in nonfracture GC patients. BMD at lumbar spine showed the best ability in discriminating GC patients with or without fractures. Among QUS parameters, stiffness showed a discriminatory ability significantly better than AD-SoS. BMD at lumbar spine and total femur, stiffness, and AD-SoS are able to predict the odds of fragility fracture event. QUS parameters of the postmenopausal GC patients (n = 105) and of the postmenopausal healthy controls (n = 101) were also compared with those obtained in a separate sample of 90 postmenopausal osteoporotic women (PMO). All parameters were significantly lower in GC patients and in PMO than in controls, without any significant difference between GC and PMO. Our findings show that QUS can be useful in the assessment of glucocorticoid-induced bone impairment. In addition, in this study we found no alteration in QUS parameters or in the graphic trace analysis which could differentiate between GIO and PMO. Further longitudinal

  4. 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.

  5. 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.

  6. [The role of fetus decalcified bone matrix (FDBM) in inducing pure titanium-bone implant integration].

    PubMed

    Zou, L; Zhang, D; Wang, W

    1998-05-01

    Because of its high biological compatibility, titanium has been a good biomaterial. The implanted artificial bone made from titanium can contact with the vital and mature osseous tissue directly within 3-6 months, the so-called osteointergration. In order to promote the process of osteointergration, FDBM of rabbit was prepared and was combined with pure titanium so as to speed up osteointergration. The study focused on bone density, bone intergration rate, new bone growth rate around the pure titanium, and the Ca2+ and PO(4)3- density of titanium-bone interface. A control group of pure titanium inplant without FDBM was set up. The results showed FDBM had no antigenicity. It could induce and speed up the new bone formation at titanium-bone interface. The titanium-bone intergration time was within 2 months. It was suggested that there were more bone morphogenesis protein (BMP) or other bone induction and bone formation factors in brephobone than that in child and adult bone. As a kind of bone induction material, FDBM was easy prepared, cheap in price, easy to storage, no antigenicity and obvious bone-inductive function.

  7. 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.

  8. 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.

  9. Spaceflight-induced bone loss: is there an osteoporosis risk?

    PubMed

    Sibonga, Jean D

    2013-06-01

    Currently, the measurement of areal bone mineral density (aBMD) is used at NASA to evaluate the effects of spaceflight on the skeletal health of astronauts. Notably, there are precipitous declines in aBMD with losses >10 % detected in the hip and spine in some astronauts following a typical 6-month mission in space. How those percentage changes in aBMD relate to fracture risk in the younger-aged astronaut is unknown. Given the unique set of risk factors that could be contributing to this bone loss (eg, adaptation to weightlessness, suboptimal diet, reduced physical activity, perturbed mineral metabolism), one might not expect skeletal changes due to spaceflight to be similar to skeletal changes due to aging. Consequently, dual-energy X-ray absorptiometry (DXA) measurement of aBMD may be too limiting to understand fracture probability in the astronaut during a long-duration mission and the risk for premature osteoporosis after return to Earth. Following a brief review of the current knowledge-base, this paper will discuss some innovative research projects being pursued at NASA to help understand skeletal health in astronauts.

  10. [The effect of weightlessness on amphibians. The skeleton and mineral metabolism].

    PubMed

    Besova, N V; Savel'ev, S V; Chernikov, V P

    1993-07-01

    The visceral and somatic skeleton of Pleurodeles waltilii was investigated after a series of two-week space flights on the biosatellites. It was shown that under conditions of weightlessness osteoporosis of the skeleton and its demineralisation were stimulated. In weightlessness, calcium, phosphorus and sulfur were lost and potassium accumulated. Trabeculae of endochondral part of the extremity bones were destroyed by osteoclasts. Proliferation of osteoclasts was disrupted, appositional growth stopped, and the cartilage of hyoid system was resorbed. Skeleton readaptation during two months did not result in the complete regeneration of morphological structure of the bones.

  11. Radiation-induced osteosarcoma of the sphenoid bone

    SciTech Connect

    Tanaka, S.; Nishio, S.; Morioka, T.; Fukui, M.; Kitamura, K.; Hikita, K. )

    1989-10-01

    The case of a patient who developed osteosarcoma in the sphenoid bone 15 years after radiation therapy for a craniopharyngioma is reported. Radiation-induced osteosarcoma of the sphenoid bone has not been reported previously. Reported cases of radiation-induced osteosarcomas are reviewed.

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

    PubMed Central

    Tang, Tian Tian; Zhang, Lucia; Bansal, Anil; Grynpas, Marc

    2016-01-01

    ABSTRACT 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. PMID:27956598

  13. 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.

  14. 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

  15. Analysis of 20 KEV Electron Induced X-Ray Production in Skull, Femur/tibia Bones of Rats

    NASA Astrophysics Data System (ADS)

    Mehta, Rahul; Watson, Alec; Ali, Nawab; Soulsby, Michael; Chowdhury, Parimal

    2010-04-01

    Hind-limb suspension (HLS) of rats is a NASA validated model of simulated weightlessness. This study examines the effects of microgravity on the skeletal system of rats to assess whether or not exposure of rats to HLS for one week will induce alteration of structural features in selected bones. Four groups of rats were used: two unsuspended controls and two suspended groups. Body weight, food, and water intake were monitored daily before and after suspension. X-rays were measured by a liquid nitrogen cooled Si(li) detector on a Scanning Electron Microscope (SEM) that provided the 20 keV electron beam. X-ray data were collected from square cross sections between 100 μm2 and 104 μm2. The bones were measured for elemental levels of calcium, phosphorus, oxygen and carbon from both control and HLS rats. The average body weight of all HLS groups decreased compared to their respective unsuspended controls. Food and water intake was also lower in both suspended groups. A correlation among HLS and control samples in terms of the distribution of the primary elements was found in the bone tissue when analyzed as a function of position along the hind-leg and within the cross sections.

  16. 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.

  17. 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.

  18. Cardiopulmonary adaptation to weightlessness

    NASA Technical Reports Server (NTRS)

    Prisk, G. K.; Guy, H. J.; Elliott, A. R.; West, J. B.

    1994-01-01

    The lung is profoundly affected by gravity. The absence of gravity (microgravity) removes the mechanical stresses acting on the lung paranchyma itself, resulting in a reduction in the deformation of the lung due to its own weight, and consequently altering the distribution of fresh gas ventilation within the lung. There are also changes in the mechanical forces acting on the rib cage and abdomen, which alters the manner in which the lung expands. The other way in which microgravity affects the lung is through the removal of the gravitationally induced hydrostatic gradients in vascular pressures, both within the lung itself, and within the entire body. The abolition of a pressure gradient within the pulmonary circulation would be expected to result in a greater degree of uniformity of blood flow within the lung, while the removal of the hydrostatic gradient within the body should result in an increase in venous return and intra-thoracic blood volume, with attendant changes in cardiac output, stroke volume, and pulmonary diffusing capacity. During the 9 day flight of Spacelab Life Sciences-1 (SLS-1) we collected pulmonary function test data on the crew of the mission. We compared the results obtained in microgravity with those obtained on the ground in both the standing and supine positions, preflight and in the week immediately following the mission. A number of the tests in the package were aimed at studying the anticipated changes in cardiopulmonary function, and we report those in this communication.

  19. Cardiopulmonary adaptation to weightlessness

    NASA Technical Reports Server (NTRS)

    Prisk, G. K.; Guy, H. J.; Elliott, A. R.; West, J. B.

    1994-01-01

    The lung is profoundly affected by gravity. The absence of gravity (microgravity) removes the mechanical stresses acting on the lung paranchyma itself, resulting in a reduction in the deformation of the lung due to its own weight, and consequently altering the distribution of fresh gas ventilation within the lung. There are also changes in the mechanical forces acting on the rib cage and abdomen, which alters the manner in which the lung expands. The other way in which microgravity affects the lung is through the removal of the gravitationally induced hydrostatic gradients in vascular pressures, both within the lung itself, and within the entire body. The abolition of a pressure gradient within the pulmonary circulation would be expected to result in a greater degree of uniformity of blood flow within the lung, while the removal of the hydrostatic gradient within the body should result in an increase in venous return and intra-thoracic blood volume, with attendant changes in cardiac output, stroke volume, and pulmonary diffusing capacity. During the 9 day flight of Spacelab Life Sciences-1 (SLS-1) we collected pulmonary function test data on the crew of the mission. We compared the results obtained in microgravity with those obtained on the ground in both the standing and supine positions, preflight and in the week immediately following the mission. A number of the tests in the package were aimed at studying the anticipated changes in cardiopulmonary function, and we report those in this communication.

  20. 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.

  1. Influence of bone osteocalcin levels on bone loss induced by ovariectomy in rats.

    PubMed

    Hara, Kuniko; Kobayashi, Masatoshi; Akiyama, Yasuhiro

    2007-01-01

    To investigate the role of osteocalcin (OC) in bones, bone parameters in warfarin (WF)-treated rats after ovariectomy (OVX) were compared with those in intact rats. Rats were divided into an intact group and WF-treated group. Warfarin was orally given to rats for 16 weeks, and then OVX was performed and rats in the WF-treated groups continued receiving WF. Twelve weeks after OVX, bone properties were observed. The diaphysial bone OC level in the WF group was 10%-14% of the normal level at the preoperative point and 12 weeks after surgery. On comparison of the intact and WF groups before surgery, no significant differences were noted in bone mass parameters or mechanical properties, but 12 weeks after surgery, the diaphysial bone mineral content (BMC), bone area, and cortical thickness (Cth) were significantly higher in the WF-sham group than in the intact-sham group. Ovariectomy significantly decreased the diaphysial BMC, bone mineral density (BMD), Cth, and maximum load, and increased the endosteal perimeter in the WF group. In the intact group, no such OVX-induced changes were noted, and the metaphysial bone area and the endosteal and periosteal perimeters were increased by OVX. The CO(3)/PO(4) ratio in the femur measured by Fourier-transform infrared imaging using reflection preparations was higher in the WF-sham group than the intact-sham group, and higher in the intact-OVX group than the intact-sham group, but no significant difference was noted between the WF-sham and WF-OVX groups. It has been reported that CO(3)(-) is contained in new bone and decreases with mineral maturation. These data suggest that long-term reduction in bone OC levels may induce the formation of immature bone, which is easily resorbed with changes in bone metabolism such as OVX, and that OC may be one of the factors affecting bone turnover.

  2. 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.

  3. 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.

  4. 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

  5. [Non-corticosteroid drug-induced metabolic bone disease].

    PubMed

    Briot, Karine

    2006-10-01

    After osteoporotic fracture or low bone mineral density measurements, it is necessary to look for secondary causes of osteoporosis, such as drugs. Corticosteroids are the most common cause of drug-induced metabolic bone disease. Other drugs responsible for bone disease include: aromatase inhibitors, GnRH agonists, anticonvulsants, heparin, and L thyroxin at TSH-suppressive doses. Confirmation is required of data about neuroleptics and antivitamin K.

  6. 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

  7. 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; hide

    2009-01-01

    Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss (Bisphosphonates) will determine whether antiresorptive agents, in conjunction with the routine inflight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density documented on previous ISS missions.

  8. ANA deficiency enhances bone morphogenetic protein-induced ectopic bone formation via transcriptional events.

    PubMed

    Miyai, Kentaro; Yoneda, Mitsuhiro; Hasegawa, Urara; Toita, Sayaka; Izu, Yayoi; Hemmi, Hiroaki; Hayata, Tadayoshi; Ezura, Yoichi; Mizutani, Shuki; Miyazono, Kohei; Akiyoshi, Kazunari; Yamamoto, Tadashi; Noda, Masaki

    2009-04-17

    Ectopic bone formation after joint replacement or brain injury in humans is a serious complication that causes immobility of joints and severe pain. However, mechanisms underlying such ectopic bone formation are not fully understood. Bone morphogenetic protein (BMPs) are defined as inducers of ectopic bone formation, and they are regulated by several types of inhibitors. ANA is an antiproliferative molecule that belongs to Tob/BTG family, but its activity in bone metabolism has not been known. Here, we examined the role of ANA on ectopic bone formation activity of BMP. In ANA-deficient and wild-type mice, BMP2 was implanted to induce ectopic bone formation in muscle. ANA deficiency increased mass of newly formed bone in vivo compared with wild-type based on 3D-muCT analyses. ANA mRNA was expressed in bone in vivo as well as in osteoblastic cells in vitro. Such ANA mRNA levels were increased by BMP2 treatment in MC3T3-E1 osteoblastic cells. Overexpression of ANA suppressed BMP-induced expression of luciferase reporter gene linked to BMP response elements in these cells. Conversely, ANA mRNA knockdown by small interference RNA enhanced the BMP-dependent BMP response element reporter expression. It also enhanced BMP-induced osteoblastic differentiation in muscle-derived C2C12 cells. Immunoprecipitation assay indicated that ANA interacts with Smad8. Thus, ANA is a suppressor of ectopic bone formation induced by BMP, and this inhibitory ANA activity is a part of the negative feedback regulation of BMP function.

  9. 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; hide

    2011-01-01

    Experiment Hypothesis -- The combined effect of anti-resorptive drugs plus in-flight exercise regimen will have a measurable effect in preventing space flight induced bone mass and strength loss and reducing renal stone risk.

  10. 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.

  11. 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.

  12. 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

  13. Schwann cells induce neuronal differentiation of bone marrow stromal cells.

    PubMed

    Zurita, Mercedes; Vaquero, Jesús; Oya, Santiago; Miguel, Miriam

    2005-04-04

    Bone marrow stromal cells are multipotent stem cells that have the potential to differentiate into bone, cartilage, fat and muscle. Recently, bone marrow stromal cells have been shown to have the capacity to differentiate into neurons under specific experimental conditions, using chemical factors. We now describe how bone marrow stromal cells can be induced to differentiate into neuron-like cells when they are co-cultured with Schwann cells. When compared with chemical differentiation, expression of neuronal differentiation markers begins later, but one week after beginning co-culture, most bone marrow stromal cells showed a typical neuronal morphology. Our present findings support the transdifferentiation of bone marrow stromal cells, and the potential utility of these cells for the treatment of degenerative and acquired disorders of the nervous system.

  14. Botox induced muscle paralysis rapidly degrades bone

    PubMed Central

    Warner, Sarah E.; Sanford, David A.; Becker, Blair A.; Bain, Steven D.; Srinivasan, Sundar; Gross, Ted S.

    2006-01-01

    The means by which muscle function modulates bone homeostasis is poorly understood. To begin to address this issue, we have developed a novel murine model of unilateral transient hindlimb muscle paralysis using botulinum toxin A (Botox). Female C57BL/6 mice (16 weeks) received IM injections of either saline or Botox (n = 10 each) in both the quadriceps and calf muscles of the right hindleg. Gait dysfunction was assessed by multi-observer inventory, muscle alterations were determined by wet mass, and bone alterations were assessed by micro-CT imaging at the distal femur, proximal tibia, and tibia mid-diaphysis. Profound degradation of both muscle and bone was observed within 21 days despite significant restoration of weight bearing function by 14 days. The muscle mass of the injected quadriceps and calf muscles was diminished −47.3% and −59.7%, respectively, vs. saline mice (both P < 0.001). The ratio of bone volume to tissue volume (BV/TV) within the distal femoral epiphysis and proximal tibial metaphysis of Botox injected limbs was reduced −43.2% and −54.3%, respectively, while tibia cortical bone volume was reduced −14.6% (all P < 0.001). Comparison of the contralateral non-injected limbs indicated the presence of moderate systemic effects in the model that were most probably associated with diminished activity following muscle paralysis. Taken as a whole, the micro-CT data implied that trabecular and cortical bone loss was primarily achieved by bone resorption. These data confirm the decisive role of neuromuscular function in mediating bone homeostasis and establish a model with unique potential to explore the mechanisms underlying this relation. Given the rapidly expanding use of neuromuscular inhibitors for indications such as pain reduction, these data also raise the critical need to monitor bone loss in these patients. PMID:16185943

  15. Periarticular Bone Loss in Antigen-Induced Arthritis

    PubMed Central

    Engdahl, Cecilia; Lindholm, Catharina; Stubelius, Alexandra; Ohlsson, Claes; Carlsten, Hans; Lagerquist, Marie K

    2013-01-01

    Objective Bone loss in arthritis is a complex process characterized by bone erosions and periarticular and generalized bone loss. The antigen-induced arthritis (AIA) model is mainly used to study synovitis and joint destruction, including bone erosions; however, periarticular bone loss has been less extensively investigated. The objectives of this study were to characterize and establish AIA as a model for periarticular bone loss, and to determine the importance of NADPH oxidase 2 (NOX-2)–derived reactive oxygen species (ROS) in periarticular bone loss. Methods Arthritis was induced in mice by local injection of antigen in one knee; the other knee was used as a nonarthritis control. At study termination, the knees were collected for histologic assessment. Periarticular bone mineral density (BMD) was investigated by peripheral quantitative computed tomography. Flow cytometric analyses were performed using synovial and bone marrow cells. Results AIA resulted in decreased periarticular trabecular BMD and increased frequencies of preosteoclasts, neutrophils, and monocytes in the arthritic synovial tissue. Arthritis induction resulted in an increased capability to produce ROS. However, induction of arthritis in Ncf1*/* mice, which lack NOX-2–derived ROS, and control mice resulted in similar reductions in periarticular trabecular BMD. Conclusion The initiation of AIA resulted in periarticular bone loss associated with local effects on inflammatory cells and osteoclasts. Furthermore, based on our observations using this model, we conclude that NOX-2–derived ROS production is not essential for inflammation-mediated periarticular bone loss. Thus, AIA can be used as a model to investigate the pathogenesis of local inflammation–mediated bone loss. PMID:23918694

  16. Weightlessness simulation system and process

    NASA Technical Reports Server (NTRS)

    Vykukal, Hubert C. (Inventor)

    1987-01-01

    A weightlessness simulator has a chamber and a suit in the chamber. O-rings and valves hermetically seal the chamber. A vacuum pump connected to the chamber establishes a pressure in the chamber less than atmospheric pressure. A water supply tank and water supply line supply a body of water to the chamber as a result of partial vacuum created in the chamber. In use, an astronaut enters the pressure suit through a port, which remains open to ambient atmosphere, thus supplying air to the astronaut during use. The pressure less than atmospheric pressure in the chamber is chosen so that the pressure differential from the inside to the outside of the suit corresponds to the pressure differential with the suit in outer space.

  17. 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.

  18. Stromal cell-derived factor-1 potentiates bone morphogenetic protein-2 induced bone formation.

    PubMed

    Higashino, Kosaku; Viggeswarapu, Manjula; Bargouti, Maggie; Liu, Hui; Titus, Louisa; Boden, Scott D

    2011-02-01

    The mechanisms driving bone marrow stem cell mobilization are poorly understood. A recent murine study found that circulating bone marrow-derived osteoprogenitor cells (MOPCs) were recruited to the site of recombinant human bone morphogenetic protein-2 (BMP-2)-induced bone formation. Stromal cell-derived factor-1α (SDF-1α) and its cellular receptor CXCR4 have been shown to mediate the homing of stem cells to injured tissues. We hypothesized that chemokines, such as SDF-1, are also involved with mobilization of bone marrow cells. The CD45(-) fraction is a major source of MOPCs. In this report we determined that the addition of BMP-2 or SDF-1 to collagen implants increased the number of MOPCs in the peripheral blood. BMP-2-induced mobilization was blocked by CXCR4 antibody, confirming the role of SDF-1 in mobilization. We determined for the first time that addition of SDF-1 to implants containing BMP-2 enhances mobilization, homing of MOPCs to the implant, and ectopic bone formation induced by suboptimal BMP-2 doses. These results suggest that SDF-1 increases the number of osteoprogenitor cells that are mobilized from the bone marrow and then home to the implant. Thus, addition of SDF-1 to BMP-2 may improve the efficiency of BMPs in vivo, making their routine use for orthopaedic applications more affordable and available to more patients.

  19. Histological characterization of bone marrow in ectopic bone, induced by devitalized Saos-2 human osteosarcoma cells.

    PubMed

    Nahar, Niru N; Tague, Sarah E; Wang, Jinxi; Danley, Marsha; Garimella, Rama; Anderson, H Clarke

    2013-01-01

    Devitalized Saos-2, cultured human osteosarcoma cells, or guanidinium-hydrochloride (GuHCl) extracts of these cells, induce ectopic bone and marrow formation when implanted subcutaneously in Nu/Nu mice. The aim of the present study was to characterize the bone marrow induced by Saos-2 cell extracts, specifically to determine which of the four major hematopoietic cell lineages: erythropoietic, granulopoietic, lymphopoietic and megakaryocytic, are induced by Saos-2 cell derivatives. Immunohistochemical localization of specific antigens was used to determine the presence of each major cell type (glycophorin A for erythropoietic, neutrophil elastase for granulopoietic, factor-VIII related antigen for megakaryocytes, and CD79a for B lymphocytes). Standard H & E stains confirmed the presence of normally organized apparently complete bone marrow within all newly induced bone at 3 weeks post-implantation of devitalized Saos-2 cells. Immunohistochemistry confirmed the presence of erythropoietic cells, granulopoietic cells, megakaryocytes and B lymphocytes in the ectopic marrow. Saos-2 cells (freeze-dried) or their extracts, implanted subcutaneously into Nu/Nu mice, can induce normal marrow that is host-derived, and contains all major hematopoietic cell lineages. Saos-2 induced marrow could potentially restore deficient marrow and promote bone repair.

  20. Histological characterization of bone marrow in ectopic bone, induced by devitalized Saos-2 human osteosarcoma cells

    PubMed Central

    Nahar, Niru N; Tague, Sarah E; Wang, Jinxi; Danley, Marsha; Garimella, Rama; Anderson, H Clarke

    2013-01-01

    Devitalized Saos-2, cultured human osteosarcoma cells, or guanidinium-hydrochloride (GuHCl) extracts of these cells, induce ectopic bone and marrow formation when implanted subcutaneously in Nu/Nu mice. The aim of the present study was to characterize the bone marrow induced by Saos-2 cell extracts, specifically to determine which of the four major hematopoietic cell lineages: erythropoietic, granulopoietic, lymphopoietic and megakaryocytic, are induced by Saos-2 cell derivatives. Methods: Immunohistochemical localization of specific antigens was used to determine the presence of each major cell type (glycophorin A for erythropoietic, neutrophil elastase for granulopoietic, factor-VIII related antigen for megakaryocytes, and CD79a for B lymphocytes). Results: Standard H & E stains confirmed the presence of normally organized apparently complete bone marrow within all newly induced bone at 3 weeks post-implantation of devitalized Saos-2 cells. Immunohistochemistry confirmed the presence of erythropoietic cells, granulopoietic cells, megakaryocytes and B lymphocytes in the ectopic marrow. Conclusion: Saos-2 cells (freeze-dried) or their extracts, implanted subcutaneously into Nu/Nu mice, can induce normal marrow that is host-derived, and contains all major hematopoietic cell lineages. Clinical Significance: Saos-2 induced marrow could potentially restore deficient marrow and promote bone repair. PMID:23386915

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. '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.

  8. Acute hemodynamic responses to weightlessness in humans

    NASA Technical Reports Server (NTRS)

    Lathers, C. M.; Charles, J. B.; Elton, K. F.; Holt, T. A.; Mukai, C.; Bennett, B. S.; Bungo, M. W.

    1989-01-01

    As NASA designs space flights requiring prolonged periods of weightlessness for a broader segment of the population, it will be important to know the acute and sustained effects of weightlessness on the cardiovascular system since this information will contribute to understanding of the clinical pharmacology of drugs administered in space. Due to operational constraints on space flights, earliest effects of weightlessness have not been documented. We examined hemodynamic responses of humans to transitions from acceleration to weightlessness during parabolic flight on NASA's KC-135 aircraft. Impedance cardiography data were collected over four sets of 8-10 parabolas, with a brief rest period between sets. Each parabola included a period of 1.8 Gz, then approximately 20 seconds of weightlessness, and finally a period of 1.6 Gz; the cycle repeated almost immediately for the remainder of the set. Subjects were semi-supine (Shuttle launch posture) for the first set, then randomly supine, sitting and standing for each subsequent set. Transition to weightlessness while standing produced decreased heart rate, increased thoracic fluid content, and increased stroke index. Surprisingly, the onset of weightlessness in the semi-supine posture produced little evidence of a headward fluid shift. Heart rate, stroke index, and cardiac index are virtually unchanged after 20 seconds of weightlessness, and thoracic fluid content is slightly decreased. Semi-supine responses run counter to Shuttle crewmember reports of noticeable fluid shift after minutes to hours in orbit. Apparently, the headward fluid shift commences in the semi-supine posture before launch. is augmented by launch acceleration, but briefly interrupted immediately in orbit, then resumes and is completed over the next hours.

  9. Acute hemodynamic responses to weightlessness in humans

    NASA Technical Reports Server (NTRS)

    Lathers, C. M.; Charles, J. B.; Elton, K. F.; Holt, T. A.; Mukai, C.; Bennett, B. S.; Bungo, M. W.

    1989-01-01

    As NASA designs space flights requiring prolonged periods of weightlessness for a broader segment of the population, it will be important to know the acute and sustained effects of weightlessness on the cardiovascular system since this information will contribute to understanding of the clinical pharmacology of drugs administered in space. Due to operational constraints on space flights, earliest effects of weightlessness have not been documented. We examined hemodynamic responses of humans to transitions from acceleration to weightlessness during parabolic flight on NASA's KC-135 aircraft. Impedance cardiography data were collected over four sets of 8-10 parabolas, with a brief rest period between sets. Each parabola included a period of 1.8 Gz, then approximately 20 seconds of weightlessness, and finally a period of 1.6 Gz; the cycle repeated almost immediately for the remainder of the set. Subjects were semi-supine (Shuttle launch posture) for the first set, then randomly supine, sitting and standing for each subsequent set. Transition to weightlessness while standing produced decreased heart rate, increased thoracic fluid content, and increased stroke index. Surprisingly, the onset of weightlessness in the semi-supine posture produced little evidence of a headward fluid shift. Heart rate, stroke index, and cardiac index are virtually unchanged after 20 seconds of weightlessness, and thoracic fluid content is slightly decreased. Semi-supine responses run counter to Shuttle crewmember reports of noticeable fluid shift after minutes to hours in orbit. Apparently, the headward fluid shift commences in the semi-supine posture before launch. is augmented by launch acceleration, but briefly interrupted immediately in orbit, then resumes and is completed over the next hours.

  10. 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.

  11. 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.

  12. 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.

  13. Regulation of BMP-induced ectopic bone formation by Ahsg.

    PubMed

    Rittenberg, B; Partridge, E; Baker, G; Clokie, C; Zohar, R; Dennis, J W; Tenenbaum, H C

    2005-05-01

    alpha2-HS-glycoprotein (Ahsg), also known as fetuin is a serum and bone resident glycoprotein, which binds to TGF-beta superfamily members including bone morphogenetic proteins (BMP) and inhibits dexamethasone-induced osteogenesis in bone marrow cultures in vitro. Here we demonstrate that Ahsg reduces cytokine binding to its cognate receptor in HOS osteocyte cells and suppresses intracellular signaling, while in vivo, we test the hypothesis that Ahsg-deficient mice are hyper-responsive to BMP-induced osteogenesis. Human native BMP was implanted into the hindquarter muscles of Ahsg(+/+), Ahsg(+/-) and Ahsg(-/-) mice and 4 weeks later, ossicle formation was analyzed by radiography, bone density scanning (DEXA) and histomorphometry. Alkaline phosphatase (AP) activity was measured in ossicles as a marker for bone cell differentiation, and was significantly higher in Ahsg(-/-) versus Ahsg(+/-) and/or Ahsg(+/+) mice. Ectopic ossicle size in the Ahsg(+/-) mouse was 4-fold greater than that in the wild type (Ahsg(+/+)), and intermediate to that shown in Ahsg(-/-) mouse. Bone mineral density (BMD) was lower in the Ahsg(-/+) and Ahsg(-/-) mice compared to Ahsg(+/+) littermates. The ratio of cortical to cancellous bone was found to be >2-fold higher in Ahsg(-/-) mouse in comparison to the Ahsg(+/+) mice with no significant change in the Ahsg(-/+) mouse. Finally, a significantly higher incidence of satellite ossification; small islands of immature bone, was shown in Ahsg(-/-) mice as compared to Ahsg(+/+) mice. Although Ahsg binds to TGF-beta/BMP and blocks receptor signalling, it may also sequester cytokines in matrix, thereby acting as a reservoir of osteoinductive activity when released. This may explain the non-linear relationship between ectopic bone formation characteristics and Ahsg(+/+), Ahsg(+/-) and Ahsg(-/-) genotypes, although the increase in satellite bone formation might also explain this phenomenon. Our results suggest that Ahsg may be useful for prevention of

  14. 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.; hide

    2011-01-01

    This poster reviews the possibility of using Bisphosphonates to counter the bone loss that is experienced during space flight. The Hypothesis that is tested in this experiment is that the combined effect of anti-resorptive drugs plus in-flight exercise regimen will attenuate space flight induced loss in bone mass and strength and reduce renal stone risk. The experiment design, the status and the results are described.

  15. 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.

  16. Protocadherin-7 induces bone metastasis of breast cancer

    SciTech Connect

    Li, Ai-Min; Tian, Ai-Xian; Zhang, Rui-Xue; Ge, Jie; Sun, Xuan; Cao, Xu-Chen

    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 bone 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.

  17. Artesunate Inhibits RANKL-induced Osteoclastogenesis and Bone Resorption In Vitro and Prevents LPS-induced Bone Loss In Vivo.

    PubMed

    Wei, Cheng-Ming; Liu, Qian; Song, Fang-Ming; Lin, Xi-Xi; Su, Yi-Ji; Xu, Jiake; Huang, Lin; Zong, Shao-Hui; Zhao, Jin-Min

    2017-03-15

    Osteoclasts are multinuclear giant cells responsible for bone resorption in lytic bone diseases such as osteoporosis, arthritis, periodontitis, and bone tumors. Due to the severe side-effects caused by the currently available drugs, a continuous search for novel bone-protective therapies is essential. Artesunate (Art), the water-soluble derivative of artemisinin has been investigated owing to its anti-malarial properties. However, its effects in osteoclastogenesis have not yet been reported. In this study, Art was shown to inhibit the nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, the mRNA expression of osteoclastic-specific genes, and resorption pit formation in a dose-dependent manner in primary bone marrow-derived macrophages cells (BMMs). Furthermore, Art markedly blocked the RANKL-induced osteoclastogenesis by attenuating the degradation of IκB and phosphorylation of NF-κB p65. Consistent with the in vitro results, Art inhibited lipopolysaccharide (LPS)-induced bone resorption by suppressing the osteoclastogenesis. Together our data demonstrated that Art inhibits RANKL-induced osteoclastogenesis by suppressing the NF-κB signaling pathway and that it is a promising agent for the treatment of osteolytic diseases. This article is protected by copyright. All rights reserved.

  18. [Effects of BMP-2 on the gene expression of rat osteosarcoma cells under simulated weightlessness].

    PubMed

    Wang, Bing; Zhang, Shu; Wu, Xing-yu

    2004-06-01

    To investigate the effect of BMP-2 on (the) gene expression of rat osteosarcoma cells (ROS17/2.8) under rotating clinostat simulated weightlessness. ROS17/2.8 cells were cultivated in 1 G control and rotating clinostat simulated weightlessness with 500 ng/ml BMP-2 in the culture medium. Total RNA in cells was isolated after 24, 48 and 72 h. Reverse transcription PCR analysis was made to examine the gene expression of alpha 1 chain of type I collagen (collagen I alpha 1) and alkaline phosphatase (ALP). The expression of COL-I alpha 1 mRNA induced by BMP-2 was much more than that without BMP-2 in 24 h and 48 h group (P<0.01). The level of ALP mRNA induced by BMP-2 was significantly high in 48 h or 72 h group (respectively P<0.01, P<0.05). The level of BMP-2 induced expression of COL-I alpha 1 mRNA was significantly lower under 48 h of simulated weightlessness than in 1 G condition (P<0.01). The level of ALP mRNA was significantly lower under simulated weightlessness for 48 h or 72 h (P<0.01). BMP-2 can stimulate the differentiation of ROS17/2.8 cells in 1 G condition and this process is reduced under simulated weightlessness.

  19. Research advance in effects of weightlessness or simulated weightlessness on tumor cells.

    PubMed

    Chang, De; Guo, Ying-hua; Liu, Chang-ting

    2012-08-01

    Weightless environment is a rare phenomenon on the ground where the interactions among cells and internal cellular structures disappear or become weakened. Studies on the biological features and molecular expression of tumors cells in weightlessness condition may provide new clues to the tumor initiation, process, diagnosis, and therapy.

  20. 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.

  1. 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.

  2. 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.

  3. Weightlessness experiments on Biosatellite II.

    PubMed

    Edwards, B F

    1969-01-01

    maximum age of wheat seedlings was only 65 hours, coleoptile and root growth rates during that time had not been significantly altered by flight or by slow rotation on a horizontal clinostat. There was some evidence that growth was accelerated after normal gravity was restored. The orientation of coleoptiles and of primary and lateral roots of orbited plants varied significantly from the normal erect seedlings but was almost identical with that of clinostat plants. The Periodic-Acid-Schiff technique on sectioned material showed starch grains at the bottom of cells of erect control coleoptile and root tips, while in orbited and clinostated plants the grains were located more or less at random. Histochemical differences between clinostat and orbited tissues are apparent however. Peroxidase localization varied and its activity was higher in both clinostat and orbited tissues; five other enzymes studied biochemically showed no differences. These experiments all suggest that there is no deleterious effect on living organisms or their activities from short-term weightlessness. Several results indicate that the horizontal clinostat may simulate the weightless state effectively here on Earth.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Secreted Wnt Signaling Inhibitors in Disuse-Induced Bone Loss

    DTIC Science & Technology

    2011-05-01

    first series, adult female mice were subjected to unilateral Botox -induced muscle paralysis of the lower limb via Botox (20 U/kg) injection into the...equal loss in muscle mass induced by Botox , Sost+/+ mice lost a significant percentage of their initial lower-limb aBMD and BMC over the experimental...trabecular thickness, and trabecular bone mineral content (Tb.BMC) in the distal femur. We also investigated the osteopenic effects of Botox

  9. Periosteal response in translation-induced bone remodelling.

    PubMed Central

    Feik, S A; Ellender, G; Crowe, D M; Ramm-Anderson, S M

    1990-01-01

    Translation of transplanted bones induces strain in the periosteum and subsequent bone remodelling. This study examines the periosteal response on the leading and trailing sides of translated bones using an in vivo model where internal bone strain is virtually eliminated. Caudal vertebrae from 4 days old rats were threaded onto the arms of pre-stressed helical torsion springs and transplanted subcutaneously. In the experimental rats, the appliances were activated seven days later causing the bones to translate. Tissues were examined both optically and by transmission electron microscopy. A connective tissue sheath or capsule forms around the bones and, as the arms of the appliance move apart, traction on the enveloping soft tissues produces compression of the periosteum on the leading side and tension on the trailing side with remodelling occurring in a direction opposite to translation. The control periosteum has an ordered structure with well-delineated osteogenic, mid- and fibrous zones. During translation the periosteum on the leading side is consistently narrower than on the trailing side and shows a gradual reduction in formative activity followed by resorption in select areas. Cells and fibres are aligned predominantly parallel to the bone surface. Accelerated formation characterises the trailing side during the translation phase with increased activity and widening of all three periosteal layers. The fibrous layer merges with the connective tissue sheath which frequently is oriented approximately perpendicular to the bone surface. The direction of remodelling is reversed when translation ceases with corresponding changes visible in the periosteum, the osteoblastic layer being the last to show changes. A normal periosteal structure and remodelling pattern is regained when equilibrium of the bones within the soft tissues is attained. This study shows that the enveloping soft tissues profoundly influence the nature and rate of bone remodelling. The changes are

  10. 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.

  11. 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.

  12. Porphyromonas gingivalis infection-induced tissue and bone transcriptional profiles

    PubMed Central

    Meka, Archana; Bakthavatchalu, Vasudevan; Sathishkumar, Sabapathi; Lopez, M. Cecilia; Verma, Raj K.; Wallet, Shannon M.; Bhattacharyya, Indraneel; Boyce, Brendan F.; Handfield, Martin; Lamont, Richard J.; Baker, Henry V.; Ebersole, Jeffrey L.; Lakshmyya, Kesavalu N.

    2010-01-01

    Introduction Porphyromonas gingivalis has been associated with subgingival biofilms in adult periodontitis. However, the molecular mechanisms of its contribution to chronic gingival inflammation and loss of periodontal structural integrity remain unclear. The objectives of this investigation were to examine changes in the host transcriptional profiles during a P. gingivalis infection using a murine calvarial model of inflammation and bone resorption. Methods P. gingivalis FDC 381 was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and calvarial bones were excised. RNA was isolated from infected soft tissues and calvarial bones and analyzed for transcript profiles using Murine GeneChip® arrays to provide a molecular profile of the events that occur following infection of these tissues. Results After P. gingivalis infection, 5517 and 1900 probe sets in the infected soft tissues and calvarial bone, respectively, were differentially expressed (P ≤ 0.05) and up-regulated. Biological pathways significantly impacted by P. gingivalis infection in tissues and calvarial bone included cell adhesion (immune system) molecules, Toll-like receptors, B cell receptor signaling, TGF-β cytokine family receptor signaling, and MHC class II antigen processing pathways resulting in proinflammatory, chemotactic effects, T cell stimulation, and down regulation of antiviral and T cell chemotactic effects. P. gingivalis-induced inflammation activated osteoclasts, leading to local bone resorption. Conclusion This is the first in vivo evidence that localized P. gingivalis infection differentially induces transcription of a broad array of host genes that differed between inflamed soft tissues and calvarial bone. PMID:20331794

  13. Porphyromonas gingivalis infection-induced tissue and bone transcriptional profiles.

    PubMed

    Meka, A; Bakthavatchalu, V; Sathishkumar, S; Lopez, M C; Verma, R K; Wallet, S M; Bhattacharyya, I; Boyce, B F; Handfield, M; Lamont, R J; Baker, H V; Ebersole, J L; Kesavalu, L

    2010-02-01

    Porphyromonas gingivalis has been associated with subgingival biofilms in adult periodontitis. However, the molecular mechanisms of its contribution to chronic gingival inflammation and loss of periodontal structural integrity remain unclear. This investigation aimed to examine changes in the host transcriptional profiles during a P. gingivalis infection using a murine calvarial model of inflammation and bone resorption. P. gingivalis FDC 381 was injected into the subcutaneous soft tissue over the calvaria of BALB/c mice for 3 days, after which the soft tissues and calvarial bones were excised. RNA was isolated from infected soft tissues and calvarial bones and was analysed for transcript profiles using Murine GeneChip((R)) arrays to provide a molecular profile of the events that occur following infection of these tissues. After P. gingivalis infection, 6452 and 2341 probe sets in the infected soft tissues and calvarial bone, respectively, were differentially expressed (P bone included cell adhesion (immune system) molecules, Toll-like receptors, B-cell receptor signaling, transforming growth factor-beta cytokine family receptor signaling, and major histocompatibility complex class II antigen processing pathways resulting in proinflammatory, chemotactic effects, T-cell stimulation, and downregulation of antiviral and T-cell chemotactic effects. P. gingivalis-induced inflammation activated osteoclasts, leading to local bone resorption. This is the first in vivo evidence that localized P. gingivalis infection differentially induces transcription of a broad array of host genes, the profiles of which differed between inflamed soft tissues and calvarial bone.

  14. 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

  15. Rhus javanica Gall Extract Inhibits the Differentiation of Bone Marrow-Derived Osteoclasts and Ovariectomy-Induced Bone Loss

    PubMed Central

    Kim, Tae-Ho; Park, Eui Kyun; Huh, Man-Il; Kim, Hong Kyun; Kim, Shin-Yoon; Lee, Sang-Han

    2016-01-01

    Inhibition of osteoclast differentiation and bone resorption is a therapeutic strategy for the management of postmenopausal bone loss. This study investigated the effects of Rhus javanica (R. javanica) extracts on bone marrow cultures to develop agents from natural sources that may prevent osteoclastogenesis. Extracts of R. javanica (eGr) cocoons spun by Rhus javanica (Bell.) Baker inhibited the osteoclast differentiation and bone resorption. The effects of aqueous extract (aeGr) or 100% ethanolic extract (eeGr) on ovariectomy- (OVX-) induced bone loss were investigated by various biochemical assays. Furthermore, microcomputed tomography (µCT) was performed to study bone remodeling. Oral administration of eGr (30 mg or 100 mg/kg/day for 6 weeks) augmented the inhibition of femoral bone mineral density (BMD), bone mineral content (BMC), and other factors involved in bone remodeling when compared to OVX controls. Additionally, eGr slightly decreased bone turnover markers that were increased by OVX. Therefore, it may be suggested that the protective effects of eGr could have originated from the suppression of OVX-induced increase in bone turnover. Collectively, the findings of this study indicate that eGr has potential to activate bone remodeling by inhibiting osteoclast differentiation and bone loss. PMID:27313644

  16. Pain and nociception: mechanisms of cancer-induced bone pain.

    PubMed

    Falk, Sarah; Dickenson, Anthony H

    2014-06-01

    Cancer pain, especially pain caused by metastasis to bone, is a severe type of pain, and unless the cause and consequences can be resolved, the pain will become chronic. As detection and survival among patients with cancer have improved, pain has become an increasing challenge, because traditional therapies are often only partially effective. Until recently, knowledge of cancer pain mechanisms was poor compared with understanding of neuropathic and inflammatory pain states. We now view cancer-induced bone pain as a complex pain state involving components of both inflammatory and neuropathic pain but also exhibiting elements that seem unique to cancer pain. In addition, the pain state is often unpredictable, and the intensity of the pain is highly variable, making it difficult to manage. The establishment of translational animal models has started to reveal some of the molecular components involved in cancer pain. We present the essential pharmacologic and neurobiologic mechanisms involved in the generation and continuance of cancer-induced bone pain and discuss these in the context of understanding and treating patients. We discuss changes in peripheral signaling in the area of tumor growth, examine spinal cord mechanisms of sensitization, and finally address central processing. Our aim is to provide a mechanistic background for the sensory characteristics of cancer-induced bone pain as a basis for better understanding and treating this condition.

  17. Weightlessness affects cytoskeleton of rat utricular hair cells during maturation in vitro.

    PubMed

    Gaboyard, Sophie; Blanchard, Marie-Pierre; Travo, Cécile; Viso, Michel; Sans, Alain; Lehouelleur, Jacques

    2002-11-15

    The aim of this study was to investigate whether an altered gravitational environment affected the phenotype of vestibular hair cells during maturation. We developed, using an automated incubator, a 3D culture of utricles from newborn rats. These cultures were subjected to weightlessness for 1 or 3 days, and then compared with control cultures developed in natural and induced 1G gravity. Immunocytochemistry for alpha-tubulin and calretinin revealed disorganisation of the microtubules and a loss of hair cell shape in cells subjected to weightlessness during maturation. We conclude that the lack of gravitational strain affected cytoskeletal dynamics, resulting in loss of the specific morphological phenotype of the cells.

  18. Bone sarcoma in humans induced by radium: A threshold response?

    SciTech Connect

    Rowland, R.E.

    1996-08-01

    The radium 226 and radium 228 have induced malignancies in the skeleton (primarily bone sarcomas) of humans. They have also induced carcinomas in the paranasal sinuses and mastoid air cells. There is no evidence that any leukemias or any other solid cancers have been induced by internally deposited radium. This paper discuses a study conducted on the dial painter population. This study made a concerted effort to verify, for each of the measured radium cases, the published values of the skeletal dose and the initial intake of radium. These were derived from body content measurements made some 40 years after the radium intake. Corrections to the assumed radium retention function resulted in a considerable number of dose changes. These changes have changed the shape of the dose response function. It now appears that the induction of bone sarcomas is a threshold process.

  19. [Changes of learning and memory function under weightlessness or simulated weightlessness].

    PubMed

    Wu, D W; Shen, X Y

    2000-12-01

    The work efficiency of astronauts has an intimate connection with the brain function state during space flight. The research results of the learning and memory mechanism of the brain in recent years were introduced. The effects of weightlessness or simulated weightlessness on brain's learning, memory, focused attention and many other higher neural activities and on the relative neural transmitters were summarized. Several research aspects were put forward in the future.

  20. A hypomagnetic field aggravates bone loss induced by hindlimb unloading in rat femurs.

    PubMed

    Jia, Bin; Xie, Li; Zheng, Qi; Yang, Peng-fei; Zhang, Wei-ju; Ding, Chong; Qian, Ai-rong; Shang, Peng

    2014-01-01

    A hypomagnetic field is an extremely weak magnetic field--it is considerably weaker than the geomagnetic field. In deep-space exploration missions, such as those involving extended stays on the moon and interplanetary travel, astronauts will experience abnormal space environments involving hypomagnetic fields and microgravity. It is known that microgravity in space causes bone loss, which results in decreased bone mineral density. However, it is unclear whether hypomagnetic fields affect the skeletal system. In the present study, we aimed to investigate the complex effects of a hypomagnetic field and microgravity on bone loss. To study the effects of hypomagnetic fields on the femoral characteristics of rats in simulated weightlessness, we established a rat model of hindlimb unloading that was exposed to a hypomagnetic field. We used a geomagnetic field-shielding chamber to generate a hypomagnetic field of <300 nT. The results show that hypomagnetic fields can exacerbate bone mineral density loss and alter femoral biomechanical characteristics in hindlimb-unloaded rats. The underlying mechanism might involve changes in biological rhythms and the concentrations of trace elements due to the hypomagnetic field, which would result in the generation of oxidative stress responses in the rat. Excessive levels of reactive oxygen species would stimulate osteoblasts to secrete receptor activator of nuclear factor-κB ligand and promote the maturation and activation of osteoclasts and thus eventually cause bone resorption.

  1. A Hypomagnetic Field Aggravates Bone Loss Induced by Hindlimb Unloading in Rat Femurs

    PubMed Central

    Jia, Bin; Xie, Li; Zheng, Qi; Yang, Peng-fei; Zhang, Wei-ju; Ding, Chong; Qian, Ai-rong; Shang, Peng

    2014-01-01

    A hypomagnetic field is an extremely weak magnetic field—it is considerably weaker than the geomagnetic field. In deep-space exploration missions, such as those involving extended stays on the moon and interplanetary travel, astronauts will experience abnormal space environments involving hypomagnetic fields and microgravity. It is known that microgravity in space causes bone loss, which results in decreased bone mineral density. However, it is unclear whether hypomagnetic fields affect the skeletal system. In the present study, we aimed to investigate the complex effects of a hypomagnetic field and microgravity on bone loss. To study the effects of hypomagnetic fields on the femoral characteristics of rats in simulated weightlessness, we established a rat model of hindlimb unloading that was exposed to a hypomagnetic field. We used a geomagnetic field-shielding chamber to generate a hypomagnetic field of <300 nT. The results show that hypomagnetic fields can exacerbate bone mineral density loss and alter femoral biomechanical characteristics in hindlimb-unloaded rats. The underlying mechanism might involve changes in biological rhythms and the concentrations of trace elements due to the hypomagnetic field, which would result in the generation of oxidative stress responses in the rat. Excessive levels of reactive oxygen species would stimulate osteoblasts to secrete receptor activator of nuclear factor-κB ligand and promote the maturation and activation of osteoclasts and thus eventually cause bone resorption. PMID:25157571

  2. 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.

  3. 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.

  4. Ion implantation induced nanotopography on titanium and bone cell adhesion

    NASA Astrophysics Data System (ADS)

    Braceras, Iñigo; Vera, Carolina; Ayerdi-Izquierdo, Ana; Muñoz, Roberto; Lorenzo, Jaione; Alvarez, Noelia; de Maeztu, Miguel Ángel

    2014-08-01

    Permanent endo-osseous implants require a fast, reliable and consistent osseointegration, i.e. intimate bonding between bone and implant, so biomechanical loads can be safely transferred. Among the parameters that affect this process, it is widely admitted that implant surface topography, surface energy and composition play an important role. Most surface treatments to improve osseointegration focus on micro-scale features, as few can effectively control the effects of the treatment at nanoscale. On the other hand, ion implantation allows controlling such nanofeatures. This study has investigated the nanotopography of titanium, as induced by different ion implantation surface treatments, its similarity with human bone tissue structure and its effect on human bone cell adhesion, as a first step in the process of osseointegration. The effect of ion implantation treatment parameters such as energy (40-80 keV), fluence (1-2 e17 ion/cm2) and ion species (Kr, Ar, Ne and Xe) on the nanotopography of medical grade titanium has been measured and assessed by AFM and contact angle. Then, in vitro tests have been performed to assess the effect of these nanotopographies on osteoblast adhesion. The results have shown that the nanostructure of bone and the studied ion implanted surfaces, without surface chemistry modification, are in the same range and that such modifications, in certain conditions, do have a statistically significant effect on bone tissue forming cell adhesion.

  5. 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

  6. Novel Resorbable and Osteoconductive Calcium Silicophosphate Scaffold Induced Bone Formation.

    PubMed

    Ros-Tárraga, Patricia; Mazón, Patricia; Rodríguez, Miguel A; Meseguer-Olmo, Luis; De Aza, Piedad N

    2016-09-20

    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.

  7. Alterations in calcium homeostasis and bone during actual and simulated space flight

    NASA Technical Reports Server (NTRS)

    Wronski, T. J.; Morey, E. R.

    1983-01-01

    Skeletal alteration in experimental animals induced by actual and simulated spaceflight are discussed, noting that the main factor contributing to bone loss in growing rats placed in orbit aboard Soviet Cosmos biosatellites appears to be diminished bone formation. Mechanical unloading is seen as the most obvious cause of bone loss in a state of weightlessness. Reference is made to a study by Roberts et al. (1981), which showed that osteoblast differentiation in the periodontal ligament of the maxilla was suppressed in rats flown in space. Since the maxilla lacks a weight-bearing function, this finding indicates that the skeletal alterations associated with orbital flight may be systemic rather than confined to weight-bearing bones. In addition, the skeletal response to simulated weightlessness may also be systemic (wronski and Morey, 1982). In suspended rats, the hindlimbs lost all weight-bearing functions, while the forelimbs maintained contact with the floor of the hypokinetic model. On this basis, it was to be expected that there would be different responses at the two skeletal sites if the observed abnormalities were due to mechanical unloading alone. The changes induced by simulated weightlessness in the proximal tibia and humerus, however, were generally comparable. This evidence for systemic skeletal responses has drawn attention to endocrine factors.

  8. Heterotopically induced bone marrow. I. Cellular composition of bone marrow derived from the heterotopic ossicles induced in mice by xenogeneic epithelia of human amnion and dog's transitional epithelium.

    PubMed

    Włodarski, K; Jakóbisiak, M

    1978-01-01

    Following heterotopic osteogenesis by implantation of xenogeneic epithelia (FL and WISH cell line, transitional epithelium of dog) in mice a biogenesis of hemopoietic tissue among induced ossicles is observed. Precursors and mature forms of all types of blood cells are found in the induced bone marrow. The concentration of lymphocytes in the induced bone marrow is higher, and that of erythropoietic cells lower as compared with orthotopic femur bone marrow. The yield of myeloid cells varied from 0.14 to 3.61 x 10(6) cells per induced bone-containing nodule.

  9. Cancer-induced bone pain: Mechanisms and models.

    PubMed

    Lozano-Ondoua, A N; Symons-Liguori, A M; Vanderah, T W

    2013-12-17

    Cancerous cells can originate in a number of different tissues such as prostate, breast and lung, but often go undetected and are non-painful. Many types of cancers have a propensity to metastasize to the bone microenvironment first. Tumor burden within the bone causes excruciating breakthrough pain with properties of ongoing pain that is inadequately managed with current analgesics. Part of this failure is due to the poor understanding of the etiology of cancer pain. Animal models of cancer-induced bone pain (CIBP) have revealed that the neurochemistry of cancer has features distinctive from other chronic pain states. For example, preclinical models of metastatic cancer often result in the positive modulation of neurotrophins, such as NGF and BDNF, that can lead to nociceptive sensitization. Preclinical cancer models also demonstrate nociceptive neuronal expression of acid-sensing receptors, such as ASIC1 and TRPV1, which respond to cancer-induced acidity within the bone. CIBP is correlated with a significant increase in pro-inflammatory mediators acting peripherally and centrally, contributing to neuronal hypersensitive states. Finally, cancer cells generate high levels of oxidative molecules that are thought to increase extracellular glutamate concentrations, thus activating primary afferent neurons. Knowledge of the unique neuro-molecular profile of cancer pain will ultimately lead to the development of novel and superior therapeutics for CIBP.

  10. NMR assessment on bone simulated under microgravity

    NASA Astrophysics Data System (ADS)

    Ni, Q.; Qin, Y.

    Introduction Microgravity-induced bone loss has been suggested to be similar to disuse-osteoporosis on Earth which constitutes a challenging public health problem No current non-destructive method can provide the microstructural changes in bone particularly on cortical bone Recently the authors have applied low field nuclear magnetic resonance NMR spin-spin relaxation technique and computational analysis method to determine the porosity pore size distribution and microdamage of cortical bone 1-3 The studies by the authors have shown that this technology can be used to characterize microstructural changes as well as bone water distribution bound and mobile water changes of weightless treated simulating a microgravity condition turkey and mouse cortical bone We further determinate that the NMR spin-spin relaxation time T 2 spectrum derived parameters can be used as descriptions of bone quality e g matrix water distribution and porosity size distributions and alone or in combination with current techniques bone mineral density measurements more accurately predict bone mechanical properties Methods underline Bone sample preparation Two kinds of animal samples were collected and prepared for designed experiments from SUNY Cortical bones of the mid-diaphyses of the ulnae of 1-year-old male turkeys were dissected from freshly slaughtered animals Eight samples were categorized from normal or control and four samples were 4-week disuse treated by functionally isolated osteotomies disuse A total of 12

  11. ACTH protects against glucocorticoid-induced osteonecrosis of bone.

    PubMed

    Zaidi, Mone; Sun, Li; Robinson, Lisa J; Tourkova, Irina L; Liu, Li; Wang, Yujuan; Zhu, Ling-Ling; Liu, Xuan; Li, Jianhua; Peng, Yuanzhen; Yang, Guozhe; Shi, Xingming; Levine, Alice; Iqbal, Jameel; Yaroslavskiy, Beatrice B; Isales, Carlos; Blair, Harry C

    2010-05-11

    We report that adrenocorticotropic hormone (ACTH) protects against osteonecrosis of the femoral head induced by depot methylprednisolone acetate (depomedrol). This therapeutic response likely arises from enhanced osteoblastic support and the stimulation of VEGF by ACTH; the latter is largely responsible for maintaining the fine vascular network that surrounds highly remodeling bone. We suggest examining the efficacy of ACTH in preventing human osteonecrosis, a devastating complication of glucocorticoid therapy.

  12. Effects of real and simulated weightlessness on the cardiac and peripheral vascular functions of humans: A review.

    PubMed

    Zhu, Hui; Wang, Hanqing; Liu, Zhiqiang

    2015-01-01

    Weightlessness is an extreme environment that can cause a series of adaptive changes in the human body. Findings from real and simulated weightlessness indicate altered cardiovascular functions, such as reduction in left ventricular (LV) mass, cardiac arrhythmia, reduced vascular tone and so on. These alterations induced by weightlessness are detrimental to the health, safety and working performance of the astronauts, therefore it is important to study the effects of weightlessness on the cardiovascular functions of humans. The cardiovascular functional alterations caused by weightlessness (including long-term spaceflight and simulated weightlessness) are briefly reviewed in terms of the cardiac and peripheral vascular functions. The alterations include: changes of shape and mass of the heart; cardiac function alterations; the cardiac arrhythmia; lower body vascular regulation and upper body vascular regulation. A series of conclusions are reported, some of which are analyzed, and a few potential directions are presented. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  13. 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.

  14. BONE FORMATION INDUCED IN MOUSE THIGH BY CULTURED HUMAN CELLS

    PubMed Central

    Anderson, H. Clarke; Coulter, P. R.

    1967-01-01

    Cultured FL human amnion cells injected intramuscularly into cortisone-conditioned mice proliferate to form discrete nodules which become surrounded by fibroblasts. Within 12 days, fibroblastic zones differentiate into cartilage which calcifies to form bone. Experiments were conducted to test the hypothesis that FL cells behave as an inductor of bone formation. In the electron microscope, FL cells were readily distinguished from surrounding fibroblasts. Transitional forms between the two cell types were not recognized. Stains for acid mucopolysaccharides emphasized the sharp boundary between metachromatic fibroblastic and cartilaginous zones and nonmetachromatic FL cells. 35S was taken up preferentially by fibroblasts and chondrocytes and then deposited extracellularly in a manner suggesting active secretion of sulfated mucopolysaccharides. FL cells showed negligible 35S utilization and secretion. FL cells, labeled in vitro with thymidine-3H, were injected and followed radioautographically, during bone formation. Nuclear label of injected FL cells did not appear in adjacent fibroblasts in quantities sufficient to indicate origin of the latter from FL cells. The minimal fibroblast nuclear labeling seen may represent reutilization of label from necrotic FL cells. It is suggested that FL cells injected into the mouse thigh induced cartilage and bone formation by host fibroblasts. PMID:4226746

  15. Bone formation induced in mouse thigh by cultured human cells.

    PubMed

    Anderson, H C; Coulter, P R

    1967-04-01

    Cultured FL human amnion cells injected intramuscularly into cortisone-conditioned mice proliferate to form discrete nodules which become surrounded by fibroblasts. Within 12 days, fibroblastic zones differentiate into cartilage which calcifies to form bone. Experiments were conducted to test the hypothesis that FL cells behave as an inductor of bone formation. In the electron microscope, FL cells were readily distinguished from surrounding fibroblasts. Transitional forms between the two cell types were not recognized. Stains for acid mucopolysaccharides emphasized the sharp boundary between metachromatic fibroblastic and cartilaginous zones and nonmetachromatic FL cells. (35)S was taken up preferentially by fibroblasts and chondrocytes and then deposited extracellularly in a manner suggesting active secretion of sulfated mucopolysaccharides. FL cells showed negligible (35)S utilization and secretion. FL cells, labeled in vitro with thymidine-(3)H, were injected and followed radioautographically, during bone formation. Nuclear label of injected FL cells did not appear in adjacent fibroblasts in quantities sufficient to indicate origin of the latter from FL cells. The minimal fibroblast nuclear labeling seen may represent reutilization of label from necrotic FL cells. It is suggested that FL cells injected into the mouse thigh induced cartilage and bone formation by host fibroblasts.

  16. Minimizing Laboratory-Induced Decay in Bone Proteomics.

    PubMed

    Procopio, Noemi; Buckley, Michael

    2017-02-03

    Proteomics methods are being increasingly used to study archaeological and palaeontological bone, assisting in species identification and phylogenetic studies as well as improving our understanding of bone diagenesis. More recently, there are developing interests in the study of post-translational modifications, some of which are potentially diagnostic of decay, but none of the previous extraction methods have been developed in light of this. To be able to record close to natural deamidation levels of samples, an extraction procedure should minimize laboratory-induced decay, such as asparagine and glutamine deamidations, which are considered most strongly related with decay and known to occur frequently with standard laboratory procedures. Here we tested numerous methods to identify an optimal approach of extracting proteins from bone while minimizing artificial decay. Using a weak acid to partially demineralize the bone sample, then subsequent incubation of the acid insoluble fraction with guanidine hydrochloride and enzymatic digestion in ammonium acetate, we observed an ∼50% reduction in deamidation while also substantially decreasing the protocol length. We propose this optimized method as appropriate for studies of archaeological, palaeontological, as well as potentially forensic investigations using proteomics where decay measurements could act as "molecular timers".

  17. 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.

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

    SciTech Connect

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

    2015-02-16

    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.

  19. Nardosinone Suppresses RANKL-Induced Osteoclastogenesis and Attenuates Lipopolysaccharide-Induced Alveolar Bone Resorption

    PubMed Central

    Niu, Chenguang; Xiao, Fei; Yuan, Keyong; Hu, XuChen; Lin, Wenzhen; Ma, Rui; Zhang, Xiaoling; Huang, Zhengwei

    2017-01-01

    Periodontitis is a chronic inflammatory disease that damages the integrity of the tooth-supporting tissues, known as the periodontium, and comprising the gingiva, periodontal ligament and alveolar bone. In this study, the effects of nardosinone (Nd) on bone were tested in a model of lipopolysaccharide (LPS)-induced alveolar bone loss, and the associated mechanisms were elucidated. Nd effectively suppressed LPS-induced alveolar bone loss and reduced osteoclast (OC) numbers in vivo. Nd suppressed receptor activator of nuclear factor-κB ligand (RANKL)-mediated OC differentiation, bone resorption, and F-actin ring formation in a dose-dependent manner. Further investigation revealed that Nd suppressed osteoclastogenesis by suppressing the ERK and JNK signaling pathways, scavenging reactive oxygen species, and suppressing the activation of PLCγ2 that consequently affects the expression and/or activity of the OC-specific transcription factors, c-Fos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). In addition, Nd significantly reduced the expression of OC-specific markers in mouse bone marrow-derived pre-OCs, including c-Fos, cathepsin K (Ctsk), VATPase d2, and Nfatc1. Collectively, these findings suggest that Nd has beneficial effects on bone, and the suppression of OC number implies that the effect is exerted directly on osteoclastogenesis. PMID:28955231

  20. Calcification preceding new bone formation induced by demineralized bone matrix gelatin.

    PubMed

    Yamashita, K; Takagi, T

    1992-03-01

    Demineralized bone matrix gelatin (BMG) was implanted into the skeletal muscle of Sprague-Dawley (S.D.) rats, and histological changes were examined 3, 5, 7, 10 and 15 days later. Before bone formation, a specific calcification process was found in most of the BMG from day 5 and 7 after implantation. The heterotopic calcified sites were not always consistent with the sites of the alkaline phosphatase activity. It was considered that this calcification progresses without any cellular components, and we distinguished this type of calcification as "acellular mineral deposition" from the calcification which occurs in new bone formation. This "acellular mineral deposition" was first observed as small spherical calcified deposits in the BMG on day 7 after implantation; these deposits then gradually grew and fused with each other. Some multinucleated cells appeared near the site of calcification on day 7 after implantation, but osteoblasts or osteoblast-like cells were scarcely observed around the calcified deposits in BMG until day 7. Vascularization was often observed near the "acellular mineral deposition" and the new bone formation. Fourier transform infrared spectroscopy showed that the calcified deposits in BMG were composed of hydroxyapatite, carbonateapatite and other calcium phosphate components, and that the first two components became prominent with time. It is believed that the "acellular mineral deposition" is due to the deposition of calcium and phosphate into the BMG by a process of heterogenic nucleation that does not involve osteoblasts or matrix vesicles. Bone formation induced by the BMG occurred after the "acellular mineral deposition." The experimental calcification shown in this paper seems a useful model for the study of biocalcification.

  1. Oral bone loss induced by mineral deficiency in a rat model: effect of a synthetic bone mineral (SBM) preparation.

    PubMed

    Mijares, Dindo; Kulkarni, Anupama; Lewis, Kanthi; Yao, Fang; Xi, Qing; Tannous, Samar; Dias, Renata; LeGeros, Racquel Z

    2012-09-01

    Osteoporosis affects the craniofacial and oral structures and has been associated with periodontal bone loss, tooth loss and reduced jaw bone mass. This study aimed to test the therapeutic efficacy of synthetic bone mineral (SBM) in minimizing alveolar bone loss induced by mineral deficiency in a rat model. SBM consists of a calcium carbonate apatite (similar to bone apatite) matrix incorporating magnesium, zinc, and fluoride ions. Thirty female Sprague Dawley rats (2 months old) were randomly distributed into 3 groups (10 rats per group): GA (control), on basic diet; GB, on mineral deficient (MD) diet; and GC, on MD+SBM. The rats were sacrificed after 3 months, the jawbones were isolated and the soft tissues removed. Bone density was determined using X-ray radiography (Faxitron); mandibular cortical width, panoramic mandibular index, and alveolar resorption degree (M/M ratio) using BioquantOsteo; and bone micro-architecture micro-computed tomography and scanning electron microscopy. Compared to control (GA), the rats on MD diet (GB) experienced significant mandibular bone loss while the rats on MD+SBM diet (GC) experienced significantly less bone loss compared to the GB group. SBM, administered orally, may have the potential as an osteoporosis therapeutic agent in minimizing or preventing alveolar bone loss induced by mineral deficiency. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Plasma viscosity elevations with simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Martin, D. G.; Convertino, V. A.; Goldwater, D.; Ferguson, E. W.; Schoomaker, E. B.

    1986-01-01

    A hypothesis correlating an increase in blood viscosity during bed rest to a decrease in aerobic capacity during simulated weightlessness is tested. Eight human subjects were studied on the sixth day of bed rest during two consecutive 10-d bed rest periods separated by a 14-d recovery interval designed to simulate the flight-layover schedule of Shuttle astronauts. Plasma viscosity and volume were measured, together with maximal aerobic capacity (VO2max). An increase in hematocrit, plasma protein, and fibrinogen concentrations was found, contributing to an elevation in plasma viscosity. VO2max decreased significantly in the first, but not the second bed rest cycle, and though many individuals exhibited a decrease in plasma volume and aerobic capacity coupled with elevated plasma viscosity, correlations between these variables were lacking. It is concluded that the decrease in VO2max observed following simulated weightlessness cannot be attributed to alterations in muscle blood flow resulting from increased blood viscosity.

  3. Plasma viscosity elevations with simulated weightlessness

    NASA Technical Reports Server (NTRS)

    Martin, D. G.; Convertino, V. A.; Goldwater, D.; Ferguson, E. W.; Schoomaker, E. B.

    1986-01-01

    A hypothesis correlating an increase in blood viscosity during bed rest to a decrease in aerobic capacity during simulated weightlessness is tested. Eight human subjects were studied on the sixth day of bed rest during two consecutive 10-d bed rest periods separated by a 14-d recovery interval designed to simulate the flight-layover schedule of Shuttle astronauts. Plasma viscosity and volume were measured, together with maximal aerobic capacity (VO2max). An increase in hematocrit, plasma protein, and fibrinogen concentrations was found, contributing to an elevation in plasma viscosity. VO2max decreased significantly in the first, but not the second bed rest cycle, and though many individuals exhibited a decrease in plasma volume and aerobic capacity coupled with elevated plasma viscosity, correlations between these variables were lacking. It is concluded that the decrease in VO2max observed following simulated weightlessness cannot be attributed to alterations in muscle blood flow resulting from increased blood viscosity.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Peptide-induced de novo bone formation after tooth extraction prevents alveolar bone loss in a murine tooth extraction model.

    PubMed

    Arai, Yuki; Aoki, Kazuhiro; Shimizu, Yasuhiro; Tabata, Yasuhiko; Ono, Takashi; Murali, Ramachandran; Mise-Omata, Setsuko; Wakabayashi, Noriyuki

    2016-07-05

    Tooth extraction causes bone resorption of the alveolar bone volume. Although recombinant human bone morphogenetic protein 2 (rhBMP-2) markedly promotes de novo bone formation after tooth extraction, the application of high-dose rhBMP-2 may induce side effects, such as swelling, seroma, and an increased cancer risk. Therefore, reduction of the necessary dose of rhBMP-2 which can still obtain sufficient bone mass is necessary by developing a new osteogenic reagent. Recently, we showed that the systemic administration of OP3-4 peptide, which was originally designed as a bone resorption inhibitor, had osteogenic ability both in vitro and in vivo. This study evaluated the ability of the local application of OP3-4 peptide to promote bone formation in a murine tooth extraction model with a very low-dose of BMP. The mandibular incisor was extracted from 10-week-old C57BL6/J male mice and a gelatin hydrogel containing rhBMP-2 with or without OP3-4 peptide (BMP/OP3-4) was applied to the socket of the incisor. Bone formation inside the socket was examined radiologically and histologically at 21 days after the extraction. The BMP/OP3-4-group showed significant bone formation inside the mandibular extraction socket compared to the gelatin-hydrogel-carrier-control group or rhBMP-2-applied group. The BMP/OP3-4-applied mice showed a lower reduction of alveolar bone and fewer osteoclast numbers, suggesting that the newly formed bone inside the socket may prevent resorption of the cortical bone around the extraction socket. Our data revealed that OP3-4 peptide promotes BMP-mediated bone formation inside the extraction socket of mandibular bone, resulting in preservation from the loss of alveolar bone.

  10. 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

  11. 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

  12. Proteoglycans in bones of streptozotocin-induced diabetic rats.

    PubMed

    Perez, C; Suarez, C; Kofoed, J

    1990-01-01

    Insulin seems to regulate the biosynthesis of proteoglycans in some tissues such as growth plate and glomeruli. The present investigation was undertaken to assess the ex vivo influence of insulin on proteoglycan metabolism in bones. Mandible and femur bones were used. Xiphoid cartilage was used as a control tissue of high glycosaminoglycan content. Diabetes was induced by 0.12 mg/g b.w. streptozotocin in male Sprague-Dawley rats, a number of which was treated with insulin (1 I.U./100 g b.w.) for 6 days. As compared with control animals, diabetic rats exhibited a decreased [35S]sulfate uptake as well as a shift to the right in Sephacryl S-500 chromatography. In addition, they showed lower density of proteoglycans in sucrose gradient and shorter glycosaminoglycan side chains in Sephadex G-200 chromatography. These changes were partly reversed by insulin.

  13. 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.

  14. 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.

  15. 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

  16. [Contribution of weightlessness in respiratory physiology].

    PubMed

    Paiva, M

    2006-01-01

    Before the first experiences performed in space, it was already known that the lung and the chest are sensitive to gravity. In the vertical position, the weight of the lung causes top to bottom differences in ventilation, perfusion and gas exchange. Furthermore, the functional residual capacity is position dependent. Thoracic mechanics allows for the explanation of large modifications observed in weightlessness, such as a 40% increase of abdominal respiration. We review few results obtained in weightless conditions and will focus on those where the results were contradicted by predictions. For example, the classical indexes of ventilation inhomogeneity derived from the single and multiple inert gas washout are not sensitive to weightless conditions. These results led to the demonstration of the dependence of these indexes on the structure of the alveolar zone of the lung and found an application on the follow up of lung transplanted subjects and smokers. Contrary to predictions, lung tissue volume decreases after one week in space. The study of aerosol deposition has shown that particles of diameter between 0,5 and one micron diameter penetrate deeper than predicted in the lungs.

  17. Lysophosphatidic acid-induced chemotaxis of bone cells.

    SciTech Connect

    Karagiosis, Sue A.; Masiello, Lisa M.; Bollinger, Nikki; Karin, Norm J.

    2006-07-01

    Lysophosphatidic acid (LPA) is a platelet-derived bioactive lipid that is postulated to regulate wound healing. LPA activates G protein-coupled receptors to induce Ca2+ signaling in MC3T3-E1 pre-osteoblasts, and is a potent chemotactic stimulus for these cells. Since bone fracture healing requires the migration of osteoblast progenitors, we postulate that LPA is among the factors that stimulate bone repair. UMR 106-01 cells, which express a more mature osteoblastic phenotype than MC3T3-E1 cells, did not migrate in response to LPA, although they express LPA receptors and exhibit LPA-induced Ca2+ signals. This suggests that LPA differentially induces pre-osteoblast chemotaxis, consistent with our hypothesis that LPA stimulates the motility of osteoblast progenitors during bone healing. LPA-stimulated MC3T3-E1 cells exhibit striking changes in morphology and F-actin architecture, and phosphatidylinositol-3 kinase (PI3K) is required for motility-associated cytoskeletal rearrangements in many cell types. We found a dose-dependent reduction in LPA-induced osteoblast migration when cells also were treated with the PI3K inhibitor, LY294002. Treatment of many cell types with LPA is associated with an autocrine/paracrine transactivation of the EGF receptor (EGFR) via shedding of surface-tethered EGFR ligands, a phenomenon often required for LPA-induced chemotaxis. MC3T3-E1 cells express multiple EGFR ligands (epigen, epiregulin, HB-EGF and amphiregulin) and migrated in response to EGF. However, while EGF-stimulated motility in MC3T3-E1 cells was blocked by an EGFR inhibitor, there was no significant effect on LPA-induced chemotaxis. Activation of MAP kinases is a hallmark of EGFR-mediated signaling, and EGF treatment of MC3T3-E1 cells led to a strong stimulation of ERK1/2 kinase. In contrast, LPA induced only a minor elevation in ERK activity. Thus, it is likely that the increase in ERK activity by LPA is related to cell proliferation associated with lipid treatment. We

  18. Bone Regeneration Induced by Bone Porcine Block with Bone Marrow Stromal Stem Cells in a Minipig Model of Mandibular “Critical Size” Defect

    PubMed Central

    Di Benedetto, Adriana; Cozzolino, Valerio; Podaliri Vulpiani, Michele; Grano, Maria; Kalemaj, Zamira; Grassi, Felice Roberto

    2017-01-01

    Introduction. Adding stem cells to biodegradable scaffolds to enhance bone regeneration is a valuable option. Different kinds of stem cells with osteoblastic activity were tested, such as bone marrow stromal stem cells (BMSSCs). Aim. To assess a correct protocol for osteogenic stem cell differentiation, so BMSSCs were seeded on a bone porcine block (BPB). Materials and Methods. Bone marrow from six minipigs was extracted from tibiae and humeri and treated to isolate BMSSCs. After seeding on BPB, critical-size defects were created on each mandible of the minipigs and implanted with BPB and BPB/BMSSCs. After three months, histomorphometric analysis was performed. Results. Histomorphometric analysis provided percentages of the three groups. Tissues present in control defects were 23 ± 2% lamellar bone, 28 ± 1% woven bone, and 56 ± 4% marrow spaces; in BPB defects were 20 ± 5% BPB, 32 ± 2% lamellar bone, 24 ± 1% woven bone, and 28 ± 2% marrow spaces; in BPB/BMSSCs defects were 17 ± 4% BPB/BMSSCs, 42 ± 2% lamellar bone, 12 ± 1% woven bone, and 22 ± 3% marrow spaces. Conclusion. BPB used as a scaffold to induce bone regeneration may benefit from the addition of BDPSCs in the tissue-engineered constructs. PMID:28553359

  19. [Recent progress of weightlessness impact on the eye].

    PubMed

    Yang, Zhenfei; Zhu, Siquan

    2015-04-01

    The impact of weightlessness on the eye becomes more and more important with the increase of human space exploration. There is significant elevation in cephalad fluid and ophthalmic vein when individuals are in the state of weightlessness. In this paper, we review adverse effects in weightlessness station, including: retina damage (disc edema, choroidal folds, cotton wool spots, nerve fiber layer thickening), visual function decrease (decreased near vision, decreased ability of acquire and fixate on the target), and intraocular pressure increase.

  20. The traumatic bone: trauma-induced heterotopic ossification.

    PubMed

    Dey, Devaveena; Wheatley, Benjamin M; Cholok, David; Agarwal, Shailesh; Yu, Paul B; Levi, Benjamin; Davis, Thomas A

    2017-08-01

    Heterotopic ossification (HO) is a common occurrence after multiple forms of extensive trauma. These include arthroplasties, traumatic brain and spinal cord injuries, extensive burns in the civilian setting, and combat-related extremity injuries in the battlefield. Irrespective of the form of trauma, heterotopic bone is typically endochondral in structure and is laid down via a cartilaginous matrix. Once formed, the heterotopic bone typically needs to be excised surgically, which may result in wound healing complications, in addition to a risk of recurrence. Refinements of existing diagnostic modalities, like micro- and nano-CT are being adapted toward early intervention. Trauma-induced HO is a consequence of aberrant wound healing, systemic and local immune system activation, infections, extensive vascularization, and innervation. This intricate molecular crosstalk culminates in activation of stem cells that initiate heterotopic endochondral ossification. Development of animal models recapitulating the unique traumatic injuries has greatly facilitated the mechanistic understanding of trauma-induced HO. These same models also serve as powerful tools to test the efficacy of small molecules which specifically target the molecular pathways underlying ectopic ossification. This review summarizes the recent advances in the molecular understanding, diagnostic and treatment modalities in the field of trauma-induced HO. Published by Elsevier Inc.

  1. Proteomic analysis of pulmonary tissue in tail-suspended rats under simulated weightlessness.

    PubMed

    Wang, Junfeng; Liu, Changting; Li, Tianzhi; Wang, Yang; Wang, Delong

    2012-09-18

    Weightlessness affects lung function and even causes certain damages to pulmonary tissue. This study used rat tail-suspension model to simulate the physiological effects of weightlessness and investigate the alterations of lung proteome, to reveal the mechanism of lung injury under weightlessness condition. Twenty male Sprague-Dawley rats were randomly divided into two groups: tail-suspended and control. Protein samples from pulmonary tissue of tail-suspended and control groups were separated by two-dimensional (2D) gel electrophoresis and analyzed with ImageMaster 2D elite software. Differentially expressed proteins were identified by high definition mass spectrometry (HDMS) in combination with database searching. Seventeen differentially expressed proteins were identified, among which 13 proteins were upregulated, and four proteins downregulated. The functions of these identified proteins can be classified into six classes related to: metabolism, oxidative stress, cellular functions, cytoskeletal proteins, signal tranduction, and protein degradation. They are mainly related to cellular energy metabolism, stress and inflammatory response, cell injury and repair, intracellular signal transduction, and other cellular functions, playing important roles in weightlessness-induced lung injury. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. 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.

  3. Prefabrication of vascularized bone flap induced by recombinant human bone morphogenetic protein 2 (rhBMP-2).

    PubMed

    Alam, M I; Asahina, I; Seto, I; Oda, M; Enomoto, S

    2003-10-01

    An experimental model for the prefabrication of a vascularized bone flap was developed in this study. To form vascularized bone in the desired configuration and to increase the survival rate of the grafted bone, a muscle vascularized pedicle (MVP) was transformed into vascularized bone by the inducer recombinant human bone morphogenetic protein 2 (rhBMP-2). The muscle flap (8 x 8 mm) raised on saphenous vessels in the rat thigh was sandwiched between same-size collagen (Terudermis) sheets in the presence or absence of impregnated 25 microg of rhBMP-2 for the experimental group and the control group, respectively. The flaps were harvested 1, 2 and 3 weeks postoperatively. Bone transformation was detected by gross examination, radiology, and histologic testing. No evidence of muscle tissue transformation was found in control flaps, whereas all of the experimental flaps produced new bone. Saphenous vessels were observed to supply the new bone upon harvesting, and the newly formed vascularized bone showed good configuration with shape of the Terudermis sheet. This study indicates that this model of effective bone reconstruction could be potentially applied in a therapeutic setting.

  4. Segmental Bone Defect Treated With the Induced Membrane Technique.

    PubMed

    Konda, Sanjit R; Gage, Mark; Fisher, Nina; Egol, Kenneth A

    2017-08-01

    Posttraumatic bone defects in the setting of severe open injuries of the lower extremity present a significant challenge for orthopaedic trauma surgeons. The induced membrane technique, also known as the Masquelet technique, has been shown to be generally successful in achieving bony union. This video demonstrates the use of the Masquelet technique for a large (18 cm) femoral defect. The Masquelet technique is a 2-stage process. The first stage involves debridement of all devitalized tissue, using open reduction and internal fixation, and placement of a cement spacer with or without antibiotics. In the second stage, which is performed at least 6 weeks after the first, the spacer is removed and the resulting void is filled with bone graft. This surgical case video reviews the relevant patient injury presentation, initial management, and indications for the Masquelet technique. The second stage of the Masquelet technique is featured in this video. The Masquelet technique is a generally reliable method for treating large segmental bone defects. In addition, this relatively simple technique is suitable for both infected and noninfected cases.

  5. Sleep deprivation induces abnormal bone metabolism in temporomandibular joint

    PubMed Central

    Geng, Wei; Wu, Gaoyi; Huang, Fei; Zhu, Yong; Nie, Jia; He, Yuhong; Chen, Lei

    2015-01-01

    Background: The purpose of this study was to explore the effect of experimental sleep deprivation (SD) on the temporomandibular joint (TMJ) of rats and the possible mechanism related to abnormal bone metabolism. Material and methods: SD was induced by a modified multiple platform method and assessed by serum adrenocorticotropic hormone (ACTH) level. TMJs were detached and stained with hematoxylin and eosin (H&E). Expression of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) was evaluated by quantitative reverse transcription polymerase chain reaction, H&E staining, immunohistochemical staining and enzyme linked immunosorbent assay. Results: Compared with controls, SD significantly increased serum ACTH, indicating that the SD model was successful. In the SD group, H&E staining revealed greater vessel hyperplasia in the synovial membrane and thicker hypertrophic layers in condylar cartilages. Compared with controls, RNA and protein expression of the inflammatory factors IL-1β and TNF-α and the bone metabolism-related factor RANKL increased in condylar cartilage in the SD group, whereas OPG and the OPG/RANKL ratio decreased. Immunohistochemical staining revealed that OPG/RANKL immunopositive cells were mainly located in hypertrophic layers. Conclusions: These results suggest that sleep deprivation might play an important role in the occurrence and development of temporomandibular disorders, which may occur through abnormal secretion of inflammatory and bone metabolism-related factors. PMID:25785010

  6. 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.

  7. Swimming velocity of Paramecium under the conditions of weightlessness.

    PubMed

    Hemmersbach-Krause, R; Briegleb, W; Vogel, K; Hader, D P

    1993-10-01

    During the 6 min-lasting "free-fall conditions" (4 x 10(-6) g) of the parabolic flight of a sounding rocket Paramecium aurelia cells showed an increase of 7.5 % in their mean swimming velocity. A detailed analysis revealed that the kinetic response was transient: after 3 min the velocity decreased to the speed of the former horizontal swimming at 1 g. Control experiments simulating the influence of vibration and hypergravity during launch of the rocket lead to the conclusion that the increase of the velocity during the parabolic flight was exclusively induced by the transition to 0 g. An increased velocity was also observed under the condition of simulated weightlessness on a fast-rotating clinostat microscope.

  8. Metal melting, joining, and alloying under weightlessness. [on Skylab

    NASA Technical Reports Server (NTRS)

    Snyder, R. S.

    1976-01-01

    During the Skylab mission experiments were conducted concerning the influence of weightlessness on molten metals and the solidification process. It was found that the absence of gravity-induced thermal convection and sedimentation modified the properties of the bulk melt. A metals melting experiment was conducted to study the behavior of metal melted by an electron beam and to evaluate the feasibility of joining metals in space. An exothermic brazing experiment investigated the spreading, mixing, and capillary flow of molten braze material. The containerless melting and solidification of small samples of several metals was studied in another experiment. A description is also given of a study of the directional solidification of solid solution alloys.

  9. Depression induces bone loss through stimulation of the sympathetic nervous system

    PubMed Central

    Yirmiya, Raz; Goshen, Inbal; Bajayo, Alon; Kreisel, Tirzah; Feldman, Sharon; Tam, Joseph; Trembovler, Victoria; Csernus, Valér; Shohami, Esther; Bab, Itai

    2006-01-01

    Major depression is associated with low bone mass and increased incidence of osteoporotic fractures. However, causality between depression and bone loss has not been established. Here, we show that mice subjected to chronic mild stress (CMS), an established model of depression in rodents, display behavioral depression accompanied by impaired bone mass and structure, as portrayed by decreases in trabecular bone volume density, trabecular number, and trabecular connectivity density assessed in the distal femoral metaphysis and L3 vertebral body. Bone remodeling analysis revealed that the CMS-induced skeletal deficiency is accompanied by restrained bone formation resulting from reduced osteoblast number. Antidepressant therapy, which prevents the behavioral responses to CMS, completely inhibits the decrease in bone formation and markedly attenuates the CMS-induced bone loss. The depression-triggered bone loss is associated with a substantial increase in bone norepinephrine levels and can be blocked by the β-adrenergic antagonist propranolol, suggesting that the sympathetic nervous system mediates the skeletal effects of stress-induced depression. These results define a linkage among depression, excessive adrenergic activity, and reduced bone formation, thus demonstrating an interaction among behavioral responses, the brain, and the skeleton, which leads to impaired bone structure. Together with the common occurrence of depression and bone loss in the aging population, the present data implicate depression as a potential major risk factor for osteoporosis and the associated increase in fracture incidence. PMID:17075068

  10. Delayed Donor Bone Marrow Infusion Induces Liver Transplant Tolerance.

    PubMed

    Xie, Yan; Wu, Yang; Xin, Kang; Wang, Jiao-Jing; Xu, Hong; Ildstad, Suzanne T; Leventhal, Joseph; Yang, Guang-Yu; Zhang, Zheng; Levitsky, Josh

    2017-05-01

    Nonmyeloablative conditioning followed by donor bone marrow infusion (BMI) to induce tolerance has not been robustly tested in liver transplantation (LT) and may be unsafe at the time of LT. We hypothesized T cell-depleted BMI is effective in inducing tolerance when delayed after LT, resulting in potentially safer future clinical applications. Nonimmunosuppressed syngeneic (Lewis to Lewis) and allogeneic (ACI to Lewis) rat LT transplants were initially performed as controls. Three experimental allogeneic LT groups were treated with tacrolimus (TAC) for 3 to 4 weeks and then underwent: (1) TAC withdrawal alone; (2) nonmyeloablative conditioning (anti-αβTCR mAb + total body irradiation [300 cGy]) followed by TAC withdrawal; (3) Nonmyeloablative conditioning + donor BMI (100 × 10 T cell-depleted bone marrow cells) followed by TAC withdrawal. All group 1 recipients developed chronic rejection. Group 2 had long-term survival but impaired liver function and high donor-specific antibody (DSA) levels. In contrast, group 3 (conditioning + BMI) had long-term TAC-free survival with preserved liver function and histology, high mixed chimerism and blood/liver/spleen CD4 + CD25 + Foxp3+ regulatory T cells, and low DSA titers, similar to syngeneic grafts. While donor-specific tolerance was observed post-BMI, graft-versus-host disease was not. These results support that donor-specific tolerance can be achieved with BMI even when delayed after LT and this tolerance correlates with increased mixed chimerism, regulatory T cell generation, and diminished DSA.

  11. 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.

  12. 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

  13. Modes of action associated with uranium induced adverse effects in bone function and development.

    PubMed

    Arzuaga, Xabier; Gehlhaus, Martin; Strong, Jamie

    2015-07-16

    Uranium, a naturally occurring element used in military and industrial applications, accumulates in the skeletal system of animals and humans. Evidence from animal and in-vitro studies demonstrates that uranium exposure is associated with alterations in normal bone functions. The available studies suggest that upon absorption uranium directly affects bone development and maintenance by inhibiting osteoblast differentiation and normal functions, and indirectly by disrupting renal production of Vitamin D. Animal studies also provide evidence for increased susceptibility to uranium-induced bone toxicity during early life stages. The objective of this review is to provide a summary of uranium-induced bone toxicity and the potential mechanisms by which uranium can interfere with bone development and promote fragility. Since normal Vitamin D production and osteoblast functions are essential for bone growth and maintenance, young individuals and the elderly may represent potentially susceptible populations to uranium-induced bone damage.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. Sudden infant death syndrome: near-weightlessness and delayed neural transformation.

    PubMed

    Reid, G M; Tervit, H M

    1996-04-01

    Dilation of the pulmonary arteries and increased pulmonary blood volume are recorded in sudden infant death syndrome and in infants living at low barometric pressures (high altitude). Low barometric pressure leads to chronic alveolar hypoxia (1,2). There is diversion and loss of body-fluid under conditions of microgravity (near-weightlessness) encountered in human space-travel and prolonged bedrest (3). The condition mimics shock and oligemia (4,5). The human neonate has underdeveloped postural mechanisms and low muscle-power. A transformation begins at about two months of age, which enables the human infant to adapt to the extrauterine environment (6). The neonate resembles the space traveller who, in a near-weightlessness antigravity environment, develops baroreceptor incompetence, visceral and venous congestion and oliguria. The low birthweight infant displays many of the disorders of the space traveller, viz. poor circulation, high blood-glucose, insulin resistance, weak muscles, slow gut absorption and bone demineralization (7-10). These conditions are virtually identical with the internal adjustments the body makes on lying down (negative gravity or near-weightlessness). We discuss the similarities of sudden infant death syndrome to low barometric pressure environment, orthostatic intolerance, the Pickwickian syndrome and X disease.

  19. [Effect of a Chinese herbal prescription on collagen I in rat's femur under simulated weightlessness].

    PubMed

    Hu, Su-min; Zhou, Peng; Fu, Qian; Yang, Jia-jia; Gao, Xue-min

    2010-02-01

    To investigate the effect of a Chinese herbal prescription on collagen I in rat's femur under simulated weightlessness. Thirty Wistar rats were randomly divided into 3 groups: blank control group (10 rats), tail suspension group (TS, 10 rats), TS with Chinese medicine group (10 rats). Rats in TS with Chinese medicine group took a Chinese herbal prescription (contains Radix Rehmanniae Praeparata, Radix Achyranthis Bidentatae, Radix Astragali, Radix Angelicae Sinensis, Concha Ostreae prepared by acetic acid)by oral administration. After 1 week adaption and 3 weeks tail suspending, rat's left femur was colleced, and collagen I in femur neck was detected by immunohistochemical method. Counts and integral optical density (IOD) of collagen I coloration decreased significantly in TS group (P < 0.001), but no significant change in TS with Chinese medicine group (P > 0.05), as compared with control group. Generation of collagen I become weaken under simulated weightlessness, while the Chinese herbal prescription is effective to prevent the change, thus biochemistry environment of bone calcium deposition may be improved by this Chinese herbal prescription under simulated weightlessness.

  20. Bone scintigraphy of severe hypercalcemia following simvastatin induced rhabdomyolysis

    PubMed Central

    Mirza, Zubair B.; Hu, Sophia; Amorosa, Louis F.

    2016-01-01

    Summary Simvastatin induced rhabdomyolysis with renal failure is a well reported clinical entity with hyperkalemia recognized as a life threatening risk. The risk of delayed hypercalcemia during the recovery of renal function is not well appreciated as this varies in severity and can be caused by multiple mechanisms. We present a patient with high dose simvastatin induced rhabdomyolysis leading to late onset of severe hypercalcemia due to calcium phosphate deposition in muscles diagnosed by distinctive bone scintigraphy. A 60-year-old Asian male was admitted to the hospital for profound weakness one week following the initiation of simvastatin 80 mg daily post myocardial infarction. His clinical course was complicated by contrast nephropathy. One week later, he developed progressive weakness in all his extremities and inability to raise his head and eat. Simvastatin was discontinued at this point. CPK elevation to greater than 425,000 U was found, consistent with rhabdomyolysis. He became oliguric requiring hemodialysis. Muscle biopsy showed severe muscle necrosis and type 2 fiber atrophy. One month later, he developed hypercalcemia with suppressed intact PTH and 1, 25(OH) D levels. Whole body bone scintigraphy showed calcium phosphate deposition throughout his musculature. His calcium levels normalized in 1 week on hemodialysis. This patient’s experience illustrates the marked risk of delayed severe hypercalcemia from rhabdomyolysis due to dissolution of myocellular calcium phosphate deposits. It also provides an opportunity to review the different mechanisms of hypercalcemia especially in statin induced rhabdomyolysis. Recognition of this phenomenon is critical for appropriate follow up and treatment of such patients. PMID:28228795

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

    PubMed

    Herlin, Maria; Finnilä, Mikko A J; Zioupos, Peter; Aula, Antti; Risteli, Juha; Miettinen, Hanna M; Jämsä, Timo; Tuukkanen, Juha; Korkalainen, Merja; Håkansson, Helen; Viluksela, Matti

    2013-11-15

    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(-/-)) and wild-type (Ahr(+/+)) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200μg/kgbw. Bones were examined with micro-computed tomography, nanoindentation and biomechanical testing. Serum levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr(+/+) 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(-/-) mice displayed a slightly modified bone phenotype as compared with untreated Ahr(+/+) mice, while TCDD exposure caused only a few changes in bones of Ahr(-/-) 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(+/+) mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. © 2013.

  2. New Mechanism of Bone Cancer Pain: Tumor Tissue-Derived Endogenous Formaldehyde Induced Bone Cancer Pain via TRPV1 Activation.

    PubMed

    Wan, You

    2016-01-01

    In recent years, our serial investigations focused on the role of cancer cells-derived endogenous formaldehyde in bone cancer pain. We found that cancer cells produced formaldehyde through demethylation process by serine hydroxymethyltransferase (SHMT1 and SHMT2) and lysine-specific histone demethylase 1 (LSD1). When the cancer cells metastasized into bone marrow, the elevated endogenous formaldehyde induced bone cancer pain through activation on the transient receptor potential vanilloid subfamily member 1 (TRPV1) in the peripheral nerve fibers. More interestingly, TRPV1 expressions in the peripheral fibers were upregulated by the local insulin-like growth factor I (IGF-I) produced by the activated osteoblasts. In conclusion, tumor tissue-derived endogenous formaldehyde induced bone cancer pain via TRPV1 activation.

  3. 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.

  4. 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.

  5. Alfacalcidol versus plain vitamin D in inflammation induced bone loss.

    PubMed

    Scharla, Stephan H; Schacht, Erich; Lempert, Uta G

    2005-09-01

    Inflammatory diseases lead to systemic osteoporosis. Causal factors include increased circulating concentrations of inflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), glucocorticoid medication, and reduced physical activity. In addition, disturbances of vitamin D metabolism play an important role for the development of inflammation induced osteoporosis. Therefore, D-hormone analogs offer an important treatment option. 1,25-dihydroxyvitamin D (D-hormone) prevented bone loss in the rat model of inflammation mediated osteopenia and in an arthritis model. One explanation is that animals and humans with inflammatory diseases exhibit markedly reduced circulating concentrations of D-hormone, partly the result of inhibition of renal 1-alpha-hydroxylase by TNF-alpha. In addition, the number of vitamin D receptors is reduced by glucocorticoids. Moreover, D-hormone has pleiotropic effects not only on calcium homoeostasis but also on muscle (improving power), the nervous system, and the immune system. D-hormone inhibits the release of cytokines (IL-1, IL-6, TNF-alpha) from macrophages and stimulates osteoprotegerin secretion in vitro and improves arthritis in animal models. This article reviews the interaction between inflammatory disease and vitamin D metabolism, summarizes the rationale for the therapeutic use of alfacalcidol, and provides recent data from controlled clinical trials comparing the effect of alfacalcidol versus plain vitamin D in secondary osteoporosis. Alfacalcidol, but not plain vitamin D, has pleiotropic effects improving bone and muscle metabolism and clinical symptoms in patients with rheumatoid arthritis.

  6. Chlorpromazine-induced liver and bone marrow granulomas associated with agranulocytosis.

    PubMed

    Ben-Yehuda, A; Bloom, A; Lijovetzky, G; Flusser, D; Tur-Kaspa, R

    1990-08-01

    Chlorpromazine-induced liver damage is usually manifested by intrahepatic cholestasis. Hypoplastic bone marrow associated with agranulocytosis is a well-known side effect of chlorpromazine treatment. A 35-year-old woman with liver and bone marrow granulomas associated with agranulocytosis induced by chlorpromazine treatment is described.

  7. Bone Microenvironment Specific Roles of ITAM Adapter Signaling during Bone Remodeling Induced by Acute Estrogen-Deficiency

    PubMed Central

    Wu, Yalei; Torchia, James; Yao, Wei; Lane, Nancy E.; Lanier, Lewis L.; Nakamura, Mary C.; Humphrey, Mary Beth

    2007-01-01

    Immunoreceptor tyrosine-based activation motif (ITAM) signaling mediated by DAP12 or Fcε receptor Iγ chain (FcRγ) have been shown to be critical for osteoclast differentiation and maturation under normal physiological conditions. Their function in pathological conditions is unknown. We studied the role of ITAM signaling during rapid bone remodeling induced by acute estrogen-deficiency in wild-type (WT), DAP12-deficient (DAP12-/-), FcRγ-deficient (FcRγ-/-) and double-deficient (DAP12-/-FcRγ-/-) mice. Six weeks after ovariectomy (OVX), DAP12-/-FcRγ-/- mice showed resistance to lumbar vertebral body (LVB) trabecular bone loss, while WT, DAP12-/- and FcRγ-/- mice had significant LVB bone loss. In contrast, all ITAM adapter-deficient mice responded to OVX with bone loss in both femur and tibia of approximately 40%, relative to basal bone volumes. Only WT mice developed significant cortical bone loss after OVX. In vitro studies showed microenvironmental changes induced by OVX are indispensable for enhanced osteoclast formation and function. Cytokine changes, including TGFβ and TNFα, were able to induce osteoclastogenesis independent of RANKL in BMMs from WT but not DAP12-/- and DAP12-/-FcRγ-/- mice. FSH stimulated RANKL-induced osteoclast differentiation from BMMs in WT, but not DAP12-/- and DAP12-/-FcRγ-/- mice. Our study demonstrates that although ITAM adapter signaling is critical for normal bone remodeling, estrogen-deficiency induces an ITAM adapter-independent bypass mechanism allowing for enhanced osteoclastogenesis and activation in specific bony microenvironments. PMID:17611621

  8. 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…

  9. 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…

  10. 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

  11. Effects of weightlessness on body composition in the rat.

    PubMed

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

    1983-03-01

    Five male rats were exposed to 18.5 days of weightlessness in the Soviet mission COSMOS 1129 (flight group) and killed after reentry. They were immediately dissected into three major body subdivisions: musculoskeletal system, skin, and pooled viscera analyzed for fat, water, solids, and six elements. These results, expressed as percentages of the fat-free body or its components, were compared with two groups of terrestrial controls: one subjected to a flight simulation in a spacecraft mock-up and the other under standard vivarium conditions. Relative to the control groups the flight group showed 1) a reduced fraction of total body water, 2) a net shift of body water from skin to viscera, 3) a marked diminution in fraction of extracellular water in the fat-free body, 4) a marked reduction in fraction of bone mineral, 5) no change in the quantity of stored fat or adrenal masses, and 6) a net increase in total muscle mass as indicated by total body creatine, protein, and body cell mass.

  12. Associated among endocrine, inflammatory, and bone markers, body composition and weight loss induced bone loss

    USDA-ARS?s Scientific Manuscript database

    Weight loss reduces co-¬morbidities of obesity but decreases bone mass. Our aims were to determine whether adequate dairy intake could prevent weight loss related bone loss and to evaluate the contribution of energy-related hormones and inflammatory markers to bone metabolism. Overweight and obese w...

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

    SciTech Connect

    Herlin, Maria; Finnilä, Mikko A.J.; Zioupos, Peter; Aula, Antti; Risteli, Juha; Miettinen, Hanna M.; Jämsä, Timo; Tuukkanen, Juha; Korkalainen, Merja; Håkansson, Helen; Viluksela, Matti

    2013-11-15

    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. Serum 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 ablation

  14. Tail-suspended mice lacking calponin H1 experience decreased bone loss.

    PubMed

    Yotsumoto, Naoki; Takeoka, Michiko; Yokoyama, Minesuke

    2010-07-01

    Calponin h1 (CNh1) is an actin-binding protein originally isolated from vascular smooth muscle and has been reported to suppress bone formation. We are therefore curious how CNh1 is involved in bone loss that is caused by space flight in microgravity. We assessed the effects of tail suspension (TS) in C57BL/6J wild (CN+/+) and CNh1-deleted (CN-/-) mice to elucidate the role of CNh1 in bone loss under weightless conditions. Bone mineral density (BMD) of tibiae was measured by single energy X-ray absorptiometry, and bone volume fraction (BV/TV), mineral apposition rate (MAR), and bone formation rate (BFR/BS) were measured by bone histomorphometry. BMD, BV/TV, MAR, and BFR/BS were lower in CN+/+ mice with TS than in those without. In the CN-/- group, however, the decrease in each of these parameters by TS was ameliorated. Decreases in serum osteocalcin levels by TS in CN+/+ mice were attenuated in CN-/- mice. Furthermore, urinary deoxypyridinolin (DPD), an indicator of bone resorption, was increased in CN+/+ mice following TS, but not in CN-/- mice. In transfection experiments, the degree of induction of bone formation markers, alkaline phosphatase (ALP) activity and bone morphogenetic protein (BMP)-4 mRNA expression, under stimulation with BMP-2, was lower in MC3T3-E1 mouse osteoblast-like cells expressing CNh1 than that in mock transfected cells. Notably, the BMP-2-induced ALP activity was decreased by CNh1 expression, which was partially rescued by treatment with the Rho kinase inhibitor Y27632. Taken together, these results indicate that CNh1 is responsible for weightlessness-induced bone loss in part through Rho signaling pathway.

  15. Parathyroid Hormone (PTH)–Induced Bone Gain Is Blunted in SOST Overexpressing and Deficient Mice

    PubMed Central

    Kramer, Ina; Loots, Gabriela G; Studer, Anne; Keller, Hansjoerg; Kneissel, Michaela

    2010-01-01

    Intermittent parathyroid hormone (PTH) treatment is a potent bone anabolic principle that suppresses expression of the bone formation inhibitor Sost. We addressed the relevance of Sost suppression for PTH-induced bone anabolism in vivo using mice with altered Sost gene dosage. Six-month-old Sost overexpressing and 2-month-old Sost deficient male mice and their wild-type littermates were subjected to daily injections of 100 µg/kg PTH(1–34) or vehicle for a 2-month period. A follow-up study was performed in Sost deficient mice using 40 and 80 µg/kg PTH(1–34). Animals were sacrificed 4 hours after the final PTH administration and Sost expression in long bone diaphyses was determined by qPCR. Bone changes were analyzed in vivo in the distal femur metaphysis by pQCT and ex vivo in the tibia and lumbar spine by DXA. Detailed ex vivo analyses of the femur were performed by pQCT, µCT, and histomorphometry. Overexpression of Sost resulted in osteopenia and Sost deletion in high bone mass. As shown before, PTH suppressed Sost in wild-type mice. PTH treatment induced substantial increases in bone mineral density, content, and cortical thickness and in aging wild-type mice also led to cancellous bone gain owing to amplified bone formation rates. PTH-induced bone gain was blunted at all doses and skeletal sites in Sost overexpressing and deficient mice owing to attenuated bone formation rates, whereas bone resorption was not different from that in PTH-treated wild-type controls. These data suggest that suppression of the bone formation inhibitor Sost by intermittent PTH treatment contributes to PTH bone anabolism. © 2010 American Society for Bone and Mineral Research PMID:19594304

  16. Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice.

    PubMed

    Govey, Peter M; Zhang, Yue; Donahue, Henry J

    2016-01-01

    Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone's capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure.

  17. Regulation of breast cancer-induced bone lesions by β-catenin protein signaling.

    PubMed

    Chen, Yan; Shi, Heidi Y; Stock, Stuart R; Stern, Paula H; Zhang, Ming

    2011-12-09

    Breast cancer patients have an extremely high rate of bone metastases. Morphological analyses of the bones in most of the patients have revealed the mixed bone lesions, comprising both osteolytic and osteoblastic elements. β-Catenin plays a key role in both embryonic skeletogenesis and postnatal bone regeneration. Although this pathway is also involved in many bone malignancy, such as osteosarcoma and prostate cancer-induced bone metastases, its regulation of breast cancer bone metastases remains unknown. Here, we provide evidence that the β-catenin signaling pathway has a significant impact on the bone lesion phenotype. In this study, we established a novel mouse model of mixed bone lesions using intratibial injection of TM40D-MB cells, a breast cancer cell line that is highly metastatic to bone. We found that both upstream and downstream molecules of the β-catenin pathway are up-regulated in TM40D-MB cells compared with non-bone metastatic TM40D cells. TM40D-MB cells also have a higher T cell factor (TCF) reporter activity than TM40D cells. Inactivation of β-catenin in TM40D-MB cells through expression of a dominant negative TCF4 not only increases osteoclast differentiation in a tumor-bone co-culture system and enhances osteolytic bone destruction in mice, but also inhibits osteoblast differentiation. Surprisingly, although tumor cells overexpressing β-catenin did induce a slight increase of osteoblast differentiation in vitro, these cells display a minimal effect on osteoblastic bone formation in mice. These data collectively demonstrate that β-catenin acts as an important determinant in mixed bone lesions, especially in controlling osteoblastic effect within tumor-harboring bone environment.

  18. Regulation of Breast Cancer-induced Bone Lesions by β-Catenin Protein Signaling*

    PubMed Central

    Chen, Yan; Shi, Heidi Y.; Stock, Stuart R.; Stern, Paula H.; Zhang, Ming

    2011-01-01

    Breast cancer patients have an extremely high rate of bone metastases. Morphological analyses of the bones in most of the patients have revealed the mixed bone lesions, comprising both osteolytic and osteoblastic elements. β-Catenin plays a key role in both embryonic skeletogenesis and postnatal bone regeneration. Although this pathway is also involved in many bone malignancy, such as osteosarcoma and prostate cancer-induced bone metastases, its regulation of breast cancer bone metastases remains unknown. Here, we provide evidence that the β-catenin signaling pathway has a significant impact on the bone lesion phenotype. In this study, we established a novel mouse model of mixed bone lesions using intratibial injection of TM40D-MB cells, a breast cancer cell line that is highly metastatic to bone. We found that both upstream and downstream molecules of the β-catenin pathway are up-regulated in TM40D-MB cells compared with non-bone metastatic TM40D cells. TM40D-MB cells also have a higher T cell factor (TCF) reporter activity than TM40D cells. Inactivation of β-catenin in TM40D-MB cells through expression of a dominant negative TCF4 not only increases osteoclast differentiation in a tumor-bone co-culture system and enhances osteolytic bone destruction in mice, but also inhibits osteoblast differentiation. Surprisingly, although tumor cells overexpressing β-catenin did induce a slight increase of osteoblast differentiation in vitro, these cells display a minimal effect on osteoblastic bone formation in mice. These data collectively demonstrate that β-catenin acts as an important determinant in mixed bone lesions, especially in controlling osteoblastic effect within tumor-harboring bone environment. PMID:22009747

  19. 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.

  20. 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.

  1. Induced membrane for treatment of critical sized bone defect: a review of experimental and clinical experiences.

    PubMed

    Aurégan, Jean-Charles; Bégué, Thierry

    2014-09-01

    The purpose of this study was to review experimental and clinical experiences about the use of an induced membrane to address critical bone size defect of the limbs. From a review of published experimental and clinical data and from our clinical experience, we present the key data about the use of an induced membrane to address critical bone size defect of the limbs. After reviewing the concept of critical sized bone defect, we present the different indications of an induced membrane, the key points of the surgical technique and the strategy of bone grafting given the indication, localization and importance of the critical sized bone defect. Finally, we discuss the perspective of the use of an induced membrane with various bone substitutes. The use of an induced membrane to treat critical sized bone defects of the limbs is a simple, reliable and reproducible technique. Certain technical steps should be pointed out and observed with great caution in order to avoid any pitfalls. This technique will probably be a key step for facilitating bone inclusion of new bone substitutes proposed by recent bioengineering.

  2. Fracture induced mobilization and incorporation of bone marrow-derived endothelial progenitor cells for bone healing.

    PubMed

    Matsumoto, Tomoyuki; Mifune, Yutaka; Kawamoto, Atsuhiko; Kuroda, Ryosuke; Shoji, Taro; Iwasaki, Hiroto; Suzuki, Takahiro; Oyamada, Akira; Horii, Miki; Yokoyama, Ayumi; Nishimura, Hiromi; Lee, Sang Yang; Miwa, Masahiko; Doita, Minoru; Kurosaka, Masahiro; Asahara, Takayuki

    2008-04-01

    We recently reported that systemic administration of peripheral blood (PB) CD34+ cells, an endothelial progenitor cell (EPC)-enriched population, contributed to fracture healing via vasculogenesis/angiogenesis. However, pathophysiological role of EPCs in fracture healing process has not been fully clarified. Therefore, we investigated the hypothesis whether mobilization and incorporation of bone marrow (BM)-derived EPCs may play a pivotal role in appropriate fracture healing. Serial examinations of Laser doppler perfusion imaging and histological capillary density revealed that neovascularization activity at the fracture site peaked at day 7 post-fracture, the early phase of endochondral ossifification. Fluorescence-activated cell sorting (FACS) analysis demonstrated that the frequency of BM cKit+Sca1+Lineage- (Lin-) cells and PB Sca1+Lin- cells, which are EPC-enriched fractions, significantly increased post-fracture. The Sca1+ EPC-derived vasuculogenesis at the fracture site was confirmed by double immunohistochemistry for CD31 and Sca1. BM transplantation from transgenic donors expressing LacZ transcriptionally regulated by endothelial cell-specific Tie-2 promoter into wild type also provided direct evidence that EPCs contributing to enhanced neovascularization at the fracture site were specifically derived from BM. Animal model of systemic administration of PB Sca1+Lin- Green Fluorescent Protein (GFP)+ cells further confirmed incorporation of the mobilized EPCs into the fracture site for fracture healing. These findings indicate that fracture may induce mobilization of EPCs from BM to PB and recruitment of the mobilized EPCs into fracture sites, thereby augment neovascularization during the process of bone healing. EPCs may play an essential role in fracture healing by promoting a favorable environment through neovascularization in damaged skeletal tissue.

  3. Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice

    PubMed Central

    Govey, Peter M.; Zhang, Yue; Donahue, Henry J.

    2016-01-01

    Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure. PMID:27936104

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

    PubMed

    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

    2006-06-01

    Activating receptor activator of NF-kappaB (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-alpha-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-alpha 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.

  5. Surgically-induced mouse models in the study of bone regeneration: Current models and future directions

    PubMed Central

    Ning, Bin; Zhao, Yunpeng; Buza, John A.; Li, Wei; Wang, Wenzhao; Jia, Tanghong

    2017-01-01

    Bone regeneration has been extensively studied over the past several decades. The surgically-induced mouse model is the key animal model for studying bone regeneration, of the various research strategies used. These mouse models mimic the trauma and recovery processes in vivo and serve as carriers for tissue engineering and gene modification to test various therapies or associated genes in bone regeneration. The present review introduces a classification of surgically induced mouse models in bone regeneration, evaluates the application and value of these models and discusses the potential development of further innovations in this field in the future. PMID:28138711

  6. Bone

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  7. Changes in osteoblastic activity due to simulated weightless conditions

    NASA Technical Reports Server (NTRS)

    Doty, S. B.; Morey-Holton, E. R.

    1982-01-01

    Using histochemistry and electron microscopy, the reduced bone formation which occurs in the hypokinetic, orthostatically treated adult rat has been studied. The two major changes noted occurred in the osteoblast population, indicated by a reduced alkaline phosphatase activity and reduced numbers of gap junctions between cells. These results were most noticeable in the periosteum and endosteum of the long bones. Changes in osteoblasts lining the surface of trabecular bone were not as evident. These results indicate that the cells lining the surfaces of weight bearing bones are most affected by hypokinesia and this reduction in cellular activity may be a mechanically induced effect.

  8. Islet in weightlessness: biological experiments on board COSMOS 1129 satellite

    SciTech Connect

    Zhuk, Y.

    1980-09-01

    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.

  9. 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.

  10. Effect of weightlessness on lymphocyte proliferation

    NASA Technical Reports Server (NTRS)

    Cogoli, A.

    1981-01-01

    An experiment to study the effect of weightlessness on lymphocyte proliferation to detect possible alteration of the cells responsible for the immune response during long-duration space flights is described. Human lymphocytes in culture medium will be delivered shortly before launch in an incubator which will be kept at 37C. Mitogen will be added to the culture. A control without mitogen will be run in parallel. After 70 hours of incubation, radioactive thymidine will be added. After two hours, cellular activity will be stopped by fixation and incubator power switched off. Later, the amount of incorporated thymidine will be determined and the cell morphology and the distribution of cell organelles will be investigated.

  11. Effect of weightlessness on lymphocyte proliferation

    NASA Technical Reports Server (NTRS)

    Cogoli, A.

    1981-01-01

    An experiment to study the effect of weightlessness on lymphocyte proliferation to detect possible alteration of the cells responsible for the immune response during long-duration space flights is described. Human lymphocytes in culture medium will be delivered shortly before launch in an incubator which will be kept at 37C. Mitogen will be added to the culture. A control without mitogen will be run in parallel. After 70 hours of incubation, radioactive thymidine will be added. After two hours, cellular activity will be stopped by fixation and incubator power switched off. Later, the amount of incorporated thymidine will be determined and the cell morphology and the distribution of cell organelles will be investigated.

  12. Sperm motility under conditions of weightlessness.

    PubMed

    Engelmann, U; Krassnigg, F; Schill, W B

    1992-01-01

    The aim of this study was to determine the differences in motility of frozen and thawed bull spermatozoa under conditions of weightlessness compared with ground conditions. The tests were performed within a series of scientific and technologic experiments under microgravity using sounding rockets in the Technologische Experimente unter Schwerelosigkeit (TEXUS) program launched in Kiruna, North Sweden. Using a computerized sperm motility analyzer, significant differences were found in sperm motility under microgravity compared with sperm under gravitational conditions on earth. Computer analysis showed alterations in straight line and curvilinear velocity, as well as in linearity values. The amount of progressively motile spermatozoa, including all spermatozoa with a velocity > 20 microns/second, increased significantly from 24% +/- 9.5% in the reference test to 49% +/- 7.6% in the microgravity test. In conclusion, there is strong evidence that gravity influences sperm motility.

  13. Hemodynamic studies of the legs under weightlessness

    NASA Technical Reports Server (NTRS)

    Thornton, W. E.; Hoffler, G. W.

    1974-01-01

    Following exposure to weightlessness, alterations in the return of blood from the legs play a crucial role in orthostatic tolerance and may be an important factor in work tolerance. To investigate some of the hemodynamic mechansism involved, an experiment was performed on the Skylab 3 and Skylab 4 missions to study arterial blood flow, venous compliance, and muscle pumping of blood. Skylab 4 results indicated that the most likely cause of increased blood flow was an increase in cardiac output secondary to increased central venous pressure caused by blood redistribution. Changes in venous compliance are thought to be primarily changes in somatic musculature which is postulated to primarily determine venous compliance of the legs. This was also thought to be demonstrated by the changes in muscle pumping. It is thought that these compliance changes, when taken with the decreased blood volume; provide a basis for the changes seen in orthostatic tolerance, work capacity and lower body negative pressure response.

  14. Loss of Prostaglandin E2-induced Extra Cortical Bone After its Withdrawal in Rats

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Ke, Hua Zhu; Li, Xiao Jian

    1992-01-01

    The object of this study was to determine the fate of PGE2-(Prostaglandin E2) induced new cortical bone mass after withdrawal of PGE2 administration. Seven-month-old male Sprague-Dawley rats were given subcutaneous injections of 1, 3 and 6 mg PGE2/kg/day for 60 days and then withdrawn for 60 and 120 days (on/off treatment). Histomorphometric analyses were performed on double-fluorescent-labeled undecalcified tibial shaft sections (proximal to the tibiofibular junction). In a previous report we showed that after 60, 120 and 180 days of daily PGE2 (on)treatment, a new steady state was achieved marked by increased total bone area (+16%, +25% and +34% with 1, 3 and 6 mg PGE2/kg/day) when compared to age-matched controls. The continuous PGE2 treatment stimulated periosteal and endocortical lamellar bone formation, activated endocortical woven trabecular bone formation and intracortical bone resorption. These responses increased cortical bone mass since the bone formation exceeded bone resorption. The current study showed that after withdrawal of PGE2 for 60 and 120 days, the extra endocortical bone, which was induced by the first 60-days treatment, was resorbed, but the new subperiosteal bone persisted resulting in a tibial shaft with larger cross sectional and marrow areas. Despite that, there was still the same amount of bone mass in these shafts as in age-related controls. A new steady state was achieved after 60 days of withdrawal, in which the bone mass and bone formation activity approximated that of age-related controls. It was concluded that maintaining the extra PGE2-induced cortical bone mass depends on continuous daily administration of PGE2.

  15. Loss of Prostaglandin E2-induced Extra Cortical Bone after its Withdrawal in Rats

    NASA Technical Reports Server (NTRS)

    Jee, Webster S. S.; Ke, Hua Zhu; Li, Xiao Jian

    1992-01-01

    The object of this study was to determine the fate of PGE2-induced new cortical bone mass after withdrawal of PGE2 administration. Seven-month-old male Sprague-Dawley rats were given subcutaneous injections of 1, 3 and 6 mg PGE2/kg/day for 60 days and then withdrawn for 60 and 120 days (on/off treatment). Histomorphometric analyses were performed on double-fluorescent-labeled undecalcified tibial shaft sections (proximal to the tibiofibular junction). In a previous report we showed that after 60, 120 and 180 days of daily PGE2 (on)treatment, a new steady state was achieved marked by increased total bone area (+ 16%, +25% and + 34% with 1, 3 and 6 mg PGE2/kg/day) when compared to age-matched controls. The continuous PGE2 treatment stimulated periosteal and endocortical lamellar bone formation, activated endocortical woven trabecular bone formation and intracortical bone resorption. These responses increased cortical bone mass since the bone formation exceeded bone resorption. The current study showed that after withdrawal of PGE2 for 60 and 120 days, the extra endocortical bone, which was induced by the first 60-days treatment, was resorbed, but the new subperiosteal bone persisted resulting in a tibial shaft with larger cross sectional and marrow areas. Despite that, there was still the same amount of bone mass in these shafts as in age-related controls. A new steady state was achieved after 60 days of withdrawal, in which the bone mass and bone formation activity approximated that of age-related controls. It was concluded that maintaining the extra PGE2-induced cortical bone mass depends on continuous daily administration of PGE2.

  16. 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

  17. Bone tissue engineering via human induced pluripotent, umbilical cord and bone marrow mesenchymal stem cells in rat cranium.

    PubMed

    Wang, Ping; Liu, Xian; Zhao, Liang; Weir, Michael D; Sun, Jirun; Chen, Wenchuan; Man, Yi; Xu, Hockin H K

    2015-05-01

    Human induced pluripotent stem cells (hiPSCs) are an exciting cell source with great potential for tissue engineering. Human bone marrow mesenchymal stem cells (hBMSCs) have been used in clinics but are limited by several disadvantages, hence alternative sources of MSCs such as umbilical cord MSCs (hUCMSCs) are being investigated. However, there has been no report comparing hiPSCs, hUCMSCs and hBMSCs for bone regeneration. The objectives of this pilot study were to investigate hiPSCs, hUCMSCs and hBMSCs for bone tissue engineering, and compare their bone regeneration via seeding on biofunctionalized macroporous calcium phosphate cement (CPC) in rat cranial defects. For all three types of cells, approximately 90% of the cells remained alive on CPC scaffolds. Osteogenic genes were up-regulated, and mineral synthesis by cells increased with time in vitro for all three types of cells. The new bone area fractions at 12weeks (mean±sd; n=6) were (30.4±5.8)%, (27.4±9.7)% and (22.6±4.7)% in hiPSC-MSC-CPC, hUCMSC-CPC and hBMSC-CPC respectively, compared to (11.0±6.3)% for control (p<0.05). No significant differences were detected among the three types of stem cells (p>0.1). New blood vessel density was higher in cell-seeded groups than control (p<0.05). De novo bone formation and participation by implanted cells was confirmed via immunohistochemical staining. In conclusion, (1) hiPSCs, hUCMSCs and hBMSCs greatly enhanced bone regeneration, more than doubling the new bone amount of cell-free CPC control; (2) hiPSC-MSCs and hUCMSCs represented viable alternatives to hBMSCs; (3) biofunctionalized macroporous CPC-stem cell constructs had a robust capacity for bone regeneration.

  18. Directly auto-transplanted mesenchymal stem cells induce bone formation in a ceramic bone substitute in an ectopic sheep model

    PubMed Central

    Boos, Anja M; Loew, Johanna S; Deschler, Gloria; Arkudas, Andreas; Bleiziffer, Oliver; Gulle, Heinz; Dragu, Adrian; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P

    2011-01-01

    Abstract Bone tissue engineering approaches increasingly focus on the use of mesenchymal stem cells (MSC). In most animal transplantation models MSC are isolated and expanded before auto cell transplantation which might be critical for clinical application in the future. Hence this study compares the potential of directly auto-transplanted versus in vitro expanded MSC with or without bone morphogenetic protein-2 (BMP-2) to induce bone formation in a large volume ceramic bone substitute in the sheep model. MSC were isolated from bone marrow aspirates and directly auto-transplanted or expanded in vitro and characterized using fluorescence activated cell sorting (FACS) and RT-PCR analysis before subcutaneous implantation in combination with BMP-2 and β-tricalcium phosphate/hydroxyapatite (β-TCP/HA) granules. Constructs were explanted after 1 to 12 weeks followed by histological and RT-PCR evaluation. Sheep MSC were CD29+, CD44+ and CD166+ after selection by Ficoll gradient centrifugation, while directly auto-transplanted MSC-populations expressed CD29 and CD166 at lower levels. Both, directly auto-transplanted and expanded MSC, were constantly proliferating and had a decreasing apoptosis over time in vivo. Directly auto-transplanted MSC led to de novo bone formation in a heterotopic sheep model using a β-TCP/HA matrix comparable to the application of 60 μg/ml BMP-2 only or implantation of expanded MSC. Bone matrix proteins were up-regulated in constructs following direct auto-transplantation and in expanded MSC as well as in BMP-2 constructs. Up-regulation was detected using immunohistology methods and RT-PCR. Dense vascularization was demonstrated by CD31 immunohistology staining in all three groups. Ectopic bone could be generated using directly auto-transplanted or expanded MSC with β-TCP/HA granules alone. Hence BMP-2 stimulation might become dispensable in the future, thus providing an attractive, clinically feasible approach to bone tissue engineering. PMID

  19. Directly auto-transplanted mesenchymal stem cells induce bone formation in a ceramic bone substitute in an ectopic sheep model.

    PubMed

    Boos, Anja M; Loew, Johanna S; Deschler, Gloria; Arkudas, Andreas; Bleiziffer, Oliver; Gulle, Heinz; Dragu, Adrian; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P

    2011-06-01

    Bone tissue engineering approaches increasingly focus on the use of mesenchymal stem cells (MSC). In most animal transplantation models MSC are isolated and expanded before auto cell transplantation which might be critical for clinical application in the future. Hence this study compares the potential of directly auto-transplanted versus in vitro expanded MSC with or without bone morphogenetic protein-2 (BMP-2) to induce bone formation in a large volume ceramic bone substitute in the sheep model. MSC were isolated from bone marrow aspirates and directly auto-transplanted or expanded in vitro and characterized using fluorescence activated cell sorting (FACS) and RT-PCR analysis before subcutaneous implantation in combination with BMP-2 and β-tricalcium phosphate/hydroxyapatite (β-TCP/HA) granules. Constructs were explanted after 1 to 12 weeks followed by histological and RT-PCR evaluation. Sheep MSC were CD29(+), CD44(+) and CD166(+) after selection by Ficoll gradient centrifugation, while directly auto-transplanted MSC-populations expressed CD29 and CD166 at lower levels. Both, directly auto-transplanted and expanded MSC, were constantly proliferating and had a decreasing apoptosis over time in vivo. Directly auto-transplanted MSC led to de novo bone formation in a heterotopic sheep model using a β-TCP/HA matrix comparable to the application of 60 μg/ml BMP-2 only or implantation of expanded MSC. Bone matrix proteins were up-regulated in constructs following direct auto-transplantation and in expanded MSC as well as in BMP-2 constructs. Up-regulation was detected using immunohistology methods and RT-PCR. Dense vascularization was demonstrated by CD31 immunohistology staining in all three groups. Ectopic bone could be generated using directly auto-transplanted or expanded MSC with β-TCP/HA granules alone. Hence BMP-2 stimulation might become dispensable in the future, thus providing an attractive, clinically feasible approach to bone tissue engineering.

  20. Low-frequency vibration treatment of bone marrow stromal cells induces bone repair in vivo

    PubMed Central

    He, Shengwei; Zhao, Wenzhi; Zhang, Lu; Mi, Lidong; Du, Guangyu; Sun, Chuanxiu; Sun, Xuegang

    2017-01-01

    Objective(s): To study the effect of low-frequency vibration on bone marrow stromal cell differentiation and potential bone repair in vivo. Materials and Methods: Forty New Zealand rabbits were randomly divided into five groups with eight rabbits in each group. For each group, bone defects were generated in the left humerus of four rabbits, and in the right humerus of the other four rabbits. To test differentiation, bones were isolated and demineralized, supplemented with bone marrow stromal cells, and implanted into humerus bone defects. Varying frequencies of vibration (0, 12.5, 25, 50, and 100 Hz) were applied to each group for 30 min each day for four weeks. When the bone defects integrated, they were then removed for histological examination. mRNA transcript levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor κ-B ligan, and pre-collagen type 1 α were measured. Results: Humeri implanted with bone marrow stromal cells displayed elevated callus levels and wider, more prevalent, and denser trabeculae following treatment at 25 and 50 Hz. The mRNA levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor κ-B ligand, and pre-collagen type 1 α were also markedly higher following 25 and 50 Hz treatment. Conclusion: Low frequency (25–50 Hz) vibration in vivo can promote bone marrow stromal cell differentiation and repair bone injury. PMID:28133520

  1. Low-frequency vibration treatment of bone marrow stromal cells induces bone repair in vivo.

    PubMed

    He, Shengwei; Zhao, Wenzhi; Zhang, Lu; Mi, Lidong; Du, Guangyu; Sun, Chuanxiu; Sun, Xuegang

    2017-01-01

    To study the effect of low-frequency vibration on bone marrow stromal cell differentiation and potential bone repair in vivo. Forty New Zealand rabbits were randomly divided into five groups with eight rabbits in each group. For each group, bone defects were generated in the left humerus of four rabbits, and in the right humerus of the other four rabbits. To test differentiation, bones were isolated and demineralized, supplemented with bone marrow stromal cells, and implanted into humerus bone defects. Varying frequencies of vibration (0, 12.5, 25, 50, and 100 Hz) were applied to each group for 30 min each day for four weeks. When the bone defects integrated, they were then removed for histological examination. mRNA transcript levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor κ-B ligan, and pre-collagen type 1 α were measured. Humeri implanted with bone marrow stromal cells displayed elevated callus levels and wider, more prevalent, and denser trabeculae following treatment at 25 and 50 Hz. The mRNA levels of runt-related transcription factor 2, osteoprotegerin, receptor activator of nuclear factor κ-B ligand, and pre-collagen type 1 α were also markedly higher following 25 and 50 Hz treatment. Low frequency (25-50 Hz) vibration in vivo can promote bone marrow stromal cell differentiation and repair bone injury.

  2. MR imaging of therapy-induced changes of bone marrow

    PubMed Central

    Henning, Tobias; Link, Thomas M.

    2006-01-01

    MR imaging of bone marrow infiltration by hematologic malignancies provides non-invasive assays of bone marrow cellularity and vascularity to supplement the information provided by bone marrow biopsies. This article will review the MR imaging findings of bone marrow infiltration by hematologic malignancies with special focus on treatment effects. MR imaging findings of the bone marrow after radiation therapy and chemotherapy will be described. In addition, changes in bone marrow microcirculation and metabolism after anti-angiogenesis treatment will be reviewed. Finally, new specific imaging techniques for the depiction of regulatory events that control blood vessel growth and cell proliferation will be discussed. Future developments are directed to yield comprehensive information about bone marrow structure, function and microenvironment. PMID:17021706

  3. 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.

  4. 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.

  5. Streptozotocin-induced diabetes in rats diminishes the size of the osteoprogenitor pool in bone marrow.

    PubMed

    Weinberg, E; Maymon, T; Moses, O; Weinreb, M

    2014-01-01

    Bone formation is reduced in animals and humans with type 1 diabetes, leading to lower bone mass and inferior osseous healing. Since bone formation greatly depends on the recruitment of osteoblasts from their bone marrow precursors, we tested whether experimental type 1 diabetes in rats diminishes the number of bone marrow osteoprogenitors. Diabetes was induced by 65 mg/kg streptozotocin and after 4 weeks, femoral bone marrow cells were extracted and cultured. Tibia and femur were frozen for further analysis. The size of the osteoprogenitor pool in bone marrow of diabetic rats was significantly reduced, as evidenced by (1) lower (~35 %) fraction of adherent stromal cells (at 24h of culture); (2) lower (20-25%) alkaline phosphatase activity at 10 days of culture; and (3) lower (~40 %) mineralized nodule formation at 21 days of culture. Administration of insulin to hyperglycemic rats normalized glycemia and abrogated most of the decline in ex vivo mineralized nodule formation. Apoptotic cells in tibial bone marrow were more numerous in hyperglycemic rats. Also, the levels of malondialdehyde (indicator of oxidative stress) were significantly elevated in bone marrow of diabetic animals. Experimental type 1 diabetes diminishes the osteoprogenitor population in bone marrow, possibly due to increased apoptosis via Oxidative Stress. Reduced number of osteoprogenitors is likely to impair osteoblastogenesis, bone formation, and bone healing in diabetic animals. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. A combination of methotrexate and zoledronic acid prevents bone erosions and systemic bone mass loss in collagen induced arthritis

    PubMed Central

    2009-01-01

    Introduction Osteoclasts play a key role in the pathogenesis of bone erosion and systemic bone mass loss during rheumatoid arthritis (RA). In this study, we aimed to determine the effect of methotrexate (MTX) and zoledronic acid (ZA), used alone or in combination, on osteoclast-mediated bone erosions and systemic bone mass loss in a rat model of collagen induced arthritis (CIA). We hypothesized that MTX and ZA could have an additive effect to prevent both bone erosion and systemic bone loss. Methods Arthritis was induced in 64 female Sprague-Dawley rats. After the clinical onset of CIA, rats were assigned to treatment with MTX (1 mg/kg/week), ZA (100 μg/kg twice weekly), both treatments at the same regimens, or vehicle. Arthritis score and paw thickness were recorded twice weekly. The rats were sacrificed on D28 and hind paws were removed for radiographic, histological and immunohistochemical analysis. The effects of treatments on osteoclastogenesis were determined by Tartrate resistant acid phosphatase (TRAP) staining. Micro-CT of the tibia was carried out for histomorphometric analysis. Bone mass density was evaluated by densitometry. Results MTX significantly decreased the severity of CIA, whereas ZA slightly exacerbated it. When these two drugs were used in combination, MTX prevented the pro-inflammatory effect of ZA. The combination of ZA with MTX was more effective than MTX alone for reducing structural joint damage with a dramatic decrease of osteoclasts' number in the eroded joints. However, MTX alone also significantly reduced the number of osteoclasts and the number of CD68+ mononuclear cells. ZA alone, or ZA with MTX, significantly increased the systemic bone mass density measured by densitometry and bone volume on histomorphometric analysis. Conclusions A combination of MTX and ZA prevented both bone erosion and systemic bone loss in a rat model of arthritis. Both treatments independently decreased the number of osteoclasts in the eroded joint. However

  7. 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. .

  8. Mechanisms of Radiation-Induced Bone Loss and Effects on Prostate Cancer Bone Metastases

    DTIC Science & Technology

    2013-06-01

    and in vivo bone imaging [months 6-10]. b. Determine apoptosis of bone cells (OT, OB & OC) by quantifying TUNEL staining [months 6-10]. Animal...Zoledronic acid will be used as positive control for inhibition of apoptosis and also inhibition of resorption [month 10]. c. Perform in vivo bone imaging ...described and presented in Task 3. Task 5: Image calvarial osteocytes in real-time after single dose exposure of 2 Gy [months 6-12] A single dose of

  9. Diet-induced weight loss: the effect of dietary protein on bone.

    PubMed

    Tang, Minghua; O'Connor, Lauren E; Campbell, Wayne W

    2014-01-01

    High-protein (>30% of energy from protein or >1.2 g/kg/day) and moderately high-protein (22% to 29% of energy from protein or 1.0 to 1.2 g/kg/day) diets are popular for weight loss, but the effect of dietary protein on bone during weight loss is not well understood. Protein may help preserve bone mass during weight loss by stimulating insulin-like growth factor 1, a potent bone anabolism stimulator, and increasing intestinal calcium absorption. Protein-induced acidity is considered to have minimal effect on bone resorption in adults with normal kidney function. Both the quantity and predominant source of protein influence changes in bone with diet-induced weight loss. Higher-protein, high-dairy diets may help attenuate bone loss during weight loss.

  10. 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.

  11. Expression of PGK1 By Prostate Cancer Cells Induces Bone Formation

    PubMed Central

    Jung, Younghun; Shiozawa, Yusuke; Wang, Jianhua; Wang, Jingcheng; Wang, Zhuo; Pedersen, Elisabeth A.; Lee, Clara H.; Hall, Christopher L.; Hogg, Phillip J.; Krebsbach, Paul H.; Keller, Evan T.; Taichman, Russell S.

    2009-01-01

    Prostate cancer (PCa) is one of the solid tumors that metastasize to the bone. Once there, the phenotype of the bone lesions becomes depends upon the balance between osteoblastogenesis and osteoclastogenesis. We previously reported that over-expression of phosphoglycerate kinase 1 (PGK1) in PCa cell lines enhanced bone formation at the metastatic site in vivo. Here, the role of PGK1 in the bone formation was further explored. We demonstrate that PCa-derived PGK1 induces osteoblastic differentiation of bone marrow stromal cells. We also found that PGK1 secreted by PCa inhibits osteoclastogenesis. Finally, the expression levels of the bone specific markers in PCa cell themselves were higher in cells over expressing PGK1 than controls. Together, these data suggest that PGK1 secreted by PCa regulates bone formation at the metastatic site by increasing osteoblastic activity, decreasing osteoclastic function, and expressing an osteoblastic phenotype by PCa themselves. PMID:19825988

  12. 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.

  13. 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.

  14. Diagram of Weightlessness effects at cell level aboard Gemini Spacecraft

    NASA Technical Reports Server (NTRS)

    1965-01-01

    Diagram of experimemt on weightlessness effects at cell level aboard Gemini spacecraft. The round canister (top) shows the experiment package. The bottom portion of the diagram shows the breakdown of the experiment package, and how the experiment will proceed.

  15. 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.

  16. 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.

  17. Daily parathyroid hormone administration enhances bone turnover and preserves bone structure after severe immobilization-induced bone loss.

    PubMed

    Harlow, Lauren; Sahbani, Karim; Nyman, Jeffry S; Cardozo, Christopher P; Bauman, William A; Tawfeek, Hesham A

    2017-09-01

    Immobilization, as a result of motor-complete spinal cord injury (SCI), is associated with severe osteoporosis. Whether parathyroid hormone (PTH) administration would reduce bone loss after SCI remains unclear. Thus, female mice underwent sham or surgery to produce complete spinal cord transection. PTH (80 μg/kg) or vehicle was injected subcutaneously (SC) daily starting on the day of surgery and continued for 35 days. Isolated tibias and femurs were examined by microcomputed tomography scanning (micro-CT) and histology and serum markers of bone turnover were measured. Micro-CT analysis of tibial metaphysis revealed that the SCI-vehicle animals exhibited 49% reduction in fractional trabecular bone volume and 18% in trabecular thickness compared to sham-vehicle controls. SCI-vehicle animals also had 15% lower femoral cortical thickness and 16% higher cortical porosity than sham-vehicle counterparts. Interestingly, PTH administration to SCI animals restored 78% of bone volume, increased connectivity to 366%, and lowered structure model index by 10% compared to sham-vehicle animals. PTH further favorably attenuated femoral cortical bone loss to 5% and prevented the SCI-associated cortical porosity. Histomorphometry evaluation of femurs of SCI-vehicle animals demonstrated a marked 49% and 38% decline in osteoblast and osteoclast number, respectively, and 35% reduction in bone formation rate. In contrast, SCI-PTH animals showed preserved osteoblast and osteoclast numbers and enhanced bone formation rate. Furthermore, SCI-PTH animals had higher levels of bone formation and resorption markers than either SCI- or sham-vehicle groups. Collectively, these findings suggest that intermittent PTH receptor activation is an effective therapeutic strategy to preserve bone integrity after severe immobilization. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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

    SciTech Connect

    Yoshikawa, H.; Masuhara, K.; Takaoka, K.; Ono, K.; Tanaka, H.; Seino, Y.

    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 Hyp 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.

  19. 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.

  20. [The effect of weightlessness on amphibians. The ultimobranchial body].

    PubMed

    Besova, N V; Savelev, S V

    1993-07-01

    C-cells of Pleurodeles waltilii ultimobranchial bodies (ULT) were studied after a series of two-week spaceflight on the biosatellites. It was shown that under conditions of weightlessness the hypertrophy of ULT and calcitonin secretion activation occurred. Calcitonin accumulated into the ULT which resulted in metaplasia of the surrounding tissues, organ calcification and C-cells death. After landing, the regenerative processes which were not manifest in weightlessness occurred. They were similar to those of embryonic development of the organ.

  1. Statistical analysis of vibration-induced bone and joint damages.

    PubMed

    Schenk, T

    1995-01-01

    Vibration-induced damages to bones and joints are still occupational diseases with insufficient knowledge about causing and moderating factors and resulting damages. For a better understanding of these relationships also retrospective analyses of already acknowledged occupational diseases may be used. Already recorded detailed data for 203 in 1970 to 1979 acknowledged occupational diseases in the building industry and the building material industry of the GDR are the basis for the here described investigations. The data were gathered from the original documents of the occupational diseases and scaled in cooperation of an industrial engineer and an industrial physician. For the purposes of this investigations the data are to distinguish between data which describe the conditions of the work place (e.g. material, tools and posture), the exposure parameters (e.g. beginning of exposure and latency period) and the disease (e.g. anamnestical and radiological data). These data are treated for the use with sophisticated computerized statistical methods. The following analyses were carried out. Investigation of the connections between the several characteristics, which describe the occupational disease (health damages), including the comparison of the severity of the damages at the individual joints. Investigation of the side dependence of the damages. Investigation of the influence of the age at the beginning of the exposure and the age at the acknowledgement of the occupational disease and herewith of the exposure duration. Investigation of the effect of different occupational and exposure conditions.

  2. Radiation-induced sarcomas of bone: factors that affect outcome.

    PubMed

    Kalra, S; Grimer, R J; Spooner, D; Carter, S R; Tillman, R M; Abudu, A

    2007-06-01

    We identified 42 patients who presented to our unit over a 27-year period with a secondary radiation-induced sarcoma of bone. We reviewed patient, tumour and treatment factors to identify those that affected outcome. The mean age of the patients at presentation was 45.6 years (10 to 84) and the mean latent interval between radiotherapy and diagnosis of the sarcoma was 17 years (4 to 50). The median dose of radiotherapy given was estimated at 50 Gy (mean 49; 20 to 66). There was no correlation between radiation dose and the time to development of a sarcoma. The pelvis was the most commonly affected site (14 patients (33%)). Breast cancer was the most common primary tumour (eight patients; 19%). Metastases were present at diagnosis of the sarcoma in nine patients (21.4%). Osteosarcoma was the most common diagnosis and occurred in 30 cases (71.4%). Treatment was by surgery and chemotherapy when indicated: 30 patients (71.4%) were treated with the intention to cure. The survival rate was 41% at five years for those treated with the intention to cure but in those treated palliatively the mean survival was only 8.8 months (2 to 22), and all had died by two years. The only factor found to be significant for survival was the ability to completely resect the tumour. Limb sarcomas had a better prognosis (66% survival at five years) than central ones (12% survival at five years) (p = 0.009). Radiation-induced sarcoma is a rare complication of radiotherapy. Both surgical and oncological treatment is likely to be compromised by the treatment received previously by the patient.

  3. Simulated weightlessness affects the expression and activity of neuronal nitric oxide synthase in the rat brain

    PubMed Central

    Yoon, Nara; Na, Kiyong; Kim, Hyun-Soo

    2017-01-01

    Spaceflight induces pathophysiological alterations in various organs. To study pathophysiological adaptations to weightlessness on the ground, the tail suspension (TS) rat model has been used to simulate the effects of weightlessness. There is currently little information on the effect of TS on the expression and activity of nitric oxide synthase (NOS) in the brain. In this study, we examined time-dependent alterations in the expression and activity of neuronal NOS (nNOS) in the brains of TS rats. Male Sprague-Dawley rats were tail-suspended for 1 (TS1), 7 (TS7), and 14 (TS14) days or rested on the ground for 3 days after 14 days of TS. TS1 and TS7 rats exhibited no significant alterations in the expression of nNOS compared to control rats, whereas nNOS expression in TS14 rats was significantly upregulated compared to control rats. Normalized expression of nNOS mRNA and protein in TS14 rats (1.86 ± 0.48 and 1.84 ± 0.29, respectively) were significantly higher than that of control rats (P < 0.001 and P < 0.001, respectively). Consistent with these results, significant elevations in NOS activity and NO production were observed in TS14 rats. Thus, we demonstrated a significant upregulation of nNOS expression, accompanied by significant increases in NOS activity and NO production, in the brain of rats exposed to simulated weightlessness. PMID:28430607

  4. Simulated weightlessness affects the expression and activity of neuronal nitric oxide synthase in the rat brain.

    PubMed

    Yoon, Nara; Na, Kiyong; Kim, Hyun-Soo

    2017-05-09

    Spaceflight induces pathophysiological alterations in various organs. To study pathophysiological adaptations to weightlessness on the ground, the tail suspension (TS) rat model has been used to simulate the effects of weightlessness. There is currently little information on the effect of TS on the expression and activity of nitric oxide synthase (NOS) in the brain. In this study, we examined time-dependent alterations in the expression and activity of neuronal NOS (nNOS) in the brains of TS rats. Male Sprague-Dawley rats were tail-suspended for 1 (TS1), 7 (TS7), and 14 (TS14) days or rested on the ground for 3 days after 14 days of TS. TS1 and TS7 rats exhibited no significant alterations in the expression of nNOS compared to control rats, whereas nNOS expression in TS14 rats was significantly upregulated compared to control rats. Normalized expression of nNOS mRNA and protein in TS14 rats (1.86 ± 0.48 and 1.84 ± 0.29, respectively) were significantly higher than that of control rats (P < 0.001 and P < 0.001, respectively). Consistent with these results, significant elevations in NOS activity and NO production were observed in TS14 rats. Thus, we demonstrated a significant upregulation of nNOS expression, accompanied by significant increases in NOS activity and NO production, in the brain of rats exposed to simulated weightlessness.

  5. Study of astronaut restraints and mobility aids in a weightless shirtsleeve environment

    NASA Technical Reports Server (NTRS)

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

    1972-01-01

    A study, established to produce needed information about manual performance limits in intravehicular weightlessness such as the motions induced by the astronaut's direct application of force against the body of the vehicle or an object to be moved, is presented. Using both conventional and water immersion techniques, it was possible to develop realistic time estimates for astronaut station-to-station translation in Skylab, to simulate and analyze specific Skylab tasks involving force application and motion dynamics, and to evaluate certain thresholds of force application in weightlessness. The study was divided into three tasks. The first related to locomotion and verification or modification of present Skylab translation timelines. In all cases, translation times were less than the Skylab timelines indicated. The second task studied mass handling and transfer. Specifically, this involved measurement of the astronaut's ability to relocate the Skylab food lockers to stowage levels of three different heights and his ability to transfer the M509 PSS bottles between the OWS and the recharge station. The third task helped define the physical limits of man's ability to perform Skylab translation tasks under weightless conditions.

  6. Evaluation of the three-dimensional clinostat as a simulator of weightlessness.

    PubMed

    Hoson, T; Kamisaka, S; Masuda, Y; Yamashita, M; Buchen, B

    1997-01-01

    Concerns regarding the reliability of slow-and fast-rotating uni-axial clinostats in simulating weightlessness have induced the construction of devices considered to simulate weightlessness more adequately. A new three-dimensional (3-D) clinostat equipped with two rotation axes placed at right angles has been constructed. In the clinostat, the rotation achieved with two motors is computer-controlled and monitored with encoders attached to the motors. By rotating plants three-dimensionally at random rates on the clinostat, their dynamic stimulation by gravity in every direction can be eliminated. Some of the vegetative growth phases of plants dependent on the gravity vector, such as morphogenesis, are shown to be influenced by rotation on the 3-D clinostat. The validity of 3-D clinostatting has been evaluated by comparing structural parameters of cress roots and Chara rhizoids obtained under real microgravity with those obtained after 3-D clinostatting. The parameters analyzed up to now (organization of the root cap, integrity and polarity of statocytes, dislocation of statoliths, amount of starch and ER) demonstrate that the 3-D clinostat is a valuable device for simulating weightlessness.

  7. VDR in Osteoblast-Lineage Cells Primarily Mediates Vitamin D Treatment-Induced Increase in Bone Mass by Suppressing Bone Resorptiontdg%ang*tok.

    PubMed

    Nakamichi, Yuko; Udagawa, Nobuyuki; Horibe, Kanji; Mizoguchi, Toshihide; Yamamoto, Yoko; Nakamura, Takashi; Hosoya, Akihiro; Kato, Shigeaki; Suda, Tatsuo; Takahashi, Naoyuki

    2017-02-08

    Long-term treatment with active vitamin D [1α,25(OH)2 D3 ] and its derivatives is effective for increasing bone mass in patients with primary and secondary osteoporosis. Derivatives of 1α,25(OH)2 D3 , including eldecalcitol (ELD), exert their actions through the vitamin D receptor (VDR). ELD is more resistant to metabolic degradation than 1α,25(OH)2 D3 . It is reported that ELD treatment causes a net increase in bone mass by suppressing bone resorption rather than by increasing bone formation in animals and humans. VDR in bone and extraskeletal tissues regulates bone mass and secretion of osteotropic hormones. Therefore, it is unclear what types of cells expressing VDR preferentially regulate the vitamin D-induced increase in bone mass. Here, we examined the effects of 4-week treatment with ELD (50 ng/kg/day) on bone using osteoblast lineage-specific VDR conditional knockout (Ob-VDR-cKO) and osteoclast-specific VDR cKO (Ocl-VDR-cKO) male mice aged 10 weeks. Immunohistochemically, VDR in bone was detected preferentially in osteoblasts and osteocytes. Ob-VDR-cKO mice showed normal bone phenotypes, despite no appreciable immunostaining of VDR in bone. Ob-VDR-cKO mice failed to increase bone mass in response to ELD treatment. Ocl-VDR-cKO mice also exhibited normal bone phenotypes, but normally responded to ELD. ELD-induced FGF23 production in bone was regulated by VDR in osteoblast-lineage cells. These findings suggest that the vitamin D treatment-induced increase in bone mass is mediated by suppressing bone resorption through VDR in osteoblast-lineage cells. © 2017 American Society for Bone and Mineral Research.

  8. Alcohol-induced bone loss is blocked in p47phox -/- mice lacking functional nadph oxidases

    USDA-ARS?s Scientific Manuscript database

    Chronic ethanol (EtOH) consumption produces bone loss. Previous data suggest a role for NADPH oxidase enzymes (Nox) since the pan-Nox inhibitor diphenylene iodonium (DPI) blocks EtOH-induced bone loss in rats. The current study utilized mice in which Nox enzymes 1,2,3 and 5 are inactivated as a resu...

  9. AQP9: a novel target for bone loss induced by microgravity.

    PubMed

    Bu, Guoyun; Shuang, Feng; Wu, Ye; Ren, Dongfeng; Hou, Shuxun

    2012-03-23

    The aim of current study was to elucidate whether aquaporin-9 (AQP9) expression was involved in the progression of bone loss induced by microgravity. We used the hind-limb suspension (HLS) mice model to simulate microgravity and induce bone loss. It was found that HLS exposure decreased femur bone mineral density (BMD), and enhanced femur AQP9 mRNA and protein levels. Then, the relationship between AQP9 mRNA expression and BMD was studied and it was showed that femur AQP9 mRNA level was negatively related to femur BMD in mice exposed to HLS. We sought to exam the function of AQP9 in the femur using the AQP9-null mice. It was found that AQP9 knockout attenuated bone loss and inhibited osteoclastogenesis under the condition of HLS exposure, but had no similar effect on bone under normal physiological conditions. In addition, it was found that exposure to simulated hypergravity or exercise training, main countermeasures against microgravity, reduced AQP9 mRNA and protein levels in femur of mice. Moreover, it was found that both aging and estrogen deprivation, another two risk factors of bone loss, had no significant effect on femur AQP9 expression. In conclusion, AQP9 plays an important role in the development of microgravity-induced bone loss, and may be a potential target for the prevention or management of microgravity-induced bone loss.

  10. TLR2 signaling and Th2 responses drive Tannerella forsythia-induced periodontal bone loss.

    PubMed

    Myneni, Srinivas R; Settem, Rajendra P; Connell, Terry D; Keegan, Achsah D; Gaffen, Sarah L; Sharma, Ashu

    2011-07-01

    Periodontal disease (PD) is a chronic inflammation of the tooth-supporting soft tissue and alveolar bone due to infection by a select group of gram-negative microbes, which leads to tooth loss if untreated. Because mice deficient in CD4(+) cells are resistant to infection-induced alveolar bone loss, Th cells have been implicated in bone-destructive processes during PD. However, the extent to which different Th cell subtypes play roles in pathogenesis or host protection remains to be defined and is likely to vary depending on the dominant microorganism involved. By far, Porphyromonas gingivalis is the best-studied periodontal microbe in PD. Although the gram-negative anaerobe Tannerella forsythia is also a vital contributor to periodontal bone loss, almost nothing is known about immune responses to this organism. Previous studies from our laboratory revealed that T. forsythia induces periodontal bone loss in mice and that this bone loss depends on the bacterially expressed BspA protein. In this study, we showed that T. forsythia activates murine APCs primarily through TLR2-dependent signaling via BspA. Furthermore, T. forsythia infection causes a pronounced Th2 bias, evidenced by T cell expression of IL-5, but not IFN-γ or IL-17, in draining lymph nodes. Consistently, deficiencies in TLR2 or STAT6 result in resistance to T. forsythia-induced alveolar bone loss. Thus, TLR2 signaling and Th2 cells play pathogenic roles in T. forsythia-induced alveolar bone destruction.

  11. Muscle Paralysis Induces Bone Marrow Inflammation and Predisposition to Formation of Giant Osteoclasts.

    PubMed

    Ausk, Brandon J; Worton, Leah E; Smigiel, Kate S; Kwon, Ronald Y; Bain, Steven D; Srinivasan, Sundar; Gardiner, Edith M; Gross, Ted S

    2017-08-30

    Transient muscle paralysis engendered by a single injection of botulinum toxin A (BTxA) rapidly induces profound focal bone resorption within the medullary cavity of adjacent bones. While initially conceived as a model of mechanical disuse, osteoclastic resorption in this model is disproportionately severe compared to the modest gait defect that is created. Preliminary studies of bone marrow following muscle paralysis suggested acute upregulation of inflammatory cytokines, including TNF and IL-1. We therefore hypothesized that BTxA-induced muscle paralysis would rapidly alter the inflammatory microenvironment and the osteoclastic potential of bone marrow. We tested this hypothesis by defining the time course of inflammatory cell infiltration, osteoinflammatory cytokine expression, and alteration in osteoclastogenic potential in the tibia bone marrow following transient muscle paralysis of the calf muscles. Our findings identified inflammatory cell infiltration within 24 hours of muscle paralysis. By 72 hours, osteoclast fusion and pro-osteoclastic inflammatory gene expression were upregulated in tibia bone marrow. These alterations coincided with bone marrow becoming permissive to the formation of osteoclasts of greater size and greater nuclei numbers. Taken together, our data are consistent with the thesis that transient calf muscle paralysis induces acute inflammation within the marrow of the adjacent tibia and that these alterations are temporally consistent with a role in mediating muscle paralysis-induced bone resorption. Copyright © 2017, American Journal of Physiology-Cell Physiology.

  12. 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...

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

    PubMed

    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

    2016-02-15

    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.

  14. Antiresorptive Treatment for Spaceflight Induced Bone Atrophy - Preliminary Results

    NASA Technical Reports Server (NTRS)

    LeBlanc, Adrian; Matsumoto, toshio; Jones, Jeff; Shapiro, Jay; Lang, Thomas; Shackelford, Linda C.; Smith, Scott M.; Evans, Harlan J.; Spector, Elisabeth R.; Ploutz-Snyder, Robert; Sibonga, Jean; Nakamura, Toshitaka; Kohri, Kenjiro; Ohshima, Hiroshi

    2011-01-01

    Detailed measurements from the Mir and ISS long duration missions have documented losses in bone mineral density (BMD) from critical skeletal sub-regions. The most important BMD losses are from the femoral hip, averaging about -1.6%/mo integral to -2.3%/mo trabecular. Importantly these studies have documented the wide range in individual BMD loss from -0.5 to -5%/mo. Associated elevated urinary Ca increases the risk of renal stone formation during flight, a serious impact to mission success. To date, countermeasures have not been satisfactory. The purpose of this study is to determine if the combined effect of anti-resorptive drugs plus the standard in-flight exercise regimen will have a measurable effect on preventing space flight induced bone loss (mass and strength) and reducing renal stone risk. To date, 4 crewmembers have completed the flight portion of the protocol in which crewmembers take a 70-mg alendronate tablet once a week before and during flight, starting 17 days before launch. Compared to previous ISS crewmembers (n=14) not taking alendronate, DXA measurements of the spine, femur neck and total hip were significantly improved from -0.8 +/- 0.5%/mo to 1.0 +/- 1.1%/mo, -1.1 +/- 0.5%/mo to -0.2 +/- 0.3%/mo, -1.1 +/- 0.5%/mo to 0.04 +/- 0.3%/mo respectively. QCT-determined trabecular BMD of the femur neck, trochanter and total hip were significantly improved from -2.7 +/- 1.9%/mo to -0.2 +/- 0.8%/mo, -2.2 +/- 0.9%/mo to -0.3 +/- 1.9%/mo and -2.3 +/- 1.0%/mo to -0.2 +/- 1.8%/mo respectively. Significance was calculated from a one-tailed t test. Resorption markers were unchanged, in contrast to measurements from previous ISS crewmembers that showed typical increases of 50-100% above baseline. Urinary Ca showed no increase compared to baseline levels, also distinct from the elevated levels of 50% or greater in previous crews. While these results are encouraging, the current n (4) is small, and the large SDs indicate that, while the means are improved, there

  15. Disruption of PTH Receptor 1 in T Cells Protects against PTH-Induced Bone Loss

    PubMed Central

    Tawfeek, Hesham; Bedi, Brahmchetna; Li, Jau-Yi; Adams, Jonathan; Kobayashi, Tatsuya; Weitzmann, M. Neale; Kronenberg, Henry M.; Pacifici, Roberto

    2010-01-01

    Background Hyperparathyroidism in humans and continuous parathyroid hormone (cPTH) treatment in mice cause bone loss by regulating the production of RANKL and OPG by stromal cells (SCs) and osteoblasts (OBs). Recently, it has been reported that T cells are required for cPTH to induce bone loss as the binding of the T cell costimulatory molecule CD40L to SC receptor CD40 augments SC sensitivity to cPTH. However it is unknown whether direct PTH stimulation of T cells is required for cPTH to induce bone loss, and whether T cells contribute to the bone catabolic activity of PTH with mechanisms other than induction of CD40 signaling in SCs. Methodology/Principal Findings Here we show that silencing of PTH receptor 1 (PPR) in T cells blocks the bone loss and the osteoclastic expansion induced by cPTH, thus demonstrating that PPR signaling in T cells is central for PTH-induced reduction of bone mass. Mechanistic studies revealed that PTH activation of the T cell PPR stimulates T cell production of the osteoclastogenic cytokine tumor necrosis factor α (TNF). Attesting to the relevance of this effect, disruption of T cell TNF production prevents PTH-induced bone loss. We also show that a novel mechanism by which TNF mediates PTH induced osteoclast formation is upregulation of CD40 expression in SCs, which increases their RANKL/OPG production ratio. Conclusions/Significance These findings demonstrate that PPR signaling in T cells plays an essential role in PTH induced bone loss by promoting T cell production of TNF. A previously unknown effect of TNF is to increase SC expression of CD40, which in turn increases SC osteoclastogenic activity by upregulating their RANKL/OPG production ratio. PPR-dependent stimulation of TNF production by T cells and the resulting TNF regulation of CD40 signaling in SCs are potential new therapeutic targets for the bone loss of hyperparathyroidism. PMID:20808842

  16. Ladder-Climbing Training Prevents Bone Loss and Microarchitecture Deterioration in Diet-Induced Obese Rats.

    PubMed

    Tang, Liang; Gao, Xiaohang; Yang, Xiaoying; Liu, Chentao; Wang, Xudan; Han, Yanqi; Zhao, Xinjuan; Chi, Aiping; Sun, Lijun

    2016-01-01

    Resistance exercise has been proved to be effective in improving bone quality in both animal and human studies. However, the issue about whether resistance exercise can inhibit obesity-induced bone loss has not been previously investigated. In the present study, we have evaluated the effects of ladder-climbing training, one of the resistance exercises, on bone mechanical properties and microarchitecture in high-fat (HF) diet-induced obese rats. Twenty-four rats were randomly assigned to the Control, HF + sedentary (HF-S) and HF + ladder-climbing training (HF-LCT) groups. Rats in the HF-LCT group performed ladder-climbing training for 8 weeks. The results showed that ladder-climbing training significantly reduced body and fat weight, and increased muscle mass along with a trend toward enhanced muscle strength in diet-induced obese rats. MicroCT analysis demonstrated that obesity-induced bone loss and architecture deterioration were significantly mitigated by ladder-climbing training, as evidenced by increased trabecular bone mineral density, bone volume over total volume, trabecular number and thickness, and decreased trabecular separation and structure model index. However, neither HF diet nor ladder-climbing training had an impact on femoral biomechanical properties. Moreover, ladder-climbing training significantly increased serum adiponectin, decreased serum leptin, TNF-α, IL-6 levels, and downregulated myostatin (MSTN) expression in diet-induced obese rats. Taken together, ladder-climbing training prevents bone loss and microarchitecture deterioration in diet-induced obese rats through multiple mechanisms including increasing mechanical loading on bone due to improved skeletal muscle mass and strength, regulating the levels of myokines and adipokines, and suppressing the release of pro-inflammatory cytokines. It indicates that resistance exercise may be a promising therapy for treating obesity-induced bone loss.

  17. The bone marrow microenvironment contributes to type I diabetes induced osteoblast death.

    PubMed

    Coe, Lindsay M; Irwin, Regina; Lippner, Dennean; McCabe, Laura R

    2011-02-01

    Type I diabetes increases an individual's risk for bone loss and fracture, predominantly through suppression of osteoblast activity (bone formation). During diabetes onset, levels of blood glucose and pro-inflammatory cytokines (including tumor necrosis factor α (TNFα)) increased. At the same time, levels of osteoblast markers are rapidly decreased and stay decreased chronically (i.e., 40 days later) at which point bone loss is clearly evident. We hypothesized that early bone marrow inflammation can promote osteoblast death and hence reduced osteoblast markers. Indeed, examination of type I diabetic mouse bones demonstrates a greater than twofold increase in osteoblast TUNEL staining and increased expression of pro-apoptotic factors. Osteoblast death was amplified in both pharmacologic and spontaneous diabetic mouse models. Given the known signaling and inter-relationships between marrow cells and osteoblasts, we examined the role of diabetic marrow in causing the osteoblast death. Co-culture studies demonstrate that compared to control marrow cells, diabetic bone marrow cells increase osteoblast (MC3T3 and bone marrow derived) caspase 3 activity and the ratio of Bax/Bcl-2 expression. Mouse blood glucose levels positively correlated with bone marrow induced osteoblast death and negatively correlated with osteocalcin expression in bone, suggesting a relationship between type I diabetes, bone marrow and osteoblast death. TNF expression was elevated in diabetic marrow (but not co-cultured osteoblasts); therefore, we treated co-cultures with TNFα neutralizing antibodies. The antibody protected osteoblasts from bone marrow induced death. Taken together, our findings implicate the bone marrow microenvironment and TNFα in mediating osteoblast death and contributing to type I diabetic bone loss.

  18. Management of traumatic tibial diaphyseal bone defect by “induced-membrane technique”

    PubMed Central

    Gupta, Gaurav; Ahmad, Sohail; Mohd. Zahid; Khan, A H; Sherwani, M K A; Khan, Abdul Qayyum

    2016-01-01

    Background: Gap nonunion of long bones is a challenging problem, due to the limitation of conventional reconstructive techniques more so if associated with infection and soft tissue defect. Treatment options such as autograft with non-vascularized fibula and cancellous bone graft, vascularized bone graft, and bone transportation are highly demanding on the part of surgeons and hospital setups and have many drawbacks. This study aims to analyze the outcome of patients with wide diaphyseal bone gap treated with induced-membrane technique (Masquelet technique). Materials and Methods: This study included 9 patients (7 males and 2 females), all with tibial bone-gap. Eight of the 9 patients were infected and in 3 patients there was associated large soft tissue defect requiring flap cover. This technique is two-stage procedure. Stage I surgery included debridement, fracture stabilization, application of spacer between bone ends, and soft tissue reconstruction. Stage II surgery included removal of spacer with preservation of induced membrane formed at spacer surface and filling the bone-gap with morselized iliac crest bone-graft within the membrane sleeve. Average bone-gap of 5.2 cm was treated. The spacer was always found to be encapsulated by a thick glistening membrane which did not collapse after its removal. All patients were followed up for an average period of 21.5 months. Results: Serial Radiographs showed regular uptake of autograft and thus consolidation within themselves in the region of bone gap and also with host bone. Bone-union was documented in all patients and all patients are walking full weight-bearing without support. Conclusions: The study highlights that the technique provide effective and practical management for difficult gap nonunion. It does not require specialized equipment, investigations, and surgery. Thus, it provides a reasonable alternative to the developing infrastructures and is a reliable and reproducible technique. PMID:27293290

  19. A Computational Model for Simulating Spaceflight Induced Bone Remodeling

    NASA Technical Reports Server (NTRS)

    Pennline, James A.; Mulugeta, Lealem

    2014-01-01

    An overview of an initial development of a model of bone loss due to skeletal unloading in weight bearing sites is presented. The skeletal site chosen for the initial application of the model is the femoral neck region because hip fractures can be debilitating to the overall performance health of astronauts. The paper begins with the motivation for developing such a model of the time course of change in bone in order to understand the mechanism of bone demineralization experienced by astronauts in microgravity, to quantify the health risk, and to establish countermeasures. Following this, a general description of a mathematical formulation of the process of bone remodeling is discussed. Equations governing the rate of change of mineralized bone volume fraction and active osteoclast and osteoblast are illustrated. Some of the physiology of bone remodeling, the theory of how imbalance in remodeling can cause bone loss, and how the model attempts to capture this is discussed. The results of a preliminary validation analysis that was carried out are presented. The analysis compares a set of simulation results against bone loss data from control subjects who participated in two different bed rest studies. Finally, the paper concludes with outlining the current limitations and caveats of the model, and planned future work to enhance the state of the model.

  20. Nitidine chloride prevents OVX-induced bone loss via suppressing NFATc1-mediated osteoclast differentiation

    PubMed Central

    Liu, Qian; Wang, Tao; Zhou, Lin; Song, Fangming; Qin, An; Feng, Hao Tian; Lin, Xi Xi; Lin, Zhen; Yuan, Jin Bo; Tickner, Jennifer; Liu, Hua Gang; Zheng, Ming Hao; Xu, Jiake; Zhao, Jin Min

    2016-01-01

    Nitidine chloride (NC), a bioactive alkaloid isolated from Zanthoxylum nitidum, has been used as a herbal ingredient in toothpaste that prevents cavities for decades. It also displays potential antitumor and anti-inflammation properties. However, its anticatabolic effect on bone is not known. We investigated the effect of NC on osteoclastogenesis, bone resorption and RANKL-induced NF-κB and NFATc1 signalling. In mouse-derived bone marrow monocytes (BMMs), NC suppressed RANKL-induced multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation and bone resorption in a dose dependent manner. NC attenuated the expression of osteoclast marker genes including cathepsin K, D2, calcitonin receptor, NFATc1, and TRAP. Further, NC inhibited RANKL-activated NF-κB and NFATc1 signalling pathways. In vivo study revealed that NC abrogated oestrogen deficiency-induced bone loss in ovariectomized mice. Histological analysis showed that the number of osteoclasts was significantly lower in NC-treated groups. Collectively, our data demonstrate that NC suppressed osteoclastogenesis and prevented OVX-induced bone loss by inhibiting RANKL-induced NF-κB and NFATc1 signalling pathways. NC may be a natural and novel treatment for osteoclast-related bone lytic diseases. PMID:27821837

  1. 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

  2. NADPH oxidases are critical targets for prevention of ethanol-induced bone loss

    USDA-ARS?s Scientific Manuscript database

    The molecular mechanisms through which chronic alcohol consumption induce bone loss and osteoporosis are largely unknown. Ethanol increases expression and activates NADPH (nicotinamide adenine dinucleotide phosphate) oxidase enzymes (Nox) in osteoblasts leading to accumulation of reactive oxygen spe...

  3. Induced membrane technique for the treatment of bone defects due to post-traumatic osteomyelitis.

    PubMed

    Wang, X; Luo, F; Huang, K; Xie, Z

    2016-03-01

    Induced membrane technique is a relatively new technique in the reconstruction of large bone defects. It involves the implantation of polymethylmethacrylate (PMMA) cement in the bone defects to induce the formation of membranes after radical debridement and reconstruction of bone defects using an autologous cancellous bone graft in a span of four to eight weeks. The purpose of this study was to explore the clinical outcomes of the induced membrane technique for the treatment of post-traumatic osteomyelitis in 32 patients. A total of 32 cases of post-traumatic osteomyelitis were admitted to our department between August 2011 and October 2012. This retrospective study included 22 men and ten women, with a mean age of 40 years (19 to 70). Within this group there were 20 tibias and 12 femurs with a mean defect of 5 cm (1.5 to 12.5). Antibiotic-loaded PMMA cement was inserted into the defects after radical debridement. After approximately eight weeks, the defects were implanted with bone graft. The patients were followed for 27.5 months (24 to 32). Radiographic bone union occurred at six months for 26 cases (81%) and clinical healing occurred in 29 cases (90%) at ten months. A total of six cases had a second debridement before bone grafting because of recurrence of infection and one patient required a third debridement. No cases of osteomyelitis had recurred at the time of the last follow-up visit. The induced membrane technique for the treatment of post-traumatic osteomyelitis is a simple, reliable method, with good early results. However, there are many challenges in determining the scope of the debridement, type of limb fixation and source of bone graft to be used.Cite this article: Dr Z. Xie. Induced membrane technique for the treatment of bone defects due to post-traumatic osteomyelitis. Bone Joint Res 2016;5:101-105. DOI: 10.1302/2046-3758.53.2000487. © 2016 Xie et al.

  4. Induced membrane technique for the treatment of bone defects due to post-traumatic osteomyelitis

    PubMed Central

    Wang, X.; Luo, F.; Huang, K.

    2016-01-01

    Objectives Induced membrane technique is a relatively new technique in the reconstruction of large bone defects. It involves the implantation of polymethylmethacrylate (PMMA) cement in the bone defects to induce the formation of membranes after radical debridement and reconstruction of bone defects using an autologous cancellous bone graft in a span of four to eight weeks. The purpose of this study was to explore the clinical outcomes of the induced membrane technique for the treatment of post-traumatic osteomyelitis in 32 patients. Methods A total of 32 cases of post-traumatic osteomyelitis were admitted to our department between August 2011 and October 2012. This retrospective study included 22 men and ten women, with a mean age of 40 years (19 to 70). Within this group there were 20 tibias and 12 femurs with a mean defect of 5 cm (1.5 to 12.5). Antibiotic-loaded PMMA cement was inserted into the defects after radical debridement. After approximately eight weeks, the defects were implanted with bone graft. Results The patients were followed for 27.5 months (24 to 32). Radiographic bone union occurred at six months for 26 cases (81%) and clinical healing occurred in 29 cases (90%) at ten months. A total of six cases had a second debridement before bone grafting because of recurrence of infection and one patient required a third debridement. No cases of osteomyelitis had recurred at the time of the last follow-up visit. Conclusion The induced membrane technique for the treatment of post-traumatic osteomyelitis is a simple, reliable method, with good early results. However, there are many challenges in determining the scope of the debridement, type of limb fixation and source of bone graft to be used. Cite this article: Dr Z. Xie. Induced membrane technique for the treatment of bone defects due to post-traumatic osteomyelitis. Bone Joint Res 2016;5:101–105. DOI: 10.1302/2046-3758.53.2000487. PMID:27033845

  5. Adipose-Derived Mesenchymal Stem Cells Prevent Systemic Bone Loss in Collagen-Induced Arthritis

    PubMed Central

    Garimella, Manasa G.; Kour, Supinder; Piprode, Vikrant; Mittal, Monika; Kumar, Anil; Rani, Lekha; Pote, Satish T.; Mishra, Gyan C.; Chattopadhyay, Naibedya

    2015-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammatory synovitis leading to joint destruction and systemic bone loss. The inflammation-induced bone loss is mediated by increased osteoclast formation and function. Current antirheumatic therapies primarily target suppression of inflammatory cascade with limited or no success in controlling progression of bone destruction. Mesenchymal stem cells (MSCs) by virtue of their tissue repair and immunomodulatory properties have shown promising results in various autoimmune and degenerative diseases. However, the role of MSCs in prevention of bone destruction in RA is not yet understood. In this study, we investigated the effect of adipose-derived MSCs (ASCs) on in vitro formation of bone-resorbing osteoclasts and pathological bone loss in the mouse collagen-induced arthritis (CIA) model of RA. We observed that ASCs significantly inhibited receptor activator of NF-κB ligand (RANKL)–induced osteoclastogenesis in both a contact-dependent and -independent manner. Additionally, ASCs inhibited RANKL-induced osteoclastogenesis in the presence of proinflammatory cytokines such as TNF-α, IL-17, and IL-1β. Furthermore, treatment with ASCs at the onset of CIA significantly reduced clinical symptoms and joint pathology. Interestingly, ASCs protected periarticular and systemic bone loss in CIA mice by maintaining trabecular bone structure. We further observed that treatment with ASCs reduced osteoclast precursors in bone marrow, resulting in decreased osteoclastogenesis. Moreover, ASCs suppressed autoimmune T cell responses and increased the percentages of peripheral regulatory T and B cells. Thus, we provide strong evidence that ASCs ameliorate inflammation-induced systemic bone loss in CIA mice by reducing osteoclast precursors and promoting immune tolerance. PMID:26538398

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

    SciTech Connect

    Cheon, Yoon-Hee; Kim, Ju-Young; Baek, Jong Min; Ahn, Sung-Jun; So, Hong-Seob; Oh, Jaemin

    2016-02-05

    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 inhibition 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.

  7. Diet-induced obesity, gut microbiota and bone, including alveolar bone loss.

    PubMed

    Eaimworawuthikul, Sathima; Thiennimitr, Parameth; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2017-02-07

    Obesity is a major risk factor for several pathologies, including jaw bone resorption. The underlying mechanisms involved in pathological conditions resulting from obesity include chronic systemic inflammation and the development of insulin resistance. Although numerous studies have indicated the importance of the role of gut microbiota in the pathogenesis of inflammation and insulin resistance in obesity, only a few studies have established a relationship between obesity, gut microbiota and status of the jaw bone. This review aims to summarize current findings relating to these issues, focusing on the role of obesity and gut microbiota on jaw bone health, including possible mechanisms which can explain this link.

  8. 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

  9. 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.

  10. Radiation-induced craniofacial bone growth inhibition: acute and long-term effects on bone histopathology with and without cytoprotection.

    PubMed

    Oʼdonovan, David A; La Scala, Giorgio C; Leong, Iona; Mendes, Maria; Rogers, Marianne; Pritzker, Kenneth H; Yeung, Ivan; Pang, Cho Y; Neligan, Peter C; Forrest, Christopher R

    2012-04-01

    The authors previously established an animal model of radiation-induced craniofacial bone growth inhibition and demonstrated the effectiveness of cytoprotection in preserving growth using amifostine, but the mechanism is unclear. The objective of this study was to investigate the acute and long-term histopathologic effects of single-dose orthovoltage irradiation on craniofacial bone with and without cytoprotection. Sixty infant New Zealand White rabbits (7-week-old) were randomized into three groups (n = 20 per group): group 1, 0-Gy, sham irradiation; group 2, 35-Gy single-dose orthovoltage irradiation; and group 3, cytoprotection with amifostine before irradiation. Orbitozygomatic complex bone was harvested from animals 12 hours after irradiation and at skeletal maturity (21 weeks of age). Histologic parameters measured included native bone cell (osteoblast, osteoclast, and osteocyte) populations, periosteal proliferation indices (MIB-1 stains), bone turnover rates [triple fluorochromes: tetracycline administered at 7 weeks of age (before irradiation), alizarin complexone at 12 weeks, and calcein at 16 weeks of age], and endosteal space fibrosis levels. Orthovoltage irradiation significantly (p < 0.05) reduced osteoblast and osteoclast counts 12 hours after irradiation (age, 7 weeks) with or without pretreatment with amifostine but had no effect on osteocyte populations. Long-term analysis at age 21 weeks demonstrated significantly (p < 0.05) increased osteoblast counts, reduced endosteal space fibrosis, reduced periosteal proliferation indices, and improved bone turnover (fluorochrome stains) in amifostine-treated animals. This study suggests that amifostine cytoprotection is mediated through a combination of reduced cellular injury with enhanced promotion of cellular bone rebuilding potential.

  11. 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.

  12. Ursolic acid derivative ameliorates streptozotocin-induced diabestic bone deleterious effects in mice

    PubMed Central

    Yu, Su-Guo; Zhang, Cheng-Jie; Xu, Xiu-E; Sun, Ji-Hua; Zhang, Li; Yu, Peng-Fei

    2015-01-01

    Objective: This study was performed to investigate bone deteriorations of diabetic mice in response to the treatment of ursolic acid derivative (UAD). Methods: The biomarkers in serum and urine were measured, tibias were taken for the measurement on gene and protein expression and histomorphology analysis, and femurs were taken for the measurement on bone Ca and three-dimensional architecture of trabecular bone. Results: UAD showed a greater increase in bone Ca, BMD and significantly increased FGF-23 and OCN, reduced PTH and CTX in diabetic mice. UAD reversed STZ-induced trabecular deleterious effects and stimulated bone remodeling. The treatment of STZ group with UAD significantly elevated the ratio of OPG/RANKL. Moreover, insulin and IGF-1 showed a negative correlation with both FBG and Hb1Ac in STZ group. We attributed down-regulating the level of Hb1Ac in diabetic mice to that ursolic acid derivative could primely control blood sugar levels. After analyzing of two adipocyte markers, PPARγ and aP2, increased expression in the tibias of diabetic mice, and UAD could improve STZ-induced adipocyte dysfunction. Conclusions: These results demonstrated that UAD could ameliorate STZ-induced bone deterioration through improving adipocyte dysfunction and enhancing new bone formation and inhibiting absorptive function of osteoclast in the bone of diabetic mice. PMID:26097549

  13. 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.

  14. AST-induced bone loss in men with prostate cancer: exercise as a potential countermeasure.

    PubMed

    Bolam, K A; Galvão, D A; Spry, N; Newton, R U; Taaffe, D R

    2012-12-01

    Androgen suppression treatment (AST) for men with prostate cancer is associated with a number of treatment-related side effects including an accelerated rate of bone loss. This loss of bone is greatest within the first year of AST and increases the risk for fracture. Pharmaceutical treatment in the form of bisphosphonates is currently used to counter the effects of hormone suppression on bone but is costly and associated with potential adverse effects. Recently, exercise has been shown to be an important adjuvant therapy to manage a range of treatment-related toxicities and enhance aspects of quality of life for men receiving AST. We propose that physical exercise may also have an important role in not only attenuating the bone loss associated with AST but in improving bone health and reducing fracture risk. In this review, the rationale underlying exercise as a countermeasure to AST-induced bone loss is provided.

  15. High-dose bone morphogenetic protein-induced ectopic abdomen bone growth.

    PubMed

    Deutsch, Harel

    2010-02-01

    Infuse [bone morphogenetic protein (BMP)] is increasingly used in spinal fusion surgery. The authors report a rare complication of BMP use. This is a case report. A 55-year-old male underwent a thoracic T8 to the pelvis fusion for degenerative lumbar disc disease and pseudarthrosis at another institution. The procedure involved an anterior and posterior approach with the use of multiple units of BMP. The patient presented to our institution with complaints of weight loss, pain, tenderness, and increasing solid growth in the left lower quadrant several months after his surgery. A computed tomography revealed ectopic bone growth in the retroperitoneal area and pelvis contiguous to the anterior lumbar exposure. The anterior wound was re-explored, and a large sheet of ectopic bone was removed from the retroperitoneal space. We report a rare case of extraspinal ectopic bone growth because of the use of multiple packages of BMP. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  16. Impact of weightlessness on muscle function

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.; Slentz, M.

    1995-01-01

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

  17. Impact of weightlessness on muscle function

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.; Slentz, M.

    1995-01-01

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

  18. 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.

  19. 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.

  20. Morphological and histological adaptation of muscle and bone to loading induced by repetitive activation of muscle

    PubMed Central

    Vickerton, Paula; Jarvis, Jonathan C.; Gallagher, James A.; Akhtar, Riaz; Sutherland, Hazel; Jeffery, Nathan

    2014-01-01

    Muscular contraction plays a pivotal role in the mechanical environment of bone, but controlled muscular contractions are rarely used to study the response of bone to mechanical stimuli. Here, we use implantable stimulators to elicit programmed contractions of the rat tibialis anterior (TA) muscle. Miniature stimulators were implanted in Wistar rats (n = 9) to induce contraction of the left TA every 30 s for 28 days. The right limb was used as a contralateral control. Hindlimbs were imaged using microCT. Image data were used for bone measurements, and to construct a finite-element (FE) model simulation of TA forces propagating through the bone. This simulation was used to target subsequent bone histology and measurement of micromechanical properties to areas of high strain. FE mapping of simulated strains revealed peak values in the anterodistal region of the tibia (640 µε ± 30.4 µε). This region showed significant increases in cross-sectional area (28.61%, p < 0.05) and bone volume (30.29%, p < 0.05) in the stimulated limb. Histology revealed a large region of new bone, containing clusters of chondrocytes, indicative of endochondral ossification. The new bone region had a lower elastic modulus (8.8 ± 2.2 GPa) when compared with established bone (20 ± 1.4 GPa). Our study provides compelling new evidence of the interplay between muscle and bone. PMID:24966314

  1. Remodeling of the Mandibular Bone Induced by Overdentures Supported by Different Numbers of Implants.

    PubMed

    Li, Kai; Xin, Haitao; Zhao, Yanfang; Zhang, Zhiyuan; Wu, Yulu

    2016-05-01

    The objective of this study was to investigate the process of mandibular bone remodeling induced by implant-supported overdentures. computed tomography (CT) images were collected from edentulous patients to reconstruct the geometry of the mandibular bone and overdentures supported by implants. Based on the theory of strain energy density (SED), bone remodeling models were established using the user material subroutine (UMAT) in abaqus. The stress distribution in the mandible and bone density change was investigated to determine the effect of implant number on the remodeling of the mandibular bone. The results indicated that the areas where high Mises stress values were observed were mainly situated around the implants. The stress was concentrated in the distal neck region of the distal-most implants. With an increased number of implants, the biting force applied on the dentures was almost all taken up by implants. The stress and bone density in peri-implant bone increased. When the stress reached the threshold of remodeling, the bone density began to decrease. In the posterior mandible area, the stress was well distributed but increased with decreased implant numbers. Changes in bone density were not observed in this area. The computational results were consistent with the clinical data. The results demonstrate that the risk of bone resorption around the distal-most implants increases with increased numbers of implants and that the occlusal force applied to overdentures should be adjusted to be distributed more in the distal areas of the mandible.

  2. Leukemia cells induce changes in human bone marrow stromal cells

    PubMed Central

    2013-01-01

    Background Bone marrow stromal cells (BMSCs) are multipotent cells that support angiogenesis, wound healing, and immunomodulation. In the hematopoietic niche, they nurture hematopoietic cells, leukemia, tumors and metastasis. BMSCs secrete of a wide range of cytokines, growth factors and matrix proteins which contribute to the pro-tumorigenic marrow microenvironment. The inflammatory cytokines IFN-γ and TNF-α change the BMSC secretome and we hypothesized that factors produced by tumors or leukemia would also affect the BMSC secretome and investigated the interaction of leukemia cells with BMSCs. Methods BMSCs from healthy subjects were co-cultured with three myeloid leukemia cell lines (TF-1, TF-1α and K562) using a trans-well system. Following co-culture, the BMSCs and leukemia cells were analyzed by global gene expression analysis and culture supernatants were analyzed for protein expression. As a control, CD34+ cells were also cocultured with BMSCs. Results Co-culture induced leukemia cell gene expression changes in stem cell pluripotency, TGF-β signaling and carcinoma signaling pathways. BMSCs co-cultured with leukemia cells up-regulated a number of proinflammatory genes including IL-17 signaling-related genes and IL-8 and CCL2 levels were increased in co-culture supernatants. In contrast, purine metabolism, mTOR signaling and EIF2 signaling pathways genes were up-regulated in BMSCs co-cultured with CD34+ cells. Conclusions BMSCs react to the presence of leukemia cells undergoing changes in the cytokine and chemokine secretion profiles. Thus, BMSCs and leukemia cells both contribute to the creation of a competitive niche more favorable for leukemia stem cells. PMID:24304929

  3. C-met inhibition blocks bone metastasis development induced by renal cancer stem cells

    PubMed Central

    D'Amico, Lucia; Belisario, Dimas; Migliardi, Giorgia; Grange, Cristina; Bussolati, Benedetta; D'Amelio, Patrizia; Perera, Timothy; Dalmasso, Ettore; Carbonare, Luca Dalle; Godio, Laura; Comoglio, Paolo; Trusolino, Livio; Ferracini, Riccardo; Roato, Ilaria

    2016-01-01

    Cancer stem cells (CSCs) are key players in bone metastasis. In some renal tumors CSCs overexpress the HGF receptor c-MET, speculating that c-MET targeting could lead to bone metastasis inhibition. To address this hypothesis we isolated renal CD105+/CD24−CSCs, expressing c-MET receptor from a primary renal carcinoma. Then, to study their ability to metastasize to bone, we injected renal CSCs in NOD/SCID mice implanted with a human bone and we tested the effect of a c-MET inhibitor (JNJ-38877605) on bone metastasis development. JNJ-38877605 inhibited the formation of metastases at bone implant site. We showed that JNJ-38877605 inhibited the activation of osteoclasts induced by RCC stem cells and it stimulated osteoblast activity, finally resulting in a reduction of bone turnover consistent with the inhibition of bone metastases. We measured the circulating levels of osteotropic factors induced by RCC stem cells in the sera of mice treated with c-Met inhibitor, showing that IL-11 and CCL20 were reduced in mice treated with JNJ-38877605, strongly supporting the involvement of c-MET in the regulation of this process. To address the clinical relevance of c-MET upregulation during tumor progression, we analysed c-MET in renal cancer patients detecting an increased expression in the bone metastatic lesions by IHC. Then, we dosed CCL20 serum levels resulting significantly increased in patients with bone metastases compared to non-metastatic ones. Collectively, our data highlight the importance of the c-MET pathway in the pathogenesis of bone metastases induced by RCC stem cells in mice and humans. PMID:27322553

  4. KDM5A controls bone morphogenic protein 2-induced osteogenic differentiation of bone mesenchymal stem cells during osteoporosis

    PubMed Central

    Wang, Chuandong; Wang, Jing; Li, Jiao; Hu, Guoli; Shan, Shengzhou; Li, Qingfeng; Zhang, Xiaoling

    2016-01-01

    Bone morphogenetic protein 2 (BMP2) has been used to induce bone regeneration by promoting osteogenic differentiation of bone marrow-derived mesenchymal stem cells (MSCs). However, its effect is attenuated in osteoporotic conditions by unknown mechanisms. In this study, we investigated the molecular mechanisms of reduced osteogenic effect of BMP2 in osteoporotic conditions. By interrogating the microarray data from osteoporosis patients, we revealed an upregulation of the epigenetic modifying protein lysine (K)-specific demethylase 5A (KDM5A) and decreased Runt-related transcription factor 2 (RUNX2) expression. Further studies were focused on the role of KDM5A in osteoporosis. We first established ovariectomized (OVX) mouse model and found that the BMP2-induced osteogenic differentiation of osteoporotic MSCs was impaired. The elevated level of KDM5A was confirmed in osteoporotic MSCs. Overexpression of KDM5A in normal MSCs inhibited BMP2-induced osteogenesis. Moreover, osteogenic differentiation of osteoporotic MSCs was restored by specific KDM5A short hairpin RNA or inhibitor. Furthermore, by chromatin immunoprecipitation assay we demonstrated that KDM5A functions as endogenous modulator of osteogenic differentiation by decreasing H3K4me3 levels on promoters of Runx2, depend on its histone methylation activity. More importantly, we found an inhibitory role of KDM5A in regulating bone formation in osteoporotic mice, and pretreatment with KDM5A inhibitor partly rescued the bone loss during osteoporosis. Our results show, for the first time, that KDM5A-mediated H3K4me3 modification participated in the etiology of osteoporosis and may provide new strategies to improve the clinical efficacy of BMP2 in osteoporotic conditions. PMID:27512956

  5. STING Contributes to Abnormal Bone Formation Induced by Deficiency of DNase II in Mice.

    PubMed

    Baum, Rebecca; Sharma, Shruti; Organ, Jason M; Jakobs, Christopher; Hornung, Veit; Burr, David B; Marshak-Rothstein, Ann; Fitzgerald, Katherine A; Gravallese, Ellen M

    2017-02-01

    Cytosolic DNA sensors detect microbial DNA and promote type I interferon (IFN) and proinflammatory cytokine production through the adaptor stimulator of IFN genes (STING) to resolve infection. Endogenous DNA also engages the STING pathway, contributing to autoimmune disease. This study sought to identify the role of STING in regulating bone formation and to define the bone phenotype and its pathophysiologic mechanisms in arthritic mice double deficient in DNase II and IFN-α/β/ω receptor (IFNAR) (DNase II(-/-) /IFNAR(-/-) double-knockout [DKO] mice) compared with controls. Bone parameters were evaluated by micro-computed tomography and histomorphometry in DKO mice in comparison with mice triple deficient in STING, DNase II, and IFNAR and control mice. Cell culture techniques were employed to determine the parameters of osteoclast and osteoblast differentiation and function. NanoString and Affymetrix array analyses were performed to identify factors promoting ectopic bone formation. Despite the expression of proinflammatory cytokines that would be expected to induce bone loss in the skeleton of DKO mice, the results, paradoxically, demonstrated an accumulation of bone in the long bones and spleens, sites of erythropoiesis and robust DNA accrual. In addition, factors promoting osteoblast recruitment and function were induced. Deficiency of STING significantly inhibited bone accrual. These data reveal a novel role for cytosolic DNA sensor pathways in bone in the setting of autoimmune disease. The results demonstrate the requirement of an intact STING pathway for bone formation in this model, a finding that may have relevance to autoimmune diseases in which DNA plays a pathogenic role. Identification of pathways linking innate immunity and bone could reveal novel targets for the treatment of bone abnormalities in human autoimmune diseases. © 2016, American College of Rheumatology.

  6. Intercellular Communication between Keratinocytes and Fibroblasts Induces Local Osteoclast Differentiation: a Mechanism Underlying Cholesteatoma-Induced Bone Destruction.

    PubMed

    Iwamoto, Yoriko; Nishikawa, Keizo; Imai, Ryusuke; Furuya, Masayuki; Uenaka, Maki; Ohta, Yumi; Morihana, Tetsuo; Itoi-Ochi, Saori; Penninger, Josef M; Katayama, Ichiro; Inohara, Hidenori; Ishii, Masaru

    2016-06-01

    Bone homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. Shifting the balance toward bone resorption causes osteolytic bone diseases such as rheumatoid arthritis and periodontitis. Osteoclast differentiation is regulated by receptor activator of nuclear factor κB ligand (RANKL), which, under some pathological conditions, is produced by T and B lymphocytes and synoviocytes. However, the mechanism underlying bone destruction in other diseases is little understood. Bone destruction caused by cholesteatoma, an epidermal cyst in the middle ear resulting from hyperproliferation of keratinizing squamous epithelium, can lead to lethal complications. In this study, we succeeded in generating a model for cholesteatoma, epidermal cyst-like tissue, which has the potential for inducing osteoclastogenesis in mice. Furthermore, an in vitro coculture system composed of keratinocytes, fibroblasts, and osteoclast precursors was used to demonstrate that keratinocytes stimulate osteoclast differentiation through the induction of RANKL in fibroblasts. Thus, this study demonstrates that intercellular communication between keratinocytes and fibroblasts is involved in the differentiation and function of osteoclasts, which may provide the molecular basis of a new therapeutic strategy for cholesteatoma-induced bone destruction. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  7. Intercellular Communication between Keratinocytes and Fibroblasts Induces Local Osteoclast Differentiation: a Mechanism Underlying Cholesteatoma-Induced Bone Destruction

    PubMed Central

    Iwamoto, Yoriko; Nishikawa, Keizo; Imai, Ryusuke; Furuya, Masayuki; Uenaka, Maki; Ohta, Yumi; Morihana, Tetsuo; Itoi-Ochi, Saori; Penninger, Josef M.; Katayama, Ichiro; Inohara, Hidenori

    2016-01-01

    Bone homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. Shifting the balance toward bone resorption causes osteolytic bone diseases such as rheumatoid arthritis and periodontitis. Osteoclast differentiation is regulated by receptor activator of nuclear factor κB ligand (RANKL), which, under some pathological conditions, is produced by T and B lymphocytes and synoviocytes. However, the mechanism underlying bone destruction in other diseases is little understood. Bone destruction caused by cholesteatoma, an epidermal cyst in the middle ear resulting from hyperproliferation of keratinizing squamous epithelium, can lead to lethal complications. In this study, we succeeded in generating a model for cholesteatoma, epidermal cyst-like tissue, which has the potential for inducing osteoclastogenesis in mice. Furthermore, an in vitro coculture system composed of keratinocytes, fibroblasts, and osteoclast precursors was used to demonstrate that keratinocytes stimulate osteoclast differentiation through the induction of RANKL in fibroblasts. Thus, this study demonstrates that intercellular communication between keratinocytes and fibroblasts is involved in the differentiation and function of osteoclasts, which may provide the molecular basis of a new therapeutic strategy for cholesteatoma-induced bone destruction. PMID:27001307

  8. Effects of simulated weightlessness on liver Hsp70 and Hsp70mRNA expression in rats.

    PubMed

    Cui, Yan; Zhou, Jinlian; Li, Chenglin; Wang, Ping; Zhang, Ming; Liu, Zipei; Yi, Yong; Zhang, Jianzhong

    2010-01-10

    Space flight is known to induce a number of hepatic physiological alterations. In this study, we investigated Hsp70 expressing features of rat liver under simulated weightlessness. Tail-suspension was used to simulate the weightlessness animal model. Forty-eight male Wistar rats were randomly assigned to 6 experimental groups and Hsp70 protein and mRNA expressions in the liver were detected by Western blot and RT-PCR respectively. The tail-suspension significantly increased Hsp70mRNA expression levels in rat liver (P<0.05). The semi-quantitative PCR showed that Hsp70mRNA was upregulated as early as 6 hours of suspension. Western blot analysis indicated that Hsp70 protein was significantly upregulated in the early stage of suspension as compared with controls (P<0.05). The results suggest that simulated weightlessness acts as a kind of stress to elevate liver Hsp70 expression both at protein and mRNA levels. This may be meaningful in astronaut's trainings by preadaptation to non-damaging stress exposures or other environmental factors to foster the astronaut's ability of weightless tolerance.

  9. Effects of simulated weightlessness on liver Hsp70 and Hsp70mRNA expression in rats

    PubMed Central

    Cui, Yan; Zhou, Jinlian; Li, Chenglin; Wang, Ping; Zhang, Ming; Liu, Zipei; Yi, Yong; Zhang, Jianzhong

    2010-01-01

    Space flight is known to induce a number of hepatic physiological alterations. In this study, we investigated Hsp70 expressing features of rat liver under simulated weightlessness. Tail-suspension was used to simulate the weightlessness animal model. Forty-eight male Wistar rats were randomly assigned to 6 experimental groups and Hsp70 protein and mRNA expressions in the liver were detected by Western blot and RT-PCR respectively. The tail-suspension significantly increased Hsp70mRNA expression levels in rat liver (P<0.05). The semi-quantitative PCR showed that Hsp70mRNA was upregulated as early as 6 hours of suspension. Western blot analysis indicated that Hsp70 protein was significantly upregulated in the early stage of suspension as compared with controls (P<0.05). The results suggest that simulated weightlessness acts as a kind of stress to elevate liver Hsp70 expression both at protein and mRNA levels. This may be meaningful in astronaut's trainings by preadaptation to non-damaging stress exposures or other environmental factors to foster the astronaut's ability of weightless tolerance. PMID:20369040

  10. The Walker 256 Breast Cancer Cell- Induced Bone Pain Model in Rats.

    PubMed

    Shenoy, Priyank A; Kuo, Andy; Vetter, Irina; Smith, Maree T

    2016-01-01

    The majority of patients with terminal breast cancer show signs of bone metastasis, the most common cause of pain in cancer. Clinically available drug treatment options for the relief of cancer-associated bone pain are limited due to either inadequate pain relief and/or dose-limiting side-effects. One of the major hurdles in understanding the mechanism by which breast cancer causes pain after metastasis to the bones is the lack of suitable preclinical models. Until the late twentieth century, all animal models of cancer induced bone pain involved systemic injection of cancer cells into animals, which caused severe deterioration of animal health due to widespread metastasis. In this mini-review we have discussed details of a recently developed and highly efficient preclinical model of breast cancer induced bone pain: Walker 256 cancer cell- induced bone pain in rats. The model involves direct localized injection of cancer cells into a single tibia in rats, which avoids widespread metastasis of cancer cells and hence animals maintain good health throughout the experimental period. This model closely mimics the human pathophysiology of breast cancer induced bone pain and has great potential to aid in the process of drug discovery for treating this intractable pain condition.

  11. The Walker 256 Breast Cancer Cell- Induced Bone Pain Model in Rats

    PubMed Central

    Shenoy, Priyank A.; Kuo, Andy; Vetter, Irina; Smith, Maree T.

    2016-01-01

    The majority of patients with terminal breast cancer show signs of bone metastasis, the most common cause of pain in cancer. Clinically available drug treatment options for the relief of cancer-associated bone pain are limited due to either inadequate pain relief and/or dose-limiting side-effects. One of the major hurdles in understanding the mechanism by which breast cancer causes pain after metastasis to the bones is the lack of suitable preclinical models. Until the late twentieth century, all animal models of cancer induced bone pain involved systemic injection of cancer cells into animals, which caused severe deterioration of animal health due to widespread metastasis. In this mini-review we have discussed details of a recently developed and highly efficient preclinical model of breast cancer induced bone pain: Walker 256 cancer cell- induced bone pain in rats. The model involves direct localized injection of cancer cells into a single tibia in rats, which avoids widespread metastasis of cancer cells and hence animals maintain good health throughout the experimental period. This model closely mimics the human pathophysiology of breast cancer induced bone pain and has great potential to aid in the process of drug discovery for treating this intractable pain condition. PMID:27630567

  12. Secreted Wnt Signaling Inhibitors in Disuse-Induced Bone Loss

    DTIC Science & Technology

    2014-07-01

    10 4  INTRODUCTION  Osteoporosis  (porous bone disease) is a disease characterized by low bone mass and structural...deteriora on of  bone  ssue, leading to bone fragility and an increased suscep bility to fractures. Disuse  osteoporosis  occurs  when the normal loading... osteoporosis .  Once that compound makes it to market,  there is significant precedent to try that compound in veterans returning from the ba lefield that are

  13. 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

  14. Mechanical strain, induced noninvasively in the high-frequency domain, is anabolic to cancellous bone, but not cortical bone.

    PubMed

    Rubin, C; Turner, A S; Mallinckrodt, C; Jerome, C; McLeod, K; Bain, S

    2002-03-01

    Departing from the premise that it is the large-amplitude signals inherent to intense functional activity that define bone morphology, we propose that it is the far lower magnitude, high-frequency mechanical signals that continually barrage the skeleton during longer term activities such as standing, which regulate skeletal architecture. To examine this hypothesis, we proposed that brief exposure to slight elevations in these endogenous mechanical signals would suffice to increase bone mass in those bones subject to the stimulus. This was tested by exposing the hind limbs of adult female sheep (n = 9) to 20 min/day of low-level (0.3g), high-frequency (30 Hz) mechanical signals, sufficient to induce a peak of approximately 5 microstrain (micro epsilon) in the tibia. Following euthanasia, peripheral quantitative computed tomography (pQCT) was used to segregate the cortical shell from the trabecular envelope of the proximal femur, revealing a 34.2% increase in bone density in the experimental animals as compared with controls (p = 0.01). Histomorphometric examination of the femur supported these density measurements, with bone volume per total volume increasing by 32% (p = 0.04). This density increase was achieved by two separate strategies: trabecular spacing decreased by 36.1% (p = 0.02), whereas trabecular number increased by 45.6% (p = 0.01), indicating the formation of cancellous bone de novo. There were no significant differences in the radii of animals subject to the stimulus, indicating that the adaptive response was local rather than systemic. The anabolic potential of the signal was evident only in trabecular bone, and there were no differences, as measured by any assay, in the cortical bone. These data suggest that subtle mechanical signals generated during predominant activities such as posture may be potent determinants of skeletal morphology. Given that these strain levels are three orders of magnitude below strains that can damage bone tissue, we

  15. 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.

  16. 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.

  17. Single-Limb Irradiation Induces Local and Systemic Bone Loss in a Murine Model.

    PubMed

    Wright, Laura E; Buijs, Jeroen T; Kim, Hun-Soo; Coats, Laura E; Scheidler, Anne M; John, Sutha K; She, Yun; Murthy, Sreemala; Ma, Ning; Chin-Sinex, Helen J; Bellido, Teresita M; Bateman, Ted A; Mendonca, Marc S; Mohammad, Khalid S; Guise, Theresa A

    2015-07-01

    Increased fracture risk is commonly reported in cancer patients receiving radiotherapy, particularly at sites within the field of treatment. The direct and systemic effects of ionizing radiation on bone at a therapeutic dose are not well-characterized in clinically relevant animal models. Using 20-week-old male C57Bl/6 mice, effects of irradiation (right hindlimb; 2 Gy) on bone volume and microarchitecture were evaluated prospectively by microcomputed tomography and histomorphometry and compared to contralateral-shielded bone (left hindlimb) and non-irradiated control bone. One week postirradiation, trabecular bone volume declined in irradiated tibias (-22%; p < 0.0001) and femurs (-14%; p = 0.0586) and microarchitectural parameters were compromised. Trabecular bone volume declined in contralateral tibias (-17%; p = 0.003), and no loss was detected at the femur. Osteoclast number, apoptotic osteocyte number, and marrow adiposity were increased in irradiated bone relative to contralateral and non-irradiated bone, whereas osteoblast number was unchanged. Despite no change in osteoblast number 1 week postirradiation, dynamic bone formation indices revealed a reduction in mineralized bone surface and a concomitant increase in unmineralized osteoid surface area in irradiated bone relative to contralateral and non-irradiated control bone. Further, dose-dependent and time-dependent calvarial culture and in vitro assays confirmed that calvarial osteoblasts and osteoblast-like MC3T3 cells were relatively radioresistant, whereas calvarial osteocyte and osteocyte-like MLO-Y4 cell apoptosis was induced as early as 48 hours postirradiation (4 Gy). In osteoclastogenesis assays, radiation exposure (8 Gy) stimulated murine macrophage RAW264.7 cell differentiation, and coculture of irradiated RAW264.7 cells with MLO-Y4 or murine bone marrow cells enhanced this effect. These studies highlight the multifaceted nature of radiation-induced bone loss by demonstrating direct

  18. 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

  19. Arthritis induces early bone high turnover, structural degradation and mechanical weakness.

    PubMed

    Vidal, Bruno; Cascão, Rita; Vale, Ana Catarina; Cavaleiro, Inês; Vaz, Maria Fátima; Brito, José Américo Almeida; Canhão, Helena; Fonseca, João Eurico

    2015-01-01

    We have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months) inflammation directly leads to high collagen bone turnover, disorganization of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone. Twenty eight Wistar adjuvant-induced arthritis (AIA) rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for compar-ison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histomorphometrical, energy dispersive X-ray spectroscopical analysis and 3-point bending. Blood samples were also collected for bone turnover markers. AIA rats had an increased bone turnover (as inferred from increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively) and this was paralleled by a decreased mineral content (calcium p = 0.0046 and phos-phorus p = 0.0046). Histomorphometry showed a lower trabecular thickness (p = 0.0002) and bone volume (p = 0.0003) and higher trabecular sepa-ration (p = 0.0009) in the arthritic group as compared with controls. In addition, bone mechanical tests showed evidence of fragility as depicted by diminished values of yield stress and ultimate fracture point (p = 0.0061 and p = 0.0279, re-spectively) in the arthritic group. We have shown in an AIA rat model that arthritis induc-es early bone high turnover, structural degradation, mineral loss and mechanical weak-ness.

  20. Effects of glucocorticoid-induced osteoporosis on bone tissue of rats with experimental periodontitis.

    PubMed

    Sousa, Luzia Hermínia Teixeira; Moura, Eveline Valeriano; Queiroz, Ana Larissa; Val, Danielle; Chaves, Hellíada; Lisboa, Mario; Furlaneto, Flávia; Brito, Gerly Anne; Goes, Paula

    2017-05-01

    To evaluate the effects of osteoporosis induced by glucocorticoid (GIOP) on bone tissue of rats with experimental periodontitis (EP). 48 male Wistar rats divided into groups: Naïve, EP, GIOP and GIOP+EP. Rats of GIOP and GIOP+EP groups received 7mg/kg of dexamethasone intramuscularly once a week for 5 weeks. Following, EP and GIOP+EP groups were subjected to ligature-induced periodontitis. Naïve group experienced no manipulation. After 11 days, the animals were euthanized and left maxillae collected for macroscopic, radiographic, micro-tomographic and microscopic analysis of alveolar bone loss (ABL). Blood samples were collected for determination of bone-specific alkaline phosphatase (BALP) levels and the right femurs were removed for radiographic and biomechanical analysis. EP caused ABL and reduced BALP levels (p<0,05), but it did not change the architecture or biomechanics of femur, compared to Naïve. GIOP did not cause ABL, but it significantly decreased alveolar bone mineral density (ABMD), bone percentage and trabecular thickness (Tb.Th) and increased alveolar bone porosity (p<0.05) and significantly reduced BALP serum levels, as well as radiographic density and Young's module of femur, compared to Naïve. There was a greater ABL in group GIOP+EP when compared to EP (p<0.05). GIOP+EP caused a greater decrease on ABMD, Tb.Th, bone percentage and increased bone porosity (p<0.05) and also presented a significant reduction in BALP levels (p<0.05), in radiographic density and in Young's module of femur compared to EP (p<0.05). GIOP can potentiate the destructive effects of EP on alveolar bone and alter the systemic bone loss, by promoting bone resorption and reducing osteoblast activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. 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

  2. Lineage tracking of mesenchymal and endothelial progenitors in BMP-induced bone formation.

    PubMed

    Kolind, Mille; Bobyn, Justin D; Matthews, Brya G; Mikulec, Kathy; Aiken, Alastair; Little, David G; Kalajzic, Ivo; Schindeler, Aaron

    2015-12-01

    To better understand the relative contributions of mesenchymal and endothelial progenitor cells to rhBMP-2 induced bone formation, we examined the distribution of lineage-labeled cells in Tie2-Cre:Ai9 and αSMA-creERT2:Col2.3-GFP:Ai9 reporter mice. Established orthopedic models of ectopic bone formation in the hind limb and spine fusion were employed. Tie2-lineage cells were found extensively in the ectopic bone and spine fusion masses, but co-staining was only seen with tartrate-resistant acid phosphatase (TRAP) activity (osteoclasts) and CD31 immunohistochemistry (vascular endothelial cells), and not alkaline phosphatase (AP) activity (osteoblasts). To further confirm the lack of a functional contribution of Tie2-lineage cells to BMP-induced bone, we developed conditional knockout mice where Tie2-lineage cells are rendered null for key bone transcription factor osterix (Tie2-cre:Osx(fx/fx) mice). Conditional knockout mice showed no difference in BMP-induced bone formation compared to littermate controls. Pulse labeling of mesenchymal cells with Tamoxifen in mice undergoing spine fusion revealed that αSMA-lineage cells contributed to the osteoblastic lineage (Col2.3-GFP), but not to endothelial cells or osteoclast populations. These data indicate that the αSMA+ and Tie2+ progenitor lineages make distinct cellular contributions to bone formation, angiogenesis, and resorption/remodeling. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

  3. TNF-induced osteoclastogenesis and inflammatory bone resorption are inhibited by transcription factor RBP-J

    PubMed Central

    Zhao, Baohong; Grimes, Shannon N.; Hu, Xiaoyu

    2012-01-01

    Tumor necrosis factor (TNF) plays a key role in the pathogenesis of inflammatory bone resorption and associated morbidity in diseases such as rheumatoid arthritis and periodontitis. Mechanisms that regulate the direct osteoclastogenic properties of TNF to limit pathological bone resorption in inflammatory settings are mostly unknown. Here, we show that the transcription factor recombinant recognition sequence binding protein at the Jκ site (RBP-J) strongly suppresses TNF-induced osteoclastogenesis and inflammatory bone resorption, but has minimal effects on physiological bone remodeling. Myeloid-specific deletion of RBP-J converted TNF into a potent osteoclastogenic factor that could function independently of receptor activator of NF-κB (RANK) signaling. In the absence of RBP-J, TNF effectively induced osteoclastogenesis and bone resorption in RANK-deficient mice. Activation of RBP-J selectively in osteoclast precursors suppressed inflammatory osteoclastogenesis and arthritic bone resorption. Mechanistically, RBP-J suppressed induction of the master regulator of osteoclastogenesis (nuclear factor of activated T cells, cytoplasmic 1) by attenuating c-Fos activation and suppressing induction of B lymphocyte–induced maturation protein-1, thereby preventing the down-regulation of transcriptional repressors such as IRF-8 that block osteoclast differentiation. Thus, RBP-J regulates the balance between activating and repressive signals that regulate osteoclastogenesis. These findings identify RBP-J as a key upstream negative regulator of osteoclastogenesis that restrains excessive bone resorption in inflammatory settings. PMID:22249448

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

    PubMed

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

    2015-08-06

    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.

  5. 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

  6. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    NASA Technical Reports Server (NTRS)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

  7. Changes in alveolar bone support induced by the Herbst appliance: a tomographic evaluation

    PubMed Central

    Schwartz, João Paulo; Raveli, Taisa Boamorte; Schwartz-Filho, Humberto Osvaldo; Raveli, Dirceu Barnabé

    2016-01-01

    ABSTRACT Objective: This study evaluated alveolar bone loss around mandibular incisors, induced by the Herbst appliance. Methods: The sample consisted of 23 patients (11 men, 12 women; mean age of 15.76 ± 1.75 years), Class II, Division 1 malocclusion, treated with the Herbst appliance. CBCT scans were obtained before treatment (T0) and after Herbst treatment (T1). Vertical alveolar bone level and alveolar bone thickness of mandibular incisors were assessed. Buccal (B), lingual (L) and total (T) bone thicknesses were assessed at crestal (1), midroot (2) and apical (3) levels of mandibular incisors. Student's t-test and Wilcoxon t-test were used to compare dependent samples in parametric and nonparametric cases, respectively. Pearson's and Spearman's rank correlation analyses were performed to determine the relationship of changes in alveolar bone thickness. Results were considered at a significance level of 5%. Results: Mandibular incisors showed no statistical significance for vertical alveolar bone level. Alveolar bone thickness of mandibular incisors significantly reduced after treatment at B1, B2, B3, T1 and significantly increased at L2. The magnitude of the statistically significant changes was less than 0.2 mm. The changes in alveolar bone thickness showed no statistical significance with incisor inclination degree. Conclusions: CBCT scans showed an association between the Herbst appliance and alveolar bone loss on the buccal surface of mandibular incisors; however, without clinical significance. PMID:27275621

  8. Protective effect of Pycnogenol® on ovariectomy-induced bone loss in rats.

    PubMed

    Mei, Lin; Mochizuki, Miyako; Hasegawa, Noboru

    2012-01-01

    Pycnogenol® (PYC) is a natural plant extract from the bark of Pinus pinaster and has potent antioxidant activities. The protective effect of PYC on bone loss was studied in multiparous ovariectomized (OVX) female rats. Pycnogenol® (30 or 15 mg/kg body weight/day) was administered orally to 8-month-old OVX rats for 3 months. At the end of the experiment, bone strength was measured by a three-point bending test and bone mineral density was estimated by peripheral quantitative computed tomography. Ovariectomy significantly decreased femur bone strength and bone density. Supplementation with PYC suppressed the bone loss induced by OVX. The OVX treatment significantly increased serum osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTx). Supplementation with PYC reduced the serum OC and CTx in OVX rats to a level similar to that of the sham-operated group. The results indicated that orally administered PYC can decrease the bone turnover rate in OVX rats, resulting in positive effects on the biomechanical strength of bone and bone mineral density.

  9. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    NASA Technical Reports Server (NTRS)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

  10. Zoledronic acid at the time of castration prevented castration-induced bone metastasis in mice.

    PubMed

    Ghosh, Paramita M; Gao, Allen C

    2014-10-01

    Androgen deprivation therapy (ADT) is known to cause bone loss in a majority of patients with castration-resistant prostate cancer (CRPC). A study published in this issue of Endocrine-Related Cancer by Ottewell and colleagues shows that ADT increased bone resorption and triggered growth of disseminated prostate cancer (CaP) cells to form bone metastasis using an in vivo model. However, prevention of bone decay by weekly administration of zoledronic acid (ZOL) at the time of castration prevented ADT-induced tumor growth in bone. Recently, two publications from Japan have demonstrated that ZOL combined with ADT improved outcomes for patients with treatment-naïve CaP with bone metastasis. The mechanistic cause for these patients having an improved overall survival compared with those who were treated with ZOL after ADT initiation or before metastasis development was never explained. Ottewell and colleague's study now suggests that it is the bone loss caused by ADT that promoted bone metastasis, and if ZOL is administered at the time of ADT initiation, it would prevent this bone loss and prolong skeletal-related event-free survival.

  11. 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.

  12. Aromatase inhibitor-induced bone loss increases the progression of estrogen receptor-negative breast cancer in bone and exacerbates muscle weakness in vivo.

    PubMed

    Wright, Laura E; Harhash, Ahmed A; Kozlow, Wende M; Waning, David L; Regan, Jenna N; She, Yun; John, Sutha K; Murthy, Sreemala; Niewolna, Maryla; Marks, Andrew R; Mohammad, Khalid S; Guise, Theresa A

    2017-01-31

    Aromatase inhibitors (AIs) cause muscle weakness, bone loss, and joint pain in up to half of cancer patients. Preclinical studies have demonstrated that increased osteoclastic bone resorption can impair muscle contractility and prime the bone microenvironment to accelerate metastatic growth. We hypothesized that AI-induced bone loss could increase breast cancer progression in bone and exacerbate muscle weakness associated with bone metastases. Female athymic nude mice underwent ovariectomy (OVX) or sham surgery and were treated with vehicle or AI (letrozole; Let). An OVX-Let group was then further treated with bisphosphonate (zoledronic acid; Zol). At week three, trabecular bone volume was measured and mice were inoculated with MDA-MB-231 cells into the cardiac ventricle and followed for progression of bone metastases. Five weeks after tumor cell inoculation, tumor-induced osteolytic lesion area was increased in OVX-Let mice and reduced in OVX-Let-Zol mice compared to sham-vehicle. Tumor burden in bone was increased in OVX-Let mice relative to sham-vehicle and OVX-Let-Zol mice. At the termination of the study, muscle-specific force of the extensor digitorum longus muscle was reduced in OVX-Let mice compared to sham-vehicle mice, however, the addition of Zol improved muscle function. In summary, AI treatment induced bone loss and skeletal muscle weakness, recapitulating effects observed in cancer patients. Prevention of AI-induced osteoclastic bone resorption using a bisphosphonate attenuated the development of breast cancer bone metastases and improved muscle function in mice. These findings highlight the bone microenvironment as a modulator of tumor growth locally and muscle function systemically.

  13. Alendronate as an Effective Countermeasure to Disuse Induced Bone loss

    NASA Technical Reports Server (NTRS)

    LeBlanc, Adrian D.; Driscol, Theda B.; Shackelford, Linda C.; Evans, Harlan J.; Rianon, Nahid J.; Smith, Scott M.; Lai, Dejian

    2002-01-01

    Microgravity, similar to diuse immobilization on earth, causes rapid bone loss. This loss is believed to be an adaptive response to the reduced musculoskelatal forces in space and occurs gradually enough that changes occurring during short duration space flight are not a concern. Bone loss, however, will be a major impediment for long duration missions if effective countermeasures are not developed and implemented. Bed rest is used to simulate the reduced mechanical forces in humans and was used to test the hypothesis that oral alendronate would reduce the effects of long duration (17 weeks) inactivity on bone. Eight male subjects were given daily oral doses of alendronate during 17 weeks of horizontal bed rest and compared with 13 male control subjects not given the drug. Efficacy was evaluated based on measurements of bone markers, calcium balance and bone density performed before, during and after the bed rest. The results show that oral alendronate attenuates most of the characteristic changes associated with long duration bed rest and presumably space flight.

  14. Polymethylmethacrylate-induced release of bone-resorbing factors

    SciTech Connect

    Herman, J.H.; Sowder, W.G.; Anderson, D.; Appel, A.M.; Hopson, C.N. )

    1989-12-01

    A pseudomembranous structure that has the histological characteristics of a foreign-body-like reaction invariably develops at the bone-cement interface in the proximity of resorption of bone around aseptically loosened cemented prostheses. This study was an attempt to implicate polymethylmethacrylate in this resorptive process. Unfractionated peripheral-blood mononuclear cells (consisting of lymphocytes and monocytes) and surface-adherent cells (monocyte-enriched) were prepared from control subjects who did and did not have clinical evidence of osteoarthrosis and from patients who had osteoarthrosis and were having a revision for failure of a cemented hip or knee implant. Cells were cultured for varying periods in the presence and absence of nonpolymerized methacrylate (one to two-micrometer spherules), pulverized polymerized material, or culture chambers that were pre-coated with polymerized cement. Conditioned media that were derived from both methacrylate-stimulated cell populations were shown to contain specific bone-resorbing mediators (interleukin-1, tumor necrosis factor, or prostaglandin E2) and to directly affect bone resorption in 45Ca-labeled murine limb-bone assays.

  15. Inhibitory effect of menaquinone-7 (vitamin K2) on the bone-resorbing factors-induced bone resorption in elderly female rat femoral tissues in vitro.

    PubMed

    Yamaguchi, Masayoshi; Uchiyama, Satoshi; Tsukamoto, Yoshinori

    2003-03-01

    The inhibitory effect of menaquinone-7 (MK-7; vitamin K2) on osteoclast-like cell formation and osteoclastic bone resorption in vitro is found (Mol Cell Biochem 228: 39-47, 2001). This study, furthermore, was undertaken to determine the effect of MK-7 on the bone-resorbing factor-induced bone resorption using the femoral-diaphyseal and -metaphyseal tissues obtained from elderly female rats in vitro. Femoral-diaphyseal and -metaphyseal tissues were cultured for 48 h in Dulbecco's modified Eagle's medium (high glucose, 4.5%) supplemented with antibiotics and bovine serum albumin. The experimental cultures contained MK-7 (10(-7)-10(-5) M). The bone-resorbing factors, parathyroid hormone (1-34) (PTH; 10(-7) M) and prostaglandin E2 (PGE2; 10(-5) M), caused a significant decrease in calcium content in the diaphyseal and metaphyseal tissues. The PTH or PGE2-induced decrease in bone calcium content was completely inhibited in the presence of MK-7 (10(-7)-10(-5) M). In addition, MK-7 (10(-7)-10(-5) M) completely prevented the PTH (10(-7) M)- or PGE2 (10(-5) M)-induced increase in medium glucose consumption and lactic acid production by bone tissues. These results support the view that MK-7 has a direct inhibitory effect on the bone-resorbing factor-induced bone resorption in bone culture using female aged femoral tissues in vitro.

  16. Disease Modification of Breast Cancer–Induced Bone Remodeling by Cannabinoid 2 Receptor Agonists

    PubMed Central

    Symons-Liguori, Ashley M; Largent-Milnes, Tally M; Havelin, Josh J; Ferland, Henry L; Chandramouli, Anupama; Owusu-Ankomah, Mabel; Nikolich-Zugich, Tijana; Bloom, Aaron P; Jimenez-Andrade, Juan Miguel; King, Tamara; Porreca, Frank; Nelson, Mark A; Mantyh, Patrick W; Vanderah, Todd W

    2015-01-01

    Most commonly originating from breast malignancies, metastatic bone cancer causes bone destruction and severe pain. Although novel chemotherapeutic agents have increased life expectancy, patients are experiencing higher incidences of fracture, pain, and drug-induced side effects; furthermore, recent findings suggest that patients are severely undertreated for their cancer pain. Strong analgesics, namely opiates, are first-line therapy in alleviating cancer-related pain despite the severe side effects, including enhanced bone destruction with sustained administration. Bone resorption is primarily treated with bisphosphonates, which are associated with highly undesirable side effects, including nephrotoxicity and osteonecrosis of the jaw. In contrast, cannabinoid receptor 2 (CB2) receptor-specific agonists have been shown to reduce bone loss and stimulate bone formation in a model of osteoporosis. CB2 agonists produce analgesia in both inflammatory and neuropathic pain models. Notably, mixed CB1/CB2 agonists also demonstrate a reduction in ErbB2-driven breast cancer progression. Here we demonstrate for the first time that CB2 agonists reduce breast cancer–induced bone pain, bone loss, and breast cancer proliferation via cytokine/chemokine suppression. Studies used the spontaneously-occurring murine mammary cell line (66.1) implanted into the femur intramedullary space; measurements of spontaneous pain, bone loss, and cancer proliferation were made. The systemic administration of a CB2 agonist, JWH015, for 7 days significantly attenuated bone remodeling, assuaged spontaneous pain, and decreased primary tumor burden. CB2-mediated effects in vivo were reversed by concurrent treatment with a CB2 antagonist/inverse agonist but not with a CB1 antagonist/inverse agonist. In vitro, JWH015 reduced cancer cell proliferation and inflammatory mediators that have been shown to promote pain, bone loss, and proliferation. Taken together, these results suggest CB2 agonists as a

  17. Analysis of the Role of Insulin Signaling in Bone Turnover Induced by Fluoride.

    PubMed

    Liu, Qinyi; Liu, Hui; Yu, Xiuhua; Wang, Yan; Yang, Chen; Xu, Hui

    2016-06-01

    The role of insulin signaling on the mechanism underlying fluoride induced osteopathology was studied. We analyzed the expression of genes related with bone turnover and insulin signaling in rats treated by varying dose of fluoride with or without streptozotocin (STZ) in vivo. Furthermore, insulin receptor (InR) expression in MC3T3-E1 cells (pre-osteoblast cell line) was interfered with small interfering RNA (siRNA), and genes related with osteoblastic and osteoclastic differentiation were investigated in cells exposed to fluoride in vitro for 2 days. The in vivo study indicated the possible role of insulin in bone lesion induced by excessive amount of fluoride. Fluoride activated the InR and Insulin-like growth factor 1 (IGF1) signaling, which were involved in the mechanism underlying fluoride induced bone turnover. The TGFβ1 and Wnt10/β-catenin pathway took part in the mechanism of bone lesion induced by fluoride, and insulin probably modulated the TGFβ1 and β-catenin to exert action on bone turnover during the development of bone lesion. The in vitro study showed the concomitant decrease of OPG, osterix and OCN with inhibition of InR expression in osteoblast, and three genes still was low in cells co-treated with fluoride and InR siRNA, which suggested that fluoride probably stimulated the expression of OPG, osterix and OCN through InR signaling. In conclusion, insulin played the important role in bone lesion induced by excessive amount of fluoride through mediating InR receptor signaling, and IGF1 signaling probably exerted action on bone turnover caused by overdose of fluoride.

  18. Static-kinetic reactions of man under conditions of brief weightlessness

    NASA Technical Reports Server (NTRS)

    Kolosov, I. A.

    1975-01-01

    Physical characteristics of human responses to weightlessness simulation during parabolic flights establish body immobilization and visual illusions as the most manifest causes of sensory distrubances. Repeated brief weightlessness exposures gradually decreased expressions of static-kinetic disorders.

  19. Severe pegfilgrastim-induced bone pain completely alleviated with loratadine: A case report.

    PubMed

    Romeo, Cristina; Li, Quan; Copeland, Larry

    2015-08-01

    Febrile neutropenia is an oncologic emergency that can result in serious consequences. Granulocyte colony stimulating factors (G-CSFs) are often used as prophylaxis for febrile neutropenia. Bone pain is the most notorious adverse effect caused by G-CSFs. Specifically, with pegfilgrastim (Neulasta(®)), the incidence of bone pain is higher in practice than was observed during clinical trials. Traditional analgesics, such as non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, can be ineffective in severe pegfilgrastim-induced bone pain. With the high frequency of this adverse effect, it is clear that health practitioners need additional treatment options for patients who experience severe pegfilgrastim-induced bone pain. The mechanisms of bone pain secondary to G-CSFs are not fully known, but research has shown that histamine release is involved in the inflammatory process. There is scant previous clinical data on antihistamine use in the management of G-CSF-induced pain. We present the first case report in which loratadine prophylaxis completely alleviated NSAID-resistant severe pain secondary to pegfilgrastim. The result showed that loratadine may be a promising option for severe, resistant pegfilgrastim-induced bone pain. Further clinical studies are warranted and ongoing.

  20. Associations among Endocrine, Inflammatory, and Bone Markers, Body Composition and Physical Activity to Weight Loss Induced Bone Loss

    PubMed Central

    Labouesse, Marie A.; Gertz, Erik R.; Piccolo, Brian D.; Souza, Elaine C.; Schuster, Gertrud U.; Witbracht, Megan G.; Woodhouse, Leslie R.; Adams, Sean H.; Keim, Nancy L.; Van Loan, Marta D.

    2015-01-01

    INTRODUCTION Weight loss reduces co-morbidities of obesity, but decreases bone mass. PURPOSE Our aims were to 1) determine if adequate dairy intake attenuates weight loss-induced bone loss; 2) evaluate the associations of endocrine, inflammatory and bone markers, anthropometric and other parameters to bone mineral density and content (BMD, BMC) pre- and post-weight loss; 3) model the contribution of these variables to post weight-loss BMD and BMC METHODS Overweight/obese women (BMI: 28–37 kg/m2) were enrolled in an energy reduced (−500 kcal/d; −2092 kJ/d) diet with adequate dairy (AD: 3–4 servings/d; n=25, 32.2 ± 8.8y) or low dairy (LD: ≤ 1 serving/d; n=26, 31.7 ± 8.4 y). BMD, BMC and body composition were measured by DXA. Bone markers (CTX, PYD, BAP, OC), endocrine (PTH, vitamin D, leptin, adiponectin, ghrelin, amylin, insulin, GLP-1, PAI-1, HOMA) and inflammatory markers (CRP, IL1-β, IL-6, IL-8, TNF-α, cortisol) were measured in serum or plasma. PA was assessed by accelerometry. RESULTS Following weight loss, AD intake resulted in significantly greater (p= 0.004) lumbar spine BMD and serum osteocalcin (p=0.004) concentration compared to LD. Pre- and post- body fat were negatively associated with hip and lumbar spine BMC (r= −0.28, p=0.04 to −0.45, p=0.001). Of note were the significant negative associations among bone markers and IL-1β, TNFα and CRP ranging from r = −0.29 (p=0.04) to r = −0.34 (p=0.01); magnitude of associations did not change with weight loss. Adiponectin was negatively related to change in osteocalcin. Factor analysis resulted in 8 pre- and post-weight loss Factors. Pre-weight loss Factors accounted for 13.7% of the total variance in pre-weight loss hip BMD; post-weight loss Factors explained 19.6% of the total variance in post-weight loss hip BMD. None of the Factors contributed to the variance in lumbar spine BMD. CONCLUSION AD during weight loss resulted in higher lumbar spine BMD and osteocalcin compared to LD

  1. Osteoblasts of calvaria induce higher numbers of osteoclasts than osteoblasts from long bone.

    PubMed

    Wan, Qilong; Schoenmaker, Ton; Jansen, Ineke D C; Bian, Zhuan; de Vries, Teun J; Everts, Vincent

    2016-05-01

    Several studies have demonstrated the existence of functional differences between osteoclasts harbored in different bones. The mechanisms involved in the occurrence of such a heterogeneity are not yet understood. Since cells of the osteoblast lineage play a critical role in osteoclastogenesis, osteoclast heterogeneity may be due to osteoblasts that differ at the different bone sites. In the present study we evaluated possible differences in the capacity of calvaria and long bone osteoblasts to induce osteoclastogenesis. Osteoblasts were isolated from calvaria and long bone of mice and co-cultured with osteoclast precursors obtained from bone marrow of both types of bone, spleen and peripheral blood. Irrespective of the source of the precursors, a significantly higher number of TRACP-positive multinucleated cells were formed with calvaria osteoblasts. The expression of osteoclastogenesis related genes was analyzed by qPCR. OPG was significantly higher expressed by long bone osteoblasts. The RANKL/OPG ratio and TNF-α gene expression were significantly higher in calvaria osteoblast cultures. OPG added to the culture system inhibited osteoclastogenesis in both groups. Blocking TNF-α had no effect on osteoclastogenesis. Calvaria and long bone osteoblasts were pre-stimulated with VitD3 for 5days. Subsequently, osteoclast precursors were added to these cultures. After a co-culture of 6days, it was shown that VitD3 pre-stimulation of long bone osteoblasts strongly improved their capacity to induce osteoclast formation. This coincided with an increased ratio of RANKL/OPG. Taken together, the data demonstrated differences in the capacity of calvaria and long bone osteoblasts to induce osteoclastogenesis. This appeared to be due to differences in the expression of RANKL and OPG. VitD3 pre-stimulation improved the ability of long bone osteoblasts to induce osteoclast formation. Our findings demonstrate bone-site specific differences in osteoblast-mediated formation of

  2. Pegfilgrastim-Induced Bone Pain: A Review on Incidence, Risk Factors, and Evidence-Based Management.

    PubMed

    Moore, Donald C; Pellegrino, Annie E

    2017-09-01

    To review the incidence, risk factors, and management of pegfilgrastim-induced bone pain (PIBP). PubMed was searched from 1980 to March 31, 2017, using the terms pegfilgrastim and bone pain. English-language, human studies and reviews assessing the incidence, risk factors, and management of PIBP were incorporated. A total of 3 randomized, prospective studies and 2 retrospective studies evaluated pharmacological management of PIBP. Naproxen compared with placebo demonstrated a reduction in the degree, incidence, and duration of bone pain secondary to pegfilgrastim. Loratadine was not effective in reducing the incidence of bone pain prophylactically, but a retrospective study evaluating dual antihistamine blockade with loratadine and famotidine demonstrated a decreased incidence in bone pain when administered before pegfilgrastim. Naproxen is effective at managing PIBP. Although commonly used, antihistamines have a paucity of data supporting their use. Dose reductions of pegfilgrastim and opioids may also be potential management options; however, data supporting these treatment modalities are scarce.

  3. Trabecular bone remodelling simulation considering osteocytic response to fluid-induced shear stress.

    PubMed

    Adachi, Taiji; Kameo, Yoshitaka; Hojo, Masaki

    2010-06-13

    In bone functional adaptation by remodelling, osteocytes in the lacuno-canalicular system are believed to play important roles in the mechanosensory system. Under dynamic loading, bone matrix deformation generates an interstitial fluid flow in the lacuno-canalicular system; this flow induces shear stress on the osteocytic process membrane that is known to stimulate the osteocytes. In this sense, the osteocytes behave as mechanosensors and deliver mechanical information to neighbouring cells through the intercellular communication network. In this study, bone remodelling is assumed to be regulated by the mechanical signals collected by the osteocytes. From the viewpoint of multi-scale biomechanics, we propose a mathematical model of trabecular bone remodelling that takes into account the osteocytic mechanosensory network system. Based on this model, a computational simulation of trabecular bone remodelling was conducted for a single trabecula under cyclic uniaxial loading, demonstrating functional adaptation to the applied mechanical loading as a load-bearing construct.

  4. Reversal of drug-induced rhabdomyolysis on bone scan.

    PubMed

    Abrams, Joseph; Tiu, Serafin

    2011-08-01

    A 75-year-old man with prostate cancer was referred for metastatic workup. A Tc-99m methylene diphosphonate bone scan was performed which revealed diffusely increased radiopharmaceutical uptake in the muscles of the arms and thighs. The patient was taking simvastatin 80 mg per day and gemfibrozil 600 mg twice a day for high cholesterol. The patient reported myalgias, and laboratory evaluation was consistent with rhabdomyolysis. After discontinuation of the anticholesterol medications, the clinical and laboratory evaluations normalized. Bone scan performed 1 year later demonstrated complete resolution of muscle uptake.

  5. Fish bone-induced hepatic abscess: medical treatment.

    PubMed

    Ng, C T; Htoo, A; Tan, S Y

    2011-03-01

    We report a case of a 59-year-old man admitted for acute myocardial infarction. He subsequently spiked a high-grade fever on the second day after percutaneous coronary intervention. Computed tomography imaging of the abdomen revealed a hepatic abscess secondary to gastrointestinal perforation by a fish bone. Medical therapy with antibiotics was preferred over surgical drainage of the hepatic abscess in view of the fact that the patient was on dual antiplatelet agents. The hepatic abscess was completely resolved with conservative antimicrobial therapy. Antimicrobial therapy appears to be a viable option in selected patients with hepatic abscess secondary to fish bone perforation, especially if they have contraindications to surgery.

  6. 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.

  7. 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...

  8. Skeletal maturity leads to a reduction in the strain magnitudes induced within the bone: a murine tibia study.

    PubMed

    Razi, Hajar; Birkhold, Annette I; Zaslansky, Paul; Weinkamer, Richard; Duda, Georg N; Willie, Bettina M; Checa, Sara

    2015-02-01

    Bone adapts to changes in the local mechanical environment (e.g. strains) through formation and resorption processes. However, the bone adaptation response is significantly reduced with increasing age. The mechanical strains induced within the bone by external loading are determined by bone morphology and tissue material properties. Although it is known that changes in bone mass, architecture and bone tissue quality occur with age, to what extent they contribute to the altered bone adaptation response remains to be determined. This study investigated alterations in strains induced in the tibia of different aged female C57Bl/6J mice (young, 10-week-old; adult, 26-week-old; and elderly, 78-week-old) subjected to in vivo compressive loading. Using a combined in vivo/in silico approach, the strains in the bones were assessed by both strain gauging and finite element modeling experiments. In cortical bone, strain magnitudes induced at the mid-diaphysis decreased by 20% from young to adult mice and by 15% from adult to elderly mice. In the cancellous bone (at the proximal metaphysis), induced strains were 70% higher in young compared with adult and elderly mice. Taking into account previous studies showing a reduced bone adaptation response to mechanical loading in adulthood, these results suggest that the diminished adaptive response is in part due to a reduction in the strains induced within the bone.

  9. [Expectation of the study of weightlessness physiology in the 21st century].

    PubMed

    Shen, Xian-yun

    2003-01-01

    Weightlessness physiology is an applied subject to study the influence of weightlessness on human body, the mechanism of the changes and countermeasures. This paper introduces the effects of weightlessness on human physiological system, and on the basis of the general research situation of weightlessness physiology at home and abroad, the research goal, the division of research stages and implement methods of our country in the 21st century are proposed.

  10. Parathyroid Hormone (1-34) Transiently Protects Against Radiation-Induced Bone Fragility.

    PubMed

    Oest, Megan E; Mann, Kenneth A; Zimmerman, Nicholas D; Damron, Timothy A

    2016-06-01

    Radiation therapy for soft tissue sarcoma or tumor metastases is frequently associated with damage to the underlying bone. Using a mouse model of limited field hindlimb irradiation, we assessed the ability of parathyroid hormone (1-34) fragment (PTH) delivery to prevent radiation-associated bone damage, including loss of mechanical strength, trabecular architecture, cortical bone volume, and mineral density. Female BALB/cJ mice received four consecutive doses of 5 Gy to a single hindlimb, accompanied by daily injections of either PTH or saline (vehicle) for 8 weeks, and were followed for 26 weeks. Treatment with PTH maintained the mechanical strength of irradiated femurs in axial compression for the first eight weeks of the study, and the apparent strength of irradiated femurs in PTH-treated mice was greater than that of naïve bones during this time. PTH similarly protected against radiation-accelerated resorption of trabecular bone and transient decrease in mid-diaphyseal cortical bone volume, although this benefit was maintained only for the duration of PTH delivery. Overall, PTH conferred protection against radiation-induced fragility and morphologic changes by increasing the quantity of bone, but only during the period of administration. Following cessation of PTH delivery, bone strength and trabecular volume fraction rapidly decreased. These data suggest that PTH does not negate the longer-term potential for osteoclastic bone resorption, and therefore, finite-duration treatment with PTH alone may not be sufficient to prevent late onset radiotherapy-induced bone fragility.

  11. Botulinum toxin induces muscle paralysis and inhibits bone regeneration in zebrafish.

    PubMed

    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

    2014-11-01

    Intramuscular administration of Botulinum toxin (BTx) has been associated with impaired osteogenesis in diverse conditions of bone formation (eg, 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 we 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.

  12. Increased circulating estradiol in mice fed a high-fat diet does not attenuate ovariectomy-induced bone structural deterioration

    USDA-ARS?s Scientific Manuscript database

    Ovariectomy-induced estrogen deficiency increases adiposity and induces substantial bone loss by increasing osteoclast activity. This study investigated whether obesity induced by a high-fat diet alter circulating estradiol levels, mitigates or exacerbates bone structure deterioration, and changes m...

  13. Oestrogen-induced bone marrow aplasia in a dog.

    PubMed

    Bland-van den Berg, P; Bomzon, L; Lurie, A

    1978-12-01

    A case of oestrogen toxicity in the dog is described. The bone marrow was primarily affected with resultant non-regenerative anaemia, leukocytosis followed by leukopaenia, and thrombocytopaenia. Endometritis, toxaemia and disseminate intravascular coagulation were complicating factors. The case terminated fatally intensive therapy.

  14. Managing cancer treatment-induced bone loss and osteoporosis in patients with breast or prostate cancer.

    PubMed

    Michaud, Laura Boehnke

    2010-04-01

    To discuss trends in breast and prostate cancer prevalence and survival; risk factors for bone loss, osteoporosis, and fractures and the approach to risk assessment in patients with these malignancies; established and investigational drug therapies for managing cancer treatment-induced bone loss and osteoporosis; and the role of health-system pharmacists in promoting bone health in patients with breast or prostate cancer. Breast cancer and prostate cancer are common, deadly diseases, but many survivors are alive today because of improvements in early detection and treatment over the past 10-15 years. Cancer chemotherapy, corticosteroids, hormone-ablation therapy, and other common risk factors place patients with breast or prostate cancer at high risk for bone loss, osteoporosis, and fractures. Most patients with breast or prostate cancer should undergo assessment of risk for bone loss and osteoporosis that involves a bone-related history and physical examination, dual-energy X-ray absorptiometry scanning, and the FRAX fracture risk assessment tool from the World Health Organization. A recent National Comprehensive Cancer Network task force report on bone health in cancer care provides recommendations for considering the use of pharmacologic therapy on the basis of the results of this assessment. Bisphosphonates are useful for slowing or preventing bone loss associated with hormone-ablation therapy in women with breast cancer and men with prostate cancer, although fracture data are limited in women and not available in men. The usefulness of other therapies (selective estrogen receptor modulators, teriparatide, calcitonin salmon, and estrogens) is limited by adverse effects, a lack of experience with the drugs in these patient populations, or both. Various drug therapies are in development for managing cancer treatment-induced bone loss and osteoporosis. The agent closest to approval by the Food and Drug Administration, denosumab, has been shown to improve bone

  15. Effect of cryo-induced microcracks on microindentation of hydrated cortical bone tissue

    SciTech Connect

    Yin Ling; Venkatesan, Sudharshan; Webb, Daryl; Kalyanasundaram, Shankar; Qin Qinghua

    2009-08-15

    Microcracks accumulate in cortical bone tissue as a consequence of everyday cyclic loading. However, it remains unclear to what extent microdamage accumulation contributes to an increase in fracture risk. A cryo-preparation technique was applied to induce microcracks in cortical bone tissue. Microcracks with lengths up to approximately 20 {mu}m, which were initiated mainly on the boundaries of haversian canals, were observed with cryo-scanning electron microscopy. A microindentation technique was applied to study the mechanical loading effect on the microcracked hydrated bone tissue. The microindentation patterns were section-scanned using confocal laser scanning microscopy to understand the deformation and bone damage mechanisms made by mechanical loading. The results show that there was no significant difference with respect to microhardness between the original and microcracked hydrated cortical bone tissues (ANOVA, p > 0.05). The cryo-induced microcracks in the bone tissue were not propagated further under the mechanical loads applied. The deformation mechanism of the microcracked cortical bone tissue was plastic deformation, not brittle fracture.

  16. Antiresorptive therapy in the management of cancer treatment-induced bone loss.

    PubMed

    Garg, Ashwani; Leitzel, Kim; Ali, Suhail; Lipton, Allan

    2015-04-01

    Cancer treatment-induced bone loss treatment has an important role to prevent bone loss-related events like fracture, significant morbidity, mortality, disfigurement and loss of self-esteem, and health-care expenditure. Numerous factors, including treatment regimens and bone metastasis, increase the risk of osteoporosis or local bone destruction in most breast and prostate cancer patients. Cytotoxic chemotherapies, radiation, and hormonal therapies can lead to premature menopause and decrease bone mineral density. Over 60 % of breast cancer patients within 1 year of beginning postoperative adjuvant chemotherapy experience ovarian failure. Also, ovarian ablation and aromatase inhibitors used to treat breast cancer and orchiectomy and androgen deprivation therapy (ADT; to treat prostate cancer) cause substantial bone loss. In this article, we will focus mainly on antiresorptive therapy in the management of cancer treatment-induced bone loss (CTIBL). An understanding of CTIBL is critical for determining how to assess the risk and identify which patients may benefit from preventive therapy.

  17. 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.

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

    NASA Astrophysics Data System (ADS)

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

    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, thermoneutral chamber implanted around intact skeletal muscle on the back of a rat. Using this technique, the preformed 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.

  19. 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.

  20. 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.

  1. 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).

  2. 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.

  3. FPGA implementation of a pyramidal Weightless Neural Networks learning system.

    PubMed

    Al-Alawi, Raida

    2003-08-01

    A hardware architecture of a Probabilistic Logic Neuron (PLN) is presented. The suggested model facilitates the on-chip learning of pyramidal Weightless Neural Networks using a modified probabilistic search reward/penalty training algorithm. The penalization strategy of the training algorithm depends on a predefined parameter called the probabilistic search interval. A complete Weightless Neural Network (WNN) learning system is modeled and implemented on Xilinx XC4005E Field Programmable Gate Array (FPGA), allowing its architecture to be configurable. Various experiments have been conducted to examine the feasibility and performance of the WNN learning system. Results show that the system has a fast convergence rate and good generalization ability.

  4. Short-term Outcomes of Induced Membrane Technique in Treatment of Long Bone Defects in Iran

    PubMed Central

    Yeganeh, Ali; Mahmodi, Mani; Farahini, Hosein; Moghtadaei, Mehdi

    2016-01-01

    Introduction: Severe defects in long bones can be caused by several factors such as trauma that lead to open wound and secondary infections after surgery. Induced membrane technique is one of the therapeutic strategies that can be used for these patients. Due to importance of this method and lack of information about this technique in Iran. Aim: this study was performed to investigate technical strengths and weakness of induced membrane technique. Material and Methods: This case series study conducted on 21 patients with bone defects in the femur and tibia and metatarsal bones referred to orthopedic clinic of Rasoul Akram Hospital, Tehran, Iran, for induced membrane surgery in 2012-2015. Demographic and clinical data were obtained using history, clinical examinations and observations for each patient. Union achievement was the main outcome of this study, which was confirmed by radiographic findings and physical examination. Obtained data was analyzed by SPSS ver. 16. Results: All patients were male except one and their mean age was 30.52 years old. Bone defects were in tibia, femur and metatarsus in 9, 9 and 3 patients, respectively. Three patients received soft tissue reconstruction with flap before induced membrane surgery. Age, defects size, cigarette addiction and drug use and delay to start the treatment had no significant effect on union status. In total, 90% of patients had successful surgery. Conclusion: using induced membrane technique in patients with defects in their long bone such as tibia, femur and metatarsus would lead to high success for reconstruction. PMID:27703290

  5. Mechanisms of fluid-flow-induced matrix production in bone tissue engineering.

    PubMed

    Morris, H L; Reed, C I; Haycock, J W; Reilly, G C

    2010-12-01

    Matrix production by tissue-engineered bone is enhanced when the growing tissue is subjected to mechanical forces and/or fluid flow in bioreactor culture. Cells deposit collagen and mineral, depending upon the mechanical loading that they receive. However, the molecular mechanisms of flow-induced signal transduction in bone are poorly understood. The hyaluronan (HA) glycocalyx has been proposed as a potential mediator of mechanical forces in bone. Using a parallel-plate flow chamber the effects of removal of HA on flow-induced collagen production and NF-kappaB activation in MLO-A5 osteoid osteocytes were investigated. Short periods of fluid flow significantly increased collagen production and induced translocation of the NF-kappaB subunit p65 to the cell's nuclei in 65 per cent of the cell population. Enzymatic removal of the HA coat and antibody blocking of CD44 (a transmembrane protein that binds to HA) eliminated the fluid-flow-induced increase in collagen production but had no effect on the translocation of p65. HA and CD44 appear to play roles in transducing the flow signals that modulate collagen production over long-term culture but not in the short-term flow-induced activation of NF-kappaB, implying that multiple signalling events are initiated from the commencement of flow. Understanding the mechanotransduction events that enable fluid flow to stimulate bone matrix production will allow the optimization of bioreactor design and flow profiles for bone tissue engineering.

  6. 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.

  7. 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

  8. Intravenous Immunoglobulin (IVIG) Attenuates TNF-induced Pathologic Bone Resorption and Suppresses Osteoclastogenesis by Inducing A20 Expression

    PubMed Central

    Mun, Sehwan; Bae, Seyeon; Murata, Koichi; Ivashkiv, Lionel B.; Park-Min, Kyung-Hyun

    2016-01-01

    Investigations on the therapeutic effects of intravenous immunoglobulin (IVIG) have focused on the suppression of autoantibody- and immune complex-mediated inflammatory pathogenesis. Inflammatory diseases such as rheumatoid arthritis are often accompanied by excessive bone erosion but the effect of IVIG on osteoclasts, bone-resorbing cells, has not been studied. Here, we investigate whether IVIG directly regulates osteoclast differentiation and has therapeutic potential for suppressing osteoclast-mediated pathologic bone resorption. IVIG or cross-linking of Fcγ receptors with plate-bound IgG suppressed receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and expression of osteoclast-related genes such as integrin β3 and cathepsin K in a dose-dependent manner. Mechanistically, IVIG or plate-bound IgG suppressed osteoclastogenesis by downregulating RANKL-induced expression of NFATC1, the master regulator of osteoclastogenesis. IVIG suppressed NFATC1 expression by attenuating RANKL-induced NF-κB signaling, explained in part by induction of the inflammatory signaling inhibitor A20. IVIG administration attenuated in vivo osteoclastogenesis and suppressed bone resorption in the tumor necrosis factor (TNF)-induced calvarial osteolysis model. Our findings show that, in addition to suppressing inflammation, IVIG directly inhibits osteoclastogenesis through a mechanism involving suppression of RANK signaling. Direct suppression of osteoclast differentiation may provide beneficial effects on preserving bone mass when IVIG is used to treat rheumatic disorders. PMID:26189496

  9. 32k Da protein improve ovariectomy-induced bone loss in rats

    PubMed Central

    Zhou, Yingtang; Jiang, Shenhua; Chen, Jing; Wang, Tao; Jiang, DengZhao; Chen, Hui; Yu, Huan

    2013-01-01

    The objective of the present study was to systematically explore the effects of 32K Da protein (32KP) on postmenopausal osteoporosis. Eighty 3-mo-old female Sprague-Dawley rats were employed and randomly divided into one sham-operated group (SHAM) and five ovariectomy (OVX) subgroups as OVX (control), OVX with 17-ethinylestradiol (E2, 25 g/kg/day), OVX with 32KP of graded doses (50, 50, or 150 mg/kg/day). 32KP or E2 diet was fed on week 4 after operation, for 16 weeks. Bone mass, bone turnover and strength were evaluated by dual-energy X-ray absorptiometry (DEXA), biochemical markers and three-point bending test, respectively. Femur marrow cavity was observed by light microscopy via hematoxylin-eosin staining. It is observed that different dosage treatment of 32KP increased the body weight and prevented the loss of bone mass induced by OVX. The prevention effect against bone loss was presumably due to the altering of the rate of bone remodeling. The bone mineral density and bone calcium content in OVX rats were lower than that in the control group, suggesting that 32KP was able to prevent significant bone loss. In addition, the data from three point bending test and femur sections showed that 32KP treatment enhanced bone strength and reduced the marrow cavity of the femur in OVX rats. In the serum and urine assay, 32KP decreased urinary deoxypyridinoline and calcium concentrations; however, serum alkaline phosphatase activities were not inhibited. It suggested that amelioration of bone loss was changed via inhibition of bone reabsorption. Our findings indicated that 32KP might be a potential alternative drug for the prevention and treatment of postmenopausal osteoporosis. PMID:23924638

  10. Oral administration of 5-hydroxytryptophan aggravated periodontitis-induced alveolar bone loss in rats.

    PubMed

    Li, Xianxian; Wu, Xiangnan; Ma, Yuanyuan; Hao, Zhichao; Chen, Shenyuan; Fu, Taozi; Chen, Helin; Wang, Hang

    2015-05-01

    5-Hydroxytryptophan (5-HTP) is the precursor of serotonin and 5-HTP has been widely used as a dietary supplement to raise serotonin level. Serotonin has recently been discovered to be a novel and important player in bone metabolism. As peripheral serotonin negatively regulates bone, the regular take of 5-HTP may affect the alveolar bone metabolism and therefore influence the alveolar bone loss induced by periodontitis. The aim of this study was to investigate the effect of 5-HTP on alveolar bone destruction in periodontitis. Male Sprague-Dawley rats were randomly divided into the following four groups: (1) the control group (without ligature); (2) the 5-HTP group (5-HTP at 25 mg/kg/day without ligature); (3) the L group (ligature+saline placebo); and (4) the L+5-HTP group (ligature+5-HTP at 25 mg/kg/day). Serum serotonin levels were determined by ELISA. The alveolar bones were evaluated with micro-computed tomography and histology. Tartrate-resistant acid phosphatase staining was used to assess osteoclastogenesis. The receptor activator of NF-kB ligand (RANKL) and osteoprotegerin (OPG) expression in the periodontium as well as the interleukin-6 positive osteocytes were analysed immunohistochemically. 5-HTP significantly increased serum serotonin levels. In rats with experimental periodontitis, 5-HTP increased alveolar bone resorption and worsened the micro-structural destruction of the alveolar bone. 5-HTP also stimulated osteoclastogenesis and increased RANKL/OPG ratio and the number of IL-6 positive osteocytes. However, 5-HTP treatment alone did not cause alveolar bone loss in healthy rats. The present study showed that 5-HTP aggravated alveolar bone loss, deteriorated alveolar bone micro-structure in the presence of periodontitis, which suggests 5-HTP administration may increase the severity of periodontitis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Bone-induced expression of integrin β3 enables targeted nanotherapy of breast cancer metastases.

    PubMed

    Ross, Michael H; Esser, Alison K; Fox, Gregory C; Schmieder, Anne H; Yang, Xiaoxia; Hu, Grace; Pan, Dipanjan; Su, Xinming; Xu, Yalin; Novack, Deborah V; Walsh, Thomas; Colditz, Graham A; Lukaszewicz, Gabriel H; Cordell, Elizabeth; Novack, Joshua S; Fitzpatrick, James A J; Waning, David L; Mohammad, Khalid S; Guise, Theresa A; Lanza, Gregory M; Weilbaecher, Katherine N

    2017-08-30

    Bone metastases occur in ~70% of metastatic breast cancer patients often leading to skeletal injuries. Current treatments are mainly palliative and underscore the unmet clinical need for improved therapies. In this study, we provide preclinical evidence for an antimetastatic therapy based on targeting integrin β3 (β3) which is selectively induced on breast cancer cells in bone by the local bone microenvironment. In a preclinical model of breast cancer, β3 was strongly expressed on bone metastatic cancer cells but not primary mammary tumors or visceral metastases. In tumor tissue from breast cancer patients, β3 was significantly elevated on bone metastases relative to primary tumors from the same patient (n=42). Mechanistic investigations revealed that TGF--β signaling through SMAD2/SMAD3 was necessary for breast cancer induction of β3 within the bone. Using a micelle--based nanoparticle therapy that recognizes integrin αvβ3 (αvβ3--MPs of ~12.5nm), we demonstrated specific localization to breast cancer bone metastases in mice. Using this system for targeted delivery of the chemotherapeutic docetaxel, we showed that bone tumor burden could be reduced significantly with less bone destruction and less hepatotoxicity compared to equimolar doses of free docetaxel. Furthermore, mice treated with αvβ3--MP--docetaxel exhibited a significant decrease in bone-residing tumor cell proliferation compared to free docetaxel. Taken together, our results offer preclinical proof of concept for a method to enhance delivery of chemotherapeutics to breast cancer cells within the bone by exploiting their selective expression of integrin αvβ3 at that metastatic site. Copyright ©2017, American Association for Cancer Research.

  12. Propranolol Attenuates Risperidone-Induced Trabecular Bone Loss in Female Mice.

    PubMed

    Motyl, Katherine J; DeMambro, Victoria E; Barlow, Deborah; Olshan, David; Nagano, Kenichi; Baron, Roland; Rosen, Clifford J; Houseknecht, Karen L

    2015-07-01

    Atypical antipsychotic (AA) drugs cause significant metabolic side effects, and clinical data are emerging that demonstrate increased fracture risk and bone loss after treatment with the AA, risperidone (RIS). The pharmacology underlying the adverse effects on bone is unknown. However, RIS action in the central nervous system could be responsible because the sympathetic nervous system (SNS) is known to uncouple bone remodeling. RIS treatment in mice significantly lowered trabecular bone volume fraction (bone volume/total volume), owing to increased osteoclast-mediated erosion and reduced osteoblast-mediated bone formation. Daytime energy expenditure was also increased and was temporally associated with the plasma concentration of RIS. Even a single dose of RIS transiently elevated expression of brown adipose tissue markers of SNS activity and thermogenesis, Pgc1a and Ucp1. Rankl, an osteoclast recruitment factor regulated by the SNS, was also increased 1 hour after a single dose of RIS. Thus, we inferred that bone loss from RIS was regulated, at least in part, by the SNS. To test this, we administered RIS or vehicle to mice that were also receiving the nonselective β-blocker propranolol. Strikingly, RIS did not cause any changes in trabecular bone volume/total volume, erosion, or formation while propranolol was present. Furthermore, β2-adrenergic receptor null (Adrb2(-/-)) mice were also protected from RIS-induced bone loss. This is the first report to demonstrate SNS-mediated bone loss from any AA. Because AA medications are widely prescribed, especially to young adults, clinical studies are needed to assess whether β-blockers will prevent bone loss in this vulnerable population.

  13. Modulation of {beta}-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats.

    PubMed

    Yin, Wen; Liu, Jin-Cheng; Fan, Rong; Sun, Xi-Qing; Ma, Jin; Feng, Na; Zhang, Quan Yu; Yin, Zhao; Zhang, Shu-Miao; Guo, Hai-Tao; Bi, Hui; Wang, Yue-Min; Sun, Xin; Cheng, Liang; Cui, Qin; Yu, Shi-Qiang; Yi, Ding-Hua; Pei, Jian-Ming

    2008-08-01

    The modulation of beta-adrenoceptor signaling in the hearts of hindlimb unweighting (HU) simulated weightlessness rats has not been reported. In the present study, we adopted the rat tail suspension for 4 wk to simulate weightlessness; then the effects of simulated microgravity on beta-adrenoceptor signaling were studied. Mean arterial blood pressure (ABP), left ventricular pressure (LVP), systolic function (+dP/dtmax), and diastolic function (-dP/dtmax) were monitored in the course of the in vivo experiment. Single rat ventricular myocyte was obtained by the enzymatic dissociation method. Hemodynamics, myocyte contraction, and cAMP production in response to beta-adrenoceptor stimulation with isoproterenol or adenylyl cyclase stimulation with forskolin were measured, and Gs protein was also determined. Compared with the control group, no significant changes were found in heart weight, body weight and ABP, while LVP and +/-dP/dtmax were significantly reduced. The ABP decrease, LVP increase, and +/-dP/dtmax in response to isoproterenol administration were significantly attenuated in the HU group. The effects of isoproterenol on electrically induced single-cell contraction and cAMP production in myocytes of ventricles in the HU rats were significantly attenuated. The biologically active isoform, Gsalpha (45 kDa) in the heart, was unchanged. Both the increased electrically induced contraction and cAMP production in response to forskolin were also significantly attenuated in the simulated weightlessness rats. Above results indicated that impaired function of adenylyl cyclase causes beta-adrenoceptor desensitization, which may be partly responsible for the depression of cardiac function.

  14. Bone Tissue Properties Measurement by Reference Point Indentation in Glucocorticoid-Induced Osteoporosis.

    PubMed

    Mellibovsky, Leonardo; Prieto-Alhambra, Daniel; Mellibovsky, Fernando; Güerri-Fernández, Roberto; Nogués, Xavier; Randall, Connor; Hansma, Paul K; Díez-Perez, Adolfo

    2015-09-01

    Glucocorticoids, widely used in inflammatory disorders, rapidly increase bone fragility and, therefore, fracture risk. However, common bone densitometry measurements are not sensitive enough to detect these changes. Moreover, densitometry only partially recognizes treatment-induced fracture reductions in osteoporosis. Here, we tested whether the reference point indentation technique could detect bone tissue property changes early after glucocorticoid treatment initiation. After initial laboratory and bone density measurements, patients were allocated into groups receiving calcium + vitamin D (Ca+D) supplements or anti-osteoporotic drugs (risedronate, denosumab, teriparatide). Reference point indentation was performed on the cortical bone layer of the tibia by a handheld device measuring bone material strength index (BMSi). Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA). Although Ca+D-treated patients exhibited substantial and significant deterioration, risedronate-treated patients exhibited no significant change, and both denosumab- and teriparatide-treated participants exhibited significantly improved BMSi 7 weeks after initial treatment compared with baseline; these trends remained stable for 20 weeks. In contrast, no densitometry changes were observed during this study period. In conclusion, our study is the first to our knowledge to demonstrate that reference point indentation is sensitive enough to reflect changes in cortical bone indentation after treatment with osteoporosis therapies in patients newly exposed to glucocorticoids.

  15. 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.

  16. 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.

  17. Pyrroloquinoline quinone prevents testosterone deficiency-induced osteoporosis by stimulating osteoblastic bone formation and inhibiting osteoclastic bone resorption

    PubMed Central

    Wu, Xuan; Li, Jie; Zhang, Hengwei; Wang, Hui; Yin, Guoyong; Miao, Dengshun

    2017-01-01

    Accumulating evidences suggest that oxidative stress caused and deteriorated the aging related osteoporosis and pyrroloquinoline quinone (PQQ) is a powerful antioxidant. However, it is unclear whether PQQ can prevent testosterone deficiency-induced osteoporosis. In this study, the orchidectomized (ORX) mice were supplemented in diet with/without PQQ for 48 weeks, and compared with each other and with sham mice. Results showed that bone mineral density, trabecular bone volume, collagen deposition and osteoblast number were decreased significantly in ORX mice compared with shame mice, whereas PQQ supplementation largely prevented these alterations. In contrast, osteoclast surface and ratio of RANKL and OPG mRNA relative expression levels were increased significantly in ORX mice compared with shame mice, but were decreased significantly by PQQ supplementation. Furthermore, we found that CFU-f and ALP positive CFU-f forming efficiency and the proliferation of mesenchymal stem cells were reduced significantly in ORX mice compared with shame mice, but were increased significantly by PQQ supplementation. Reactive oxygen species (ROS) levels in thymus were increased, antioxidant enzymes SOD-1, SOD-2, Prdx I and Prdx IV protein expression levels in bony tissue were down-regulated, whereas the protein expression levels of DNA damage response related molecules including γ-H2AX, p53, Chk2 and NFκB-p65 in bony tissue were up-regulated significantly in ORX mice compared with shame mice, whereas PQQ supplementation largely rescued these alterations observed in ORX mice. Our results indicate that PQQ supplementation can prevent testosterone deficiency-induced osteoporosis by inhibiting oxidative stress and DNA damage, stimulating osteoblastic bone formation and inhibiting osteoclastic bone resorption. PMID:28386349

  18. Ameliorative effects of vanillin on potassium bromate induces bone and blood disorders in vivo.

    PubMed

    Ben Saad, H; Ben Amara, I; Krayem, N; Boudawara, T; Kallel, C; Zeghal, K M; Hakim, A

    2015-11-08

    The objective of this study was to investigate the propensity of potassium bromate (KBrO3) to induce oxidative stress in blood and bone of adult mice and its possible attenuation by vanillin. Our results demonstrated, after KBrO3 treatment, a decrease of red blood cells and hemoglobin and a significant increase of white blood cell. A decrease in plasma levels of folic acid, vitamin B12 and iron was also noted. Interestingly, an increase of lipid peroxidation, hydroperoxides, hydrogen peroxide, advanced oxidation protein products and protein carbonyl levels in erythrocytes and bone was observed, while superoxide dismutase, catalase and glutathione peroxidase activities and glutathione, non-protein thiol and vitamin C levels were decreased. KBrO3 treatment resulted in blood and bone DNA fragmentation, a hallmark of genotoxicity-KBrO3-induced, with reduction of DNA levels. Calcium and phosphorus levels showed a decrease in the bone and an increase in the plasma after KBrO3 treatment. These biochemical alterations were accompanied by histological changes in the blood smear and bone tissue. Treatment with vanillin improved the histopathological, hematotoxic and genotoxic effects induced by KBrO3. The results showed, for the first time, that the vanillin possesses a potent protective effect against the oxidative stress and genotoxicity in bone and blood of KBrO3-treated mice.

  19. A vitronectin-derived peptide reverses ovariectomy-induced bone loss via regulation of osteoblast and osteoclast differentiation.

    PubMed

    Min, Seung-Ki; Kang, Hyun Ki; Jung, Sung Youn; Jang, Da Hyun; Min, Byung-Moo

    2017-09-22

    Osteoporosis affects millions of people worldwide by promoting bone resorption and impairing bone formation. Bisphosphonates, commonly used agents to treat osteoporosis, cannot reverse the substantial bone loss that has already occurred by the time of diagnosis. Moreover, their undesirable side-effects, including osteonecrosis of the jaw, have been reported. Here, we demonstrated that a new bioactive core vitronectin-derived peptide (VnP-16) promoted bone formation by accelerating osteoblast differentiation and activity through direct interaction with β1 integrin followed by FAK activation. Concomitantly, VnP-16 inhibited bone resorption by restraining JNK-c-Fos-NFATc1-induced osteoclast differentiation and αvβ3 integrin-c-Src-PYK2-mediated resorptive function. Moreover, VnP-16 decreased the bone resorbing activity of pre-existing mature osteoclasts without changing their survival rate. Furthermore, VnP-16 had a strong anabolic effect on bone regeneration by stimulating osteoblast differentiation and increasing osteoblast number, and significantly alleviated proinflammatory cytokine-induced bone resorption by restraining osteoclast differentiation and function in murine models. Moreover, VnP-16 could reverse ovariectomy-induced bone loss by both inhibiting bone resorption and promoting bone formation. Given its dual role in promoting bone formation and inhibiting bone resorption, our results suggest that VnP-16 could be an attractive therapeutic agent for treating osteoporosis.Cell Death and Differentiation advance online publication, 22 September 2017; doi:10.1038/cdd.2017.153.