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1

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)

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

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

2

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

NASA Technical Reports Server (NTRS)

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.

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

2012-01-01

3

Weightlessness  

Microsoft Academic Search

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

Robin Shiells

1981-01-01

4

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

NASA Technical Reports Server (NTRS)

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.

Roberts, W. E.

1985-01-01

5

Weightlessness  

NASA Astrophysics Data System (ADS)

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.

Shiells, Robin

1981-01-01

6

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

NASA Technical Reports Server (NTRS)

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.

Wolinsky, Ira

1987-01-01

7

Amino acid supplementation alters bone metabolism during simulated weightlessness  

NASA Technical Reports Server (NTRS)

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.

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

2005-01-01

8

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

NASA Astrophysics Data System (ADS)

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

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

9

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

NASA Technical Reports Server (NTRS)

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%.

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

1985-01-01

10

Biochemical changes in bone in a model of weightlessness  

NASA Technical Reports Server (NTRS)

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.

Mechanic, Gerald L.

1986-01-01

11

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

NASA Technical Reports Server (NTRS)

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.

Wolinsky, I.

1986-01-01

12

Skeletal abnormalities in rats induced by simulated weightlessness  

NASA Technical Reports Server (NTRS)

A hypokinetic model has been developed which attempts to simulate the weightlessness experienced during space flight. Male rats were suspended from the model with a head-down tilt for a two-week period. Total mechanical unloading of the hind limbs and partial unloading of the fore limbs occurred. In comparison to pair-fed control rats, the skeletal alterations in the proximal tibial and humeral metaphyses of suspended rats were determined to be a diminished rate of longitudinal bone growth, a reduced mass of mineralized tissue, and an accumulation of marrow fat. Also, suspended rats exhibited decreased numbers of osteoblasts and increased numbers of osteoclasts immediately adjacent to the growth plate-metaphyseal junction at both skeletal sites. Although the reduction in mineralized tissue and the fat accumulation were more marked in the tibia, the skeletal changes in the proximal tibial and humeral metaphyses were generally comparable. The observed abnormalities may be due to mechanical unloading and/or a hypersecretion of corticosteroids.

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

1982-01-01

13

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

NASA Technical Reports Server (NTRS)

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.

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

1985-01-01

14

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

NASA Technical Reports Server (NTRS)

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.

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

1982-01-01

15

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)

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.

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

1981-01-01

16

Perspective on the impact of weightlessness on calcium and bone metabolism  

NASA Technical Reports Server (NTRS)

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.

Holick, M. F.

1998-01-01

17

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

PubMed

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. PMID:22645949

Oganov, V S; Grigor'ev, A I

2012-03-01

18

Weightless Water  

NSDL National Science Digital Library

In this physics activity (page 5 of the PDF), learners will witness the effects of free fall by observing falling water, and will gain a better understanding of the concept of weightlessness. Although this activity was created as a post-visit for a workshop about astronomy, it also makes an excellent stand alone activity!

Cosi

2009-01-01

19

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

NASA Technical Reports Server (NTRS)

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.

Doty, Stephen B.

1997-01-01

20

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

NASA Technical Reports Server (NTRS)

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.

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

1993-01-01

21

Effects of weightlessness on tissue proliferation  

NASA Technical Reports Server (NTRS)

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.

Crosby, W. H.; Tavassoli, M.

1975-01-01

22

Random root movements in weightlessness  

NASA Technical Reports Server (NTRS)

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.

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

1996-01-01

23

Suppression of osteoblast differentiation during weightlessness  

NASA Technical Reports Server (NTRS)

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.

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

1982-01-01

24

Weightlessness and Microgravity.  

ERIC Educational Resources Information Center

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 misconceptions. (MDH)

Chandler, David

1991-01-01

25

Comparison between the weightlessness syndrome and aging  

NASA Technical Reports Server (NTRS)

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.

Miquel, J.

1982-01-01

26

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

NASA Technical Reports Server (NTRS)

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.

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

2001-01-01

27

Induced healing of aneurysmal bone cysts by demineralized bone particles  

Microsoft Academic Search

Two cases of induced healing of aneurysmal bone cyst (ABC) following intralesional implantation of a bone paste made of autogeneic bone marrow and allogeneic bone powder are reported. The calcaneum in one case and the superior pubic ramus in the other were blown out by an ABC and would have required extensive surgery. Via a minimal exposure, the cyst was

C. Delloye; P. Nayer; J. Malghem; H. Noel

1996-01-01

28

Effect of simulated weightlessness on the expression of Cbf?1 induced by fluid shear stress in MG-63 osteosarcoma cells.  

NASA Astrophysics Data System (ADS)

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

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

29

Drug-induced bone loss.  

PubMed

Bone loss leading to osteoporosis is common after the menopause and in the elderly but uncommon in normal young adults without predisposing factors. The risk factors usually associated with osteoporosis include a family history of osteoporosis or fractures, aging, prior diseases, sedentary lifestyle, low calcium intake, hypogonadism, vitamin D deficiency, smoking, and excessive alcohol consumption. However, the issue of drugs has to be considered in 'normal' individuals who present with osteoporosis or bone loss without predisposing genetic or other environmental factors. The list of drugs is extensive and includes, amongst others, glucocorticoids, thyroid hormone (excess), alcohol, medroxyprogesterone acetate, luteinizing hormone-releasing hormone agonists, anti-seizure medications, cyclosporine A, aluminium, lithium, and exchange resins. This paper reviews the pathophysiology and mechanisms of drug-induced bone loss, which includes osteoporosis and osteomalacia, and treatment concepts. Undoubtedly, physician awareness, appropriate investigation, careful prescribing, monitoring, and proper therapy for this eminently preventable side effect can preserve bone in the patients receiving bone-losing drugs. PMID:11095167

Tannirandorn, P; Epstein, S

2000-01-01

30

Fluid loss during weightlessness  

Microsoft Academic Search

Eight men between 35 and 50 will participate in a study of weightlessness this month to help NASA find out why space flight causes humans to dehydrate.The study is being conducted by Joan Vernikes-Danellis, a pharmacologist with the Biomedical Research Division at NASA's Ames Research Center in Mountain View, California.

Peter M. Bell

1980-01-01

31

Rheography in weightlessness  

NASA Technical Reports Server (NTRS)

Small-scale rheographic devices for use on a space ship were developed and used during flights for the study of blood flow in vascular regions. The processes that occur during space flight and the adaptation of the human body to weightlessness are understood. The future condition of the cosmonauts' health is predicted.

Kasyan, I.; Turchaninova, V.

1980-01-01

32

Laparoscopic surgery in weightlessness  

NASA Technical Reports Server (NTRS)

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.

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

1996-01-01

33

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

PubMed

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. PMID:24758090

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

2014-03-01

34

Calcium and bone metabolism during space flight  

NASA Technical Reports Server (NTRS)

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.

Smith, Scott M.; Heer, Martina

2002-01-01

35

Microgravity and bone cell mechanosensitivity  

NASA Astrophysics Data System (ADS)

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 mechanosensitivity of bone cells is altered under near weightlessness conditions, and that this abnormal mechanosensation contributes to disturbed bone metabolism observed in astronauts. In our current project for the International Space Station, we wish to test this hypothesis experimentally using an in vitro model. The specific aim of our research project is to test whether near weightlessness decreases the sensitivity of bone cells for mechanical stress through a decrease in early signaling molecules (NO, PGs) that are involved in the mechanical loading-induced osteogenic response. Bone cells are cultured with or without gravity prior to and during mechanical loading, using our modified in vitro oscillating fluid flow apparatus. In this "FlowSpace" project we are developing a cell culture module that is used to provide further insight in the mechanism of mechanotransduction in bone.

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

2003-10-01

36

Novel Receptor-Based Countermeasures to Microgravity-Induced Bone Loss  

NASA Technical Reports Server (NTRS)

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.

OMalley, Bert W.

1999-01-01

37

Microgravity and Bone Cell Mechanosensitivity  

NASA Astrophysics Data System (ADS)

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, and that this abnormal mechanosensation contributes to disturbed bone metabolism observed in astronauts.In our current project for the International Space Station, we wish to test this hypothesis experimentally using an in vitro model. The specific aim of our research project is to test whether near weightlessness decreases the sensitivity of bone cells for mechanical stress through a decrease in early signaling molecules (NO, PGs) that are involved in the mechanical loading-induced osteogenic response. Bone cells are cultured with or without gravity prior to and during mechanical loading, using our modified in vitro oscillating fluid flow apparatus. In this "FlowSpace" project we are developing a cell culture module that is used to provide further insight in the mechanism of mechanotransduction in bone.

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

38

Bacterially induced bone destruction: mechanisms and misconceptions.  

PubMed Central

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 replacement of bone matrix. At the present time, it is not possible to define a general mechanism by which bacteria promote loss of bone matrix. Many bacteria are capable of stimulating bone matrix loss, and the information available would suggest that each organism possesses different factors which interact with bone in different ways. With the rapid increase in antibiotic resistance, particularly with Staphylococcus aureus and M. tuberculosis, organisms responsible for much bone pathology in developed countries only two generations ago, we would urge that much greater attention should be focused on the problem of bacterially induced bone remodelling in order to define pathogenetic mechanisms which could be therapeutic targets for the development of new treatment modalities. PMID:8698454

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

1996-01-01

39

An optimized index of human cardiovascular adaptation to simulated weightlessness  

NASA Technical Reports Server (NTRS)

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.

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

1996-01-01

40

Plants and weightlessness  

NASA Technical Reports Server (NTRS)

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.

Karminskiy, V.; Tarkhanovskiy, V.

1980-01-01

41

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

NASA Technical Reports Server (NTRS)

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.

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

1998-01-01

42

Vaccination against strontium-90-induced bone tumors  

SciTech Connect

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).

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

1983-09-01

43

Bone healing induced by ESWT  

PubMed Central

It has been at least two decades since the introduction of Extracorporeal Shock-Wave Treatment (ESWT) for the treatment of non-unions; despite conflicting opinions in the literature, it is recently achieving good results also in acute fractures. This paper reports Authors’ clinical experience with electromagnetic shock-waves in the treatment of delayed unions and fresh fractures. Nonunion cases experienced remarkable successful results at an average of 8-10 weeks after ESWT; high success rate is been also found for the acute fractures. It can be concluded that this therapy constitutes an important aid in treatment of non-unions and can be useful also in fresh bone fractures. PMID:22461166

Moretti, Biagio; Notarnicola, Angela; Moretti, Lorenzo; Patella, Silvio; Tatò, Ilaria; Patella, Vittorio

2009-01-01

44

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)

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.

Kravik, Stein E.

1989-01-01

45

Proprioceptive information processing in weightlessness  

Microsoft Academic Search

The ”illusions” experiment carried out on five astronauts during the last two French-Russian flights (Antars in 1992 and\\u000a Alta???r in 1993) and in the Russian Post-Antars mission (1993) was designed to investigate the adaptive changes in human\\u000a proprioceptive functions occurring in weightlessness at both the sensorimotor and cognitive levels, focusing on two kinds\\u000a of responses: (1) whole-body postural reflexes, and

R. Roll; J. C. Gilhodes; J. P. Roll; K. Popov; O. Charade; V. Gurfinkel

1998-01-01

46

Surgical Instrument Restraint in Weightlessness  

NASA Technical Reports Server (NTRS)

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.

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

2000-01-01

47

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

NASA Technical Reports Server (NTRS)

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.

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

2002-01-01

48

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

NASA Technical Reports Server (NTRS)

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.

Bikle, D. D.

1984-01-01

49

Prostaglandin E2 Prevents Disuse-Induced Cortical Bone Loss  

NASA Technical Reports Server (NTRS)

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.

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

1992-01-01

50

Extracorporeal Shock Wave Therapy Induces Alveolar Bone Regeneration  

Microsoft Academic Search

Periodontal inflammation with alveolar bone resorption is a hallmark of periodontitis. We hypothesized that extracorporeal shock wave therapy (ESWT) could promote the regeneration of alveolar bone following Porphyromonas gingivalis-induced periodontitis in rats. Rats were infected with P. gingivalis for 10 wks, which caused alveolar bone resorption. The rats were then treated with a single episode of 100, 300, or 1000

S. Sathishkumar; A. Meka; D. Dawson; N. House; W. Schaden; M. J. Novak; J. L. Ebersole; L. Kesavalu

2008-01-01

51

Osteoblast histogenesis in periodontal ligament and tibial metaphysis during simulated weightlessness  

NASA Technical Reports Server (NTRS)

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.

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

1986-01-01

52

Calcitonin control of calcium metabolism during weightlessness  

NASA Technical Reports Server (NTRS)

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.

Soliman, Karam F. A.

1993-01-01

53

Acute hemodynamic responses to weightlessness in humans  

NASA Technical Reports Server (NTRS)

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.

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

1989-01-01

54

Musculoskeletal adaptations to weightlessness and development of effective countermeasures  

NASA Technical Reports Server (NTRS)

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.

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

55

Unfocused Extracorporeal Shock Waves Induce Anabolic Effects in Rat Bone  

Microsoft Academic Search

ABSTRACT\\\\BACKGROUND:Extracorporeal shock waves are known to stimulate the differentiation of mesenchymal stem cells toward osteoprogenitors and induce the expression of osteogenic-related growth hormones. The aim of this study was to investigate if and how extracorporeal shock waves affected new bone formation, bone microarchitecture, and the mechanical properties of bone in a healthy rat model, in order to evaluate whether extracorporeal

Jagt van der O. P; T. M. Piscaer; W. Schaden; J. Li; N. Kops; H. Jahr; Linden van der J. C; J. H. Waarsing; J. A. N. Verhaar; Jong de M; H. H. Weinans

2011-01-01

56

Prediction of mandibular bone remodelling induced by fixed partial dentures  

Microsoft Academic Search

Fixed partial dentures (FPD) or dental bridges have been extensively utilised in prosthodontic restoration. Despite considerable clinical success to date, there has been limited fundamental understanding of the biomechanical consequences induced by FPD treatment. It is noted that FPD construction significantly alters the biological and mechanical environment in the supporting bone region. Thus, the surrounding bones will be engaged to

Clarice Field; Qing Li; Wei Li; Mark Thompson; Michael Swain

2010-01-01

57

Microcapsule-Induced Toughening of Bone Cement Gina M. Miller  

E-print Network

27 Microcapsule-Induced Toughening of Bone Cement Gina M. Miller Senior in Aerospace Engineering R. White, and TAM Prof. Nancy R. Sottos Acrylic bone cement is the primary material used cement, it may be possible to extend the lifetime of the implant, thus reducing the occurrence

Sottos, Nancy R.

58

Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss  

NASA Technical Reports Server (NTRS)

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.

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

2011-01-01

59

Periarticular Bone Loss in Antigen-Induced Arthritis  

PubMed Central

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

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

2013-01-01

60

Effects of weightlessness on body composition in the rat  

NASA Technical Reports Server (NTRS)

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.

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

1983-01-01

61

Blood circulation under conditions of weightlessness  

NASA Technical Reports Server (NTRS)

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.

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

1980-01-01

62

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

NASA Technical Reports Server (NTRS)

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.

Gould, C. L.

1985-01-01

63

Demonstration of Electrostatic Orbits in Weightlessness  

NASA Astrophysics Data System (ADS)

In August 2006, a team of students from Rhodes College performed an experiment in microgravity aboard NASA’s specialized C-9B aircraft known as the “Weightless Wonder.” The goal of the experiment was to establish an orbit between two electrically charged spheres. The similar forms of Newton’s Law of Gravitation and Coulomb’s Law suggest that such electrostatic orbits are possible. However, to our knowledge, an electrostatic orbit has not previously been demonstrated. This presentation will describe our experiment and show video footage of the electrostatic orbits that we achieved in weightlessness. Professor Brent Hoffmeister is the AAPT sponsor.

Janeski, John; Andring, K.; Banerjee, S.; Campbell, D.; Keedy, D.; Hoffmeister, B.; Quinn, S.

2006-12-01

64

Sclerostin Inhibition Prevents Spinal Cord Injury Induced Cancellous Bone Loss.  

PubMed

Spinal cord injury (SCI) results in rapid and extensive sublesional bone loss. Sclerostin, an osteocyte-derived glycoprotein that negatively regulates intraskeletal Wnt-signaling, is elevated after SCI and may represent a mechanism underlying this excessive bone loss. However, it remains unknown whether pharmacologic sclerostin inhibition ameliorates bone loss subsequent to SCI. Our primary purposes were to determine whether a sclerostin antibody (Scl-Ab) prevents hindlimb cancellous bone loss in a rodent SCI model and to compare the effects of a Scl-Ab to that of testosterone-enanthate (TE), an agent that we have previously shown prevents SCI-induced bone loss. Fifty-five (n?=?11-19/group) skeletally-mature male Sprague-Dawley rats were randomized to receive: (A) SHAM surgery (T8 laminectomy), (B) moderate-severe (250 kilodyne) SCI, (C) 250 kilodyne SCI?+?TE (7.0mg/week, i.m.), or (D) 250 kilodyne SCI?+?Scl-Ab (25mg/kg, twice weekly, s.c.) for three weeks. Twenty-one days post-injury, SCI animals exhibited reduced hindlimb cancellous bone volume at the proximal tibia (via µCT and histomorphometry) and distal femur (via µCT), characterized by reduced trabecular number and thickness. SCI also reduced trabecular connectivity and plate-like trabecular structures, indicating diminished structural integrity of the remaining cancellous network, and produced deficits in cortical bone (femoral diaphysis) strength. Scl-Ab and TE both prevented SCI-induced cancellous bone loss, albeit via differing mechanisms. Specifically, Scl-Ab increased osteoblast surface and bone formation, indicating direct bone anabolic effects, whereas TE reduced osteoclast surface with minimal effect on bone formation, indicating antiresorptive effects. The deleterious microarchitectural alterations in the trabecular network were also prevented in SCI?+?Scl-Ab and SCI?+?TE animals, while only Scl-Ab completely prevented the reduction in cortical bone strength. Our findings provide the first evidence indicating that sclerostin inhibition represents a viable treatment to prevent SCI-induced cancellous and cortical bone deficits and provides preliminary rationale for future clinical trials focused on evaluating whether Scl-Ab prevents osteoporosis in the SCI population. © 2014 American Society for Bone and Mineral Research. PMID:25359699

Beggs, Luke A; Ye, Fan; Ghosh, Payal; Beck, Darren T; Conover, Christine F; Balaez, Alexander; Miller, Julie R; Phillips, Ean G; Zheng, Nigel; Williams, Alyssa A; Aguirre, J Ignacio; Wronski, Thomas J; Bose, Prodip K; Borst, Stephen E; Yarrow, Joshua F

2014-10-31

65

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

NASA Astrophysics Data System (ADS)

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.

Maldonado, Solvey; Findeisen, Rolf

2010-06-01

66

Bone formation induced by BMP-2 in human osteosarcoma cells  

PubMed Central

Our previous studies demonstrated that BMP-2 inhibits the tumorigenicity of cancer stem cells identified as cells with high aldehyde dehydrogenase activity (ALDH br cells) from the human osteosarcoma cell line OS99-1. We further investigated whether BMP-2 is capable of inducing bone formation in OS99-1 cells. Flow cytometry sorting was used to isolate tumorigenic ALDH br and non-tumorigenic ALDH lo cells. qRT-PCR was used to quantify the gene expression. A xenograft model was used to verify the bone formation in vivo . There was significantly higher mRNA expression of BMPR1B and BMPR2 in ALDH lo cells compared with that in ALDH br cells and the BMPR1B expression in ALDH lo cells was ?8-fold higher compared to that in ALDH br cells. BMP-2 was also found to induce higher transcription of osteogenic markers Runx-2, Osterix (Osx), alkaline phosphatase (ALP) and collagen type I in ALDH lo cells compared to ALDH br cells, which were mediated by the canonical Smad signaling pathway. In vivo , BMP-2 was identified to induce bone formation in both ALDH br and ALDH lo cells. All animals receiving 1×10 4 ALDH lo cells treated with 30 ? g of BMP-2 per animal showed bone formation within 1–2 weeks after injection in mice. Bone formation induced by BMP-2 in ALDH lo cells showed significantly more bone mineral content compared to that in ALDH br cells. BMP-2 induces bone formation in heterogeneous osteosarcoma cells and BMP-2 may have a promising therapeutic role for treating human osteosarcoma by inducing differentiation along an osteogenic pathway. PMID:23900689

WANG, LIN; PARK, PAUL; LA MARCA, FRANK; THAN, KHOI; RAHMAN, SHAYAN; LIN, CHIA-YING

67

Bone formation induced by BMP-2 in human osteosarcoma cells.  

PubMed

Our previous studies demonstrated that BMP-2 inhibits the tumorigenicity of cancer stem cells identified as cells with high aldehyde dehydrogenase activity (ALDH(br) cells) from the human osteosarcoma cell line OS99-1. We further investigated whether BMP-2 is capable of inducing bone formation in OS99-1 cells. Flow cytometry sorting was used to isolate tumorigenic ALDH(br) and non-tumorigenic ALDH(lo) cells. qRT-PCR was used to quantify the gene expression. A xenograft model was used to verify the bone formation in vivo. There was significantly higher mRNA expression of BMPR1B and BMPR2 in ALDH(lo) cells compared with that in ALDH(br) cells and the BMPR1B expression in ALDH(lo) cells was ~8-fold higher compared to that in ALDHbr cells. BMP-2 was also found to induce higher transcription of osteogenic markers Runx-2, Osterix (Osx), alkaline phosphatase (ALP) and collagen type I in ALDH(lo) cells compared to ALDH(br) cells, which were mediated by the canonical Smad signaling pathway. In vivo, BMP-2 was identified to induce bone formation in both ALDH(br) and ALDH(lo) cells. All animals receiving 1 x 10()4 ALDH(lo) cells treated with 30 µg of BMP-2 per animal showed bone formation within 1-2 weeks after injection in mice. Bone formation induced by BMP-2 in ALDH(lo) cells showed significantly more bone mineral content compared to that in ALDH(br) cells. BMP-2 induces bone formation in heterogeneous osteosarcoma cells and BMP-2 may have a promising therapeutic role for treating human osteosarcoma by inducing differentiation along an osteogenic pathway. PMID:23900689

Wang, Lin; Park, Paul; La Marca, Frank; Than, Khoi; Rahman, Shayan; Lin, Chia-Ying

2013-10-01

68

Bisphosphonates as a Countermeasure to Space Flight Induced Bone Loss  

NASA Technical Reports Server (NTRS)

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.

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

2011-01-01

69

Lysophosphatidic acid-induced chemotaxis of bone cells  

Microsoft Academic Search

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

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

2006-01-01

70

Protocadherin-7 induces bone metastasis of breast cancer  

SciTech Connect

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.

Li, Ai-Min [Department of Orthopedics, The 5th Central Hospital of Tianjin, Tianjin (China)] [Department of Orthopedics, The 5th Central Hospital of Tianjin, Tianjin (China); Tian, Ai-Xian [Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)] [Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Zhang, Rui-Xue [Department of Clinical Laboratory Diagnosis, Tianjin Medical University, Tianjin (China)] [Department of Clinical Laboratory Diagnosis, Tianjin Medical University, Tianjin (China); Ge, Jie [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China) [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Sun, Xuan [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)] [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Cao, Xu-Chen, E-mail: caoxuch@126.com [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China) [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

2013-07-05

71

Demonstration of Electrostatic Orbits in Weightlessness  

Microsoft Academic Search

In August 2006, a team of students from Rhodes College performed an experiment in microgravity aboard NASA's specialized C-9B aircraft known as the ``Weightless Wonder.'' The goal of the experiment was to establish an orbit between two electrically charged spheres. The similar forms of Newton's Law of Gravitation and Coulomb's Law suggest that such electrostatic orbits are possible. However, to

John Janeski; K. Andring; S. Banerjee; D. Campbell; D. Keedy; B. Hoffmeister; S. Quinn

2006-01-01

72

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

NASA Technical Reports Server (NTRS)

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.

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

1983-01-01

73

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

NASA Technical Reports Server (NTRS)

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.

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

2004-01-01

74

Aromatase inhibitors-induced bone loss in early breast cancer.  

PubMed

Women with breast cancer have an increased prevalence and incidence of fractures. This increased risk of fracture has become most evident following the use of aromatase inhibitors (AIs) as standard adjuvant therapy. AI-induced bone loss occurs at more than twice the rate of physiologic postmenopausal bone loss. Moreover, peripheral quantitative computed tomography data indicate that effects of AIs on bone strength and on cortical bone have been substantially underestimated by dual-energy X-ray absorptiometry. All AIs have been associated with an increased fracture risk. The incidence of fractures is at least 33-43% higher in AI-treated patients than in tamoxifen-treated patients, and this increase in fracture risk is maintained at least for the duration of AI therapy. Over the last few years, clinical trials have established the effectiveness of bisphosphonates and denosumab to preserve and even increase bone mineral density (BMD) during adjuvant AIs. Most data have been obtained with zoledronic acid administered twice a year, which effectively maintains or increases BMD in women receiving AIs. In addition, zoledronic acid has been shown to delay disease recurrence and maybe prolong survival in women with hormone-responsive tumors, thereby providing an adjuvant antitumor benefit besides preserving BMD. It is likely that a combined fracture risk assessment will more accurately identify women with breast cancer who require bone protective therapy. The FRAX tool probably underestimates the net increase in fracture risk due to AI therapy. Recent guidelines for the prevention of AI-induced bone loss have adequately considered the presence of several established clinical risk factors for fractures, in addition to BMD, when selecting patients to be treated with inhibitors of bone resorption. PMID:24936287

Body, Jean-Jacques

2012-01-01

75

NMR assessment on bone simulated under microgravity  

NASA Astrophysics Data System (ADS)

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

Ni, Q.; Qin, Y.

76

Bone morphogenetic protein-2 antagonizes bone morphogenetic protein-4 induced cardiomyocyte hypertrophy and apoptosis.  

PubMed

Our previous work showed that the expression of bone morphogenetic protein-4 (BMP4) was up-regulated in pathological cardiac hypertrophy models and BMP4 induced cardiomyocyte hypertrophy and apoptosis. Bone morphogenetic protein-2 (BMP2) and BMP4 share greater than 80% amino acid homology and there exists an interaction between BMP2 and BMP4, so the aim of the present study was to elucidate the changes of BMP2 in the cardiac hypertrophy models and the effects of BMP2 on BMP4-induced cardiomyocyte hypertrophy and apoptosis. The in vivo cardiac hypertrophy models were induced by pressure-overload and swimming exercise in mice. BMP2 mRNA and protein expressions increased in pressure-overload and swimming-exercise induced cardiac hypertrophy. BMP2 itself did not elicit cardiomyocyte hypertrophy and apoptosis, but antagonized BMP4-induced cardiomyocyte hypertrophy and apoptosis. BMP2 stimulated Akt in cardiomyocytes and Akt inhibitor prevented the antagonism of BMP2 on BMP4-induced cardiomyocyte apoptosis. Furthermore, BMP2 inhibited BMP4-induced JNK activation in cardiomyocytes. In conclusion, BMP2 antagonizes BMP4-induced cardiomyocyte hypertrophy and apoptosis. The anti-apoptotic effects of BMP2 on BMP4-induced cardiomyocyte apoptosis might be through activating Akt and inhibiting JNK activation. PMID:24648278

Lu, Jing; Sun, Bo; Huo, Rong; Wang, Yu-Chun; Yang, Di; Xing, Yue; Xiao, Xiao-Lin; Xie, Xin; Dong, De-Li

2014-10-01

77

Perception of linear acceleration in weightlessness  

NASA Technical Reports Server (NTRS)

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.

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

1990-01-01

78

Astronaut activity in weightlessness and unsupported space  

NASA Technical Reports Server (NTRS)

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

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

1975-01-01

79

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

PubMed

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-?B ligand and promote the maturation and activation of osteoclasts and thus eventually cause bone resorption. PMID:25157571

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

2014-01-01

80

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

PubMed Central

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-?B ligand and promote the maturation and activation of osteoclasts and thus eventually cause bone resorption. PMID:25157571

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

2014-01-01

81

Effect of weightlessness on cytoskeleton architecture and proliferation of human breast cancer cell line MCF-7.  

NASA Astrophysics Data System (ADS)

Because cells are sensitive to mechanical forces, weightlessness might act on stress- dependent cell changes. We hypothesized that the integration of environmental factors might induce specific cytoskeletal architecture patterns, characterized by quantitative image analysis. Human breast cancer cells MCF-7, flown in space in a Photon capsule, were fixed after 1.5, 22 and 48 h in orbit. Cells subjected to weightlessness were compared to 1g in-flight and ground controls. Post-flight, fluorescent labelings were performed to visualize cell proliferation (Ki-67), three cytoskeleton components (microtubules, microfilaments and intermediate filaments) and chromatin structure. Confocal microscopy and image analysis were used to quantify cycling cells and mitosis, modifications of the cytokeratin network and chromatin structure. Two main phenomenons were observed in weightlessness: - The perinuclear cytokeratin network and chromatin structure were looser. Theseresults are in agreement with basic predictions of cellular tensegrity. - More cells were cycling and mitosis was prolonged. Finally, cell proliferation wasreduced as a consequence of a cell-cycle blockade. Microtubules were altered inmany cells.The prolongation of mitosis can be explained by an alteration of microtubule self-organization in weightlessness, involving reaction-diffusion processes. This couldbe considered as an example function of microtubules in gravisensing.

Vassy, J.; Portet, S.; Beil, M.; Millot, G.; Fauvel-Lafeve, F.; Gasset, G.; Schoevaert, D.

82

Physiological effects of microgravity on bone cells.  

PubMed

Life on Earth developed under the influence of normal gravity (1g). With evidence from previous studies, scientists have suggested that normal physiological processes, such as the functional integrity of muscles and bone mass, can be affected by microgravity during spaceflight. During the life span, bone not only develops as a structure designed specifically for mechanical tasks but also adapts for efficiency. The lack of weight-bearing forces makes microgravity an ideal physical stimulus to evaluate bone cell responses. One of the most serious problems induced by long-term weightlessness is bone mineral loss. Results from in vitro studies that entailed the use of bone cells in spaceflights showed modification in cell attachment structures and cytoskeletal reorganization, which may be involved in bone loss. Humans exposed to microgravity conditions experience various physiological changes, including loss of bone mass, muscle deterioration, and immunodeficiency. In vitro models can be used to extract valuable information about changes in mechanical stress to ultimately identify the different pathways of mechanotransduction in bone cells. Despite many in vivo and in vitro studies under both real microgravity and simulated conditions, the mechanism of bone loss is still not well defined. The objective of this review is to summarize the recent research on bone cells under microgravity conditions based on advances in the field. PMID:24687524

Arfat, Yasir; Xiao, Wei-Zhong; Iftikhar, Salman; Zhao, Fan; Li, Di-Jie; Sun, Yu-Long; Zhang, Ge; Shang, Peng; Qian, Ai-Rong

2014-06-01

83

Bone scintigraphic patterns in patients of tumor induced osteomalacia  

PubMed Central

Tumor induced osteomalacia (TIO) or oncogenic osteomalacia is a rare condition associated with small tumor that secretes one of the phosphaturic hormones, i.e., fibroblast growth factor 23, resulting in abnormal phosphate metabolism. Patients may present with non-specific symptoms leading to delay in the diagnosis. Extensive skeletal involvement is frequently seen due to delay in the diagnosis and treatment. The small sized tumor and unexpected location make the identification of tumor difficult even after diagnosis of osteogenic osteomalacia. The bone scan done for the skeletal involvement may show the presence of metabolic features and the scan findings are a sensitive indicator of metabolic bone disorders. We present the bone scan findings in three patients diagnosed to have TIO. PMID:24250028

Sood, Ashwani; Agarwal, Kanhaiyalal; Shukla, Jaya; Goel, Reema; Dhir, Varun; Bhattacharya, Anish; Rai Mittal, Bhagwant

2013-01-01

84

Bone and Calcium Metabolism During Space Flight  

NASA Technical Reports Server (NTRS)

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 ensure that the beneficial effects are seen in space flight. As we begin to plan for missions to go back to the Moon, and even off to Mars, many questions are yet to be answered. Maintaining bone is one of the greatest challenges, but with a better understanding of the mechanical processes of bone loss, countermeasures can be designed more efficiently, and the solution (or solutions) may be just over the horizon.

Smith, Scott M.

2004-01-01

85

Ion implantation induced nanotopography on titanium and bone cell adhesion  

NASA Astrophysics Data System (ADS)

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.

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

2014-08-01

86

Float-zone processing in a weightless environment  

NASA Technical Reports Server (NTRS)

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.

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

1976-01-01

87

ACTH protects against glucocorticoid-induced osteonecrosis of bone.  

PubMed

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. PMID:20421485

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

88

Ectopic bone formation induced by biodegradable hydrogels incorporating bone morphogenetic protein.  

PubMed

Biodegradable hydrogels were prepared from gelatin by glutaraldehyde cross-linking for release matrix of recombinant human bone morphogenetic protein-2 (BMP-2). BMP-2 solution was impregnated into the dried hydrogels to prepare BMP-2-incorporating gelatin hydrogels. In the in vitro study, enhanced retention of BMP-2 was observed from the BMP-2-incorporating gelatin hydrogels after an initial burst of BMP-2 incorporated initially in the hydrogel. Following subcutaneous implantation of (125)I-labeled BMP-2-incorporating gelatin hydrogels in the back of mice, the radioactivity remaining in the hydrogels was measured to estimate the in vivo release profile of BMP-2. It was found that BMP-2 was retained in the hydrogels for longer than 30 days, whereas 99% of BMP-2 injected in the solution form was cleared from the injected site within one day, completely disappearing within 3 days. Ectopic bone formation studies demonstrated that BMP-2-incorporating gelatin hydrogels exhibited a more potent ability for bone induction than solution injection of BMP-2. This finding indicates that enhanced retention of BMP-2 is promotes its ability to induce ectopic bone formation. PMID:9648026

Yamamoto, M; Tabata, Y; Ikada, Y

1998-01-01

89

Changes in muscles accompanying non-weight-bearing and weightlessness  

NASA Technical Reports Server (NTRS)

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.

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

1989-01-01

90

Regeneration of Bone- and Tendon/Ligament-Like Tissues Induced by Gene Transfer of Bone Morphogenetic Protein-12 in a Rat Bone Defect  

PubMed Central

Members of the bone morphogenetic protein (BMP) family have diverse physiological roles. For instance, BMP-2 stimulates osteogenesis, while BMP-12 induces the formation of tendon/ligament-like tissues. Here, we designed a study to determine whether BMP-12 has bone and/or cartilage regeneration abilities similar to those of BMP-2. We implanted plasmid vectors encoding either BMP-2 or BMP-12 in rats with femur defects, and monitored the bone healing process for 8-weeks. The BMP-12 transgene induced prominent fibrogenesis by 2 weeks, with bone substitution occurring by 8 weeks. BMP-2, however, was associated predominantly with osteogenesis throughout the 8 week period. Thus, we conclude that BMP-12 does not function similarly to BMP-2 during bone healing. Further work is needed to better understand the mechanisms by which it stimulates bony growths to replace the connective tissues formed during the first stages of bone healing. PMID:21350647

Kuroda, Shinji; Goto, Nobuhiro; Suzuki, Michiko; Kaneda, Kazutaka; Ohya, Keiichi; Shimokawa, Hitoyata; Kasugai, Shohei

2010-01-01

91

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

PubMed

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. PMID:11539500

Taylor, R L

1993-03-01

92

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

NASA Technical Reports Server (NTRS)

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.

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

93

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

PubMed Central

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

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

2013-01-01

94

Hypoxia-inducible Factor-1? Protein Negatively Regulates Load-induced Bone Formation*  

PubMed Central

Mechanical loads induce profound anabolic effects in the skeleton, but the molecular mechanisms that transduce such signals are still poorly understood. In this study, we demonstrate that the hypoxia-inducible factor-1? (Hif-1?) is acutely up-regulated in response to exogenous mechanical stimuli secondary to prostanoid signaling and Akt/mTOR (mammalian target of rapamycin) activation. In this context, Hif-1? associates with ?-catenin to inhibit Wnt target genes associated with bone anabolic activity. Mice lacking Hif-1? in osteoblasts and osteocytes form more bone when subjected to tibia loading as a result of increased osteoblast activity. Taken together, these studies indicate that Hif-1? serves as a negative regulator of skeletal mechanotransduction to suppress load-induced bone formation by altering the sensitivity of osteoblasts and osteocytes to mechanical signals. PMID:22081627

Riddle, Ryan C.; Leslie, Julie M.; Gross, Ted S.; Clemens, Thomas L.

2011-01-01

95

Lysophosphatidic acid-induced chemotaxis of bone cells.  

SciTech Connect

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 conclude that LPA-induced MC3T3-E1 cell chemotaxis requires PI3K-associated cytoskeletal changes, but not transactivation of the EGF receptor.

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

2006-07-01

96

Osteoprotective effect of geraniin against ovariectomy-induced bone loss in rats.  

PubMed

In the present study, we investigated the antiosteoporotic effect of geraniin on osteoporosis induced by OVX in rats. The analysis of biochemical parameters showed that geraniin could significantly increase serum calcium, estradiol and calcitonin levels, and decrease serum ALP, tartrate-resistant acid phosphatase, serum crosslinked C-terminal telopeptide of type I collagen, and urinary deoxypyridinoline/creatinine ratio levels, respectively. Geraniin was also found to prevent OVX-induced bone loss in bone mineral density and bone mineral content, to elevate femur weight and bone calcium content, and to enhance the bone mechanical properties as compared with OVX group. In addition, geraniin was demonstrated to improve the histomorphological parameters of OVX-induced bone loss, including bone trabecular number, thickness, and separation. These results indicated that geraniin have a protective effect against OVX-induced rat osteoporosis. PMID:25532904

Lu, Yiqin; He, Bo; Zhang, Xiaochao; Yang, Renhua; Li, Shude; Song, Bo; Zhang, Yue; Yun, Yu; Yan, Hongli; Chen, Peng; Shen, Zhiqiang

2015-02-01

97

Glucocorticoids induce autophagy in rat bone marrow mesenchymal stem cells.  

PubMed

Glucocorticoid?induced osteoporosis (GIOP) is a widespread clinical complication following glucocorticoid therapy. This irreversible damage to bone?forming and ?resorbing cells is essential in the pathogenesis of osteoporosis. Autophagy is a physiological process involved in the regulation of cells and their responses to diverse stimuli, however, the role of autophagy in glucocorticoid?induced damage to bone marrow mesenchymal stem cells (BMSCs) remains unclear. The current study confirmed that glucocorticoid administration impaired the proliferation of BMSCs. Transmission electron microscopy, immunohistochemistry and western blot analysis detected autophagy in vitro and in GIOP model rats (in vivo). With the addition of the autophagy inhibitor 3?methyladenine, the proliferative ability of BMSCs was further reduced, while the number of apoptotic BMSCs was significantly increased. The data suggests that in response to glucocorticoid administration, induced autophagy aids to maintain proliferation and prevent apoptosis of BMSCs. Thus, it is hypothesized that autophagy may be a novel target in the treatment or prevention of osteoporosis. PMID:25515523

Wang, Long; Fan, Jing; Lin, Yan-Shui; Guo, Yun-Shan; Gao, Bo; Shi, Qi-Yue; Wei, Bo-Yuan; Chen, Li; Yang, Liu; Liu, Jian; Luo, Zhuo-Jing

2015-04-01

98

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

NASA Technical Reports Server (NTRS)

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.

Roberts, W. E.

1984-01-01

99

Effects of Inactivity and Exercise on Bone.  

ERIC Educational Resources Information Center

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…

Smith, Everett L.; Gilligan, Catherine

1987-01-01

100

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

PubMed Central

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

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

2015-01-01

101

Islet in weightlessness: Biological experiments on board COSMOS 1129 satellite  

NASA Technical Reports Server (NTRS)

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.

Zhuk, Y.

1980-01-01

102

Induced refractive anomalies affect chick orbital bone structure.  

PubMed

Experiments have shown that it is possible to induce ametropias (myopia and hyperopia) in the eyes of young animals by distorting early visual experience through the use of negative and positive defocussing lenses mounted over the eye. Defocus lenses (+15 and -15 diopters) were mounted unilaterally over one eye of day old broiler chicks using a contact lens-goggle and velcro combination. Refractive states and ocular dimensions were measured by retinoscopy and ultrasound during the experiment. On the seventh day the birds were killed after which the eyes were removed, weighed and measured with calipers. The remaining heads were cleaned of all soft tissue to leave only the bones of the skull. Axial and equatorial orbital dimensions were then measured with vernier calipers. The frontal bone was prepared for histological analysis and sections were used to determine the relative proportions of formed bone to primitive mesenchymal cells. Prior to treatment there were no differences in refractive states or dimensions of the two eyes. After one week of defocus, the treated eyes were longer or shorter as well as more myopic or hyperopic than the contralateral eye by amounts close to the powers of the defocussing lenses (-12.3 and +11.8 diopters). Orbital sizes varied substantially. Orbital axes of myopic eyes were significantly (P < or = 0.05) longer (on average 0.77 +/- 0.23 mm) than the contralateral control orbits. The orbital axes associated with the hyperopic eyes were significantly (P < or = 0.05) shorter (on average 0.69 +/- 0.18 mm) than the contralateral control orbits. Similarly, significant differences (P < or = 0.05) were recorded for a variety of equatorial measures (naso-temporal, superior inferior, oblique (nasal-superior, temporal-superior). Histological analysis reveals that the frontal bone of the myopic chick is in a more mature state of development compared to the frontal bone of the hyperopic chick. The eyes and orbits of chicks with induced ametropias that were allowed to the recover were not significantly different from the control eyes and orbits. This study clearly shows that, in chicks, ocular refractive development is associated with orbital development and that experiments related to growth factors and retinal processing of defocus information should also consider growth and development of tissue beyond the ocular globe. PMID:9245896

Wilson, K T; Sivak, J G; Callender, M G

1997-05-01

103

Longitudinal live animal micro-CT allows for quantitative analysis of tumor-induced bone destruction  

Microsoft Academic Search

The majority of breast cancer and prostate cancer patients with metastatic disease will go on to develop bone metastases, which contribute largely to the patient's morbidity and mortality. Numerous small animal models of cancer metastasis to bone have been developed to study tumor-induced bone destruction, but the advancement of imaging modalities utilized for these models has lagged significantly behind clinical

Lindsay C. Johnson; Rachelle W. Johnson; Steve A. Munoz; Gregory R. Mundy; Todd E. Peterson; Julie A. Sterling

2011-01-01

104

Sperm motility under conditions of weightlessness.  

PubMed

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. PMID:1429219

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

1992-01-01

105

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

NASA Astrophysics Data System (ADS)

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.

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

2013-09-01

106

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

NASA Technical Reports Server (NTRS)

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-ketoprofen treatment at the highest dose levels prevented the changes in cancellous bone, and reduced marrow area to increase cortical bone in the tibial shafts.

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

1993-01-01

107

Pathophysiological analysis of the effect of weightlessness on the body  

NASA Technical Reports Server (NTRS)

A general scheme of pathogenesis of the effect of weightlessness on the human body is constructed that considers a shift of body fluids, decrease and change in afferent impulses, and metabolic changes in muscle and bony tissues.

Kovalenko, Y. A.

1975-01-01

108

Reactions of animals and people under conditions of brief weightlessness  

NASA Technical Reports Server (NTRS)

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.

Kitayev-Smik, L. A.

1975-01-01

109

Mathematical modelling of the pathogenesis of multiple myeloma-induced bone disease  

PubMed Central

Multiple myeloma (MM) is the second most common haematological malignancy and results in destructive bone lesions. The interaction between MM cells and the bone microenvironment plays an important role in the development of the tumour cells and MM-induced bone disease and forms a ‘vicious cycle’ of tumour development and bone destruction, intensified by suppression of osteoblast activity and promotion of osteoclast activity. In this paper, a mathematical model is proposed to simulate how the interaction between MM cells and the bone microenvironment facilitates the development of the tumour cells and the resultant bone destruction. It includes both the roles of inhibited osteoblast activity and stimulated osteoclast activity. The model is able to mimic the temporal variation of bone cell concentrations and resultant bone volume after the invasion and then removal of the tumour cells and explains why MM-induced bone lesions rarely heal even after the complete removal of MM cells. The behaviour of the model compares well with published experimental data. The model serves as a first step to understand the development of MM-induced bone disease and could be applied further to evaluate the current therapies against MM-induced bone disease and even suggests new potential therapeutic targets. © 2014 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd PMID:24817420

Ji, Bing; Genever, Paul G; Patton, Ronald J; Fagan, Michael J

2014-01-01

110

Mathematical modelling of the pathogenesis of multiple myeloma-induced bone disease.  

PubMed

Multiple myeloma (MM) is the second most common haematological malignancy and results in destructive bone lesions. The interaction between MM cells and the bone microenvironment plays an important role in the development of the tumour cells and MM-induced bone disease and forms a 'vicious cycle' of tumour development and bone destruction, intensified by suppression of osteoblast activity and promotion of osteoclast activity. In this paper, a mathematical model is proposed to simulate how the interaction between MM cells and the bone microenvironment facilitates the development of the tumour cells and the resultant bone destruction. It includes both the roles of inhibited osteoblast activity and stimulated osteoclast activity. The model is able to mimic the temporal variation of bone cell concentrations and resultant bone volume after the invasion and then removal of the tumour cells and explains why MM-induced bone lesions rarely heal even after the complete removal of MM cells. The behaviour of the model compares well with published experimental data. The model serves as a first step to understand the development of MM-induced bone disease and could be applied further to evaluate the current therapies against MM-induced bone disease and even suggests new potential therapeutic targets. PMID:24817420

Ji, Bing; Genever, Paul G; Patton, Ronald J; Fagan, Michael J

2014-11-01

111

Respiration, respiratory metabolism and energy consumption under weightless conditions  

NASA Technical Reports Server (NTRS)

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.

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

1975-01-01

112

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

NASA Technical Reports Server (NTRS)

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.

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

1972-01-01

113

Systemic mesenchymal stem cell administration enhances bone formation in fracture repair but not load-induced bone formation.  

PubMed

Mesenchymal stem cells (MSC) were shown to support bone regeneration, when they were locally transplanted into poorly healing fractures. The benefit of systemic MSC transplantation is currently less evident. There is consensus that systemically applied MSC are recruited to the site of injury, but it is debated whether they actually support bone formation. Furthermore, the question arises as to whether circulating MSC are recruited only in case of injury or whether they also participate in mechanically induced bone formation. To answer these questions we injected green fluorescent protein (GFP)-labelled MSC into C57BL/6J mice, which were subjected either to a femur osteotomy or to non-invasive mechanical ulna loading to induce bone formation. We detected GFP-labelled MSC in the early (day 10) and late fracture callus (day 21) by immunohistochemistry. Stromal cell-derived factor 1 (SDF-1 or CXCL-12), a key chemokine for stem cell attraction, was strongly expressed by virtually all cells near the osteotomy - indicating that SDF-1 may mediate cell migration to the site of injury. We found no differences in SDF-1 expression between the groups. Micro-computed tomography (µCT) revealed significantly more bone in the callus of the MSC treated mice compared to untreated controls. The bending stiffness of callus was not significantly altered after MSC-application. In contrast, we failed to detect GFP-labelled MSC in the ulna after non-invasive mechanical loading. Histomorphometry and µCT revealed a significant load-induced increase in bone formation; however, no further increase was found after MSC administration. Concluding, our results suggest that systemically administered MSC are recruited and support bone formation only in case of injury but not in mechanically induced bone formation. PMID:25552426

Rapp, A E; Bindl, R; Heilmann, A; Erbacher, A; Müller, I; Brenner, R E; Ignatius, A

2015-01-01

114

Early effects of tocilizumab on bone and bone marrow lesions in a collagen-induced arthritis monkey model  

Microsoft Academic Search

To understand the contribution of IL-6\\/IL-6R to subchondral bone and bone marrow abnormality in RA patients and the effects of tocilizumab on those abnormalities, we evaluated early change in a collagen-induced arthritis (CIA) monkey model with or without a single administration of tocilizumab. Six CIA cynomolgus monkeys received tocilizumab and 3 CIA monkeys received vehicle only. Their interphalangeal joints were

Atsuhiko Kato; Saori Matsuo; Hirotake Takai; Yasushi Uchiyama; Masahiko Mihara; Masami Suzuki

2008-01-01

115

New bone formation in nude mouse calvaria induced by canine prostate tissue.  

PubMed

Osteoblastic metastases are common in patients with advanced prostate cancer. The pathophysiology of the new bone formation at metastatic sites is not currently known, but it is hypothesized that growth factors secreted by the prostate may be involved. Unfortunately, most rodent models of prostate cancer with metastasis to bone are osteolytic and not osteoblastic. Significant osteolysis by tumor cells at metastatic sites also may lead to fractures or bone instability. Misinterpretation of new periosteal bone due to bone instability as tumor-cell osteo-induction is another disadvantage of the osteolytic models. To circumvent these problems, we have developed a model system of new bone formation in the calvaria of nude mice stimulated by normal canine prostate tissue. Collagenase-digested normal prostate tissue was implanted adjacent to the calvaria of nude mice. Calvaria were examined at 2 weeks post-implantation for changes in the bone microenvironment by histology, calcein uptake at sites of bone mineralization, and tartrate-resistant acid phosphatase staining for osteoclasts. The prostate tissue remained viable and induced abundant new woven bone formation on the adjacent periosteal surface. In some cases new bone formation also was induced on the distant or concave calvarial periosteum. The new bone stained intensely with calcein, which demonstrated mineralization of the bone matrix. The new bone formation on prostate-implanted calvaria significantly increased (1.7-fold) the thickness of the calvaria compared with control calvaria. New bone formation was not induced in calvaria of mice implanted with normal canine kidney, urinary bladder, spleen, or skeletal muscle tissue, or mice with surgically-induced disruption of the periosteum. Osteoclast numbers in the medullary spaces and periosteum of calvaria were mildly increased (61%) in mice with implanted prostate tissue. In conclusion, this animal model will be useful for investigating the roles of prostate-derived growth factors on new bone formation in vivo. PMID:12431820

LeRoy, Bruce E; Bahnson, Robert R; Rosol, Thomas J

2002-11-29

116

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

NASA Technical Reports Server (NTRS)

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.

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

1974-01-01

117

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

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 ?g/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 results in increased trabecular bone and softer cortical bone. • TCDD does not affect the bones of Ahr{sup –/–} mice.

Herlin, Maria, E-mail: maria.herlin@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Finnilä, Mikko A.J., E-mail: mikko.finnila@oulu.fi [Department of Medical Technology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Zioupos, Peter, E-mail: p.zioupos@cranfield.ac.uk [Biomechanics Laboratories, Department of Engineering and Applied Science, Cranfield University, Shrivenham SN6 8LA (United Kingdom); Aula, Antti, E-mail: antti.aula@gmail.com [Department of Medical Physics, Imaging Centre, Tampere University Hospital, Tampere (Finland); Department of Biomedical Engineering, Tampere University of Technology, Tampere (Finland); Risteli, Juha, E-mail: juha.risteli@ppshp.fi [Department of Clinical Chemistry, Oulu University Hospital, Oulu (Finland); Miettinen, Hanna M., E-mail: hanna.miettinen@crl.com [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Jämsä, Timo, E-mail: timo.jamsa@oulu.fi [Department of Medical Technology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Department of Diagnostic Radiology, Oulu University Hospital, Oulu (Finland); Tuukkanen, Juha, E-mail: juha.tuukkanen@oulu.fi [Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Korkalainen, Merja, E-mail: merja.korkalainen@thl.fi [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Håkansson, Helen, E-mail: Helen.Hakansson@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Viluksela, Matti, E-mail: matti.viluksela@thl.fi [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Department of Environmental Science, University of Eastern Finland, Kuopio (Finland)

2013-11-15

118

Changes of Elastic Constants and Anisotropy Patterns in Trabecular Bone During Disuse-Induced Bone Loss Assessed by Poroelastic Ultrasound.  

PubMed

Currently, the approach most widely used to examine bone loss is the measurement of bone mineral density (BMD) using dual X-ray absorptiometry (DXA). However, bone loss due to immobilization creates changes in bone microarchitecture, which in turn are related to changes in bone mechanical function and competence to resist fracture. Unfortunately, the relationship between microarchitecture and mechanical function within the framework of immobilization and antiresorptive therapy has not being fully investigated. The goal of the present study was to investigate the structure-function relationship in trabecular bone in the real-world situations of a rapidly evolving osteoporosis (disuse), both with and without antiresorptive treatment. We evaluated the structure-function relationship in trabecular bone after bone loss (disuse-induced osteoporosis) and bisphosphonate treatment (antiresorptive therapy using risedronate) in canine trabecular bone using ?CT and ultrasound wave propagation. Microstructure values determined from ?CT images were used into the anisotropic poroelastic model of wave propagation in order to compute the apparent elastic constants (EC) and elastic anisotropy pattern of bone. Immobilization resulted in a significant reduction in trabecular thickness (Tb.Th) and bone volume fraction (BV/TV), while risedronate treatment combined with immobilization exhibited a lesser reduction in Tb.Th and BV/TV, suggesting that risedronate treatment decelerates bone loss, but it was unable to fully stop it. Risedronate treatment also increased the tissue mineral density (TMD), which when combined with the decrease in Tb.Th and BV/TV may explain the lack of significant differences in vBMD in both immobilization and risedronate treated groups. Interestingly, changes in apparent EC were much stronger in the superior-inferior (SI) direction than in the medial-lateral (ML) and anterior-posterior (AP) anatomical directions, producing changes in elastic anisotropy patterns. When data were pooled together, vBMD was able to explain 58% of ultrasound measurements variability, a poroelastic wave propagation analytical model (i.e., BMD modulated by fabric directionality) was able to predict 81% of experimental wave velocity variability, and also explained 91% of apparent EC and changes in elastic anisotropy patterns. Overall, measurements of vBMD were unable to distinguish changes in apparent EC due to immobilization or risedronate treatment. However, anisotropic poroelastic ultrasound (PEUS) wave propagation was able to distinguish functional changes in apparent EC and elastic anisotropy patterns due to immobilization and antiresorptive therapy, providing an enhanced discrimination of anisotropic bone loss and the structure-function relationship in immobilized and risedronate-treated bone, beyond vBMD. PMID:25412022

Cardoso, Luis; Schaffler, Mitchell B

2015-01-01

119

Postural equilibrium following exposure to weightless space flight  

NASA Technical Reports Server (NTRS)

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.

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

1977-01-01

120

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

NASA Technical Reports Server (NTRS)

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.

Schwartz, Robert J.

1997-01-01

121

Orbital wall repair in canines with beta-tricalcium phosphate and induced bone marrow stromal cells.  

PubMed

Bone tissue engineering is a new approach for the repair of orbital defects. The aim of the present study was to evaluate prefabricated beta-tricalcium phosphate (?-TCP) combined with autologous bone marrow stromal cells (BMSCs) to repair orbital wall defect in canine models. Defects measuring 10 mm in diameter were created in the orbital medial walls of 12 dogs. The orbits were randomly divided into five groups: group 1, repaired with osteogenesis-induced BMSCs/TCP constructs; group 2, repaired with noninduced BMSCs/TCP constructs; group 3, repaired with ?-TCP scaffolds only; group 4, normal group; group 5, negative control (bone defect without treatment). Computed tomography (CT) scanning, gross observation, bone density measurements, micro-CT, and histological observations were performed. In group 1, new bone was observed with only a small amount of residual material, and bony union was achieved 3 months after surgery. In contrast, the constructs showed slow degradation with minimal bone formation in groups 2 and 3. Furthermore, the appearance and bone density of the constructs in group 1 were similar to that of normal bone: the constructs were covered with complete mucosa, and new alveolate plate grew into the ethmoidal sinuses. A large bone defect remained in group 5. This study demonstrated that biologic scaffolds composed of ?-TCP and osteogenesis-induced BMSCs have been successfully used to restore bone functionality in animal models, which may provide a potential clinical approach for orbital wall repair and bone regeneration in humans. PMID:23687075

Zhou, Huifang; Deng, Yuan; Bi, Xiaoping; Xiao, Caiwen; Wang, Yefei; Sun, Jing; Gu, Ping; Fan, Xianqun

2013-11-01

122

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)

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.

Morgan, J. L. L.; Skulan, J. L.; Gordon, G. E.; Smith, Scott M.; Romaniello, S. J.; Anbar, A. D.

2012-01-01

123

MR imaging of therapy-induced changes of bone marrow  

PubMed Central

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

Henning, Tobias; Link, Thomas M.

2006-01-01

124

Polyethylene Particle-Induced Bone Resorption in Substance P-Deficient Mice  

Microsoft Academic Search

Aseptic loosening is the major cause of total joint replacement failure. Substance P (SP) is a neurotransmitter richly distributed\\u000a in sensory nerve fibers, bone, and bone-related tissue. The purpose of this study was to investigate the potential impact\\u000a of SP on bone metabolism in polyethylene particle-induced osteolysis. We utilized the murine calvarial osteolysis model based\\u000a on ultrahigh molecular weight polyethylene

C. Wedemeyer; C. Neuerburg; A. Pfeiffer; A. Heckelei; F. von Knoch; G. Hilken; J. Brankamp; F. Henschke; M. von Knoch; F. Löer; G. Saxler

2007-01-01

125

Static-kinetic reactions of man under conditions of brief weightlessness  

NASA Technical Reports Server (NTRS)

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.

Kolosov, I. A.

1975-01-01

126

Prednisone-induced osteopenia in beagles: variable effects mediated by differential suppression of bone formation.  

PubMed

To examine the mechanism of glucocorticoid-induced osteopenia and the basis for variable bone loss after glucocorticoid administration, we gave prednisone (1.3 mg.kg-1.day-1) to normal male dogs (n = 15) for 29 wk to attempt induction of osteopenia. Compared with age-matched control dogs (n = 14), prednisone treatment rapidly decreased spinal bone density by 4.3%, as assessed by quantitative digital radiography, and reduced trabecular bone volume by 14.6%, as measured by quantitative histomorphology of iliac crest bone specimens. Bone loss was attenuated in prednisone-treated dogs after prolonged treatment (greater than 12 wk). Prednisone treatment resulted in diminished bone formation rates (15 +/- 3.4 vs. 47 +/- 4.5 microns/yr) and activation frequency (0.4 +/- 0.1 vs. 1.3 +/- 0.2/day). These findings indicate that suppression of osteoblastic function and recruitment is the primary histological abnormality mediating glucocorticoid-induced osteopenia in beagles. In contrast, prednisone administration had no effect on bone resorption or serum concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D, which suggests that these factors are not essential for prednisone-induced bone loss. Moreover, 33% of beagles were totally resistant to glucocorticoid-induced osteopenia. Such heterogeneity of bone loss was associated with variable suppressive effects of prednisone on osteoblastic function, as evidenced by greater bone formation rates and activation frequency in prednisone-resistant animals. Collectively, these observations suggest that glucocorticoid-induced bone loss results from a dynamic interplay between steroid-mediated suppression of osteoblastic function and recruitment and undefined compensatory factors that ameliorate the effects of glucocorticoids on osteoblastic precursors. PMID:1636691

Quarles, L D

1992-07-01

127

Weightlessness and the human skeleton: A new perspective  

NASA Technical Reports Server (NTRS)

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.

Holick, Michael F.

1994-01-01

128

Hydrogen and hydrocarbon diffusion flames in a weightless environment  

NASA Technical Reports Server (NTRS)

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

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

1973-01-01

129

Combination therapies prevent the neuropathic, proinflammatory characteristics of bone marrow in streptozotocin-induced diabetic rats.  

PubMed

We previously showed that peripheral neuropathy of the bone marrow was associated with loss of circadian rhythmicity of stem/progenitor cell release into the circulation. Bone marrow neuropathy results in dramatic changes in hematopoiesis that lead to microvascular complications, inflammation, and reduced endothelial repair. This series of events represents early pathogenesis before development of diabetic retinopathy. In this study we characterized early alterations within the bone marrow of streptozotocin (STZ)-induced diabetic rats following treatments that prevent experimental peripheral neuropathy. We asked whether bone marrow neuropathy and the associated bone marrow pathology were reversed with treatments that prevent peripheral neuropathy. Three strategies were tested: inhibition of neutral endopeptidase, inhibition of aldose reductase plus lipoic acid supplementation, and insulin therapy with antioxidants. All strategies prevented loss of nerve conduction velocity resulting from STZ-induced diabetes and corrected the STZ-induced diabetes-associated increase of immunoreactivity of neuropeptide Y, tyrosine hydroxylase, and somatostatin. The treatments also reduced concentrations of interleukin-1?, granulocyte colony-stimulating factor, and matrix metalloproteinase 2 in STZ-induced diabetic bone marrow supernatant and decreased the expression of NADPH oxidase 2, nitric oxide synthase 2, and nuclear factor-?B1 mRNA in bone marrow progenitor cells. These therapies represent novel approaches to attenuate the diabetic phenotype within the bone marrow and may constitute an important therapeutic strategy for diabetic microvascular complications. PMID:25204979

Dominguez, James M; Yorek, Mark A; Grant, Maria B

2015-02-01

130

Gravity, calcium, and bone - Update, 1989  

NASA Technical Reports Server (NTRS)

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.

Arnaud, Sara B.; Morey-Holton, Emily

1990-01-01

131

Combined effect of weightlessness and ionizing radiation on rats (results of morphological studies)  

Microsoft Academic Search

We submit the results of morphological studies conducted on rats exposed to radiation on Kosmos-690 satellite, in order to demonstrate the distinctions of the combined effect of weightlessness and penetrating radiation. Analysis of the changes demonstrated was made in three main directions: how weightlessness affects the course of radiation lesions; how radiation affects changes caused by weightlessness; summation of effects

V. V. Portugalov; E. A. Savina

1978-01-01

132

Laboratory simulation of the action of weightlessness on the human organism  

NASA Technical Reports Server (NTRS)

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.

Genin, A. M.

1977-01-01

133

Effect of simulated weightlessness on the immune system in rats  

NASA Technical Reports Server (NTRS)

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.

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

1980-01-01

134

Adhesion molecule deficiencies increase Porphyromonas gingivalis-induced alveolar bone loss in mice  

Microsoft Academic Search

Alveolar bone resorption can be induced in specific-pathogen-free mice by oral infection with Porphyromonas gingivalis (P. J. Baker, R. T. Evans, and D. C. Roopenian, Arch. Oral Biol. 39:1035-1040, 1994). Here we used a mouse strain, C57BL\\/6J, which is relatively resistant to P. gingivalis-induced bone loss to examine whether partial or complete deletion of various adhesion molecules would increase susceptibility.

PAMELA J. BAKER; LISA DUFOUR; MARK DIXON; DERRY C. ROOPENIAN

2000-01-01

135

Prostaglandin E2 Prevents Ovariectomy-Induced Cancellous Bone Loss in Rats  

NASA Technical Reports Server (NTRS)

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 doses) and added extra bone to metaphyses of OVX rats (in higher dose). These findings support the strategy of the use of bone stimulation agents in the prevention of estrogen depletion bone loss (postmenopausal osteoporosis).

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

1992-01-01

136

A Computational Model for Simulating Spaceflight Induced Bone Remodeling  

NASA Technical Reports Server (NTRS)

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.

Pennline, James A.; Mulugeta, Lealem

2014-01-01

137

Exercise-Induced Changes in the Cortical Bone of Growing Mice Are Bone and Gender Specific  

PubMed Central

Fracture risk and mechanical competence of bone are functions of bone mass and tissue quality, which in turn are dependent on the bone’s mechanical environment. Male mice have a greater response to non weight-bearing exercise than females, resulting in larger, stronger bones compared with control animals. The aim of this study was to test the hypothesis that short-term weight-bearing running during growth (21 days starting at 8 weeks of age; 30 minutes/day; 12 meters/minute; 5° incline; 7 days/week) would similarly have a greater impact on cross sectional geometry and mechanical competence in the femora and tibiae of male mice versus females. Based on the orientation of the legs during running and the proximity of the tibia to the point of impact, this response was hypothesized to be greatest in the tibia. Exercise-related changes relative to controls were assayed by four-point bending tests, while volumetric bone mineral density and cross-sectional geometry were also assessed. The response to running was bone and gender-specific, with male tibiae demonstrating the greatest effects. In male tibiae, periosteal perimeter, endocortical perimeter, cortical area, medial-lateral width and bending moment of inertia increased versus control mice suggesting that while growth is occurring in these mice between 8 and 11 weeks of age, exercise accelerated this growth resulting in a greater increase in bone tissue over the 3 weeks of the study. Exercise increased tissue-level strain-to-failure and structural post-yield deformation in the male tibiae, but these post-yield benefits came at the expense of decreased yield deformation, structural and tissue-level yield strength and tissue-level ultimate strength. These results suggest that exercise superimposed upon growth accelerated growth-related increases in tibial cross-sectional dimensions. Exercise also influenced the quality of this forming bone, significantly impacting structural and tissue-level mechanical properties. PMID:17240210

Wallace, Joseph M.; Rajachar, Rupak M.; Allen, Matthew R.; Bloomfield, Susan A.; Robey, Pamela G.; Young, Marian F.; Kohn, David H.

2009-01-01

138

Peripheral TGF-?1 signaling is a critical event in bone cancer-induced hyperalgesia in rodents.  

PubMed

Pain is the most common symptom of bone cancer. TGF-?, a major bone-derived growth factor, is largely released by osteoclast bone resorption during the progression of bone cancer and contributes to proliferation, angiogenesis, immunosuppression, invasion, and metastasis. Here, we further show that TGF-?1 is critical for bone cancer-induced pain sensitization. We found that, after the progression of bone cancer, TGF-?1 was highly expressed in tumor-bearing bone, and the expression of its receptors, TGF?RI and TGF?RII, was significantly increased in the DRG in a rat model of bone cancer pain that is based on intratibia inoculation of Walker 256 mammary gland carcinoma cells. The blockade of TGF-? receptors by the TGF?RI antagonist SD-208 robustly suppressed bone cancer-induced thermal hyperalgesia on post-tumor day 14 (PTD 14). Peripheral injection of TGF-?1 directly induced thermal hyperalgesia in intact rats and wide-type mice, but not in Trpv1(-/-) mice. Whole-cell patch-clamp recordings from DRG neurons showed that transient receptor potential vanilloid (TRPV1) sensitivity was significantly enhanced on PTD 14. Extracellular application of TGF-?1 significantly potentiated TRPV1 currents and increased [Ca(2+)]i in DRG neurons. Pharmacological studies revealed that the TGF-?1 sensitization of TRPV1 and the induction of thermal hyperalgesia required the TGF-?R-mediated Smad-independent PKC? and TGF-? activating kinase 1-p38 pathways. These findings suggest that TGF-?1 signaling contributes to bone cancer pain via the upregulation and sensitization of TRPV1 in primary sensory neurons and that therapeutic targeting of TGF-?1 may ameliorate the bone cancer pain in advanced cancer. PMID:24305807

Xu, Qian; Zhang, Xiao-Meng; Duan, Kai-Zheng; Gu, Xi-Yao; Han, Mei; Liu, Ben-Long; Zhao, Zhi-Qi; Zhang, Yu-Qiu

2013-12-01

139

IKKß as a target for treatment of inflammation induced bone loss  

PubMed Central

The transcription factor nuclear factor (NF)-?B is well recognised as a pivotal player in osteoclastogenesis and inflammation induced bone loss. Here, the authors discuss their recent results, obtained using a genetic approach in mice, that indicate the importance of IKKß, and not IKK?, as a transducer of signals from receptor activator of NF-?B (RANK) to NF-?B. Ablation of IKKß results in lack of osteoclastogenesis and unresponsiveness of IKKß deficient mice to inflammation induced bone loss. In the need of a more effective therapy for the treatment of inflammatory diseases causing bone resorption, specific inhibition of IKKß represents a logical alternative strategy to the current therapies. PMID:16239395

Ruocco, M; Karin, M

2005-01-01

140

Adaptation of the Human Body to Simulated Weightlessness: Clinical Studies  

Microsoft Academic Search

Problems of adaptation of functional systems of the human body to conditions of continuous weightlessness are considered (prolonged stay under conditions of antiorthostatic hypokinesia and in an immersion medium). It was revealed that, during adaptation to these conditions, polymorphic clinicofunctional disorders develop, transforming into clinicophysiological syndromes, the most frequently observed being autonomic vascular malfunction, asthenoneurotic syndrome, detraining of the blood

Yu. I. Voronkov; A. Ya. Tizul; M. P. Kuz'min; N. V. Degterenkova; E. I. Dobrokvashina; E. I. Matsnev; O. A. Smirnov; G. P. Stepanova; L. M. Filatova

2003-01-01

141

HUMAN ORIENTATION IN PROLONGED WEIGHTLESSNESS (ISS HRF-E085)  

Microsoft Academic Search

This Human Research Facility (HRF) experiment focuses on how human spatial orientation mechanisms adapt during prolonged (3-6 month) exposure to weightlessness, and the time course of readaptation after return to earth. It will utilize the HRF Rack 2 Workstation as a \\

Andrew Liu; Charles M. Oman; Andrew C. Beall; Theodore Smith; Laurence R. Young; Laurence Harris; Michael Jenkin

142

Postural reactions of circulation and its regulation during simulated weightlessness  

NASA Astrophysics Data System (ADS)

The extention and intensification of space exploration the influence of weightlessness on human organism and the formation of a new level of adaptation. The studies of blood circulation is very important because of freguent occurance of cardiovascular disorders in the middle age sudjects. In connection with extention and intensification of space exploration the influence of weightlessness on human organism and the formation of a new level of adaptation mechanisms acguires a special significance (5, 9, 10). The data obtained in recently undertaken model experiments (1, 5, 10), and also during space flights (5, 9) indicate that weightlessness in many ways affects various physiological systems of organism, and first of all cardiovascular system with the development of reflex, humoral and metabolic reactions. It also indicates, that the changes in functioning of cardiovascular system brings about the discruption of its regular responses, which is foremost expressed in decreased antigravitational response, which manifests itself in lowered orthostatic stability (2, 4, 6). It is worth mentioning, that the changes during previous investigations of haemodynamics were mainly carried out with the subjects under forty, therefore agerelated specific features of blood circulation system response are described in a few articles (5, 8). The studies of the kind are especially important because of frequent occurence of cardiovascular disorders such as heart and brain vessels atherosclerosis, hypertension in the middle age, which can to a great extent complicate and affect the "acute" period of adaptation to weightlessness and readaptation process.

Sokolov, V. I.; Valyev, V. A.; Kirillov, M. V.; Gornago, V. A.

143

Perception of time under conditions of brief weightlessness  

NASA Technical Reports Server (NTRS)

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

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

1975-01-01

144

Weightless neural nets for face recognition: a comparison  

Microsoft Academic Search

This paper considers the application of weightless neural networks (WNNs) to the problem of face recognition and compares the results with those provided using a more complicated multiple neural network approach. WNNs have significant advantages over the more common forms of neural networks, in particular in term of speed of operation and learning. A major difficulty when applying neural networks

S. Lauria; R. J. Mitchell

1998-01-01

145

The effects of prolonged exposure to weightlessness on postural equilibrium  

NASA Technical Reports Server (NTRS)

A postflight postural equilibrium rail tests on spacecrews was used to prove a pronounced decrement in ability to maintain an upright posture after prolonged exposure to weightlessness. Support for the hypothesis that central neural reorganization occurs in response to environmental change is obtained when postflight decrease in stability on the rails and the time course for recovery are compared with preflight performance.

Homick, J. L.; Reschke, M. F.; Miller, E. F., II

1977-01-01

146

Simulated weightlessness down-regulated antioxidant defense system in rats  

NASA Astrophysics Data System (ADS)

A variety of experiments suggest that space flight is associated with an increase in oxidative stress in organism The aim of the present study is to investigate whether or not simulated weightlessness by tail-suspension can affect the antioxidant defense system in rats and the possible protection effects of Chinese medicine named Liu Wei Di Huang Wan LWDHW Blood plasma of rats was taken after 21 days - tail-suspension for the assessment of the change of antioxidant defense system The total antioxidant capacity T-AOC was significantly decreased and the content of malondialdehyde MDA was increased after simulated weightlessness Activities of antioxidant enzymes such as superoxide dismutase and catalase were lower than those in the controlled groups However the activity of glutathione peroxidase was increased in comparison with the controlled groups Adequate dosage of LWDHW could inhibit the production of MAD and improve T-AOC in tail-suspension rats These results suggested that tail-suspension might break the oxidative antioxidative balance and down-regulate antioxidant defense system and Chinese medicine LWDHW was shown to protect rats from oxidative damage during simulated weightlessness Key words Simulated weightlessness Tail-suspension Antioxidant defense system Rats

Li, Qi; Qu, Lina; Li, Yingxian; Bi, Lei; Huang, Zengming; Wang, Bo

147

Weightlessness acts on human breast cancer cell line MCF-7  

NASA Astrophysics Data System (ADS)

Because cells are sensitive to mechanical forces, weightlessness might act on stress-dependent cell changes. Human breast cancer cells MCF-7, flown in space in a Photon capsule, were fixed after 1.5, 22 and 48 h in orbit. Cells subjected to weightlessness were compared to 1g in-flight and ground controls. Post-flight, fluorescent labeling was performed to visualize cell proliferation (Ki-67), three cytoskeleton components and chromatin structure. Confocal microscopy and image analysis were used to quantify cycling cells and mitosis, modifications of the cytokeratin network and chromatin structure. Several main phenomena were observed in weightlessness: The perinuclear cytokeratin network and chromatin structure were looser. More cells were cycling and mitosis was prolonged. Finally, cell proliferation was reduced as a consequence of a cell-cycle blockade. Microtubules were altered in many cells. The results reported in the first point are in agreement with basic predictions of cellular tensegrity. The prolongation of mitosis can be explained by an alteration of microtubules. We discuss here the different mechanisms involved in weightlessness alteration of microtubules: i) alteration of their self-organization by reaction-diffusion processes, and a mathematical model is proposed, ii) activation or desactivation of microtubules stabilizing proteins, acting on both microtubule and microfilament networks in cell cortex.

Vassy, J.; Portet, S.; Beil, M.; Millot, G.; Fauvel-Lafève, F.; Gasset, G.; Schoevaert, D.

2003-10-01

148

Experimental and Theoretical Challenges of Creating Electrostatic Orbits in Weightlessness  

Microsoft Academic Search

In January 2006, a team of students from Rhodes College was awarded flight time aboard NASA's specialized C-9B aircraft known as the ``Weightless Wonder'' to perform an experiment in microgravity. This experiment demonstrated a prediction of Coulomb's Law that two oppositely charged spheres should orbit each other under certain conditions. However a number of issues complicate this demonstration such as

Kevin W. Andring; B. Hoffmeister; S. Banerjee; J. Janeski; S. Quinn; D. Keedy; D. Campbell

2006-01-01

149

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

NASA Technical Reports Server (NTRS)

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

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

1999-01-01

150

Leukemia cells induce changes in human bone marrow stromal cells  

PubMed Central

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-? and TNF-? 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-1? 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-? 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

2013-01-01

151

The Role of Purinergic Receptors in Cancer-Induced Bone Pain  

PubMed Central

Cancer-induced bone pain severely compromises the quality of life of many patients suffering from bone metastasis, as current therapies leave some patients with inadequate pain relief. The recent development of specific animal models has increased the understanding of the molecular and cellular mechanisms underlying cancer-induced bone pain including the involvement of ATP and the purinergic receptors in the progression of the pain state. In nociception, ATP acts as an extracellular messenger to transmit sensory information both at the peripheral site of tissue damage and in the spinal cord. Several of the purinergic receptors have been shown to be important for the development and maintenance of neuropathic and inflammatory pain, and studies have demonstrated the importance of both peripheral and central mechanisms. We here provide an overview of the current literature on the role of purinergic receptors in cancer-induced bone pain with emphasis on some of the difficulties related to studying this complex pain state. PMID:23091774

Falk, Sarah; Uldall, Maria; Heegaard, Anne-Marie

2012-01-01

152

Minocycline-induced Periarticular Black Bones in Inflamed Joints Which Underwent Arthroplastic Reconstruction  

PubMed Central

Background Minocycline-induced pigmentation of bone (black bone) is well described in tooth-bearing intra-oral bone, but is less known in periarticular bone in patients who have undergone total joint arthroplasty. On a retrospective basis, we investigated the short-term clinico-radiological results of total joint arthroplasties in which the patient developed minocycline-induced periarticular black bone. Methods We found 5 cases (0.08%), in 4 patients, of periarticular bone pigmentation revealed during total joint arthroplasties (2 hips, 2 knees, and 1 ankle) in our series of total joint surgeries (6,548 cases) over a 10-year time period in our 3 institutes. Their mean age was 56 years at surgery. All patients had received long-term minocycline treatment. Mean dosage and duration of minocycline was 160 mg/day and 2.2 years, respectively. Minocycline had been prescribed for reactive arthritis (one), rheumatoid arthritis (two) and late infection after total joint arthroplasty (two patients). Mean follow-up period was 3.4 years after the surgeries. Results All cases had black or brown pigmentation in the periarticular bones during the surgery. There was no pigmentation in the cartilage or soft tissues of the joints. The mean Japanese Orthopaedic Association (JOA) score or Japanese Society for Surgery of the Foot (JSSF) scale for rheumatoid arthritis foot and ankle joints at latest follow-up (case 1, 66; case 2, 87; case 3, 77; case 4, 77; case 5, 80) improved compared to those of pre-surgery (case 1, 47; case 2, 45; case 3, 55; case 4, 34; case 5, 55). No implant loosening was noted on radiographic examination during the follow-up period. No abnormal bone formation, bone necrosis, hemosiderin deposition, malignancy or metallic debris was found on histological examination. Conclusions No clinico-radiological symptoms of total joint arthroplasties showed in the patients with minocycline-induced periariticular black bone in the short-term. Systemic minocycline treatment has the potential to induce significant black pigmentation of many tissues. In particular, minocycline-induced pigmentation of periarticular bone may be accelerated by inflammation due to rheumatic or pyogenic arthritis. Surgeons should recognize the risk of bone pigmentation in inflamed joints due to the systemic treatment of minocycline and explore its influence on periarticular bone and total joint arthroplasty in the long-term. PMID:22949948

Takakubo, Yuya; Kobayashi, Shinji; Asano, Tamon; Sasaki, Akiko; Sasaki, Kan; Ohki, Hiroharu; Tamaki, Yasunobu; Takagi, Michiaki

2012-01-01

153

The effect of simulated weightlessness on hypobaric decompression sickness  

NASA Technical Reports Server (NTRS)

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

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

2002-01-01

154

Arthritis Induces Early Bone High Turnover, Structural Degradation and Mechanical Weakness  

PubMed Central

Background 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. Methods 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. Results 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. Conclusions We have shown in an AIA rat model that arthritis induc-es early bone high turnover, structural degradation, mineral loss and mechanical weak-ness. PMID:25617902

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

2015-01-01

155

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

PubMed Central

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 J? 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-?B (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

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

2012-01-01

156

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

NASA Technical Reports Server (NTRS)

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.

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

1996-01-01

157

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

PubMed

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. PMID:21710590

Mei, Lin; Mochizuki, Miyako; Hasegawa, Noboru

2012-01-01

158

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

NASA Astrophysics Data System (ADS)

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

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

2014-12-01

159

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

PubMed

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. PMID:25463494

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

2015-02-01

160

Prednisolone prevents decreases in trabecular bone mass and strength by reducing bone resorption and bone formation defect in adjuvant-induced arthritic rats.  

PubMed

We examined the effects of prednisolone (PSL) administration in normal female Sprague Dawley rats and adjuvant-induced arthritic rats at the age of 6 weeks. Rats were intramuscularly injected with PSL twice a week at doses of 0 (control), 10, 30, 90, or 270 mg/kg body weight (b.w.). In the normal rats, serum osteocalcin level at 14 days and serum carboxyterminal pyridinoline cross-linked telopeptide of type 1 collagen (1CTP) level at 28 days in the 270 mg/kg dose group was lower than the respective value in control animals. The BMC and the trabecular bone formation rate (BFR/BS) of the lumbar body (L-4) in the 270 mg/kg dose group at 14 and 28 days were significantly lower than the values in the control rats. In the arthritic rats, however, serum osteocalcin levels in the PSL-treated groups did not differ compared with arthritic controls. The serum 1CTP levels in all of the PSL-treated groups were significantly reduced at 28 days. The age-dependent increases in the L4 BMC, BMD, and L-3 ultimate compressive load values were maintained. The BFR/BS values in the 90 mg/kg and 270 mg/kg dose groups were significantly higher than those in the arthritic control rats. The trabecular osteoclast number and surface values in all of the PSL-treated groups were significantly lower than the values in arthritic controls. These data demonstrate that PSL administration prevented reduction in bone mass and strength of the lumbar trabecular bone in adjuvant-induced arthritic rats by reducing the increase in bone resorption and the decrease in bone formation at both the local and systemic levels. PMID:9763147

Okazaki, Y; Tsurukami, H; Nishida, S; Okimoto, N; Aota, S; Takeda, S; Nakamura, T

1998-10-01

161

Early effects of tocilizumab on bone and bone marrow lesions in a collagen-induced arthritis monkey model.  

PubMed

To understand the contribution of IL-6/IL-6R to subchondral bone and bone marrow abnormality in RA patients and the effects of tocilizumab on those abnormalities, we evaluated early change in a collagen-induced arthritis (CIA) monkey model with or without a single administration of tocilizumab. Six CIA cynomolgus monkeys received tocilizumab and 3 CIA monkeys received vehicle only. Their interphalangeal joints were analyzed using HE, silver impregnation (SI), or immunohistochemistry (RANKL) staining. The number of osteoclasts increased in the arthritis control but was suppressed in the tocilizumab-treated animals. Osteoblast/stromal cells of the arthritis control monkeys were of monolayer, while in the tocilizumab-treated monkeys, the cells were multi-layer or differentiated osteoblasts, and the meshwork of the reticulum fibers showed recovery in the SI. Hematopoietic marrow was replaced by interstitial fluid and reticulum fibers were eliminated in the arthritic model but showed recovery in the tocilizumab-treated animals. RANKL showed overproduction with arthritis and suppressed with tocilizumab treatment. The evidence indicates that IL-6/IL-6R is involved in subchondral bone and bone marrow change in RA patients. Tocilizumab treatment recovered changes in the CIA monkeys as a result of the co-differentiation between the osteoclasts and the osteoblast/stramal cells, at least partially through the suppression of RANKL overproduction. PMID:18511040

Kato, Atsuhiko; Matsuo, Saori; Takai, Hirotake; Uchiyama, Yasushi; Mihara, Masahiko; Suzuki, Masami

2008-06-01

162

Pathological role of osteoclast costimulation in arthritis-induced bone loss  

PubMed Central

Abnormal T cell immune responses induce aberrant expression of inflammatory cytokines such as TNF-?, leading to osteoclastmediated bone erosion and osteoporosis in autoimmune arthritis. However, the mechanism underlying enhanced osteoclastogenesis in arthritis is not completely understood. Here we show that TNF-? contributes to inflammatory bone loss by enhancing the osteoclastogenic potential of osteoclast precursor cells through inducing paired Ig-like receptor-A (PIR-A), a costimulatory receptor for receptor activator of NF-?B (RANK). In fact, bone erosion and osteoporosis, but not inflammation, caused by aberrant TNF-? expression were ameliorated in mice deficient in Fc receptor common ? subunit or ?2-microglobulin, in which the expression of PIR-As and PIR-A ligands is impaired, respectively. These results establish the pathological role of costimulatory receptors for RANK in bone loss in arthritis and may provide a molecular basis for the future therapy of inflammatory diseases. PMID:17592115

Ochi, Sae; Shinohara, Masahiro; Sato, Kojiro; Gober, Hans-Jürgen; Koga, Takako; Kodama, Tatsuhiko; Takai, Toshiyuki; Miyasaka, Nobuyuki; Takayanagi, Hiroshi

2007-01-01

163

Exercise-Induced Bone Formation Is Poorly Linked to Local Strain Magnitude in the Sheep Tibia  

PubMed Central

Functional interpretations of limb bone structure frequently assume that diaphyses adjust their shape by adding bone primarily across the plane in which they are habitually loaded in order to minimize loading-induced strains. Here, to test this hypothesis, we characterize the in vivo strain environment of the sheep tibial midshaft during treadmill exercise and examine whether this activity promotes bone formation disproportionately in the direction of loading in diaphyseal regions that experience the highest strains. It is shown that during treadmill exercise, sheep tibiae were bent in an anteroposterior direction, generating maximal tensile and compressive strains on the anterior and posterior shaft surfaces, respectively. Exercise led to significantly increased periosteal bone formation; however, rather than being biased toward areas of maximal strains across the anteroposterior axis, exercise-related osteogenesis occurred primarily around the medial half of the shaft circumference, in both high and low strain regions. Overall, the results of this study demonstrate that loading-induced bone growth is not closely linked to local strain magnitude in every instance. Therefore, caution is necessary when bone shaft shape is used to infer functional loading history in the absence of in vivo data on how bones are loaded and how they actually respond to loading. PMID:24897411

Wallace, Ian J.; Demes, Brigitte; Mongle, Carrie; Pearson, Osbjorn M.; Polk, John D.; Lieberman, Daniel E.

2014-01-01

164

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

SciTech Connect

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.

Yin Ling, E-mail: ling.yin@jcu.edu.au [School of Engineering, James Cook University, Townsville, QLD 4811 (Australia); Venkatesan, Sudharshan [Department of Engineering, Australian National University, Canberra, ACT 0200 Australia (Australia); Webb, Daryl [Electron Microscopy Unit, Australian National University, Canberra, ACT 0200 (Australia); Kalyanasundaram, Shankar; Qin Qinghua [Department of Engineering, Australian National University, Canberra, ACT 0200 Australia (Australia)

2009-08-15

165

Compactin and Simvastatin, but Not Pravastatin, Induce Bone Morphogenetic Protein2 in Human Osteosarcoma Cells  

Microsoft Academic Search

Bone morphogenetic protein (BMP)-2, a member of the BMP family, plays an important role in osteoblast differentiation and bone formation. To discover small molecules that induce BMP-2, a luciferase reporter vector containing the 5?-flanking promoter region of the human BMP-2 gene was constructed and transfected into human osteosarcoma (HOS) cells. By the screening of an in-house natural product library with

Masako Sugiyama; Tohru Kodama; Kyoko Konishi; Keiichi Abe; Sumio Asami; Shinzo Oikawa

2000-01-01

166

Three-dimensional finite element analysis of overload-induced alveolar bone resorption around dental implants  

Microsoft Academic Search

\\u000a In this study, the stress, strain, and strain energy density (SED) criteria were applied to tentatively simulate overload-induced\\u000a bone resorption in implant\\/jawbone systems. By a comparative analysis, the SED criterion was found to be most suitable, based\\u000a on which the resorption process of alveolar bone was investigated, and the effects of implant diameter and loading angle were\\u000a examined. The simulations

Lihe Qian; Mitsugu Todo; Yasuyuki Matsushita; Kiyoshi Koyano

167

NOD2 contributes to Porphyromonas gingivalis-induced bone resorption.  

PubMed

The NOD-like receptors are cytoplasmic proteins that sense microbial by-products released by invasive bacteria. Although NOD1 and NOD2 are functionally expressed in cells from oral tissues and play a role triggering immune responses, the role of NOD2 receptor in the bone resorption and in the modulation of osteoclastogenesis is still unclear. We show that in an experimental model of periodontitis with Porphyromonas gingivalis W83, NOD2(-/-) mice showed lower bone resorption when compared to wild type. Quantitative polymerase chain reaction analysis revealed that wild-type infected mice showed an elevated RANKL/OPG ratio when compared to NOD2(-/-) infected mice. Moreover, the expression of 2 osteoclast activity markers-cathepsin K and matrix metalloproteinase 9-was significantly lower in gingival tissue from NOD2(-/-) infected mice compared to WT infected ones. The in vitro study reported an increase in the expression of the NOD2 receptor 24 hr after stimulation of hematopoietic bone marrow cells with M-CSF and RANKL. We also evaluated the effect of direct activation of NOD2 receptor on osteoclastogenesis, by the activation of this receptor in preosteoclasts culture, with different concentrations of muramyl dipeptide. The results show no difference in the number of TRAP-positive cells. Although it did not alter the osteoclasts differentiation, the activation of NOD2 receptor led to a significant increase of cathepsin K expression. We confirm that this enzyme was active, since the osteoclasts resorption capacity was enhanced by muramyl dipeptide stimulation, evaluated in osteoassay plate. These results show that the lack of NOD2 receptor impairs the bone resorption, suggesting that NOD2 receptor could contribute to the progression of bone resorption in experimental model of periodontitis. The stimulation of NOD2 by its agonist, muramyl dipeptide, did not affect osteoclastogenesis, but it does favor the bone resorption capacity identified by increased osteoclast activity. PMID:25239844

Prates, T P; Taira, T M; Holanda, M C; Bignardi, L A; Salvador, S L; Zamboni, D S; Cunha, F Q; Fukada, S Y

2014-11-01

168

Gravity, Calcium, And Bone: Update, 1989  

NASA Technical Reports Server (NTRS)

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

Arnaud, Sara B.; Morey-Holton, Emily

1992-01-01

169

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

PubMed

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

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

2013-01-01

170

Vascularized Bone Tissue Formation Induced by Fiber-Reinforced Scaffolds Cultured with Osteoblasts and Endothelial Cells  

PubMed Central

The repair of the damaged bone tissue caused by damage or bone disease was still a problem. Current strategies including the use of autografts and allografts have the disadvantages, namely, diseases transmission, tissue availability and donor morbidity. Bone tissue engineering has been developed and regarded as a new way of regenerating bone tissues to repair or substitute damaged or diseased ones. The main limitation in engineering in vitro tissues is the lack of a sufficient blood vessel system, the vascularization. In this paper, a new-typed hydroxyapatite/collagen composite scaffold which was reinforced by chitosan fibers and cultured with osteoblasts and endothelial cells was fabricated. General observation, histological observation, detection of the degree of vascularization, and X-ray examination had been done to learn the effect of vascularized bone repair materials on the regeneration of bone. The results show that new vessel and bone formed using implant cultured with osteoblasts and endothelial cells. Nanofiber-reinforced scaffold cultured with osteoblasts and endothelial cells can induce vascularized bone tissue formation. PMID:24369019

Liu, Xinhui; Zhang, Guoping; Hou, Chuanyong; Wang, Hua; Yang, Yelin; Guan, Guoping; Dong, Wei; Gao, Hongyang

2013-01-01

171

The mineralization inducing peptide derived from dentin sialophosphoprotein for bone regeneration.  

PubMed

Dentin sialophosphoprotein (DSPP) has been shown to play a primary role in the formation and growth of hydroxyapatite crystals in an extracellular matrix of hard tissue such as bone and teeth. We hypothesized that the mineralization ability of DSPP might depend on a specific domain within it. Three peptides, which have hydroxyapatite (HA) binding affinity, denoted as mineralization inducing peptide (MIP1, MIP2, and MIP3) were identified from DSPP. The both of MIP2 and MIP3 had HA nucleation activity demonstrated by XRD. Among three MIPs, MIP3 significantly supported the human bone marrow stromal cell differentiation into osteoblastic cells. An immunoblot with antibodies specific for the phosphorylated forms of ERK was conducted with cells treated by MIP3. MIP3 transduced intracellular signals via the ERK pathways and was able to induce osteoblastic differentiation, as seen by high expression of ALP, type 1 collagen, OC, OPN, and Runx2 in accordance with applied MIP3 concentration. The Asp, Glu, and Ser residues in MIP3 play important roles for the affinity of calcium in HA bone mineral. Further animal experiment with MIP3 in combination with hydroxyapatite mineral induced marked new bone formation for 4 weeks at rabbit calvarial defect model. The new bone area was much higher in test group, implying that the peptide modified group had excellent biocompatibility when compared with the unmodified group. Taken together, the MIP from DSPP has potential to enhance mineralization followed by to enhance osteoblastic differentiation and bone regeneration. PMID:22961875

Choi, Young Suk; Lee, Jue Yeon; Suh, Jin Sook; Lee, Gene; Chung, Chong Pyoung; Park, Yoon Jeong

2013-02-01

172

Mathematical modeling of fluid-electrolyte alterations during weightlessness  

NASA Technical Reports Server (NTRS)

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

Leonard, J. I.

1984-01-01

173

Work/control stations in Space Station weightlessness  

NASA Technical Reports Server (NTRS)

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

Willits, Charles

1990-01-01

174

Physiological changes in fast and slow muscle with simulated weightlessness  

NASA Technical Reports Server (NTRS)

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

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

1984-01-01

175

Automated potentiometric electrolyte analysis system. [for use in weightlessness  

NASA Technical Reports Server (NTRS)

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

1973-01-01

176

Effect of weightlessness on sympathetic-adrenomedullary activity of rats  

NASA Astrophysics Data System (ADS)

Three cosmic experiments were performed in which rats spent 18-20 days in space on board the biosatellites "COSMOS 782", "COSMOS 936" and "COSMOS 1129". The following indicators of the sympathetic-adrenomedullary system (SAS) activity were measured: tissue and plasma catecholamines (CA), CA-synthesizing enzymes—tyrosine hydroxylase (TH), dopamine-?-hydroxylase (DBH), phenylethanolamine-N-methyltransferase (PNMT)—as well as CA-degrading enzymes—monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). Adrenal epinephrine (EPI) and norepinephrine (NE) as well as CA-synthesizing and degrading enzymes were not significantly changed in the animals after flight on COSMOS 782. On the other hand, a significant increase was found in heart CA, the indicator which is usually decreased after stress. 26 days after landing all values were at control levels. The results obtained, compared to our previous stress experiments on Earth, suggest that prolonged weightlessness does not appear to be a pronounced stressful stimulus for the SAS. Heart and plasma CA, mainly NE, were increased both in the group living in the state of weightlessness and the group living in a centrifuge and exposed to artificial gravitation 1 g (COSMOS 936), suggesting again that prolonged weightlessness is not an intensive stressful stimulus for the SAS. The animals exposed after space flight on COSMOS 1129 to repeated immobilization stress on Earth showed a significant decrease of adrenal EPI and an expressive increase of adrenal TH activity compared to stressed animals which were not in space. Thus, the results corroborate that prolonged state of weightlessness during space flight though not representing by itself an intensive stressful stimulus for the sympathetic-adrenomedullary system, was found to potentiate the response of "cosmic rats" to stress exposure after return to Earth.

Kvet?anský, R.; Torda, T.; Macho, L.; Tigranian, R. A.; Serova, L.; Genin, A. M.

177

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

NASA Technical Reports Server (NTRS)

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

1995-01-01

178

Spatial orientation in weightlessness and readaptation to earth's gravity  

NASA Technical Reports Server (NTRS)

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

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

1984-01-01

179

Weightlessness - A case history. [for Skylab 2 crewmen  

NASA Technical Reports Server (NTRS)

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

Kerwin, J. P.

1975-01-01

180

Astronauts Hoffman and Seddon demonstrate effect of weightlessness on slinky  

NASA Technical Reports Server (NTRS)

Astronauts Jeffrey A. Hoffman and Rhea Seddon, mission specialists, demonstrate the effect of weightlessness on a slinky toy in the middeck of the Discovery. On the middeck lockers are various logos of the universities that the astronauts are affiliated with such as: Amherst, Purdue and Tennessee. There are also stickers which read 'Fly Navy' and 'Naval Reserve'. On the top locker is a sticker which shows the STS 51-D logo.

1985-01-01

181

Effects of weightlessness on human fluid and electrolyte physiology  

NASA Technical Reports Server (NTRS)

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

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

1991-01-01

182

The relevance of leukotrienes for bone resorption induced by mechanical loading.  

PubMed

5-Lipoxygenase (5-LO) metabolites are important pro-inflammatory lipid mediators. However, much still remains to be understood about the role of such mediators in bone remodeling. This study aimed to investigate the effect of 5-LO metabolites, LTB4 and CysLTs, in a model of mechanical loading-induced bone remodeling. Strain-induced tooth movement and consequently alveolar bone resorption/apposition was achieved by using a coil spring placed on molar and attached to incisors of C57BL6 (wild-type-WT), 5-LO deficient mice (5-LO(-/-)) and mice treated with 5-LO inhibitor (zileuton-ZN) or with antagonist of CysLTs receptor (montelukast-MT). The amount of bone resorption and the number of osteoclasts were determined morphometrically. The expression of inflammatory and bone remodeling markers in periodontium was analyzed by qPCR. Osteoclast differentiation and TNF-? production were evaluated in vitro using RAW 264.7 cells treated with LTB4 or LTD4. Bone resorption, TRAP(+) cells and expression of Tnfa, Il10 and Runx2 were significantly diminished in 5-LO(-/-), ZN- and MT-treated mice. The expression of Rank was also reduced in 5-LO(-/-) and MT-treated mice. Accordingly, LTB4 and LTD4 in association with RANKL promoted osteoclast differentiation and increased TNF-? release in vitro. These data demonstrate that the absence of 5-LO metabolites, LTB4 and CysLTs reduces osteoclast recruitment and differentiation, consequently diminishing bone resorption induced by mechanical loading. Thus, 5-LO might be a potential target for controlling bone resorption in physiological and pathological conditions. PMID:25270168

Moura, A P; Taddei, S R A; Queiroz-Junior, C M; Madeira, M F M; Rodrigues, L F D; Garlet, G P; Souza, D G; Machado, F S; Andrade, I; Teixeira, M M; Silva, T A

2014-12-01

183

Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats  

SciTech Connect

Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/?CT imaging. GSK-3 inhibitors caused ?-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH{sub 1–34} or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/?CT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis and mineralisation produced by GSK-3 inhibition. • In rats, 3 GSK-3 inhibitors produced a unique serum bone turnover biomarker profile. • Enhanced bone formation was seen within 7 to 14 days of compound treatment in rats.

Gilmour, Peter S., E-mail: Peter.Gilmour@astrazeneca.com [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); O'Shea, Patrick J.; Fagura, Malbinder [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Pilling, James E. [Discovery Sciences, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Sanganee, Hitesh [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Wada, Hiroki [R and I IMed, AstraZeneca R and D, Molndal (Sweden); Courtney, Paul F. [DMPK, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Kavanagh, Stefan; Hall, Peter A. [Safety Assessment, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Escott, K. Jane [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom)

2013-10-15

184

Topical Treatment with Xiaozheng Zhitong Paste (XZP) Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling  

PubMed Central

To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP) on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63?g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-? were examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P<0.05). Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-? were detected in the XZP-treated rats (P<0.05 for all). Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats.

Bao, Yanju; Gao, Yebo; Du, Maobo; Hou, Wei; Yang, Liping; Kong, Xiangying; Zheng, Honggang; Li, Weidong; Hua, Baojin

2015-01-01

185

Morphological differences in BMP-2-induced ectopic bone between solid and crushed hyaluronan hydrogel templates.  

PubMed

The possibility to affect bone formation by using crushed versus solid hydrogels as carriers for bone morphogenetic protein 2 (BMP-2) was studied. Hydrogels, based on chemical crosslinking between hyaluronic acid and poly(vinyl alcohol) derivatives, were loaded with BMP-2 and hydroxyapatite. Crushed and solid forms of the gels were analyzed both in vitro via a release study using ¹²?I radioactive labeling of BMP-2, and in vivo in a subcutaneous ectopic bone model in rats. Dramatically different morphologies were observed for the ectopic bone formed in vivo in the two types of gels, even though virtually identical release profiles were observed in vitro. Solid hydrogels induced formation of a dense bone shell around non-degraded hydrogel, while crushed hydrogels demonstrated a uniform bone formation throughout the entire sample. These results suggest that by crushing the hydrogel, the construct's three-dimensional network becomes disrupted. This could expose unreacted functional groups, making the fragment's surfaces reactive and enable limited chemical fusion between the crushed hydrogel fragments, leading to similar in vitro release profiles. However, in vivo these interactions could be broken by enzymatic activity, creating a macroporous structure that allows easier cell infiltration, thus, facilitating bone formation. PMID:23392969

Hulsart-Billström, Gry; Piskounova, Sonya; Gedda, Lars; Andersson, Britt-Marie; Bergman, Kristoffer; Hilborn, Jöns; Larsson, Sune; Bowden, Tim

2013-05-01

186

Murine bone cell lines as models for spaceflight induced effects on differentiation and gene expression  

NASA Astrophysics Data System (ADS)

Critical health factors for space crews especially on long-term missions are radiation exposure and the absence of gravity DNA double strand breaks DSB are presumed to be the most deleterious DNA lesions after radiation as they disrupt both DNA strands in close proximity Besides radiation risk the absence of gravity influences the complex skeletal apparatus concerning muscle and especially bone remodelling which results from mechanical forces exerting on the body Bone is a dynamic tissue which is life-long remodelled by cells from the osteoblast and osteoclast lineage Any imbalance of this system leads to pathological conditions such as osteoporosis or osteopetrosis Osteoblastic cells play a crucial role in bone matrix synthesis and differentiate either into bone-lining cells or into osteocytes Premature terminal differentiation has been reported to be induced by a number of DNA damaging or cell stress inducing agents including ionising and ultraviolet radiation as well as treatment with mitomycin C In the present study we compare the effects of sequential differentiation by adding osteoinductive substances ss -glycerophosphate and ascorbic acid Radiation-induced premature differentiation was investigated regarding the biosynthesis of specific osteogenic marker molecules and the differentiation dependent expression of marker genes The bone cell model established in our laboratory consists of the osteocyte cell line MLO-Y4 the osteoblast cell line OCT-1 and the subclones 4 and 24 of the osteoblast cell line MC3T3-E1 expressing several

Lau, P.; Hellweg, C. E.; Baumstark-Khan, C.; Reitz, G.

187

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

PubMed

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

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

2015-01-01

188

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

NASA Technical Reports Server (NTRS)

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

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

1985-01-01

189

Caspase-2 Maintains Bone Homeostasis by Inducing Apoptosis of Oxidatively-Damaged Osteoclasts  

PubMed Central

Osteoporosis is a silent disease, characterized by a porous bone micro-structure that enhances risk for fractures and associated disabilities. Senile, or age-related osteoporosis (SO), affects both men and women, resulting in increased morbidity and mortality. However, cellular and molecular mechanisms underlying senile osteoporosis are not fully known. Recent studies implicate the accumulation of reactive oxygen species (ROS) and increased oxidative stress as key factors in SO. Herein, we show that loss of caspase-2, a cysteine aspartate protease involved in oxidative stress-induced apoptosis, results in total body and femoral bone loss in aged mice (20% decrease in bone mineral density), and an increase in bone fragility (30% decrease in fracture strength). Importantly, we demonstrate that genetic ablation or selective inhibition of caspase-2 using zVDVAD-fmk results in increased numbers of bone-resorbing osteoclasts and enhanced tartrate-resistant acid phosphatase (TRAP) activity. Conversely, transfection of osteoclast precursors with wild type caspase-2 but not an enzymatic mutant, results in a decrease in TRAP activity. We demonstrate that caspase-2 expression is induced in osteoclasts treated with oxidants such as hydrogen peroxide and that loss of caspase-2 enhances resistance to oxidants, as measured by TRAP activity, and decreases oxidative stress-induced apoptosis of osteoclasts. Moreover, oxidative stress, quantified by assessment of the lipid peroxidation marker, 4-HNE, is increased in Casp2-/- bone, perhaps due to a decrease in antioxidant enzymes such as SOD2. Taken together, our data point to a critical and novel role for caspase-2 in maintaining bone homeostasis by modulating ROS levels and osteoclast apoptosis during conditions of enhanced oxidative stress that occur during aging. PMID:24691516

Sharma, Ramaswamy; Callaway, Danielle; Vanegas, Difernando; Bendele, Michelle; Lopez-Cruzan, Marisa; Horn, Diane; Guda, Teja; Fajardo, Roberto; Abboud-Werner, Sherry; Herman, Brian

2014-01-01

190

Computational Analysis of Artificial Gravity as a Possible Countermeasure to Spaceflight Induced Bone Loss  

NASA Technical Reports Server (NTRS)

During exploration class missions, such as to asteroids and Mars, astronauts will be exposed to reduced gravity for extended periods. Data has shown that astronauts lose bone mass at a rate of 1% to 2% a month in microgravity, particularly in lower extremities such as the proximal femur. Exercise countermeasures have not completely eliminated bone loss from long duration spaceflight missions, which leaves astronauts susceptible to early onset osteoporosis and greater risk of fracture. Introduction of the Advanced Resistive Exercise Device and other large exercise devices on the International Space Station (ISS), coupled with improved nutrition, has further minimized bone loss. However, unlike the ISS, exploration vehicles will have very limited volume and power available to accommodate such capabilities. Therefore, novel concepts like artificial gravity systems are being explored as a means to provide sufficient load stimulus to the musculoskeletal system to mitigate bone changes that may lead to early onset osteoporosis and increased risk of fracture. Currently, there is minimal data available to drive further research and development efforts to appropriately explore such options. Computational modeling can be leveraged to gain insight on the level of osteoprotection that may be achieved using artificial gravity produced by a spinning spacecraft or centrifuge. With this in mind, NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone both for gravitational unloading condition and the equivalent of 1g daily load stimulus. Using this model, it is possible to simulate vBMD changes in trabecular and cortical bone under different gravity conditions. In this presentation, we will discuss our preliminary findings regarding if and how artificial gravity may be used to mitigate spaceflight induced bone loss.

Mulugeta, L.; Werner, C. R.; Pennline, J. A.

2015-01-01

191

[Glucocorticoid and Bone. Fracture risk of steroid-induced osteoporosis].  

PubMed

Bone loss occurred early after starting oral glucocorticoid (GC) therapy and the risk of fracture increased rapidly within 3 to 6 months. Fracture risk decreased rapidly after stopping GC therapy. Strong relationships were found between cumulative dose of GC and loss of BMD and between daily dose and fracture risk. Short term use, intermittent use, and inhaled use of higher dose of GC increased fracture risk. There are insufficient data to determine if short term use, intermittent use, or inhaled use of lower dose of GC increased the fracture risk. PMID:25177001

Fujiwara, Saeko

2014-09-01

192

Longitudinal live animal micro-CT allows for quantitative analysis of tumor-induced bone destruction.  

PubMed

The majority of breast cancer and prostate cancer patients with metastatic disease will go on to develop bone metastases, which contribute largely to the patient's morbidity and mortality. Numerous small animal models of cancer metastasis to bone have been developed to study tumor-induced bone destruction, but the advancement of imaging modalities utilized for these models has lagged significantly behind clinical imaging. Therefore, there is a significant need for improvements to live small animal imaging, particularly when obtaining high-resolution images for longitudinal quantitative analyses. Recently, live animal micro-computed tomography (?CT) has gained popularity due to its ability to obtain high-resolution 3-dimensional images. However, the utility of ?CT in bone metastasis models has been limited to end-point analyses due to off-target radiation effects on tumor cells. We hypothesized that live animal in vivo ?CT can be utilized to perform reproducible and quantitative longitudinal analyses of bone volume in tumor-bearing mice, particularly in a drug treatment model of breast cancer metastasis to bone. To test this hypothesis, we utilized the MDA-MB-231 osteolytic breast cancer model in which the tumor cells are inoculated directly into the tibia of athymic nude mice and imaged mice weekly by Faxitron (radiography), Imtek ?CT (in vivo), and Maestro (GFP-imaging). Exvivo ?CT and histology were performed at end point for validation. After establishing a high-resolution scanning protocol for the Imtek CT, we determined whether clear, measurable differences in bone volume were detectable in mice undergoing bisphosphonate drug treatments. We found that in vivo ?CT could be used to obtain quantifiable and longitudinal images of the progression of bone destruction over time without altering tumor cell growth. In addition, we found that we could detect lesions as early as week 1 and that this approach could be used to monitor the effect of drug treatment on bone. Taken together, these data indicate that in vivo ?CT is an effective and reproducible method for longitudinal monitoring of tumor-associated bone destruction in mouse models of tumor-induced bone disease. PMID:20685406

Johnson, Lindsay C; Johnson, Rachelle W; Munoz, Steve A; Mundy, Gregory R; Peterson, Todd E; Sterling, Julie A

2011-01-01

193

Pulsed focused ultrasound treatment of muscle mitigates paralysis-induced bone loss in the adjacent bone: a study in a mouse model.  

PubMed

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

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

2014-09-01

194

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

NASA Technical Reports Server (NTRS)

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

Leonard, J. I.

1976-01-01

195

Bone Regeneration in Rat Cranium Critical-Size Defects Induced by Cementum Protein 1 (CEMP1)  

PubMed Central

Gene therapy approaches to bone and periodontal tissue engineering are being widely explored. While localized delivery of osteogenic factors like BMPs is attractive for promotion of bone regeneration; method of delivery, dosage and side effects could limit this approach. A novel protein, Cementum Protein 1 (CEMP1), has recently been shown to promote regeneration of periodontal tissues. In order to address the possibility that CEMP1 can be used to regenerate other types of bone, experiments were designed to test the effect of hrCEMP1 in the repair/regeneration of a rat calvaria critical-size defect. Histological and microcomputed tomography (µCT) analyses of the calvaria defect sites treated with CEMP1 showed that after 16 weeks, hrCEMP1 is able to induce 97% regeneration of the defect. Furthermore, the density and characteristics of the new mineralized tissues were normal for bone. This study demonstrates that hrCEMP1 stimulates bone formation and regeneration and has therapeutic potential for the treatment of bone defects and regeneration of mineralized tissues. PMID:24265720

Serrano, Janeth; Romo, Enrique; Bermúdez, Mercedes; Narayanan, A. Sampath; Zeichner-David, Margarita; Santos, Leticia; Arzate, Higinio

2013-01-01

196

Effect of the wavelength on laser induced breakdown spectrometric analysis of archaeological bone  

NASA Astrophysics Data System (ADS)

The analytical exploitation of the laser induced plasma suffers from its transient behavior due to some nonlinear effects. These phenomena are matrix-dependent and limit the use of LIBS to mostly semi-quantitative precision. The plasma parameters have to be kept as constant as possible during LIBS measurements. Studying archaeological bone samples using LIBS technique could be more difficult since these samples are less tough in their texture than many other solid samples. Thus, the ablation process could change the sample morphological features rapidly resulting in poor reproducibility and statistics. Furthermore archaeological bones are subjected to diagenesis effects due to burial environment and postmortem effects. In the present work comparative analytical study of UV (266 nm) and IR (1064 nm) LIBS for archaeological bone samples belonging to four ancient Egyptian dynasties representing the middle kingdom (1980-1630 BC), 2nd intermediate period (1630-1539/23 BC), Roman-Greek period (30 BC-A.D. 395) and the late period (664-332 BC). Measurements have been performed under identical experimental conditions except the laser wavelength to examine its effects. Elemental fluctuations within the same dynasty were studied for reliable information about each dynasty. The analytical results demonstrated that UV-LIBS gives a more realistic picture for bone elemental composition within the same dynasty, and bone ash could be more suitable as a reference material for bone calibration in the case of UV-LIBS.

Kasem, M. A.; Gonzalez, J. J.; Russo, R. E.; Harith, M. A.

2014-11-01

197

Possible role of lymphocytes in glucocorticoid-induced increase in trabecular bone mineral density  

PubMed Central

Treatment with anti-inflammatory glucocorticoids is associated with osteoporosis. Many of the treated patients are postmenopausal women, who even without treatment have an increased risk of osteoporosis. Lymphocytes have been shown to play a role in postmenopausal and arthritis-induced osteoporosis, and they are targeted by glucocorticoids. The aim of this study was to investigate the mechanisms behind effects of glucocorticoids on bone during health and menopause, focusing on lymphocytes. Female C57BL/6 or SCID mice were therefore sham-operated or ovariectomized and 2 weeks later treatment with dexamethasone (dex), the nonsteroidal anti-inflammatory drug carprofen, or vehicle was started and continued for 2.5 weeks. At the termination of experiments, femurs were phenotyped using peripheral quantitative computed tomography and high-resolution micro-computed tomography, and markers of bone turnover were analyzed in serum. T and B lymphocyte populations in bone marrow and spleen were analyzed by flow cytometry. Dex-treated C57BL/6 mice had increased trabecular bone mineral density, but lower cortical content and thickness compared with vehicle-treated mice. The dex-treated mice also had lower levels of bone turnover markers and markedly decreased numbers of spleen T and B lymphocytes. In contrast, these effects could not be repeated when mice were treated with the nonsteroidal anti-inflammatory drug carprofen. In addition, dex did not increase trabecular bone in ovariectomized SCID mice lacking functional T and B lymphocytes. In contrast to most literature, the results from this study indicate that treatment with dex increased trabecular bone density, which may indicate that this effect is associated with corticosteroid-induced alterations of the lymphocyte populations. PMID:25359897

Grahnemo, Louise; Jochems, Caroline; Andersson, Annica; Engdahl, Cecilia; Ohlsson, Claes; Islander, Ulrika; Carlsten, Hans

2015-01-01

198

Altered canonical hedgehog-gli signalling axis in pesticide-induced bone marrow aplasia mouse model.  

PubMed

The mechanistic interplay between pesticide exposure and development of marrow aplasia is not yet well established but there are indices that chronic pesticide exposure in some instances causes marrow aplasia like haematopoietic degenerative condition in human beings. Canonical Hedgehog (Hh) signalling has multiple roles in a wide range of developmental processes, including haematopoiesis. The present study was designed to explore the status of four important components of the canonical Hedgehog signalling cascade, the Sonic Hedgehog (Shh), Ptch1, Smo, and Gli1, in a mouse model of chronic pesticide-induced bone marrow aplasia. We used 5 % aqueous mixture of pesticides (chlorpyriphos, prophenophos, cypermethrin, alpha-methrin, and hexaconazole) for inhalation and dermal exposure of 6 hours per day and 5 days a week up to 90 days. Murine bone marrow aplasia related to chronic pesticide treatment was confirmed primarily by haemogram, bone marrow cellularity, short term bone marrow explant culture for cellular kinetics, bone marrow smear, and fl ow cytometric Lin-Sca-1+C-kit+ extracellular receptor expression pattern. Later, components of hedgehog signalling were analysed in the bone marrow of both control and pesticide-treated aplastic groups of animals. The results depicted pancytopenic feature of peripheral blood, developmental anomaly of neutrophils, depression of primitive stem and progenitor population along with Shh, Ptch1, Smo and Gli1 expression in aplasia group. This investigation suggests that pesticide-induced downregulation of two critically important proteins--Ptch1 and Gli1--inside the haematopoietic stem and progenitor cell population impairs haematopoietic homeostasis and regeneration mechanism in vivo concurrent with bone marrow aplasia. PMID:23152377

Chaklader, Malay; Das, Prosun; Pereira, Jacintha Archana; Chaudhuri, Samaresh; Law, Sujata

2012-09-01

199

Possible role of lymphocytes in glucocorticoid-induced increase in trabecular bone mineral density.  

PubMed

Treatment with anti-inflammatory glucocorticoids is associated with osteoporosis. Many of the treated patients are postmenopausal women, who even without treatment have an increased risk of osteoporosis. Lymphocytes have been shown to play a role in postmenopausal and arthritis-induced osteoporosis, and they are targeted by glucocorticoids. The aim of this study was to investigate the mechanisms behind effects of glucocorticoids on bone during health and menopause, focusing on lymphocytes. Female C57BL/6 or SCID mice were therefore sham-operated or ovariectomized and 2 weeks later treatment with dexamethasone (dex), the nonsteroidal anti-inflammatory drug carprofen, or vehicle was started and continued for 2.5 weeks. At the termination of experiments, femurs were phenotyped using peripheral quantitative computed tomography and high-resolution micro-computed tomography, and markers of bone turnover were analyzed in serum. T and B lymphocyte populations in bone marrow and spleen were analyzed by flow cytometry. Dex-treated C57BL/6 mice had increased trabecular bone mineral density, but lower cortical content and thickness compared with vehicle-treated mice. The dex-treated mice also had lower levels of bone turnover markers and markedly decreased numbers of spleen T and B lymphocytes. In contrast, these effects could not be repeated when mice were treated with the nonsteroidal anti-inflammatory drug carprofen. In addition, dex did not increase trabecular bone in ovariectomized SCID mice lacking functional T and B lymphocytes. In contrast to most literature, the results from this study indicate that treatment with dex increased trabecular bone density, which may indicate that this effect is associated with corticosteroid-induced alterations of the lymphocyte populations. PMID:25359897

Grahnemo, Louise; Jochems, Caroline; Andersson, Annica; Engdahl, Cecilia; Ohlsson, Claes; Islander, Ulrika; Carlsten, Hans

2015-01-01

200

Deficiency of Retinaldehyde Dehydrogenase 1 Induces BMP2 and Increases Bone Mass In Vivo  

PubMed Central

The effects of retinoids, the structural derivatives of vitamin A (retinol), on post-natal peak bone density acquisition and skeletal remodeling are complex and compartment specific. Emerging data indicates that retinoids, such as all trans retinoic acid (ATRA) and its precursor all trans retinaldehyde (Rald), exhibit distinct and divergent transcriptional effects in metabolism. Despite these observations, the role of enzymes that control retinoid metabolism in bone remains undefined. In this study, we examined the skeletal phenotype of mice deficient in retinaldehyde dehydrogenase 1 (Aldh1a1), the enzyme responsible for converting Rald to ATRA in adult animals. Bone densitometry and micro-computed tomography (µCT) demonstrated that Aldh1a1-deficient (Aldh1a1?/?) female mice had higher trabecular and cortical bone mass compared to age and sex-matched control C57Bl/6 wild type (WT) mice at multiple time points. Histomorphometry confirmed increased cortical bone thickness and demonstrated significantly higher bone marrow adiposity in Aldh1a1?/? mice. In serum assays, Aldh1a1?/? mice also had higher serum IGF-1 levels. In vitro, primary Aldh1a1?/? mesenchymal stem cells (MSCs) expressed significantly higher levels of bone morphogenetic protein 2 (BMP2) and demonstrated enhanced osteoblastogenesis and adipogenesis versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias of Aldh1a1?/? mice with accompanying induction of BMP2-regulated responses, including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation. In vitro, Rald, which accumulates in Aldh1a1?/? mice, potently induced BMP2 in WT MSCs in a retinoic acid receptor (RAR)-dependent manner, suggesting that Rald is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo. Collectively, these data implicate Aldh1a1 as a novel determinant of cortical bone density and marrow adiposity in the skeleton in vivo through modulation of BMP signaling. PMID:23951127

Nallamshetty, Shriram; Wang, Hong; Rhee, Eun-Jung; Kiefer, Florian W.; Brown, Jonathan D.; Lotinun, Sutada; Le, Phuong; Baron, Roland; Rosen, Clifford J.; Plutzky, Jorge

2013-01-01

201

Wnt signaling induces gene expression of factors associated with bone destruction in lung and breast cancer.  

PubMed

Parathyroid hormone-related protein (PTHrP) is an important regulator of bone destruction in bone metastatic tumors. Transforming growth factor-beta (TGF-?) stimulates PTHrP production in part through the transcription factor Gli2, which is regulated independent of the Hedgehog signaling pathway in osteolytic cancer cells. However, inhibition of TGF-? in vivo does not fully inhibit tumor growth in bone or tumor-induced bone destruction, suggesting other pathways are involved. While Wnt signaling regulates Gli2 in development, the role of Wnt signaling in bone metastasis is unknown. Therefore, we investigated whether Wnt signaling regulates Gli2 expression in tumor cells that induce bone destruction. We report here that Wnt activation by ?-catenin/T cell factor 4 (TCF4) over-expression or lithium chloride (LiCl) treatment increased Gli2 and PTHrP expression in osteolytic cancer cells. This was mediated through the TCF and Smad binding sites within the Gli2 promoter as determined by promoter mutation studies, suggesting cross-talk between TGF-? and Wnt signaling. Culture of tumor cells on substrates with bone-like rigidity increased Gli2 and PTHrP production, enhanced autocrine Wnt activity and led to an increase in the TCF/Wnt signaling reporter (TOPFlash), enriched ?-catenin nuclear accumulation, and elevated Wnt-related genes by PCR-array. Stromal cells serve as an additional paracrine source of Wnt ligands and enhanced Gli2 and PTHrP mRNA levels in MDA-MB-231 and RWGT2 cells in vitro and promoted tumor-induced bone destruction in vivo in a ?-catenin/Wnt3a-dependent mechanism. These data indicate that a combination of matrix rigidity and stromal-secreted factors stimulate Gli2 and PTHrP through Wnt signaling in osteolytic breast cancer cells, and there is significant cross-talk between the Wnt and TGF-? signaling pathways. This suggests that the Wnt signaling pathway may be a potential therapeutic target for inhibiting tumor cell response to the bone microenvironment and at the very least should be considered in clinical regimens targeting TGF-? signaling. PMID:25359619

Johnson, Rachelle W; Merkel, Alyssa R; Page, Jonathan M; Ruppender, Nazanin S; Guelcher, Scott A; Sterling, Julie A

2014-12-01

202

Bone marrow Schwann cells induce hematopoietic stem cell hibernation.  

PubMed

Hematopoietic stem cells (HSCs) are clonogenic cells capable of both self-renewal and multilineage differentiation. In adult mouse bone marrow (BM), most HSCs remain in the non-dividing G0-phase of cell cycle, in close contact with supporting cells known as the HSC "niche". In the present study, we focused on signaling mechanisms that regulate stem cell dormancy in the BM niche. We show that TGF-? type II receptor deficiency causes reduced phosphorylation of Smad2/3 and impairs long-term repopulating activity in HSCs, suggesting a significant role for TGF-?/Smad signaling in hematopoiesis. Furthermore, we aimed at defining the candidate BM niche responsible for homeostasis of hematopoiesis, and revealed that non-myelinating Schwann cells sustain HSC hibernation by converting TGF-? from its latent to its active form. PMID:24817152

Yamazaki, Satoshi; Nakauchi, Hiromitsu

2014-06-01

203

Otolith mass asymmetry: natural, and after weightlessness and hypergravity  

NASA Astrophysics Data System (ADS)

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

Lychakov, Dmitri

204

Osteogenic Effects of Dedifferentiated Fat Cell Transplantation in Rabbit Models of Bone Defect and Ovariectomy-Induced Osteoporosis  

PubMed Central

We have previously reported that mature adipocyte-derived dedifferentiated fat (DFAT) cells have a high proliferative activity and the potential to differentiate into lineages of mesenchymal tissue similar to bone marrow mesenchymal stem cells (MSCs). In the present study, we examined the effects of autologous DFAT cell transplantation on bone regeneration in a rabbit bone defect model and an ovariectomy (OVX)-induced osteoporosis model. The formation of tissue-engineered bone (TEB) was observed when rabbit DFAT cells were loaded onto a ?-tricalcium phosphate (TCP)/collagen sponge and cultured in an osteogenic differentiation medium for 3 weeks. Autologous implantation of DFAT cell-mediated TEB constructs promoted bone regeneration in a rabbit tibial defect model. Regenerated bone tissue induced by transplantation of DFAT cell-mediated TEB constructs was histologically well differentiated and exhibited higher bone strength in a three-point bending test compared to that induced by the ?-TCP/collagen sponge alone. In OVX-induced osteoporosis model rabbits, DFAT cells were obtained with the osteogenic activity similar to cells from healthy rabbits. Intrabone marrow injection of autologous DFAT cells significantly increased the bone mineral density (BMD) at the injected site in the OVX rabbits. Transplanted DFAT cells remained mainly on the injection side of the bone marrow by at least 28 days after intrabone marrow injection and a part of them expressed osteocalcin. In conclusion, these results demonstrate that autologous implantation of DFAT cells contributed to bone regeneration in a rabbit bone defect model and an OVX-induced osteoporosis model. DFAT cells may be an attractive cell source for cell-based bone tissue engineering to treat nonunion fractures in all patients, including those with osteoporosis. PMID:23566022

Kikuta, Shinsuke; Tanaka, Nobuaki; Kazama, Tomohiko; Kazama, Minako; Kano, Koichiro; Ryu, Junnosuke; Tokuhashi, Yasuaki

2013-01-01

205

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

PubMed

In normal life on earth, the locomotor system is exposed to two types of stimulation: gravity (passive stimulation) and motion (active stimulation). Both permanently combine, and the interactions between locomotion and gravity induce an overall recruitment which is repeated daily and maintains the bone tissue structure within the range of constraints to which it is adapted. This range is one of the basic hypotheses underlying the mechanical concepts of bone structure control, and it has been considered as logical to assume that weightlessness of spaceflight should produce bone loss since astronauts are outside of the terrestrial gravitational field of forces, no longer relying on muscular work to change positions or move. But, thirty years after the first changes in phospho-calcium metabolism were observed in astronauts after spaceflight, current knowledge does not provide a full understanding of this pathogeny, and prove the G-factor is now considered as an essential component of the experimental tools available to study bone physiology. The study of the physiology of bone tissue usually consists in the investigation of its two fundamental roles, i.e. reservoir of inorganic elements (calcium, phosphorus, magnesium) and mechanical support for soft tissues. Together with the combined action of muscles, tendons, and ligaments, this support permits motion and locomotion. These two functions rely on a sophisticated bone tissue architecture, and on the adaptability of this structure, with modeling and remodeling processes, themselves associated with the coupled activity of specialized bone cell populations. PMID:11543035

Zerath, E

1999-07-01

206

The Development of the Vestibular Apparatus Under Conditions of Weightlessness  

NASA Technical Reports Server (NTRS)

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

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

1984-01-01

207

Binary Orbital Motion of Electrically Charged Spheres in Weightlessness.  

NASA Astrophysics Data System (ADS)

The similar mathematical forms of Coulombs' Law of Electrostatics and Newton's Law of Gravitation predict that two oppositely charged spheres should be able to move in a binary orbit about their center of mass using only the electric force as the force of attraction. To test this prediction, we conducted an experiment in July 2008 aboard a specialized C-9B aircraft in NASA's Microgravity University Program which simulates the conditions of weightlessness. We successfully achieved multiple binary orbits between the two spheres. The orbital motion was analyzed using VideoPoint software to measure the orbital interaction of the spheres.

Li, Lulu; Atkins, Brad; Franks, Gavin; Fuchs, Joshua; Sliger, Chase; Thompson, Jennifer

2009-03-01

208

Bone marrow edema induced by a bullet after a self-inflicted accidental firing.  

PubMed

We present a case of a postmortem finding of bone marrow edema in postmortem magnetic resonance imaging (PMMR) indirectly induced by a bullet, which barely missed the bone of a 92-year-old man found kneeling in front of his bed of a tidy apartment. Additionally, a selective postmortem computed tomography angiography (PMCTA) of the left leg was performed, visualizing a laceration of the left femoral vein by the bullet with consecutive contrast media extravasation. A vast pulmonary fat embolism was diagnosed and together with the blood loss found to be the cause of death. PMID:24112989

Berger, Nicole; Paula, Pia; Gascho, Dominic; Flach, Patricia M; Thali, Michael J; Ross, Steffen G; Ampanozi, Garyfalia

2013-11-01

209

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

NASA Technical Reports Server (NTRS)

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

Leonard, J. I.

1985-01-01

210

Induced Refractive Anomalies Affect Chick Orbital Bone Structure  

Microsoft Academic Search

Experiments have shown that it is possible to induce ametropias (myopia and hyperopia) in the eyes of young animals by distorting early visual experience through the use of negative and positive defocussing lenses mounted over the eye. Defocus lenses (+15 and ?15 diopters) were mounted unilaterally over one eye of day old broiler chicks using a contact lens—goggle and velcro

K. T. WILSON; J. G. SIVAK; M. G. CALLENDER

1997-01-01

211

Optimization of corticosteroid induced osteoporosis in ovariectomized sheep. A bone histomorphometric study.  

PubMed

During osteoporosis induction in sheep, side effects of the steroids were observed in previous studies. The aim of this study was to improve the induction regimen consisting of ovariectomy, calcium/vitamin D- restricted diet and methylprednisolone (-MP)- medication with respect to the bone metabolism and to reduce the adverse side effects. Thirty-six ewes (age 6.5 +/- 0.6 years) were divided into four MP-administration groups (n = 9) with a total dose of 1800 mg MP: group 1: 20 mg/day, group 2: 60 mg/every third day, group 3: 3 x 500 mg and 1 x 300 mg at intervals of three weeks, group 4: weekly administration, starting at 70 mg and weekly reduction by 10 mg. After double-labelling with Calcein Green and Xylenol Orange, bone biopsy specimens were taken from the iliac crest (IC) at the beginning and four weeks after the last MP injection, and additionally from the vertebral body (VB) at the end of the experiment. Bone samples were processed into stained and fluorescent sections, static and dynamic measurements were performed. There were no significant differences for static parameters between the groups initially. The bone perimeter and the bone area values were significantly higher in the VB than in the IC (Pm: 26%, p < 0.0001, Ar: 11%, p < 0.0166). A significant decrease (20%) of the bone area was observed after corticosteroid-induced osteoporosis (p < 0.0004). For the dynamic parameters, no significant difference between the groups was found. Presence of Calcein Green and Xylenol Orange labels were noted in 50% of the biopsies in the IC, 100% in the VB. Group 3 showed the lowest prevalence of adverse side effects. The bone metabolism changes were observed in all four groups, and the VB bone metabolism was higher when compared to the IC. In conclusion, when using equal amounts of steroids adverse side effects can be reduced by decreasing the number of administrations without reducing the effect regarding corticosteroid-induced osteoporosis. This information is useful to reduce the discomfort of the animals in this sheep model of corticosteroid-induced osteoporosis. PMID:17364091

Klopfenstein Bregger, M D; Schawalder, P; Rahn, B; Eckhardt, C; Schneider, E; Lill, C

2007-01-01

212

PTH1-34 alleviates radiotherapy-induced local bone loss by improving osteoblast and osteocyte survival.  

PubMed

Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1-34), an anabolic agent for osteoporosis, reversed bone structural deterioration caused by multiple microcomputed tomography (microCT) scans in adolescent rats. To simulate clinical radiotherapy for cancer patients and to search for remedies, we focally irradiated the tibial metaphyseal region of adult rats with a newly available small animal radiation research platform (SARRP) and treated these rats with intermittent injections of PTH1-34. Using a unique 3D image registration method that we recently developed, we traced the local changes of the same trabecular bone before and after treatments, and observed that, while radiation caused a loss of small trabecular elements leading to significant decreases in bone mass and strength, PTH1-34 preserved all trabecular elements in irradiated bone with remarkable increases in bone mass and strength. Histomorphometry demonstrated that SARRP radiation severely reduced osteoblast number and activity, which were impressively reversed by PTH treatment. In contrast, suppressing bone resorption by alendronate failed to rescue radiation-induced bone loss and to block the rescue effect of PTH1-34. Furthermore, histological analyses revealed that PTH1-34 protected osteoblasts and osteocytes from radiation-induced apoptosis and attenuated radiation-induced bone marrow adiposity. Taken together, our data strongly support a robust radioprotective effect of PTH on trabecular bone integrity through preserving bone formation and shed light on further investigations of an anabolic therapy for radiation-induced bone damage. PMID:24998454

Chandra, Abhishek; Lin, Tiao; Tribble, Mary Beth; Zhu, Ji; Altman, Allison R; Tseng, Wei-Ju; Zhang, Yejia; Akintoye, Sunday O; Cengel, Keith; Liu, X Sherry; Qin, Ling

2014-10-01

213

?-TCP granules mixed with reticulated hyaluronic acid induce an increase in bone apposition.  

PubMed

? beta-tricalcium phosphate (?-TCP) granules are suitable for repair of bone defects. They have an osteoconductive effect shortly after implantation. However, dry granules are difficult to handle in the surgical room because of low weight and lack of cohesion. Incorporation of granules in a hydrogel could be a satisfactory solution. We have investigated the use of hyaluronic acid (HyA) as an aqueous binder of the granules. ?-TCP granules were prepared by the polyurethane foam technology. Commercially available linear (LHya) and reticulated hyaluronic acid (RHyA) in aqueous solution were used to prepare a pasty mixture that can be handled more easily than granules alone. Thirteen New Zealand White rabbits (3.5-3.75 kg) were used; a 4 mm hole was drilled in each femoral condyle. After flushing, holes were filled with either LHyA, RHyA, dry ?-TCP granules alone, ?-TCP granules + LHyA and ?-TCP granules + RHyA. Rabbits were allowed to heal for one month, sacrificed and femurs were harvested and analysed by microCT and histomorphometry. The net amount of newly formed bone was derived from measurements done after thresholding the microCT images for the material and for the material+bone. LHyA and RHyA did not result in healing of the grafted area. LHyA was rapidly eluted from the grafted zone but allowed deposition of more granules, although the amount of formed bone was not significantly higher than with ?-TCP granules alone. RHyA permitted the deposition of more granules which induced significantly more bone trabeculae without inducing an inflammatory reaction. RHyA appears to be a good vehicle to implant granules of ?-TCP, since HyA does not interfere with bone remodeling. PMID:24343316

Aguado, Eric; Pascaretti-Grizon, Florence; Gaudin-Audrain, Christine; Goyenvalle, Eric; Chappard, Daniel

2014-02-01

214

Alleviating anastrozole induced bone toxicity by selenium nanoparticles in SD rats  

SciTech Connect

Aromatase inhibitors like anastrozole play an undisputed key role in the treatment of breast cancer, but on the other hand, various side effects like osteoporosis and increased risk of bone fracture accompany the chronic administration of these drugs. Here we show for the first time that selenium nanoparticles, when given in conjugation to anastrozole, lower the bone toxicity caused by anastrozole and thus reduce the probable damage to the bone. Selenium nanoparticles at a dose of 5 ?g/ml significantly reduced the cell death caused by anastrozole (1 ?M) in HOS (human osteoblast) cells. In addition, our results also highlighted that in female SD rat model, SeNPs (0.25, 0.5, 1 mg/kg/day) significantly prevented the decrease in bone density and increase in biochemical markers of bone resorption induced by anastrozole (0.2 mg/kg/day) treatment. Histopathological examination of the femurs of SeNP treated group revealed ossification, mineralization, calcified cartilaginous deposits and a marginal osteoclastic activity, all of which indicate a marked restorative action, suggesting the protective action of the SeNPs. Interestingly, SeNPs (1 mg/kg/day) also exhibited protective effect in ovariectomized rat model, by preventing osteoporosis, which signifies that bone loss due to estrogen deficiency can be effectively overcome by using SeNPs. - Highlights: ? SeNPs significantly reduce bone toxicity in anastrozole treated rats. ? SeNPs successfully prevented osteoporosis in ovariectomized rats. ? SeNP treatment lowered the levels of TRAP and increased the levels of ALKP.

Vekariya, Kiritkumar K.; Kaur, Jasmine; Tikoo, Kulbhushan, E-mail: tikoo.k@gmail.com

2013-04-15

215

Bone quality is affected by food restriction and by nutrition-induced catch-up growth.  

PubMed

Growth stunting constitutes the most common effect of malnutrition. When the primary cause of malnutrition is resolved, catch-up (CU) growth usually occurs. In this study, we have explored the effect of food restriction (RES) and refeeding on bone structure and mechanical properties. Sprague-Dawley male rats aged 24 days were subjected to 10 days of 40% RES, followed by refeeding for 1 (CU) or 26 days long-term CU (LTCU). The rats fed ad libitum served as controls. The growth plates were measured, osteoclasts were identified using tartrate-resistant acid phosphatase staining, and micro-computed tomography (CT) scanning and mechanical testing were used to study structure and mechanical properties. Micro-CT analysis showed that RES led to a significant reduction in trabecular BV/TV and trabecular number (Tb.N), concomitant with an increase in trabecular separation (Tb.Sp). Trabecular BV/TV and Tb.N were significantly greater in the CU group than in the RES in both short- and long-term experiments. Mechanical testing showed that RES led to weaker and less compliant bones; interestingly, bones of the CU group were also more fragile after 1 day of CU. Longer term of refeeding enabled correction of the bone parameters; however, LTCU did not achieve full recovery. These results suggest that RES in young rats attenuated growth and reduced trabecular bone parameters. While nutrition-induced CU growth led to an immediate increase in epiphyseal growth plate height and active bone modeling, it was also associated with a transient reduction in bone quality. This should be taken into consideration when treating children undergoing CU growth. PMID:25248555

Pando, Rakefet; Masarwi, Majdi; Shtaif, Biana; Idelevich, Anna; Monsonego-Ornan, Efrat; Shahar, Ron; Phillip, Moshe; Gat-Yablonski, Galia

2014-12-01

216

Simulated weightlessness in fish and neurophysiological studies on memory storage  

NASA Technical Reports Server (NTRS)

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

Vonbaumgarten, R. J.

1973-01-01

217

Leg vascular responsiveness during acute orthostasis following simulated weightlessness  

NASA Technical Reports Server (NTRS)

The effect of weightlessness on vascular response to orthostatic stress was investigated in human subjects by measuring changes in the arterial pulse volume (APV) of the legs during exposure to lower body negative pressure (LBNP) applied before and after 10 days of continuous 6-deg head-down bed rest. Heart rate, mean arterial blood pressure (MAP), and impedance rheographic indices of APV were measured during rest and at 1 min of -30 mm Hg LBNP. Bed rest was found not to alter the responses of MAP to LBNP. Resting APV was decreased after bed rest; however, APV was reduced upon transfer from rest to 1-min LBPN by the same relative magnitude before and after bedrest. It is concluded that peripheral arterial vasoconstriction, as indicated by reduction in APV during LBNP, is not affected by bedrest. The results suggest that there was no apparent alteration in responsiveness of the leg vasculature following simulated weightlessness, and that the control mechanisms of peripheral resistance do not contribute significantly to reduced orthostatic tolerance following spaceflight.

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

1988-01-01

218

A histological evaluation for guided bone regeneration induced by a collagenous membrane.  

PubMed

This study was designed to evaluate the histological changes during ossification and cellular events including osteogenic differentiation responding to collagenous bioresorbable membranes utilized for GBR. Standardized artificial bony defects were prepared at rat maxillae, and covered with a collagenous bioresorbable membrane. These animals were sacrificed at 1, 2, 3 and 4 weeks after the GBR-operation. The paraffin sections were subject to tartrate resistant acid phosphatase (TRAP) enzyme histochemistry and immunohistochemistry for alkaline phosphatase (ALP), osteopontin (OP) and osteocalcin (OC). In the first week of the experimental group, woven bone with ALP-positive osteoblasts occupied the lower half of the cavity. The collagenous membrane included numerous ALP-negative cells and OP-immunoreactive extracellular matrices. At 2 weeks, the ALP-, OP- and OC-immunoreactivity came to be recognizable in the region of collagenous membrane. Since ALP-negative soft tissue separated the collagenous membrane and the new bone originating from the cavity bottom, the collagenous membrane appeared to induce osteogenesis in situ. At 3 weeks, numerous collagen fibers of the membrane were embedded in the adjacent bone matrix. At 4 weeks, the membrane-associated and the cavity-derived bones had completely integrated, showing the same height of the periosteal ridge as the surrounding alveolar bones. The collagen fibers of a GBR-membrane appear to participate in osteogenic differentiation. PMID:15885767

Taguchi, Yuya; Amizuka, Norio; Nakadate, Masayoshi; Ohnishi, Hideo; Fujii, Noritaka; Oda, Kimimitsu; Nomura, Shuichi; Maeda, Takeyasu

2005-11-01

219

Dietary emu oil supplementation suppresses 5-fluorouracil chemotherapy-induced inflammation, osteoclast formation, and bone loss.  

PubMed

Cancer chemotherapy can cause osteopenia or osteoporosis, and yet the underlying mechanisms remain unclear, and currently, no preventative treatments are available. This study investigated damaging effects of 5-fluorouracil (5-FU) on histological, cellular, and molecular changes in the tibial metaphysis and potential protective benefits of emu oil (EO), which is known to possess a potent anti-inflammatory property. Female dark agouti rats were gavaged orally with EO or water (1 ml·day(-1)·rat(-1)) for 1 wk before a single ip injection of 5-FU (150 mg/kg) or saline (Sal) was given. The treatment groups were H(2)O + Sal, H(2)O + 5-FU, EO + 5-FU, and EO + Sal. Oral gavage was given throughout the whole period up to 1 day before euthanasia (days 3, 4, and 5 post-5-FU). Histological analysis showed that H(2)O + 5-FU significantly reduced heights of primary spongiosa on days 3 and 5 and trabecular bone volume of secondary spongiosa on days 3 and 4. It reduced density of osteoblasts slightly and caused an increase in the density of osteoclasts on trabecular bone surface on day 4. EO supplementation prevented reduction of osteoblasts and induction of osteoclasts and bone loss caused by 5-FU. Gene expression studies confirmed an inhibitory effect of EO on osteoclasts since it suppressed 5-FU-induced expression of proinflammatory and osteoclastogenic cytokine TNF?, osteoclast marker receptor activator of nuclear factor-?B, and osteoclast-associated receptor. Therefore, this study demonstrated that EO can counter 5-FU chemotherapy-induced inflammation in bone, preserve osteoblasts, suppress osteoclast formation, and potentially be useful in preventing 5-FU chemotherapy-induced bone loss. PMID:22436700

Raghu Nadhanan, Rethi; Abimosleh, Suzanne M; Su, Yu-Wen; Scherer, Michaela A; Howarth, Gordon S; Xian, Cory J

2012-06-01

220

Polyethylene particle-induced bone resorption in substance P-deficient mice.  

PubMed

Aseptic loosening is the major cause of total joint replacement failure. Substance P (SP) is a neurotransmitter richly distributed in sensory nerve fibers, bone, and bone-related tissue. The purpose of this study was to investigate the potential impact of SP on bone metabolism in polyethylene particle-induced osteolysis. We utilized the murine calvarial osteolysis model based on ultrahigh molecular weight polyethylene (UHMWPE) particles in 14 wild-type mice (C57BL/J6) and 14 SP-deficient mice. Group 1 (C57BL/J 6) and group 3 (SP-knockout) received sham surgery, and group 2 (C57BL/J6) and group 4 (SP-knockout) were treated with polyethylene particles. Analytical methods included three-dimensional micro-computed tomographic (micro-CT) analysis and histomorphometry. Bone resorption was measured within the midline suture. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase-positive cells. UHMWPE-particle treated SP-deficient mice showed significantly reduced osteolysis compared to wild-type mice, as confirmed by histomorphometry (P < 0.001) and micro-CT (P = 0.035). Osteoclast numbers were significantly reduced in groups 3 and 4 compared to groups 1 and 2 (P < 0.001). Unexpectedly, SP-deficient mice (group 3) showed a significantly increased absolute bone mass compared to wild-type mice (group 1) (P = 0.02). The findings of our murine calvaria model lead to the assumption that SP is a promoter in particle-induced osteolysis. The pathophysiology of aseptic loosening is complex, and neuropeptides are not solely responsible for the progress of implant loosening; however, we conclude that there could be coherence between neurotransmitters and particle-induced osteolysis in patients with aseptic loosening. PMID:17401694

Wedemeyer, C; Neuerburg, C; Pfeiffer, A; Heckelei, A; von Knoch, F; Hilken, G; Brankamp, J; Henschke, F; von Knoch, M; Löer, F; Saxler, G

2007-04-01

221

Bone Marrow Injury Induced via Oxidative Stress in Mice by Inhalation Exposure to Formaldehyde  

PubMed Central

Objective Formaldehyde, a ubiquitous environmental pollutant has been classified as a human leukemogen. However, toxicity of formaldehyde in bone marrow, the target site of leukemia induction, is still poorly understood. Methodology/Principal Findings To investigate bone marrow toxicity (bone marrow pathology, hematotoxicity) and underlying mechanisms (oxidative stress, inflammation, apoptosis) in formaldehyde-exposed mice. Male Balb/c mice were exposed to formaldehyde (0, 0.5, and 3.0 mg/m3) by nose-only inhalation for 8 hours/day, over a two week period designed to simulate a factory work schedule, with an exposure-free “weekend” on days 6 and 7, and were sacrificed on the morning of day 13. Counts of white blood cells, red blood cells and lymphocytes were significantly (p<0.05) decreased at 0.5 mg/m3 (43%, 7%, and 39%, respectively) and 3.0 mg/m3 (52%, 27%, and 43%, respectively) formaldehyde exposure, while platelet counts were significantly increased by 109% (0.5 mg/m3) and 67% (3.0 mg/m3). Biomarkers of oxidative stress (reactive oxygen species, glutathione depletion, cytochrome P450 1A1 and glutathione s-transferase theta 1 expression), inflammation (nuclear factor kappa-B, tomour necrosis factor alpha, interleukin-1 beta), and apoptosis (activity of cysteine-aspartic acid protease 3) in bone marrow tissues were induced at one or both formaldehyde doses mentioned above. Conclusions/Significance Exposure of mice to formaldehyde by inhalation induced bone marrow toxicity, and that oxidative stress, inflammation and the consequential apoptosis jointly constitute potential mechanisms of such induced toxicity. PMID:24040369

McHale, Cliona; Li, Rui; Zhang, Luoping; Wu, Yang; Ye, Xin; Yang, Xu; Ding, Shumao

2013-01-01

222

Mechanical loading attenuates loss of bone mass and bone strength induced by immobilization and calcium-deficiency  

E-print Network

Immobilization and calcium-deficiency have been documented to cause a decrease in strength and bone mineral loss, and exercise is known to strengthen bone. The purpose of this study was to determine the effects of mechanical loading on parameters...

Inman, Cynthia Lynn

2012-06-07

223

Low-dose bone morphogenetic protein-2/stromal cell-derived factor-1? cotherapy induces bone regeneration in critical-size rat calvarial defects.  

PubMed

Increasing evidence suggests that stromal cell-derived factor-1 (SDF-1/CXCL12) is involved in bone formation, though underlying molecular mechanisms remain to be fully elucidated. Also, contributions of SDF-1?, the second most abundant splice variant, as an osteogenic mediator remain obscure. We have shown that SDF-1? enhances osteogenesis by regulating bone morphogenetic protein-2 (BMP-2) signaling in vitro. Here we investigate the dose-dependent contribution of SDF-1? to suboptimal BMP-2-induced local bone formation; that is, a dose that alone would be too low to significantly induce bone formation. We utilized a critical-size rat calvarial defect model and tested the hypotheses that SDF-1? potentiates BMP-2 osteoinduction and that blocking SDF-1 signaling reduces the osteogenic potential of BMP-2 in vivo. In preliminary studies, radiographic analysis at 4 weeks postsurgery revealed a dose-dependent relationship in BMP-2-induced new bone formation. We then found that codelivery of SDF-1? potentiates suboptimal BMP-2 (0.5??g) osteoinduction in a dose-dependent order, reaching comparable levels to the optimal BMP-2 dose (5.0??g) without apparent adverse effects. Blocking the CXC chemokine receptor 4 (CXCR4)/SDF-1 signaling axis using AMD3100 attenuated the osteoinductive potential of the optimal BMP-2 dose, confirmed by qualitative histologic analysis. In conclusion, SDF-1? provides potent synergistic effects that support BMP-induced local bone formation and thus appears a suitable candidate for optimization of bone augmentation using significantly lower amounts of BMP-2 in spine, orthopedic, and craniofacial settings. PMID:24341891

Herberg, Samuel; Susin, Cristiano; Pelaez, Manuel; Howie, R Nicole; Moreno de Freitas, Rubens; Lee, Jaebum; Cray, James J; Johnson, Maribeth H; Elsalanty, Mohammed E; Hamrick, Mark W; Isales, Carlos M; Wikesjö, Ulf M E; Hill, William D

2014-05-01

224

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

NASA Technical Reports Server (NTRS)

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

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

2011-01-01

225

Pyk2 regulates megakaryocyte-induced increases in osteoblast number and bone formation.  

PubMed

Preclinical and clinical evidence from megakaryocyte (MK)-related diseases suggests that MKs play a significant role in maintaining bone homeostasis. Findings from our laboratories reveal that MKs significantly increase osteoblast (OB) number through direct MK-OB contact and the activation of integrins. We, therefore, examined the role of Pyk2, a tyrosine kinase known to be regulated downstream of integrins, in the MK-mediated enhancement of OBs. When OBs were co-cultured with MKs, total Pyk2 levels in OBs were significantly enhanced primarily because of increased Pyk2 gene transcription. Additionally, p53 and Mdm2 were both decreased in OBs upon MK stimulation, which would be permissive of cell cycle entry. We then demonstrated that OB number was markedly reduced when Pyk2-/- OBs, as opposed to wild-type (WT) OBs, were co-cultured with MKs. We also determined that MKs inhibit OB differentiation in the presence and absence of Pyk2 expression. Finally, given that MK-replete spleen cells from GATA-1-deficient mice can robustly stimulate OB proliferation and bone formation in WT mice, we adoptively transferred spleen cells from these mice into Pyk2-/- recipient mice. Importantly, GATA-1-deficient spleen cells failed to stimulate an increase in bone formation in Pyk2-/- mice, suggesting in vivo the important role of Pyk2 in the MK-induced increase in bone volume. Further understanding of the signaling pathways involved in the MK-mediated enhancement of OB number and bone formation will facilitate the development of novel anabolic therapies to treat bone loss diseases. PMID:23362087

Cheng, Ying-Hua; Hooker, R Adam; Nguyen, Khanh; Gerard-O'Riley, Rita; Waning, David L; Chitteti, Brahmananda R; Meijome, Tomas E; Chua, Hui Lin; Plett, Artur P; Orschell, Christie M; Srour, Edward F; Mayo, Lindsey D; Pavalko, Fredrick M; Bruzzaniti, Angela; Kacena, Melissa A

2013-06-01

226

Breast cancer cells induce osteoblast apoptosis: a possible contributor to bone degradation.  

PubMed

Breast cancer cells exhibit a predilection for metastasis to bone. There, the metastases usually bring about bone loss with accompanying pain and loss of function. One way that breast cancer cells disrupt the normal pattern of bone remodeling is by activating osteoclasts, the bone degrading cells. Nevertheless, targeting the osteoclasts does not cure the disease or result in bone repair. These observations indicate that osteoblast function also may be compromised. The objective of this study was to investigate the interaction of metastatic breast cancer cells with osteoblasts. Human metastatic breast cancer cells, MDA-MB-435 or MDA-MB-231, or their conditioned media were co-cultured with a human osteoblast line hFOB1.19. The breast cancer cells caused an increase in the prevalence of apoptotic osteoblasts. Apoptotic osteoblasts detected by the TUNEL assay or by caspase activity increased approximately two to fivefold. This increase was not seen with non-metastatic MDA-MB-468 cells. In an investigation of the mechanism, it was determined that the hFOB1.19 cells expressed fas and that fas was functional. Likewise the hFOB1.19 cells were susceptible to TNF-alpha, but this cytokine was not detected in the conditioned medium of the breast cancer cells. This study indicates that osteoblasts are the target of breast cancer cell-induced apoptosis, but fas/fas-ligand and TNF-alpha, two common initiators of cell death, are probably not involved in this aspect of the metastases/bone cell axis. There are several mechanisms that remain to be explored in order to determine how breast cancer cells bring about osteoblast apoptosis. Even though the specific initiator of apoptosis remains to be identified, the results of this study suggest that the mechanism is likely to be novel. PMID:14743387

Mastro, Andrea M; Gay, Carol V; Welch, Danny R; Donahue, Henry J; Jewell, Jennifer; Mercer, Robyn; DiGirolamo, Douglas; Chislock, Elizabeth M; Guttridge, Kristin

2004-02-01

227

Loss of Tbx1 induces bone phenotypes similar to cleidocranial dysplasia.  

PubMed

T-box transcription factor, TBX1, is the major candidate gene for 22q11.2 deletion syndrome (DiGeorge/ Velo-cardio-facial syndrome) characterized by facial defects, thymus hypoplasia, cardiovascular anomalies and cleft palates. Here, we report that the loss of Tbx1 in mouse (Tbx1(-/-)) results in skeletal abnormalities similar to those of cleidocranial dysplasia (CCD) in humans, which is an autosomal-dominant skeletal disease caused by mutations in RUNX2. Tbx1(-/-) mice display short stature, absence of hyoid bone, failed closure of fontanelle, bifid xiphoid process and hypoplasia of clavicle and zygomatic arch. A cell-type-specific deletion of Tbx1 in osteochondro-progenitor (Tbx1(OPKO)) or mesodermal (Tbx1(MKO)) lineage partially recapitulates the Tbx1(-/-) bone phenotypes. Although Tbx1 expression has not been previously reported in neural crest, inactivation of Tbx1 in the neural crest lineage (Tbx1(NCKO)) leads to an absence of the body of hyoid bone and postnatal lethality, indicating an unanticipated role of Tbx1 in neural crest development. Indeed, Tbx1 is expressed in the neural crest-derived hyoid bone primordium, in addition to mesoderm-derived osteochondral progenitors. Ablation of Tbx1 affected Runx2 expression in calvarial bones and overexpression of Tbx1 induced Runx2 expression in vitro. Taken together, our current studies reveal that Tbx1 is required for mesoderm- and neural crest-derived osteoblast differentiation and normal skeletal development. TBX1 mutation could lead to CCD-like bone phenotypes in human. PMID:25209980

Funato, Noriko; Nakamura, Masataka; Richardson, James A; Srivastava, Deepak; Yanagisawa, Hiromi

2015-01-15

228

Calcium and Bone Homeostasis During 4-6 Months Space Flight  

NASA Technical Reports Server (NTRS)

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

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

2000-01-01

229

Loss of protein kinase C-? protects against LPS-induced osteolysis owing to an intrinsic defect in osteoclastic bone resorption.  

PubMed

Bone remodeling is intrinsically regulated by cell signaling molecules. The Protein Kinase C (PKC) family of serine/threonine kinases is involved in multiple signaling pathways including cell proliferation, differentiation, apoptosis and osteoclast biology. However, the precise involvement of individual PKC isoforms in the regulation of osteoclast formation and bone homeostasis remains unclear. Here, we identify PKC-? as the major PKC isoform expressed among all PKCs in osteoclasts; including classical PKCs (-?, -? and -?), novel PKCs (-?, -?, -? and -?) and atypical PKCs (-?/? and -?). Interestingly, pharmacological inhibition and genetic ablation of PKC-? impairs osteoclastic bone resorption in vitro. Moreover, disruption of PKC-? activity protects against LPS-induced osteolysis in mice, with osteoclasts accumulating on the bone surface failing to resorb bone. Treatment with the PKC-? inhibitor Rottlerin, blocks LPS-induced bone resorption in mice. Consistently, PKC-? deficient mice exhibit increased trabeculae bone containing residual cartilage matrix, indicative of an osteoclast-rich osteopetrosis phenotype. Cultured ex vivo osteoclasts derived from PKC-? null mice exhibit decreased CTX-1 levels and MARKS phosphorylation, with enhanced formation rates. This is accompanied by elevated gene expression levels of cathepsin K and PKC -?, -? and -?, as well as altered signaling of pERK and pcSrc416/527 upon RANKL-induction, possibly to compensate for the defects in bone resorption. Collectively, our data indicate that PKC-? is an intrinsic regulator of osteoclast formation and bone resorption and thus is a potential therapeutic target for pathological osteolysis. PMID:23951014

Khor, Ee Cheng; Abel, Tamara; Tickner, Jennifer; Chim, Shek Man; Wang, Cathy; Cheng, Taksum; Ng, Benjamin; Ng, Pei Ying; Teguh, Dian Astari; Kenny, Jacob; Yang, Xiaohong; Chen, Honghui; Nakayama, Keiichi I; Nakayama, Keiko; Pavlos, Nathan; Zheng, Ming H; Xu, Jiake

2013-01-01

230

Weightless Environment Training Facility (WETF) materials coating evaluation, volume 1  

NASA Technical Reports Server (NTRS)

The Weightless Environment Training Facility Material Coating Evaluation project has included preparing, coating, testing, and evaluating 800 test panels of three differing substrates. Ten selected coating systems were evaluated in six separate exposure environments and subject to three tests for physical properties. Substrate materials were identified, the manner of surface preparation described, and exposure environments defined. Exposure environments included immersion exposure, cyclic exposure, and field exposure. Cyclic exposures, specifically QUV-Weatherometer and the KTA Envirotest were found to be the most agressive of the environments included in the study when all three evaluation criteria are considered. This was found to result primarily from chalking of the coatings under ultraviolet (UV) light exposure. Volumes 2 and 3 hold the 5 appendices to this report.

1995-01-01

231

Experimental and Theoretical Challenges of Creating Electrostatic Orbits in Weightlessness  

NASA Astrophysics Data System (ADS)

In January 2006, a team of students from Rhodes College was awarded flight time aboard NASA’s specialized C-9B aircraft known as the “Weightless Wonder” to perform an experiment in microgravity. This experiment demonstrated a prediction of Coulomb’s Law that two oppositely charged spheres should orbit each other under certain conditions. However a number of issues complicate this demonstration such as polarization effects (which affect the nature of the inverse square law and thus the stability of orbits), fluctuations in the microgravity conditions, and the effects of air pressure and humidity on charge leakage. This poster will discuss how we resolved these issues to successfully perform our experiment under the mentoring of Brent Hoffmeister and Shubho Banerjee.

Andring, Kevin W.; Hoffmeister, B.; Banerjee, S.; Janeski, J.; Quinn, S.; Keedy, D.; Campbell, D.

2006-12-01

232

Reversing LRP5-dependent osteoporosis and SOST deficiency-induced sclerosing bone disorders by altering WNT signaling activity.  

PubMed

The bone formation inhibitor sclerostin encoded by SOST binds in vitro to low-density lipoprotein receptor-related protein (LRP) 5/6 Wnt co-receptors, thereby inhibiting Wnt/?-catenin signaling, a central pathway of skeletal homeostasis. Lrp5/LRP5 deficiency results in osteoporosis-pseudoglioma (OPPG), whereas Sost/SOST deficiency induces lifelong bone gain in mice and humans. Here, we analyzed the bone phenotype of mice lacking Sost (Sost(-/-) ), Lrp5 (Lrp5(-/-) ), or both (Sost(-/-) ;Lrp5(-/-) ) to elucidate the mechanism of action of Sost in vivo. Sost deficiency-induced bone gain was significantly blunted in Sost(-/-) ;Lrp5(-/-) mice. Yet the Lrp5 OPPG phenotype was fully rescued in Sost(-/-) ;Lrp5(-/-) mice and most bone parameters were elevated relative to wild-type. To test whether the remaining bone increases in Sost(-/-) ;Lrp5(-/-) animals depend on Lrp6, we treated wild-type, Sost(-/-) , and Sost(-/-) ;Lrp5(-/-) mice with distinct Lrp6 function blocking antibodies. Selective blockage of Wnt1 class-mediated Lrp6 signaling reduced cancellous bone mass and density in wild-type mice. Surprisingly, it reversed the abnormal bone gain in Sost(-/-) and Sost(-/-) ;Lrp5(-/-) mice to wild-type levels irrespective of enhancement or blockage of Wnt3a class-mediated Lrp6 activity. Thus, whereas Sost deficiency-induced bone anabolism partially requires Lrp5, it fully depends on Wnt1 class-induced Lrp6 activity. These findings indicate: first, that OPPG syndrome patients suffering from LRP5 loss-of-function should benefit from principles antagonizing SOST/sclerostin action; and second, that therapeutic WNT signaling inhibitors may stop the debilitating bone overgrowth in sclerosing disorders related to SOST deficiency, such as sclerosteosis, van Buchem disease, and autosomal dominant craniodiaphyseal dysplasia, which are rare disorders without viable treatment options. PMID:23901037

Chang, Ming-Kang; Kramer, Ina; Keller, Hansjoerg; Gooi, Jonathan H; Collett, Corinne; Jenkins, David; Ettenberg, Seth A; Cong, Feng; Halleux, Christine; Kneissel, Michaela

2014-01-01

233

Bone damage induced by different cutting instruments--an in vitro study.  

PubMed

The aim of this study was to compare the peripheral bone damage induced by different cutting systems. Four devices were tested: Er:YAG laser (2.94 mm), Piezosurgery, high-speed drill and low-speed drill. Forty-five bone sections, divided into 9 groups according to different parameters, were taken from pig mandibles within 1 h post mortem. Specimens were fixed in 10% buffered formalin, decalcified and cut in thin sections. Four different parameters were analyzed: cut precision, depth of incision, peripheral carbonization and presence of bone fragments. For statistical analysis, the Kruskal-Wallis test was applied to assess equality of sample medians among groups. All sections obtained with the Er:YAG laser showed poor peripheral carbonization. The edges of the incisions were always well-shaped and regular, no melting was observed. Piezosurgery specimens revealed superficial incisions without thermal damage but with irregular edges. The sections obtained by traditional drilling showed poor peripheral carbonization, especially if obtained at lower speed. There was statistically significant differences (p<0.01) among the cutting systems for all analyzed parameters. Er:YAG laser, gave poor peripheral carbonization, and may be considered an effective method in oral bone biopsies and permits to obtain clear and readable tissue specimens. PMID:19738951

Romeo, Umberto; Del Vecchio, Alessandro; Palaia, Gaspare; Tenore, Gianluca; Visca, Paolo; Maggiore, Claudia

2009-01-01

234

The temporal response of bone to unloading  

NASA Technical Reports Server (NTRS)

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

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

1984-01-01

235

Yaw and pitch visual-vestibular interaction in weightlessness  

NASA Technical Reports Server (NTRS)

Both yaw and pitch visual-vestibular interactions at two separate frequencies of chair rotation (0.2 and 0.8 Hz) in combination with a single velocity of optokinetic stimulus (36 degrees/s) were used to investigate the effects of sustained weightlessness on neural strategies adopted by astronaut subjects to cope with the stimulus rearrangement of spaceflight. Pitch and yaw oscillation in darkness at 0.2 and 0.8 Hz without optokinetic stimulation, and constant velocity linear optokinetic stimulation at 18, 36, and 54 degrees/s presented relative to the head with the subject stationary, were used as controls for the visual-vestibular interactions. The results following 8 days of space flight showed no significant changes in: (1) either the horizontal and vertical vestibulo-ocular reflex (VOR) gain, phase, or bias; (2) the yaw visual-vestibular response (VVR); or (3) the horizontal or vertical optokinetic (OKN) slow phase velocity (SPV). However, significant changes were observed: (1) when during pitch VVR at 0.2 Hz late inflight, the contribution of the optokinetic input to the combined oculomotor response was smaller than during the stationary OKN SPV measurements, followed by an increased contribution during the immediate postflight testing; and (2) when during pitch VVR at 0.8 Hz, the component of the combined oculomotor response due to the underlying vertical VOR was more efficiently suppressed early inflight and less suppressed immediately postflight compared with preflight observations. The larger OKN response during pitch VVR at 0.2 Hz and the better suppression of VOR during pitch VVR at 0.8 Hz postflight are presumably due to the increased role of vision early inflight and immediately after spaceflight, as previously observed in various studies. These results suggest that the subjects adopted a neural strategy to structure their spatial orientation in weightlessness by reweighting visual, otolith, and perhaps tactile/somatic signals.

Clement, G.; Wood, S. J.; Reschke, M. F.; Berthoz, A.; Igarashi, M.

1999-01-01

236

Bisphosphonate as a Countermeasure to Space Flight-Induced Bone Loss  

NASA Technical Reports Server (NTRS)

The purpose of this research is to determine whether anti-resorptive pharmaceuticals such as bisphosphonates, in conjunction with the routine in-flight exercise program, will protect ISS crewmembers from the regional decreases in bone mineral density and bone strength and the increased renal stone risk documented on previous long-duration space flights [1-3]. Losses averaged 1 to 2 percent per month in such regions as the lumbar spine and hip. Although losses showed significant heterogeneity among individuals and between bones within a given subject, space flight-induced bone loss was a consistent finding. More than 90 percent of astronauts and cosmonauts on long-duration flights (average 171 days) aboard Mir and the ISS, had a minimum 5 percent loss in at least one skeletal site, 40 percent of them had a 10 percent or greater loss in at least one skeletal site, and 22 percent of the Mir cosmonauts experienced a 15 to 20 percent loss in at least one site. These losses occurred even though the crewmembers performed time-consuming in-flight exercise regimens. Moreover, a recent study of 16 ISS astronauts using quantitative computed tomography (QCT) demonstrated trabecular bone losses from the hip averaging 2.3 percent per month [4]. These losses were accompanied by significant losses in hip bone strength that may not be recovered quickly [5]. This rapid loss of bone mass results from a combination of increased and uncoupled remodeling, as demonstrated by increased resorption with little or no change in bone formation markers [6-7]. This elevated remodeling rate likely affects the cortical and trabecular architecture and may lead to irreversible changes. In addition to bone loss, the resulting hypercalciuria increases renal stone risk. Therefore, it is logical to attempt to attenuate this increased remodeling with anti-resorption drugs such as bisphosphonates. Success with alendronate was demonstrated in a bed rest study [8]. This work has been extended to space flight and two dosing regimens: 1) an oral dose of 70 mg of alendronate taken weekly during flight or 2) a single intravenous (IV) dose of 4 mg of zoledronic acid given several weeks before flight. Currently the study is focusing on the oral option because of NASA s safety concerns with the IV-administered drug. The protocol requests 10 male or female crewmembers on ISS flights of 90 days or longer. Controls are 16 previous ISS crewmembers with QCT scans of the hip performed by these same investigators. The primary outcome measure for this study is hip trabecular bone mineral density measured by QCT, but other measures of bone mass are performed including peripheral QCT (pQCT) and dual-energy x-ray absorptiometry. Serum and urinary bone markers and renal stone risk measured before, during, and after flight are included. Postflight data are currently being collected from 2 ISS crewmembers. Two additional crewmembers will return this spring after 6-month missions. To date no untoward effects have been encountered.

Spector, Elisabeth; LeBlanc, A.; Sibonga, J.; Matsumoto, T.; Jones, J.; Smith, S. M.; Shackelford, L.; Shapiro, J.; Lang, T.; Evans, H.; Spector, E.; Nakamura, T.; Kohri, K.; Ohshima, H.

2009-01-01

237

Bone Morphogenetic Protein-9 Induces PDLSCs Osteogenic Differentiation through the ERK and p38 Signal Pathways  

PubMed Central

Periodontal ligament stem cells (PDLSCs) with bone morphogenic ability are used to treat diseases such as periodontitis. Their treatment potential is increased when used in combination with proteins that induce osteogenic differentiation. For example, bone morphogenetic protein-9 (BMP9) has been found to have potent osteogenic activity. In the present study, PDLSCs were isolated from human periodontal membrane and infected with recombinant adenoviruses expressing BMP9 (Ad-BMP9). Levels of osteogenic markers such as runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) as well as mineralization ability were measured. The results showed that BMP9 promoted bone formation of PDLSCs. In other experiments, SB203580 and PD98059, which are inhibitors of p38 and ERK1/2, respectively, were used to determine if these kinases are involved in the osteogenic differentiation process. The resulting protein expression profiles and osteogenic markers of PDLSCs revealed that the mitogen-activated protein kinase (MAPK) signaling pathway might play an important role in the process of BMP9-induced osteogenic differentiation of PDLSCs. PMID:25136261

Ye, Guo; Li, Conghua; Xiang, Xuerong; Chen, Chu; Zhang, Ruyi; Yang, Xia; Yu, Xuesong; Wang, Jinhua; Wang, Lan; Shi, Qiong; Weng, Yaguang

2014-01-01

238

Bone morphogenetic protein-9 induces PDLSCs osteogenic differentiation through the ERK and p38 signal pathways.  

PubMed

Periodontal ligament stem cells (PDLSCs) with bone morphogenic ability are used to treat diseases such as periodontitis. Their treatment potential is increased when used in combination with proteins that induce osteogenic differentiation. For example, bone morphogenetic protein-9 (BMP9) has been found to have potent osteogenic activity. In the present study, PDLSCs were isolated from human periodontal membrane and infected with recombinant adenoviruses expressing BMP9 (Ad-BMP9). Levels of osteogenic markers such as runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) as well as mineralization ability were measured. The results showed that BMP9 promoted bone formation of PDLSCs. In other experiments, SB203580 and PD98059, which are inhibitors of p38 and ERK1/2, respectively, were used to determine if these kinases are involved in the osteogenic differentiation process. The resulting protein expression profiles and osteogenic markers of PDLSCs revealed that the mitogen-activated protein kinase (MAPK) signaling pathway might play an important role in the process of BMP9-induced osteogenic differentiation of PDLSCs. PMID:25136261

Ye, Guo; Li, Conghua; Xiang, Xuerong; Chen, Chu; Zhang, Ruyi; Yang, Xia; Yu, Xuesong; Wang, Jinhua; Wang, Lan; Shi, Qiong; Weng, Yaguang

2014-01-01

239

Preliminary report on treatment of bone tumors with microwave-induced hyperthermia  

SciTech Connect

Between July, 1992, and February, 1995, 62 patients with various bone tumors were treated with microwave-induced hyperthermia. The series had 47 cases of malignant tumors and 15 cases with benign tumors; most of the tumors occurred at or near knee joints (53/62 = 85.4%). The surgical procedure consisted of separating the tumorous segment from surrounding normal tissues with a safe margin, cooling the normal tissues (including the vital neurovascular bundle and the intrajoint structures) with a water circulation system while heating the tumor simultaneously with the microwave antenna array, and providing an adequate soft-tissue cover for the dead bone. The tumor core temperature and the surface temperature reached 108 and 65 C, respectively. The duration of microwave irradiation was usually 40--50 minutes. Meanwhile, the temperature of the normal tissues was kept under 39 C. The minimal and maximal periods of clinical observation were 3 months and 36 months, respectively, and the mean follow-up period was 17 months. The 62 cases were evaluated from both oncological and orthopedic points of view. Five cases had local recurrence and required amputation. The 57 other cases had excellent local control. Six malignancy cases die of lung metastasis during a period of 1--2 years. Pathological fracture occurred at devitalized bone in five cases. In most of the cases, the knee joints functioned well, were stable and painless, and had almost full range of motion. Single-photon emission-computed tomography study in 16 cases revealed that revascularization of the devitalized tumorous bone segment could be accomplished in 1 year or more. These results show that the use of microwave hyperthermia for the treatment of bone tumors can be considered to be a definitive operation procedure that is safe and is well tolerated by patients. The oncological and orthopedic results are very encouraging.

Fan, Q.Y.; Ma, B.A.; Qiu, X.C.; Li, Y.L.; Ye, J.; Zhou, Y. [Fourth Military Medical Univ., Xi`an (China)] [Fourth Military Medical Univ., Xi`an (China)

1996-12-01

240

Ultrasonic tissue characterization for monitoring nanostructured TiO2-induced bone growth.  

PubMed

The use of bioactive nanostructured TiO2 has recently been proposed for improving orthopaedic implant adhesion due to its improved biocompatibility with bone, since it induces: (i) osteoblast function, (ii) apatite nucleation and (iii) protein adsorption. The present work focuses on a non-ionizing radiation emitting technique for quantifying in real time the improvement in terms of mechanical properties of the surrounding bone due to the presence of the nanostructured TiO2 prepared by controlled precipitation and acid ageing. The mechanical strength is the ultimate goal of a bone implant and is directly related to the elastic moduli. Ultrasonics are high frequency mechanical waves and are therefore suited for characterizing elastic moduli. As opposed to echographic techniques, which are not correlated to elastic properties and are not able to penetrate bone, a low frequency ultrasonic transmission test is proposed, in which a P-wave is transmitted through the specimen and recorded. The problem is posed as an inverse problem, in which the unknown is a set of parameters that describe the mechanical constants of the sequence of layers. A finite element numerical model that depends on these parameters is used to predict the transformation of the waveform and compare to the measurement. The parameters that best describe the real tissue are obtained by minimizing the discrepancy between the real and numerically predicted waveforms. A sensitivity study to the uncertainties of the model is performed for establishing the feasibility of using this technique to investigate the macroscopic effect on bone growth of nanostructured TiO2 and its beneficial effect on implant adhesion. PMID:17664558

Rus, G; García-Martínez, J

2007-06-21

241

Mechanical Vibration Applied in the Absence of Weight Bearing Suggest Improved Fragile Bone  

Microsoft Academic Search

Mechanical loading is critical for maintaining bone mass, while weightlessness, such as that associated with reduced physical\\u000a activity in old age, long-term bed rest, or space flight, invariably leads to bone loss. Fragile bone tissue is more susceptible\\u000a to fractures. By contrast, extremely low-level oscillatory accelerations, applied without constraint, can increase bone formation.\\u000a To examine the role of vibration in

J. Matsuda; K. Kurata; T. Hara; H. Higaki

242

Human orientation and movement control in weightless and artificial gravity environments  

NASA Technical Reports Server (NTRS)

Our goal is to summarize what has been learned from studies of human movement and orientation control in weightless conditions. An understanding of the physics of weightlessness is essential to appreciate the dramatic consequences of the absence of continuous contact forces on orientation and posture. Eye, head, arm, leg, and whole body movements are discussed, but only experiments whose results seem relatively incontrovertible are included. Emphasis is placed on distinguishing between virtually immediate adaptive compensations to weightlessness and those with longer time courses. The limitations and difficulties of performing experiments in weightless conditions are highlighted. We stress that when astronauts and cosmonauts return from extended space flight they do so with both physical "plant" and neural "controller" structurally and functionally altered. Recent developments in adapting humans to artificial gravity conditions are discussed as a way of maintaining sensory-motor and structural integrity in extended missions involving transitions between different force environments.

Lackner, J. R.; DiZio, P.

2000-01-01

243

Training of astronauts in laboratory-aircraft under weightless conditions for work in space  

NASA Technical Reports Server (NTRS)

Analyses of occupational activities of astronauts in laboratory-aircraft flights simulating weightlessness conditions permit the development of training methods and optimization of the interaction of man with various spacecraft designs.

Khrunov, Y. V.; Chekidra, I. F.; Kolosov, I. A.

1975-01-01

244

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

NASA Technical Reports Server (NTRS)

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

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

1975-01-01

245

Human orientation and movement control in weightless and artificial gravity environments.  

PubMed

Our goal is to summarize what has been learned from studies of human movement and orientation control in weightless conditions. An understanding of the physics of weightlessness is essential to appreciate the dramatic consequences of the absence of continuous contact forces on orientation and posture. Eye, head, arm, leg, and whole body movements are discussed, but only experiments whose results seem relatively incontrovertible are included. Emphasis is placed on distinguishing between virtually immediate adaptive compensations to weightlessness and those with longer time courses. The limitations and difficulties of performing experiments in weightless conditions are highlighted. We stress that when astronauts and cosmonauts return from extended space flight they do so with both physical "plant" and neural "controller" structurally and functionally altered. Recent developments in adapting humans to artificial gravity conditions are discussed as a way of maintaining sensory-motor and structural integrity in extended missions involving transitions between different force environments. PMID:10638437

Lackner, J R; DiZio, P

2000-01-01

246

Role of carbonic anhydrase in bone resorption induced by 1,25 dihydroxyvitamin D3 in vitro  

NASA Technical Reports Server (NTRS)

The calvaria of 5-to-6-day-old mice treated with 1 x 10 to the -8th M of 1,25(OH)2D3 in vitro for 48 hours are examined in order to study the function of carbonic anhydrase in bone resorption. Calcium concentrations in the culture were measured to assess bone resorption. It is observed that 1,25(OH)2D3 effectively stimulates bone resorption in vitro and the resorption is dose-dependent. The effects of azetazolamide on 1,25(OH)2D3-induced bone resorption are investigated. The data reveal that 1,25(OH)2D3-induced calcium release is associated with an increase in the carbonic anhydrase activity of bone, and bone alkaline phosphatase activity is decreased and acid phosphatase activity is increased in response to 1,25(OH)2D3. A two-fold mechanism for 1,25(OH)2D3-induced bone resorption is proposed; the first mechanism is an indirect activation of osteoclasts and the second involves an interaction between hormone and osteoclast precursors.

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

1985-01-01

247

Targeted deletion of histidine decarboxylase gene in mice increases bone formation and protects against ovariectomy-induced bone loss  

PubMed Central

Targeted disruption of the histidine decarboxylase gene (HDC?/?), the only histamine-synthesizing enzyme, led to a histamine-deficient mice characterized by undetectable tissue histamine levels, impaired gastric acid secretion, impaired passive cutaneous anaphylaxis, and decreased mast cell degranulation. We used this model to study the role of histamine in bone physiology. Compared with WT mice, HDC?/? mice receiving a histamine-free diet had increased bone mineral density, increased cortical bone thickness, higher rate of bone formation, and a marked decrease in osteoclasts. After ovariectomy, cortical and trabecular bone loss was reduced by 50% in HDC?/? mice compared with WT. Histamine deficiency protected the skeleton from osteoporosis directly, by inhibiting osteoclastogenesis, and indirectly, by increasing calcitriol synthesis. Quantitative RT-PCR showed elevated 25-hydroxyvitamin D-1?-hydroxylase and markedly decreased 25-hydroxyvitamin D-24-hydroxylase mRNA levels. Serum parameters confirming this indirect effect included elevated calcitriol, phosphorus, alkaline phosphatase, and receptor activator of NF-?B ligand concentrations, and suppressed parathyroid hormone concentrations in HDC?/? mice compared with WT mice. After ovariectomy, histamine-deficient mice were protected from bone loss by the combination of increased bone formation and reduced bone resorption. PMID:12716972

Fitzpatrick, L. A.; Buzas, E.; Gagne, T. J.; Nagy, A.; Horvath, C.; Ferencz, V.; Mester, A.; Kari, B.; Ruan, M.; Falus, A.; Barsony, J.

2003-01-01

248

Insulin prevents bone morphogenetic protein-4 induced cardiomyocyte apoptosis through activating Akt.  

PubMed

Bone morphogenetic protein-4 (BMP4) mediates pathological cardiac hypertrophy. Insulin is well-known to promote cardiomyocyte survival in heart diseases. The aim of the present study is to evaluate the effects of insulin on BMP4-induced cardiomyocyte apoptosis. Cell viability and apoptosis were measured by using MTT, live and dead staining, caspase-3 activity assays, and the protein expressions were measured by using western blot technique. Insulin did not elicit cardiomyocyte apoptosis, but antagonized BMP4-induced cardiomyocyte apoptosis. Insulin treatment rapidly activated Akt which was inhibited by Akt inhibitor in cardiomyocytes. Furthermore, Akt inhibitor canceled the anti-apoptotic effects of insulin against BMP4 in cardiomyocytes. In conclusion, insulin prevents BMP4-induced cardiomyocyte apoptosis and the underlying mechanisms include activation of Akt. The present work provides a novel mechanism of the protective effects of insulin in cardiovascular system. PMID:25490386

Xing, Yue; Yang, Di; Lu, Jing; Dong, De-Li

2015-01-01

249

Genistein supplementation increases bone turnover but does not prevent alcohol-induced bone loss in male mice.  

PubMed

Chronic alcohol consumption results in bone loss through increased bone resorption and decreased bone formation. These effects can be reversed by estradiol (E2) supplementation. Soy diets are suggested to have protective effects on bone loss in men and women, as a result of the presence of soy protein-associated phytoestrogens such as genistein (GEN). In this study, male mice were pair-fed (PF), a control diet, an ethanol (EtOH) diet, or EtOH diet supplemented with 250?mg/kg of GEN for 8 weeks to test if GEN protects against bone loss associated with chronic drinking. Interestingly, alcohol consumption reduced cortical area and thickness and trabecular bone volume in both EtOH and EtOH/GEN groups when compared to the corresponding PF and PF/GEN controls, P?bone compartment, we observed a significant increase in overall trabecular bone density in the PF/GEN group compared to the PF controls. Bone loss in the EtOH-treated mice was associated with the inhibition of osteoblastogenesis as indicated by decreased alkaline phosphatase staining in ex vivo bone marrow cultures, P?bone-formation markers, osteocalcin, and runt-related transcription factor 2 (Runx2) was also significantly up-regulated in the PF/GEN and EtOH/GEN groups compared to the PF and EtOH-treated groups. GEN supplementation also increased the expression of receptor activator of nuclear factor ?-B ligand (RANKL) in the PF/GEN, an increase that persisted in the EtOH/GEN-treated animals (P?bone marrow cultures in vitro, P?bone remodeling and, in the context of chronic alcohol consumption, does not protect against the oxidative stress-associated EtOH-mediated bone resorption. PMID:24872432

Yang, Carrie S; Mercer, Kelly E; Alund, Alexander W; Suva, Larry J; Badger, Thomas M; Ronis, Martin J J

2014-10-01

250

Plumbagin Inhibits Osteoclastogenesis and Reduces Human Breast Cancer-induced Osteolytic Bone Metastasis in Mice through Suppression of RANKL Signaling  

PubMed Central

Bone loss is one of the major complications of advanced cancers such as breast cancer, prostate cancer and multiple myeloma; agents that can suppress this bone loss have therapeutic potential. Extensive research within the last decade has revealed that RANKL, a member of the tumor necrosis factor superfamily, plays a major role in cancer-associated bone resorption, and thus is a therapeutic target. We investigated the potential of vitamin K3 analogue plumbagin (derived from Chitrak, an Ayurvedic medicinal plant), to modulate RANKL signaling, osteoclastogenesis and breast cancer–induced osteolysis. Plumbagin suppressed RANKL-induced NF-?B activation in mouse monocytes, an osteoclast precursor cell, through sequential inhibition of activation of I?B? kinase, I?B? phosphorylation and I?B? degradation. Plumbagin also suppressed differentiation of these cells into osteoclasts induced either by RANKL or by human breast cancer or human multiple myeloma cells. When examined for its ability to prevent human breast cancer–induced bone loss in animals, plumbagin (2 mg/kg body weight), when administered via the intraperitoneal route, significantly decreased osteolytic lesions resulting in preservation of bone volume in nude mice bearing human breast tumors. Overall, our results indicate that plumbagin, a vitamin K analogue, is a potent inhibitor of osteoclastogenesis induced by tumor cells and of breast cancer–induced osteolytic metastasis through suppression of RANKL signaling. PMID:22090419

Sung, Bokyung; Oyajobi, Babatunde O.; Aggarwal, Bharat B.

2011-01-01

251

What happens to the brain in weightlessness? A first approach by EEG tomography.  

PubMed

Basic changes in environmental conditions are fundamental to understanding brain cortical mechanisms. Several studies have reported impairment of central nervous processes during weightlessness. There is ongoing debate as to whether these impairments are attributable to primary physiological effects or secondary psychological effects of the weightlessness environment. This study evaluates the physiological effects of changed gravity conditions on brain cortical activity. In a first experiment, EEG activity of seven participants was recorded at normal, increased and zero gravity during a parabolic flight. Additionally an EEG under normal gravity conditions preflight was recorded. In a second experiment, 24 participants were exposed to a supine, seated and 9 degree head-down tilt position while EEG was recorded. Data were analysed using low resolution brain electromagnetic tomography (LORETA). Beta-2 EEG activity (18-35 Hz) was found to be increased in the right superior frontal gyrus under normal gravity conditions inflight. By exposure to weightlessness a distinct inhibition of this activity within the same areas could be noticed. As the tilt experiment showed changes in the left inferior temporal gyrus in supine and tilted positions we conclude that the observed changes under weightlessness are not explainable by hemodynamic changes but rather reflect emotional processes related to the experience of weightlessness. These findings suggest that weightlessness has a major impact on electro cortical activity and may affect central nervous and adaptation processes. PMID:18606233

Schneider, Stefan; Brümmer, Vera; Carnahan, Heather; Dubrowski, Adam; Askew, Christopher D; Strüder, Heiko K

2008-10-01

252

Kartogenin induces cartilage-like tissue formation in tendon–bone junction  

PubMed Central

Tendon–bone junctions (TBJs) are frequently injured, especially in athletic settings. Healing of TBJ injuries is slow and is often repaired with scar tissue formation that compromises normal function. This study explored the feasibility of using kartogenin (KGN), a biocompound, to enhance the healing of injured TBJs. We first determined the effects of KGN on the proliferation and chondrogenic differentiation of rabbit bone marrow stromal cells (BMSCs) and patellar tendon stem/progenitor cells (PTSCs) in vitro. KGN enhanced cell proliferation in both cell types in a concentration-dependent manner and induced chondrogenic differentiation of stem cells, as demonstrated by high expression levels of chondrogenic markers aggrecan, collagen II and Sox-9. Besides, KGN induced the formation of cartilage-like tissues in cell cultures, as observed through the staining of abundant proteoglycans, collagen II and osteocalcin. When injected into intact rat patellar tendons in vivo, KGN induced cartilage-like tissue formation in the injected area. Similarly, when KGN was injected into experimentally injured rat Achilles TBJs, wound healing in the TBJs was enhanced, as evidenced by the formation of extensive cartilage-like tissues. These results suggest that KGN may be used as an effective cell-free clinical therapy to enhance the healing of injured TBJs. PMID:25419468

Zhang, Jianying; Wang, James H-C

2014-01-01

253

Mollugin from Rubea cordifolia suppresses receptor activator of nuclear factor-?B ligand-induced osteoclastogenesis and bone resorbing activity in vitro and prevents lipopolysaccharide-induced bone loss in vivo.  

PubMed

Osteopenic diseases, such as osteoporosis, are characterized by progressive and excessive bone resorption mediated by enhanced receptor activator of nuclear factor-?B ligand (RANKL) signaling. Therefore, downregulation of RANKL downstream signals may be a valuable approach for the treatment of bone loss-associated disorders. In this study, we investigated the effects of the naphthohydroquinone mollugin on osteoclastogenesis and its function in vitro and in vivo. Mollugin efficiently suppressed RANKL-induced osteoclast differentiation of bone marrow macrophages (BMMs) and bone resorbing activity of mature osteoclasts by inhibiting RANKL-induced c-Fos and NFATc1 expression. Mollugin reduced the phosphorylation of signaling pathways activated in the early stages of osteoclast differentiation, including the MAP kinase, Akt, and GSK3? and inhibited the expression of different genes associated with osteoclastogenesis, such as OSCAR, TRAP, DC-STAMP, OC-STAMP, integrin ??, integrin ?3, cathepsin K, and ICAM-1. Furthermore, mice treated with mollugin showed significant restoration of lipopolysaccharide (LPS)-induced bone loss as indicated by micro-CT and histological analysis of femurs. Consequently, these results suggested that mollugin could be a novel therapeutic candidate for bone loss-associated disorders including osteoporosis, rheumatoid arthritis, and periodontitis. PMID:25636867

Baek, Jong Min; Kim, Ju-Young; Jung, Youngeun; Moon, Seong-Hee; Choi, Min Kyu; Kim, Seong Hwan; Lee, Myeung Su; Kim, Ikyon; Oh, Jaemin

2015-01-15

254

Interleukin-1-induced acute bone resorption facilitates the secretion of fibroblast growth factor 23 into the circulation.  

PubMed

Fibroblast growth factor 23 (FGF23), a central regulator of phosphate and vitamin D metabolism, is mainly produced by osteocytes in bone and exerts its effects on distant organs. Despite its endocrine function, the mechanism controlling serum FGF23 levels is not fully understood. Here we tested the hypothesis that osteoclastic bone resorption may play a role in regulating circulating levels of FGF23, using a mouse model where injections of interleukin (IL)-1? into the subcutaneous tissue over the calvaria induced rapid bone resorption. A significant amount of FGF23 was detected in the extracts from mouse bones, which supports the idea that FGF23 stays in bone for a while after its production. IL-1?-induced bone resorption was associated with elevated serum FGF23 levels, an effect abolished by pre-treatment with pamidronate. Fgf23 expression was not increased in either the calvariae or tibiae of IL-1?-injected mice, which suggests that IL-1? facilitated the entry of FGF23 protein into circulation by accelerating bone resorption rather than increasing its gene expression. The direct effect of IL-1? on bone was confirmed when it increased FGF23 levels in the conditioned media of mouse calvariae in organ culture. Repeated treatment of the cultured calvariae with IL-1? led to a refractory phase, where FGF23 was not mobilized by IL-1? anymore. Consistent with the in vivo results, treatment with IL-1? failed to increase Fgf23 mRNA in isolated primary osteocytes and osteoblasts. These results suggest that FGF23 produced by osteocytes remains in bone, and that rapid bone resorption facilitates its entry into the bloodstream. PMID:24996526

Yamazaki, Miwa; Kawai, Masanobu; Miyagawa, Kazuaki; Ohata, Yasuhisa; Tachikawa, Kanako; Kinoshita, Saori; Nishino, Jin; Ozono, Keiichi; Michigami, Toshimi

2014-07-01

255

Radiographic evaluation of the effect of obesity on alveolar bone in rats with ligature-induced periodontal disease  

PubMed Central

There is evidence that the lack of metabolic control of obese patients may accelerate periodontitis. The aim of this study was to evaluate radiographically the effect of cafeteria-diet-induced obesity on alveolar bone loss in rats subjected to periodontal disease. Twenty male Wistar rats were randomly divided into four groups: 1) control group, 2) control and ligature group; 3) cafeteria group; and 4) cafeteria and ligature group. The animals were evaluated for obesity and euthanized, and the mandible of each rat was removed to perform a radiographic evaluation of alveolar bone loss and its effect on diet-induced obesity. The results showed greater alveolar bone loss in the mice in Group 4 (P<0.01). Thus, we concluded that obese mice, on average, showed greater radiographic evidence of alveolar bone loss than mice undergoing induction of obesity. PMID:24124386

do Nascimento, Cassiane Merigo; Cassol, Tiago; da Silva, Fernanda Soares; Bonfleur, Maria Lucia; Nassar, Carlos Augusto; Nassar, Patricia Oehlmeyer

2013-01-01

256

Rapid inhibition of thyroxine-induced bone resorption in the rat by an orally active vitronectin receptor antagonist.  

PubMed

An excess of thyroid hormone results in increased bone turnover and loss of bone mass in humans. Exogenous administration of thyroid hormone to rats has served as a model of human hyperthyroidism in which antiresorptive therapies have been tested. We have further refined this model of thyroxine (T4)-induced turnover in the rat. Daily administration of T4 to aged rats for as short as 1 week resulted in elevated bone resorption determined by significantly higher urinary deoxypyridinoline (Dpd) compared with vehicle controls or animals receiving T4 plus estradiol. Three weeks of daily administration of T4 led to significantly lower bone mineral density compared with untreated controls or animals receiving T4 plus estradiol. In a follow-up study, a depot formulation of T4 caused an increase in Dpd identical to that achieved with a bolus dose. SB-273005 [(4S)-2,3,4,5-tetrahydro-8-[2-[6-(methylamino)-2-pyridinyl] ethoxy]-3-oxo-2-(2,2,2-trifluoroethyl)-1H-2-benzazepine-4- acetic acid] a potent antagonist of the integrins alpha(v)beta(3) and alpha(v)beta(5), has been shown previously to inhibit bone resorption in cultures of human osteoclasts and to protect bone in ovariectomized rats. The effect of SB-273005 by oral administration was evaluated in this thyroxine-induced turnover model. Dose-dependent inhibition of resorption was seen with SB-273005 after 7 days of dosing using Dpd as a measure of bone resorption. In summary, it has been demonstrated that the antiresorptive activity of a vitronectin receptor antagonist can be measured after only 7 days of treatment in this refined rat model of thyroxine-induced bone turnover. These data suggest that SB-273005 may be useful for the treatment of metabolic bone diseases, including those resulting from hyperthyroidism. PMID:12065718

Hoffman, Sandra J; Vasko-Moser, Janice; Miller, William H; Lark, Michael W; Gowen, Maxine; Stroup, George

2002-07-01

257

SR-BI in Bone Marrow Derived Cells Protects Mice from Diet Induced Coronary Artery Atherosclerosis and Myocardial Infarction  

PubMed Central

SR-BI deficient mice that are also hypomorphic for apolipoprotein E expression develop diet induced occlusive coronary artery atherosclerosis, myocardial infarction and early death. To test the role of SR-BI in bone marrow derived cells, we used bone marrow transplantation to generate SR-BI-null; apoE-hypomorphic mice in which SR-BI expression was restored solely in bone marrow derived cells. SR-BI-null; apoE-hypomorphic mice were transplanted with SR-BI+/+apoE-hypomorphic, or control, autologous SR-BI-null; apoE-hypomorphic bone marrow. Four weeks later, mice were fed a high-fat, high-cholesterol, cholate-containing diet to induce coronary artery atherosclerosis. Mice transplanted with autologous bone marrow developed extensive aortic atherosclerosis and severe occlusive coronary artery atherosclerosis after 4 weeks of feeding. This was accompanied by myocardial fibrosis and increased heart weights. In contrast, restoration of SR-BI expression in bone marrow derived-cells reduced diet induced aortic and coronary artery atherosclerosis, myocardial fibrosis and the increase in heart weights in SR-BI-null; apoE-hypomorphic mice. Restoration of SR-BI in bone marrow derived cells did not, however, affect steady state lipoprotein cholesterol levels, but did reduce plasma levels of IL-6. Monocytes from SR-BI-null mice exhibited a greater capacity to bind to VCAM-1 and ICAM-1 than those from SR-BI+/+ mice. Furthermore, restoration of SR-BI expression in bone marrow derived cells attenuated monocyte recruitment into atherosclerotic plaques in mice fed high fat, high cholesterol cholate containing diet. These data demonstrate directly that SR-BI in bone marrow-derived cells protects against both aortic and CA atherosclerosis. PMID:23967310

Pei, Ying; Chen, Xing; Aboutouk, Dina; Fuller, Mark T.; Dadoo, Omid; Yu, Pei; White, Elizabeth J.; Igdoura, Suleiman A.; Trigatti, Bernardo L.

2013-01-01

258

Mediators of Inflammation-Induced Bone Damage in Arthritis and Their Control by Herbal Products  

PubMed Central

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial joints leading to bone and cartilage damage. Untreated inflammatory arthritis can result in severe deformities and disability. The use of anti-inflammatory agents and biologics has been the mainstay of treatment of RA. However, the prolonged use of such agents may lead to severe adverse reactions. In addition, many of these drugs are quite expensive. These limitations have necessitated the search for newer therapeutic agents for RA. Natural plant products offer a promising resource for potential antiarthritic agents. We describe here the cellular and soluble mediators of inflammation-induced bone damage (osteoimmunology) in arthritis. We also elaborate upon various herbal products that possess antiarthritic activity, particularly mentioning the specific target molecules. As the use of natural product supplements by RA patients is increasing, this paper presents timely and useful information about the mechanism of action of promising herbal products that can inhibit the progression of inflammation and bone damage in the course of arthritis. PMID:23476694

Nanjundaiah, Siddaraju M.; Astry, Brian; Moudgil, Kamal D.

2013-01-01

259

Deer bone extract prevents against scopolamine-induced memory impairment in mice.  

PubMed

Deer bone has been used as a health-enhancing food as well as an antiaging agent in traditional Oriental medicine. Recently, the water extract of deer bone (DBE) showed a neuroprotective action against glutamate or A?1-42-induced cell death of mouse hippocampal cells by exerting antioxidant activity through the suppression of MAP kinases. The present study is to examine whether DBE improves memory impairment induced by scopolamine. DBE (50, 100 or 200?mg/kg) was administered orally to mice for 14 days, and then scopolamine (2?mg/kg, i.p.) was administered together with DBE for another 7 days. Memory performance was evaluated in the Morris water maze (MWM) test and passive avoidance test. Also, brain acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity, biomarkers of oxidative stress and the loss of neuronal cells in the hippocampus, was evaluated by histological examinations. Administration of DBE significantly restored memory impairments induced by scopolamine in the MWM test (escape latency and number of crossing platform area), and in the passive avoidance test. Treatment with DBE inhibited the AChE activity and increased the ChAT activity in the brain of memory-impaired mice induced by scopolamine. Additionally, the administration of DBE significantly prevented the increase of lipid peroxidation and the decrease of glutathione level in the brain of mice treated with scopolamine. Also, the DBE treatment restored the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase to control the level. Furthermore, scopolamine-induced oxidative damage of neurons in hippocampal CA1 and CA3 regions were prevented by DBE treatment. It is suggested that DBE may be useful for memory improvement through the regulation of cholinergic marker enzyme activities and the suppression of oxidative damage of neurons in the brain of mice treated with scopolamine. PMID:25546299

Du, Chun Nan; Min, A Young; Kim, Hyun Jeong; Shin, Suk Kyung; Yu, Ha Ni; Sohn, Eun Jeong; Ahn, Chang-Won; Jung, Sung Ug; Park, Soo-Hyun; Kim, Mee Ree

2015-02-01

260

Differentiation-Inducing Factor Purified from Conditioned Medium of Mitogen-Treated Spleen Cell Cultures Stimulates Bone Resorption  

Microsoft Academic Search

Spleen cells treated with mitogens produce a potent bone-resorbing factor called osteoclast-activating factor (OAF). To examine the relationship between the bone-resorbing factor and other protein factors produced by spleen cells, the colony-stimulating factor (CSF), the differentiation-inducing factor (DIF), the macrophage fusion factor (MFF), and the macrophage growth factor (MGF) were purified from 2.68 liters of conditioned medium of mouse spleen

Etsuko Abe; Hirofumi Tanaka; Yoshiko Ishimi; Chisato Miyaura; Takamune Hayashi; Hiroshi Nagasawa; Mikio Tomida; Yuri Yamaguchi; Motoo Hozumi; Tatsuo Suda

1986-01-01

261

Protection against Radiation-Induced Bone Marrow and Intestinal Injuries by Cordyceps sinensis, a Chinese Herbal Medicine  

Microsoft Academic Search

Liu, W-C., Wang, S-C., Tsai, M-L., Chen, M-C., Wang, Y-C., Hong, J-H., McBride, W. H. and Chiang, C-S. Protec- tion against Radiation-Induced Bone Marrow and Intestinal Injuries by Cordyceps sinensis, a Chinese Herbal Medicine. Radiat. Res. 166, 900-907 (2006). Bone marrow and intestinal damage limits the efficacy of radiotherapy for cancer and can result in death if the whole body

Wei-Chung Liu; Shu-Chi Wang; Min-Lung Tsai; Meng-Chi Chen; Ya-Chen Wang; Ji-Hong Hong; William H. McBride; Chi-Shiun Chiang

2006-01-01

262

In growing pigs, chlortetracycline induces a reversible green bone discoloration and a persistent increase of bone mineral density dependent of dosing regimen.  

PubMed

We studied in growing pigs the effects of exposure to dietary chlortetracycline on bone mineral density (BMD) and bone color. Pigs were randomly allocated to a drug-free diet (n=48) or a diet fortified with 800 ppm of chlortetracycline, starting either at 28- or 84-d of age, and for either a 28- or 56-d duration (n=16 pigs/group). The lumbar vertebral discoloration and BMD of randomly chosen pigs were evaluated at 28-d intervals up to 168-d of age. The odds of bone discoloration increased with dosing duration and age at treatment onset, and decreased with the withdrawal time and age at treatment onset interaction (p < or = 0.001). The measured trabecular BMD linearly increased with age and squared treatment duration (p < or = 0.005). Therefore, TC-induced bone discoloration is reversible, and may be prevented with proper dosing regimen design. Moreover, TC induces a persistent increase on BMD that could be detected with quantitative computed tomography. PMID:20723952

Guillot, Martin; Alexander, Kate; Pomar, Candido; Del Castillo, Jérôme R E

2011-06-01

263

The effects of vanadium (V) absorbed by Coprinus comatus on bone in streptozotocin-induced diabetic rats.  

PubMed

The purpose of this study was to evaluate the effects of vanadium absorbed by Coprinus comatus (VACC) treatment on bone in streptozotocin (STZ)-induced diabetic rats. Forty-five Wistar female rats used were divided into three groups: (1) normal rats (control), (2) diabetic rats, and (3) diabetic rats treated with VACC. Normal and diabetic rats were given physiological saline, and VACC-treated rats were administered VACC intragastrically at doses of 0.18 mg vanadium/kg body weight once daily. Treatments were performed over a 12-week period. At sacrifice, one tibia and one femur were removed, subjected to micro computed tomography (micro-CT) for determination of trabecular bone structure, and then processed for histomorphometry to assess bone turnover. Another femoral was used for mechanical testing. In addition, bone samples were collected to evaluate the content of mineral substances in bones. Treatment with VACC increased trabecular bone volume fraction in diabetic rats. Vanadium-treated animals had significant increases in ultimate load, trabecular thickness, and osteoblast surface. However, vanadium treatment did not seem to affect bone stiffness, bone energy absorption, trabecular separation, and osteoclast number. P levels in the femurs of diabetic rats treated with VACC were significantly higher than those of diabetic animals. Ca levels in diabetic and diabetic rats treated with vanadium showed no obvious changes. In conclusion, our results provide an important proof of concept that VACC may represent a powerful approach to treating or reversing diabetic osteopathy in humans. PMID:20734239

Pei, Yi; Fu, Qin

2011-09-01

264

Temporal Gene Expression Profiling during Rat Femoral Marrow Ablation-Induced Intramembranous Bone Regeneration  

PubMed Central

Enhanced understanding of differential gene expression and biological pathways associated with distinct phases of intramembranous bone regeneration following femoral marrow ablation surgery will improve future advancements regarding osseointegration of joint replacement implants, biomaterials design, and bone tissue engineering. A rat femoral marrow ablation model was performed and genome-wide microarray data were obtained from samples at 1, 3, 5, 7, 10, 14, 28, and 56 days post-ablation, with intact bones serving as controls at Day 0. Bayesian model-based clustering produced eight distinct groups amongst 9,062 significant gene probe sets based on similar temporal expression profiles, which were further categorized into three major temporal classes of increased, variable, and decreased expression. Osteoblastic- and osteoclastic-associated genes were found to be significantly expressed within the increased expression groups. Chondrogenesis was not detected histologically. Adipogenic marker genes were found within variable/decreased expression groups, emphasizing that adipogenesis was inhibited during osteogenesis. Differential biological processes and pathways associated with each major temporal group were identified, and significantly expressed genes involved were visually represented by heat maps. It was determined that the increased expression group exclusively contains genes involved in pathways for matrix metalloproteinases (MMPs), Wnt signaling, TGF-? signaling, and inflammatory pathways. Only the variable expression group contains genes associated with glycolysis and gluconeogenesis, the notch signaling pathway, natural killer cell mediated cytotoxicity, and the B cell receptor signaling pathway. The decreased group exclusively consists of genes involved in heme biosynthesis, the p53 signaling pathway, and the hematopoietic cell lineage. Significant biological pathways and transcription factors expressed at each time point post-ablation were also identified. These data present the first temporal gene expression profiling analysis of the rat genome during intramembranous bone regeneration induced by femoral marrow ablation. PMID:20957030

Wise, Joel K.; Sena, Kotaro; Vranizan, Karen; Pollock, Jacob F.; Healy, Kevin E.; Hughes, W. Frank; Sumner, D. Rick; Virdi, Amarjit S.

2010-01-01

265

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

NASA Technical Reports Server (NTRS)

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

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

1984-01-01

266

Space flight and bone formation  

NASA Technical Reports Server (NTRS)

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

Doty, St B.

2004-01-01

267

Apollo 11 Astronaut Edwin Aldrin Prepares for Weightless Conditions  

NASA Technical Reports Server (NTRS)

In preparation of the nation's first lunar landing mission, Apollo 11 crew members underwent training to practice activities they would be performing during the mission. In this photograph, astronaut Edwin E. Aldrin, donned in his space suit, gets in more time under weightless conditions aboard a KC-135 aircraft from the Wright-Patterson Air Force Base. The Apollo 11 mission launched from the Kennedy Space Center (KSC) in Florida via the Marshall Space Flight Center (MSFC) developed Saturn V launch vehicle on July 16, 1969 and safely returned to Earth on July 24, 1969. Aboard the space craft were astronauts Neil A. Armstrong, commander; Michael Collins, Command Module (CM) pilot; and Edwin E. (Buzz) Aldrin Jr., Lunar Module (LM) pilot. The CM, 'Columbia', piloted by Collins, remained in a parking orbit around the Moon while the LM, 'Eagle'', carrying astronauts Armstrong and Aldrin, landed on the Moon. On July 20, 1969, Armstrong was the first human to ever stand on the lunar surface, followed by Aldrin. During 2½ hours of surface exploration, the crew collected 47 pounds of lunar surface material for analysis back on Earth. With the success of Apollo 11, the national objective to land men on the Moon and return them safely to Earth had been accomplished.

1969-01-01

268

Postnatal development under conditions of simulated weightlessness and space flight  

NASA Technical Reports Server (NTRS)

The adaptability of the developing nervous system to environmental influences and the mechanisms underlying this plasticity has recently become a subject of interest in space neuroscience. Ground studies on neonatal rats using the tail suspension model of weightlessness have shown that the force of gravity clearly influences the events underlying the postnatal development of motor function. These effects depend on the age of the animal, duration of the perturbation and the motor function studied. A nine-day flight study has shown that a dam and neonates can develop under conditions of space flight. The motor function of the flight animals after landing was consistent with that seen in the tail suspension studies, being marked by limb joint extension. However, there were expected differences due to: (1) the unloading of the vestibular system in flight, which did not occur in the ground-based experiments; (2) differences between flight and suspension durations; and (3) the inability to evaluate motor function during the flight. The next step is to conduct experiments in space with the flexibility and rigor that is now limited to ground studies: an opportunity offered by the International Space Station. Copyright 1998 Published by Elsevier Science B.V.

Walton, K.

1998-01-01

269

Residual nutational activity of the sunflower hypocotyl in simulated weightlessness  

NASA Technical Reports Server (NTRS)

The gravity dependence of circumnutational activity in the sunflower hypocotyl is investigated under conditions of simulated weightlessness. Seedling cultures of the sunflower Helianthus annuus were placed four days after planting in clinostats rotating at a rate of 1.0 rpm in the horizontal or somersaulting configurations, and plant movements around their growth axes were recorded in infrared light by a time-lapse closed-circuit video system. The amplitudes and mean cycle durations of the plant nutations in the horizontal and tumbling clinostats are observed to be 20% and 72%, and 32% and 74%, respectively, of the values observed in stationary plants; extrapolations to a state of zero g by the imposition of small centripetal forces on horizontally clinostated plants also indicate some nutational motion in the absence of gravity. It is concluded that the results are incompatible with the model of Israelsson and Johnsson (1967) of geotropic response with overshoot for sunflower circumnutation; however, results of the Spacelab 1 mission experiment are needed to unambiguously define the role of gravitation.

Chapman, D. K.; Brown, A. H.

1979-01-01

270

Mechanism for negative water balance during weightlessness An hypothesis  

NASA Technical Reports Server (NTRS)

The mechanism for the apparent decrease in body fluid volume in astronauts during spaceflight remains obscure. The widespread postulate that the hypohydration is the result of the Henry-Gauer reflex, a diuresis caused by inhibition of vasopressin secretion resulting from increased left and perhaps right atrial (central) venous pressure, has not been established with direct measurements on astronauts. An hypothesis is proposed to account for fluid-electrolyte shifts during weightlessness. A moderate but transient increase in central venous pressure occurs when orbit is entered that is insufficient to activate the Henry-Gauer reflex but sufficient to stimulate the release of atrial natriuretic peptides. Increased sodium excretion would facilitate some increased urinary water loss. The resulting relatively dilute plasma and interstitial fluids would cause fluid to shift into the cellular space, resulting in edema in the head and trunk and inhibition of thirst and drinking. Thus, the negative water balance in astronauts would be caused by a gradual natriuresis and diuresis coupled with reduced fluid intake.

Greenleaf, J. E.

1986-01-01

271

Water immersion and its computer simulation as analogs of weightlessness  

NASA Technical Reports Server (NTRS)

Experimental studies and computer simulations of water immersion are summarized and discussed with regard to their utility as analogs of weightlessness. Emphasis is placed on describing and interpreting the renal, endocrine, fluid, and circulatory changes that take place during immersion. A mathematical model, based on concepts of fluid volume regulation, is shown to be well suited to simulate the dynamic responses to water immersion. Further, it is shown that such a model provides a means to study specific mechanisms and pathways involved in the immersion response. A number of hypotheses are evaluated with the model related to the effects of dehydration, venous pressure disturbances, the control of ADH, and changes in plasma-interstitial volume. By inference, it is suggested that most of the model's responses to water immersion are plausible predictions of the acute changes expected, but not yet measured, during space flight. One important prediction of the model is that previous attempts to measure a diuresis during space flight failed because astronauts may have been dehydrated and urine samples were pooled over 24-hour periods.

Leonard, J. I.

1982-01-01

272

Cardiovascular effects of weightlessness and ground-based simulation  

NASA Technical Reports Server (NTRS)

A large number of animal and human flight and ground-based studies were conducted to uncover the cardiovascular effects of weightlessness. Findings indicate changes in cardiovascular function during simulations and with spaceflight that lead to compromised function on reambulation and/or return to earth. This altered state termed cardiovascular deconditioning is most clearly manifest when in an erect body state. Hemodynamic parameters inidicate the presence of excessive tachnycardia, hypotension (leading to presyncope in one-third of the subjects), decreased heart volume, decreased plasma and circulating blood volumes and loss of skeletal muscle mass, particularly in the lower limbs. No clinically harmful effects were observed to date, but in-depth follow-ups were limited, as was available physiologic information. Available data concerning the causes for the observed changes indicate significant roles for mechanisms involved with body fluid-volume regulation, altered cardiac function, and the neurohumoral control of the control of the peripheral circulation. Satisfactory measures are not found. Return to preflight state was variable and only slightly dependent on flight duration. Future progress awaits availability of flight durations longer than several weeks.

Sandler, Harold

1988-01-01

273

Isolation, culture, and induced multiple differentiation of Mongolian sheep bone marrow-derived mesenchymal stem cells.  

PubMed

The aim of this paper was to explore the optimal method of isolating, purifying, and proliferating Mongolian sheep bone marrow-derived mesenchymal stem cells (BMSCs) and their multiple differentiation potentialities. Bone marrow (BM) was punctured from ?1-year-old sheep, and BMSCs were harvested through gradient centrifuge and adherent cultures. Analysis of the growth of the passage 1, 5, and 10 cultures revealed an S-shaped growth curve with a population doubling time of 31.2 h. Karyotyping indicated that the chromosome number in the Mongolian sheep was 2n?=?54, comprising 26 pairs of autosomes and one pair of sex chromosomes (XY). RT-PCR demonstrated that OCT4, SOX2, and Nanog genes at passage 3 were positively expressed. The P3 BMSCs were cultured in vitro under inductive environments and induced into adipocytes, osteoblasts, chondrocytes, neural cells, and cardiomyocytes. Their differentiation properties were confirmed by histological staining, such as oil red, Alizarin red, hematoxylin-eosin, toluidine blue, and periodic acid schiff. RT-PCR showed that the specific genes to be induced were all expressed. This proves that the isolated cells are indeed the BMSCs and also provides valuable materials for somatic cell cloning and transgenic research. PMID:24399254

Liu, Zongzheng; Wang, Wei; Gao, Jinfang; Zhou, Huanmin; Zhang, Yanru

2014-05-01

274

Cadmium-induced bone effect is not mediated via low serum 1,25-dihydroxy vitamin D  

SciTech Connect

Cadmium is a widespread environmental pollutant, which is associated with increased risk of osteoporosis. It has been proposed that cadmium's toxic effect on bone is exerted via impaired activation of vitamin D, secondary to the kidney effects. To test this, we assessed the association of cadmium-induced bone and kidney effects with serum 1,25-dihydroxyvitamin D (1,25(OH){sub 2}D); measured by enzyme immunoassay. For the assessment, we selected 85 postmenopausal women, based on low (0.14-0.39 {mu}g/L) or high (0.66-2.1 {mu}g/L) urinary cadmium, within a cross-sectional population-based women's health survey in Southern Sweden. We also measured 25-hydroxy vitamin D, cadmium in blood, bone mineral density and several markers of bone remodeling and kidney effects. Although there were clear differences in both kidney and bone effect markers between women with low and high cadmium exposure, the 1,25(OH){sub 2}D concentrations were not significantly different (median, 111 pmol/L (5-95th percentile, 67-170 pmol/L) in low- and 125 pmol/L (66-200 pmol/L) in high-cadmium groups; p=0.08). Also, there was no association between 1,25(OH){sub 2}D and markers of bone or kidney effects. It is concluded that the low levels of cadmium exposure present in the studied women, although high enough to be associated with lower bone mineral density and increased bone resorption, were not associated with lower serum concentrations of 1,25(OH){sub 2}D. Hence, decreased circulating levels of 1,25(OH){sub 2}D are unlikely to be the proposed link between cadmium-induced effects on kidney and bone.

Engstroem, Annette [Division of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Skerving, Staffan [Department of Occupational and Environmental Medicine, Lund University Hospital, Lund (Sweden); Lidfeldt, Jonas [Department of Community Health, Malmoe University Hospital, Malmoe (Sweden); Burgaz, Ann [Division of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Lundh, Thomas [Department of Occupational and Environmental Medicine, Lund University Hospital, Lund (Sweden); Samsioe, Goeran [Department of Gynecology and Obstetrics, Lund University Hospital, Lund (Sweden); Vahter, Marie [Division of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Akesson, Agneta [Division of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden)], E-mail: Agneta.Akesson@ki.se

2009-02-15

275

Identification of MicroRNAs Inhibiting TGF-?-Induced IL-11 Production in Bone Metastatic Breast Cancer Cells  

PubMed Central

Development of bone metastases is dependent on the cancer cell-bone cell interactions in the bone microenvironment. Transforming growth factor ? (TGF-?) is released from bone during osteoclastic bone resorption and induces production of osteolytic factors, such as interleukin 11 (IL-11), in breast cancer cells. IL-11 in turn increases osteolysis by stimulating osteoclast function, launching a vicious cycle of cancer growth and bone destruction. We aimed to identify and functionally characterize microRNAs (miRNAs) that mediate the bone metastatic process, focusing on miRNAs that regulate the TGF-? induction of IL-11. First, we profiled the expression of 455 miRNAs in a highly bone metastatic MDA-MB-231(SA) variant as compared to the parental MDA-MB-231 breast cancer cell line and found 16 miRNAs (3.5%) having a >3-fold expression difference between the two cell types. We then applied a cell-based overexpression screen with Pre-miRNA constructs to functionally identify miRNAs regulating TGF-?-induced IL-11 production. This analysis pinpointed miR-204, miR-211, and miR-379 as such key regulators. These miRNAs were shown to directly target IL11 by binding to its 3? UTR. MiR-379 also inhibited Smad2/3/4-mediated transcriptional activity. Gene expression analysis of miR-204 and miR-379-transfected cells indicated that these miRNAs downregulated the expression of several genes involved in TGF-? signaling, including prostaglandin-endoperoxide synthase 2 (PTGS2). In addition, there was a significant correlation between the genes downregulated by miR-379 and a set of genes upregulated in basal subtype of breast cancer. Taken together, the functional evidence and clinical correlations imply novel mechanistic links between miRNAs and the key steps in the bone metastatic process in breast cancer, with potential clinical relevance. PMID:22629385

Pollari, Sirkku; Leivonen, Suvi-Katri; Perälä, Merja; Fey, Vidal; Käkönen, Sanna-Maria; Kallioniemi, Olli

2012-01-01

276

Hispidulin attenuates bone resorption and osteoclastogenesis via the RANKL-induced NF-?B and NFATc1 pathways.  

PubMed

Hispidulin, a flavonoid that is known to have anti-inflammatory and anti-oxidant effects, attenuates osteoclastogenesis and bone resorption. To investigate the molecular mechanism of its inhibitory effect on osteoclastogenesis, we employed the receptor activator of the nuclear factor ?B (NF-?B) ligand (RANKL)-induced murine monocyte/macrophage RAW 264.7 cells and bone marrow-derived macrophages (BMMs) for osteoclastic differentiation in vitro. The inhibitory effect on in vitro osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and by measuring the expression levels of osteoclast-specific genes such as matrix metalloproteinase 9 (MMP9), TRAP and cathepsin K. Similarly, hispidulin significantly inhibited osteoclast activity in RAW 264.7 cell as well as stimulated the ALP activity of MC3T3E1 cells. Furthermore, the in vivo suppressive effect on bone loss was assessed quantitatively in a lipopolysaccharide (LPS)-induced mouse model using microcomputational tomography (?CT) and histochemical analyses. Hispidulin was found to inhibit RANKL-induced activation of Jun N-terminal kinase (JNK) and p38, in addition to NF-?B in vitro experiment. Additionally, hispidulin decreased NFATc1 transcriptional activity in RANKL-induced osteoclastogenesis. This study identifies hispidulin as a potent inhibitor of osteoclastogenesis and bone resorption and provides evidence for its therapeutic potential to treat diseases involving abnormal bone lysis. PMID:23791609

Nepal, Manoj; Choi, Hwa Jung; Choi, Bo-Yun; Yang, Moon-Shik; Chae, Jung-Il; Li, Liang; Soh, Yunjo

2013-09-01

277

The effect of deferoxamine on angiogenesis and bone repair in steroid-induced osteonecrosis of rabbit femoral heads.  

PubMed

In this study, we examined whether local deferoxamine (DFO) administration can promote angiogenesis and bone repair in steroid-induced osteonecrosis of the femoral head (ONFH). Steroid-induced ONFH was induced in 65 mature male New Zealand white rabbits by methylprednisolone in combination with lipopolysaccharide. Six weeks later, the rabbits received no treatment (model group, N?=?15), bilateral core decompression (CD group, N?=?20) or CD in combination with local DFO administration (DFO group, N?=?20). Six weeks after the surgery, vascularization in the femoral head was evaluated by ink artery infusion angiography and immunohistochemical staining for von Willebrand Factor (vWF). Bone repair was assessed by histologic analysis and micro-computed tomography (micro-CT). Immunohistochemical staining was performed to analyze the expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1? (HIF-1?), bone morphogenetic protein-2 (BMP-2), and osteocalcin (OCN). Ink artery infusion angiography and microvessel analysis by immuohistochemical staining for vWF showed more blood vessels in the DFO group than other groups. The expression of HIF-1?, VEGF, BMP-2, and OCN, indicated by immunohistochemical staining, was higher in the DFO group compared with other groups. Micro-CT scanning results indicated that the DFO group had larger volume of newly formed bone than the CD group. This work indicated that local DFO administration improved angiogenesis and bone repair of early stage ONFH in rabbit model, and it may offer an efficient, economic, and simple therapy for early stage ONFH. PMID:25294892

Li, Jia; Fan, Lihong; Yu, Zefeng; Dang, Xiaoqian; Wang, Kunzheng

2015-02-01

278

Conjugated linoleic Acid prevents ovariectomy-induced bone loss in mice by modulating both osteoclastogenesis and osteoblastogenesis.  

PubMed

Postmenopausal osteoporosis due to estrogen deficiency is associated with severe morbidity and mortality. Beneficial effects of conjugated linoleic acid (CLA) on bone mineral density (BMD) have been reported in mice, rats and humans, but the effect of long term CLA supplementation against ovariectomy-induced bone loss in mice and the mechanisms underlying this effect have not been studied yet. Eight-week old ovariectomized (Ovx) and sham operated C57BL/6 mice were fed either a diet containing 0.5 % safflower oil (SFO) or 0.5 % CLA for 24 weeks to examine BMD, bone turn over markers and osteotropic factors. Bone marrow (BM) cells were cultured to determine the effect on inflammation, osteoclastogenesis, and osteoblastogenesis. SFO/Ovx mice had significantly lower femoral, tibial and lumbar BMD compared to SFO/Sham mice; whereas, no difference was found between CLA/Ovx and CLA/Sham mice. CLA inhibited bone resorption markers whereas enhanced bone formation markers in Ovx mice as compared to SFO-fed mice. Reverse transcriptase polymerase chain reaction and fluorescence activated cell sorting analyses of splenocytes revealed that CLA inhibited pro-osteoclastogenic receptor activator of NF-?B (RANKL) and stimulated decoy receptor of RANKL, osteoprotegerin expression. CLA also inhibited pro-inflammatory cytokine and enhanced anti-inflammatory cytokine production of lipopolysaccharide-stimulated splenocytes and BM cells. Furthermore, CLA inhibited osteoclast differentiation in BM and stimulated osteoblast differentiation in BM stromal cells as confirmed by tartrate resistant acid phosphatase and Alizarin Red staining, respectively. In conclusion, CLA may prevent postmenopausal bone loss not only by inhibiting excessive bone resorption due to estrogen deficiency but also by stimulating new bone formation. CLA might be a potential alternative therapy against osteoporotic bone loss. PMID:24338525

Rahman, Md Mizanur; Fernandes, Gabriel; Williams, Paul

2014-03-01

279

Granulocyte-macrophage colony-stimulating factor-induced antibody-dependent cellular cytotoxicity in bone marrow macrophages: application in bone marrow transplantation.  

PubMed

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to induce antitumor activity in peripheral blood monocytes. We examined the role of GM-CSF on bone marrow (BM) macrophages in inducing antibody-dependent cellular cytotoxicity (ADCC) against murine and human tumor cells in vitro and in vivo with the aim of applying this approach in an autologous bone marrow transplantation (BMT) setting. GM-CSF induced a potent ADCC in BM macrophages against a murine melanoma in vitro. Treatment with GM-CSF alone or with antibody alone had no effect, whereas therapy with combination of both these agents resulted in a significant reduction in dissemination of melanoma both in a nontransplant as well as in BMT settings, with results being more optimal in the latter setting. Adoptive transfer of BM macrophages harvested from mice undergoing therapy with GM-CSF plus antibody significantly reduced the dissemination of melanoma in secondary recipients but only after irradiation, not in intact mice. GM-CSF also induced significant ADCC in human BM macrophages against a melanoma and a lymphoma in vitro and against a lymphoma implanted in nude mice in vivo. Again, these effects were more optimal after chemotherapy. These data suggest that treatment with GM-CSF plus tumor-specific monoclonal antibodies after BMT may induce an antitumor effect and help eradicate the minimal residual disease. PMID:8507882

Charak, B S; Agah, R; Mazumder, A

1993-06-15

280

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

NASA Technical Reports Server (NTRS)

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

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

1990-01-01

281

Sister chromatid exchanges and chromosome aberrations induced by radiosensitizing agents in bone marrow cells of treated tumor-bearing mice  

SciTech Connect

The frequency of sister chromatid exchanges (SCE) in vivo and chromosome aberrations and/or alterations were analyzed from the bone marrow cells of the treated dbrB tumor-bearing DBA/1J inbred mouse host. The results were compared with analogous data obtained from the bone marrow cells of untreated tumor-bearing mice for evaluation of the ''indirect,'' i.e., somatic stress, effect on the normal host cells following triple-agent therapy intended for a mammary adenocarcinoma. Misonidazole (MIS), which is a known radiosensitizing drug, microwave hyperthermia (delta), and X-radiation (X) were used as therapeutic agents. Significant (P less than 0.05) numbers of SCE were induced in the bone marrow cells of the mice whose tumors received these triple-agent treatments (MIS + delta + X) simultaneously as compared with values of SCE per cell noted in bone marrow cells of untreated tumor-bearing control mice. The highest number of chromosome aberrations and alterations, including an increase in heteroploidy, was also noticed in the bone marrow cells of the mice whose tumors were treated simultaneously with MIS + delta + X. The triple-agent therapy on dbrB tumor also resulted in an unusually high polyploid metaphase plate in the bone marrow cell consisting of 320 chromosomes, indicating that this mode of therapy may act directly on the genetic material of the tumor-bearing host cells, inducing cytogenetic abnormalities as a side effect.

Banerjee, R.; Goldfeder, A.; Mitra, J.

1983-03-01

282

Bone formation in vivo induced by Cbfa1-carrying adenoviral vectors released from a biodegradable porous ?-tricalcium phosphate (?-TCP) material  

NASA Astrophysics Data System (ADS)

Overexpression of Cbfa1 (a transcription factor indispensable for osteoblastic differentiation) is expected to induce the formation of bone directly and indirectly in vivo by accelerating osteoblastic differentiation. Adenoviral vectors carrying the cDNA of Cbfa1/til-1(Adv-Cbf1) were allowed to be adsorbed onto porous blocks of ?-tricalcium phosphate (?-TCP), a biodegradable ceramic, which were then implanted subcutaneously and orthotopically into bone defects. The adenoviral vectors were released sustainingly by biodegradation, providing long-term expression of the genes. Results of the subcutaneous implantation of Adv-Cbfa1-adsorbed ?-TCP/osteoprogenitor cells suggest that a larger amount of bone formed in the pores of the implant than in the control material. Regarding orthotopic implantation into bone defects, the released Adv-Cbfa1 accelerated regeneration in the cortical bone, whereas it induced bone resorption in the marrow cavity. A safer gene transfer using a smaller amount of the vector was achieved using biodegradable porous ?-TCP as a carrier.

Uemura, Toshimasa; Kojima, Hiroko

2011-06-01

283

Immediate periodontal bone plate changes induced by rapid maxillary expansion in the early mixed dentition: CT findings  

PubMed Central

Objective This study aimed at evaluating buccal and lingual bone plate changes caused by rapid maxillary expansion (RME) in the mixed dentition by means of computed tomography (CT). Methods The sample comprised spiral CT exams taken from 22 mixed dentition patients from 6 to 9 years of age (mean age of 8.1 years) presenting constricted maxillary arch treated with Haas-type expanders. Patients were submitted to spiral CT scan before expansion and after the screw activation period with a 30-day interval between T1 and T2. Multiplanar reconstruction was used to measure buccal and lingual bone plate thickness and buccal bone crest level of maxillary posterior deciduous and permanent teeth. Changes induced by expansion were evaluated using paired t test (p < 0.05). Results Thickness of buccal and lingual bone plates of posterior teeth remained unchanged during the expansion period, except for deciduous second molars which showed a slight reduction in bone thickness at the distal region of its buccal aspect. Buccal bone dehiscences were not observed in the supporting teeth after expansion. Conclusion RME performed in mixed dentition did not produce immediate undesirable effects on periodontal bone tissues. PMID:25162564

Garib, Daniela Gamba; Menezes, Maria Helena Ocké; da Silva Filho, Omar Gabriel; dos Santos, Patricia Bittencourt Dutra

2014-01-01

284

Bone marrow mesenchymal stem and progenitor cells induce monocyte emigration in response to circulating Toll-like receptor ligands  

PubMed Central

Inflammatory (Ly6Chi CCR2+) monocytes provide defense against infections but also contribute to autoimmune diseases and atherosclerosis. Monocytes originate from bone marrow and their entry into the bloodstream requires stimulation of CCR2 chemokine receptor by monocyte chemotactic protein-1 (MCP1). How monocyte emigration from bone marrow is triggered by remote infections remains unclear. We demonstrated that low concentrations of Toll-like receptor (TLR) ligands in the bloodstream drive CCR2-dependent emigration of monocytes from bone marrow. Bone marrow mesenchymal stem cells (MSCs) and their progeny, including CXC chemokine ligand (CXCL)12-abundant reticular (CAR) cells, rapidly expressed MCP1 in response to circulating TLR ligands or bacterial infection and induced monocyte trafficking into the bloodstream. Targeted deletion of MCP1 from MSCs impaired monocyte emigration from bone marrow. Our findings suggest that bone marrow MSCs and CAR cells respond to circulating microbial molecules and regulate bloodstream monocyte frequencies by secreting MCP1 in proximity to bone marrow vascular sinuses. PMID:21458307

Shi, Chao; Jia, Ting; Mendez-Ferrer, Simon; Hohl, Tobias M.; Serbina, Natalya V.; Lipuma, Lauren; Leiner, Ingrid; Li, Ming O.; Frenette, Paul S.; Pamer, Eric G.

2011-01-01

285

Bone marrow mesenchymal stem and progenitor cells induce monocyte emigration in response to circulating toll-like receptor ligands.  

PubMed

Inflammatory (Ly6C(hi) CCR2+) monocytes provide defense against infections but also contribute to autoimmune diseases and atherosclerosis. Monocytes originate from bone marrow and their entry into the bloodstream requires stimulation of CCR2 chemokine receptor by monocyte chemotactic protein-1 (MCP1). How monocyte emigration from bone marrow is triggered by remote infections remains unclear. We demonstrated that low concentrations of Toll-like receptor (TLR) ligands in the bloodstream drive CCR2-dependent emigration of monocytes from bone marrow. Bone marrow mesenchymal stem cells (MSCs) and their progeny, including CXC chemokine ligand (CXCL)12-abundant reticular (CAR) cells, rapidly expressed MCP1 in response to circulating TLR ligands or bacterial infection and induced monocyte trafficking into the bloodstream. Targeted deletion of MCP1 from MSCs impaired monocyte emigration from bone marrow. Our findings suggest that bone marrow MSCs and CAR cells respond to circulating microbial molecules and regulate bloodstream monocyte frequencies by secreting MCP1 in proximity to bone marrow vascular sinuses. PMID:21458307

Shi, Chao; Jia, Ting; Mendez-Ferrer, Simon; Hohl, Tobias M; Serbina, Natalya V; Lipuma, Lauren; Leiner, Ingrid; Li, Ming O; Frenette, Paul S; Pamer, Eric G

2011-04-22

286

The Hypoxia-Inducible Factor Pathway, Prolyl Hydroxylase Domain Protein Inhibitors, and Their Roles in Bone Repair and Regeneration  

PubMed Central

Hypoxia-inducible factors (HIFs) are oxygen-dependent transcriptional activators that play crucial roles in angiogenesis, erythropoiesis, energy metabolism, and cell fate decisions. The group of enzymes that can catalyse the hydroxylation reaction of HIF-1 is prolyl hydroxylase domain proteins (PHDs). PHD inhibitors (PHIs) activate the HIF pathway by preventing degradation of HIF-? via inhibiting PHDs. Osteogenesis and angiogenesis are tightly coupled during bone repair and regeneration. Numerous studies suggest that HIFs and their target gene, vascular endothelial growth factor (VEGF), are critical regulators of angiogenic-osteogenic coupling. In this brief perspective, we review current studies about the HIF pathway and its role in bone repair and regeneration, as well as the cellular and molecular mechanisms involved. Additionally, we briefly discuss the therapeutic manipulation of HIFs and VEGF in bone repair and bone tumours. This review will expand our knowledge of biology of HIFs, PHDs, PHD inhibitors, and bone regeneration, and it may also aid the design of novel therapies for accelerating bone repair and regeneration or inhibiting bone tumours. PMID:24895555

Fan, Lihong

2014-01-01

287

TGF-?1 induces senescence of bone marrow mesenchymal stem cells via increase of mitochondrial ROS production  

PubMed Central

Background Bone marrow derived mesenchymal stem cells (bmMSCs) are multipotent cells that can differentiate into diverse cell types, including cardiomyocytes. BmMSC-based transplantation is capable of repairing acute and chronic myocardial infarction. Prior to the transplantation, MSCs are usually induced in vitro by biological reagents and chemicals for directional differentiation. Transforming growth factor beta (TGF-?) is one of the most commonly used biological reagents for induction of cardiomyocyte differentiation of bmMSCs. Previous studies have shown that TGF-? induces senescence in several cell types. However, whether TGF-? affects senescence of bmMSCs has not been elucidated. The goal of this study was to investigate the effect of TGF-?1 on senescence of bmMSCs and the underlying mechanisms. Results We found that TGF-?1 increased activity of senescence-associated-galactosidase (SA-Gal) and production of mitochondrial reactive oxygen species (mtROS) in bmMSCs in a dose-dependent manner. TGF-?1 also significantly decreased expression of superoxide dismutase 2 (SOD2) and Id1, and increased expression of 4-Hydroxynonenal (4-HNE) subunits and p16 in bmMSCs in a dose-dependent manner. Pre-treatment with mtROS inhibitor acetyl-L-carnitine (ALCAR, 0.1 mM) significantly inhibited TGF-?1-induced mtROS production and SA-Gal activity. Conclusion TGF-?1 can induce senescence of bmMSCs, which at least partially depends on mtROS production. PMID:24886313

2014-01-01

288

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

NASA Technical Reports Server (NTRS)

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

Harrison, D. C.

1986-01-01

289

Macrophage-specific TLR2 signaling mediates pathogen-induced TNF-dependent inflammatory oral bone loss.  

PubMed

Porphyromonas gingivalis is a primary etiological agent of chronic periodontal disease, an infection-driven chronic inflammatory disease that leads to the resorption of tooth-supporting alveolar bone. We previously reported that TLR2 is required for P. gingivalis-induced alveolar bone loss in vivo, and our in vitro work implicated TNF as a key downstream mediator. In this study, we show that TNF-deficient (Tnf(-/-)) mice are resistant to alveolar bone loss following oral infection with P. gingivalis, and thus establish a central role for TNF in experimental periodontal disease. Using bone marrow-derived macrophages (BMDM) from wild-type and gene-specific knockout mice, we demonstrate that the initial inflammatory response to P. gingivalis in naive macrophages is MyD88 dependent and requires cooperative signaling of TLR2 and TLR4. The ability of P. gingivalis to activate cells via TLR2 or TLR4 was confirmed in TLR2- or TLR4-transformed human embryonic kidney cells. Additional studies using bacterial mutants demonstrated a role for fimbriae in the modulation of TLR-mediated activation of NF-?B. Whereas both TLR2 and TLR4 contributed to TNF production in naive macrophages, P. gingivalis preferentially exploited TLR2 in endotoxin-tolerant BMDM to trigger excessive TNF production. We found that TNF induced surface TLR2 expression and augmented TLR-induced cytokine production in P. gingivalis-stimulated BMDM, establishing a previously unidentified TNF-dependent feedback loop. Adoptive transfer of TLR2-expressing macrophages to TLR2-deficient mice restored the ability of P. gingivalis to induce alveolar bone loss in vivo. Collectively, our results identify a TLR2- and TNF-dependent macrophage-specific mechanism underlying pathogen-induced inflammatory bone loss in vivo. PMID:23264656

Papadopoulos, George; Weinberg, Ellen O; Massari, Paola; Gibson, Frank C; Wetzler, Lee M; Morgan, Elise F; Genco, Caroline A

2013-02-01

290

Is Gastrectomy-Induced High Turnover of Bone with Hyperosteoidosis and Increase of Mineralization a Typical Osteomalacia?  

PubMed Central

Gastrectomy (GX) is thought to result in osteomalacia due to deficiencies in Vitamin D and Ca. Using a GX rat model, we showed that GX induced high turnover of bone with hyperosteoidosis, prominent increase of mineralization and increased mRNA expression of both osteoclast-derived tartrate-resistant acid phosphatase 5b and osteocalcin. The increased 1, 25(OH)2D3 level and unchanged PTH and calcitonin levels suggested that conventional bone and Ca metabolic pathways were not involved or changed in compensation. Thus, GX-induced bone pathology was different from a typical osteomalacia. Gene expression profiles through microarray analysis and data mining using Ingenuity Pathway Analysis indicated that 612 genes were up-regulated and 1,097 genes were down-regulated in the GX bone. These genes were related functionally to connective tissue development, skeletal and muscular system development and function, Ca signaling and the role of osteoblasts, osteoclasts and chondrocytes. Network analysis indicated 9 genes (Aldehyde dehydrogenase 1 family, member A1; Aquaporin 9; Interleukin 1 receptor accessory protein; Very low density lipoprotein receptor; Periostin, osteoblast specific factor; Aggrecan; Gremlin 1; Angiopoietin-like 4; Wingless-type MMTV integration site family, member 10B) were hubs connected with tissue development and immunological diseases. These results suggest that chronic systemic inflammation might underlie the GX-induced pathological changes in bone. PMID:23776526

Ueyama, Takashi; Yamamoto, Yuta; Ueda, Kazuki; Yajima, Aiji; Maeda, Yoshimasa; Yamashita, Yasunobu; Ito, Takao; Tsuruo, Yoshihiro; Ichinose, Masao

2013-01-01

291

Glucocorticoids activate the local renin-angiotensin system in bone: possible mechanism for glucocorticoid-induced osteoporosis.  

PubMed

Bone metabolism disorder has been identified to play a vital role in the pathogenesis of glucocorticoid-induced osteoporosis (GIOP). The local renin-angiotensin system (RAS) in bone is newly defined to be closely related to the bone metabolism. However, it is unknown whether the local RAS is involved in GIOP. Adult male New Zealand white rabbits were treated with saline, dexamethasone (DXM) alone, or DXM combined with perindopril. The expression of main RAS components in trabecular bone was examined at mRNA and/or protein levels. Bone metabolism was analyzed using dual-energy X-ray absorptiometry, histomorphometry, biomechanics, biochemical techniques, and quantitative RT-PCR. The expressions of local bone angiotensin II, angiotensin types 1 and 2 receptors, and angiotensin-converting enzyme at mRNA and/or protein levels increased when DXM-induced osteoporosis was present. Whereas, perindopril significantly blocked the activation of the local RAS and partially reversed GIOP. Mineralizing surface, mineral apposition rate, and bone formation rate were decreased by DXM, along with serum osteocalcin being downregulated. These changes were then reversed by the use of perindopril. Osteoclast number, osteoclast surface, and eroded surface increased after the administration of DXM, and urinary deoxypyridinoline was upregulated. These were also inhibited when perindopril was given. Quantitative RT-PCR using RNA isolated from the lumbar vertebrae revealed an increase in the SOST expression and a decrease in the Runx2 expression, whereas the receptor activator of nuclear factor-?B ligand/osteoprotegerin ratio and the expression of tartrate resistant acid phosphatase were increased, which were all inhibited by perindopril. The results of this study provide evidence for the role of local RAS is involved in GIOP, and GIOP may be ameliorated by blocking the activation of local RAS in the bone. PMID:24519760

Yongtao, Zhang; Kunzheng, Wang; Jingjing, Zheng; Hu, Shan; Jianqiang, Kou; Ruiyu, Liu; Chunsheng, Wang

2014-11-01

292

Protein Malnutrition Induces Bone Marrow Mesenchymal Stem Cells Commitment to Adipogenic Differentiation Leading to Hematopoietic Failure  

PubMed Central

Protein malnutrition (PM) results in pathological changes that are associated with peripheral leukopenia, bone marrow (BM) hypoplasia and alterations in the BM microenvironment leading to hematopoietic failure; however, the mechanisms involved are poorly understood. In this context, the BM mesenchymal stem cells (MSCs) are cells intimately related to the formation of the BM microenvironment, and their differentiation into adipocytes is important because adipocytes are cells that have the capability to negatively modulate hematopoiesis. Two-month-old male Balb/c mice were subjected to protein-energy malnutrition with a low-protein diet containing 2% protein, whereas control animals were fed a diet containing 12% protein. The hematopoietic parameters and the expression of CD45 and CD117 positive cells in the BM were evaluated. MSCs were isolated from BM, and their capability to produce SCF, IL-3, G-CSF and GM-CSF were analyzed. The expression of PPAR-? and C/EBP-? as well as the expression of PPAR-? and SREBP mRNAs were evaluated in MSCs together with their capability to differentiate into adipocytes in vitro. The malnourished animals had anemia and leukopenia as well as spleen and bone marrow hypoplasia and a reduction in the expression of CD45 and CD117 positive cells from BM. The MSCs of the malnourished mice presented an increased capability to produce SCF and reduced production of G-CSF and GM-CSF. The MSCs from the malnourished animals showed increased expression of PPAR-? protein and PPAR-? mRNA associated with an increased capability to differentiate into adipocytes. The alterations found in the malnourished animals allowed us to conclude that malnutrition committed MSC differentiation leading to adipocyte decision and compromised their capacity for cytokine production, contributing to an impaired hematopoietic microenvironment and inducing the bone marrow failure commonly observed in protein malnutrition states. PMID:23516566

Cunha, Mayara Caldas Ramos; Lima, Fabiana da Silva; Vinolo, Marco Aurélio Ramirez; Hastreiter, Araceli; Curi, Rui; Borelli, Primavera; Fock, Ricardo Ambrósio

2013-01-01

293

CALCOSPHERULITES* ISOLATED FROM THE MINERALIZATION FRONT OF BONE INDUCE THE MINERALIZATION OF TYPE I COLLAGEN  

PubMed Central

Previous work has suggested that “calcospherulites” actively participate in the mineralization of developing and healing bone. This study sought to directly test this hypothesis by developing a method to isolate calcospherulites and analyzing their capacity to seed mineralization of fibrillar collagen. The periosteal surface of juvenile rat tibial diaphysis was enriched in spherulites of ~0.5-micron diameter exhibiting a Ca/P ratio of 1.3. Their identity as calcospherulites was confirmed by their uptake of calcein at the tibial mineralization front 24 h following in vivo injection. Periosteum was dissected and unmineralized osteoid removed by collagenase in order to expose calcospherulites. Calcein-labeled calcospherulites were then released from the mineralization front by dispase digestion and isolated via fluorescence flow sorting. X-ray diffraction analysis revealed they contained apatite crystals (c-axis length of 17.5 ± 0.2 nm), though their Ca/P ratio of 1.3 is lower than that of hydroxyapatite. Much of their non-mineral phosphorous content was removed by ice-cold ethanol, elevating their Ca/P ratio to 1.6, suggesting the presence of phospholipids. Western blot analyses showed the presence of bone matrix proteins and type I collagen in these preparations. Incubating isolated calcospherulites in collagen hydrogels demonstrated that they could seed a mineralization reaction on type I collagen fibers in vitro. Ultrastructural analyses revealed crystals on the collagen fibers that were distributed rather uniformly along the fiber lengths. Furthermore, crystals were observed at distances well away from the observed calcospherulites. Our results directly support an active role for calcospherulites in inducing the mineralization of type I collagen fibers at the mineralization front of bone. PMID:17936099

Midura, Ronald J.; Vasanji, Amit; Su, Xiaowei; Wang, Aimin; Midura, Sharon B.; Gorski, Jeff P.

2007-01-01

294

Calcospherulites isolated from the mineralization front of bone induce the mineralization of type I collagen.  

PubMed

Previous work has suggested that "calcospherulites" actively participate in the mineralization of developing and healing bone. This study sought to directly test this hypothesis by developing a method to isolate calcospherulites and analyzing their capacity to seed mineralization of fibrillar collagen. The periosteal surface of juvenile rat tibial diaphysis was enriched in spherulites of approximately 0.5-mum diameter exhibiting a Ca/P ratio of 1.3. Their identity as calcospherulites was confirmed by their uptake of calcein at the tibial mineralization front 24 h following in vivo injection. Periosteum was dissected and unmineralized osteoid removed by collagenase in order to expose calcospherulites. Calcein-labeled calcospherulites were then released from the mineralization front by dispase digestion and isolated via fluorescence flow sorting. X-ray diffraction analysis revealed they contained apatite crystals (c-axis length of 17.5+/-0.2 nm), though their Ca/P ratio of 1.3 is lower than that of hydroxyapatite. Much of their non-mineral phosphorous content was removed by ice-cold ethanol, elevating their Ca/P ratio to 1.6, suggesting the presence of phospholipids. Western blot analyses showed the presence of bone matrix proteins and type I collagen in these preparations. Incubating isolated calcospherulites in collagen hydrogels demonstrated that they could seed a mineralization reaction on type I collagen fibers in vitro. Ultrastructural analyses revealed crystals on the collagen fibers that were distributed rather uniformly along the fiber lengths. Furthermore, crystals were observed at distances well away from the observed calcospherulites. Our results directly support an active role for calcospherulites in inducing the mineralization of type I collagen fibers at the mineralization front of bone. PMID:17936099

Midura, Ronald J; Vasanji, Amit; Su, Xiaowei; Wang, Aimin; Midura, Sharon B; Gorski, Jeff P

2007-12-01

295

Effect of Endogenous Bone Marrow Derived Stem Cells Induced by AMD-3100 on Expanded Ischemic Flap.  

PubMed

The purpose of this study was to devise an expanded ischemic flap model and to investigate the role of AMD-3100 (Plerixafor, chemokine receptor 4 inhibitor) in this model by confirming its effect on mobilization of stem cells from the bone marrow. Male Sprague-Dawley rats were used as an animal research model. The mobilization of stem cells from the bone marrow was confirmed in the AMD-3100-treated group. The fractions of endothelial progenitor cells (EPC) and the vascular endothelial growth factor receptor (VEGFR) 2+ cells in the peripheral blood were increased in groups treated with AMD-3100. The expression of vascular endothelial growth factor (VEGF) was increased in response to expansion or AMD injection. The expression of stromal cell derived factor (SDF)-1 and VEGFR2 were increased only in unexpanded flap treated with AMD-3100. Treatment with AMD-3100 increased both the number and area of blood vessels. However, there were no statistically significant differences in the survival area or physiologic microcirculation in rats from the other groups. This endogenous neovascularization induced by AMD-3100 may be a result of the increase in both the area and number of vessels, as well as paracrine augmentation of the expression of VEGF and EPCs. However, the presence of a tissue expander under the flap could block the neovascularization between the flap and the recipient regardless of AMD-3100 treatment and expansion. PMID:25473215

Jeong, Hii-Sun; Lee, Hye-Kyung; Tark, Kwan-Chul; Lew, Dae-Hyun; Koh, Yoon-Woo; Kim, Chul-Hoon; Seo, In-Suck

2014-11-01

296

Antimutagenic effects of piperine on cyclophosphamide-induced chromosome aberrations in rat bone marrow cells.  

PubMed

Piperine is a major pungent substance and active component of black pepper (Piper nigrum Linn.) and long pepper (Piper longum Linn.). Both plants are used worldwide as household spices and condiments. They are also used as important ingredients in folklore medicine in many Asian countries. Therefore, it is of interest to study antimutagenic effects of piperine. In this study, its influence on chromosomes was investigated in rat bone marrow cells. Male Wistar rats were orally administered piperine at the doses of 100, 400 and 800 mg/kg body weight for 24 hours then challenged with cyclophosphamide at a dose of 50 mg/kg body weight by intraperitoneal injection. Twenty-four hours thereafter, all animals were sacrificed and bone marrow samples were collected for chromosomal analysis. The results demonstrated that piperine at a dose of 100 mg/kg body weight gave a statistically significant reduction in cyclophosphamide-induced chromosomal aberrations. In conclusion, piperine may have antimutagenic potential. The underlying molecular mechanisms now require attention. PMID:18260741

Wongpa, Sareeya; Himakoun, Lakana; Soontornchai, Sarisak; Temcharoen, Punya

2007-01-01

297

What Happens to bone health during and after spaceflight?  

NASA Technical Reports Server (NTRS)

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

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

2006-01-01

298

Variation of flow-induced stresses within scaffolds used in bone tissue engineering  

NASA Astrophysics Data System (ADS)

Bone tissue engineering is often based on seeding adult stem cells on porous scaffolds and subsequently placing these scaffolds in flow perfusion bioreactors to stimulate cell differentiation and cell growth. In the present study, the distribution of stresses in structured porous scaffolds under flow is investigated by calculating the probability density function of flow-induced stresses in different scaffold geometries with simulations. The physical reason for the development of particular stress distributions is further explored, and it is found that the direction of flow relative to the internal architecture of the porous scaffold is important for stress distributions. When the flow direction is random relative to the configuration of the geometric elements making up the scaffold, it is found that a common distribution, such as the one suggested by Voronov et al. (Appl. Phys. Let., 2010, 97:024101), can be used to describe the stress distribution.

Papavassiliou, Dimitrios; Pham, Ngoc; Voronov, Roman; Sikavitsas, Vassilios

2011-11-01

299

Bone morphogenetic protein-4 strongly potentiates growth factor-induced proliferation of mammary epithelial cells  

SciTech Connect

Bone morphogenetic proteins (BMPs) are multifunctional cytokines that elicit pleiotropic effects on biological processes such as cell proliferation, cell differentiation and tissue morphogenesis. With respect to cell proliferation, BMPs can exert either mitogenic or anti-mitogenic activities, depending on the target cells and their context. Here, we report that in low-density cultures of immortalized mammary epithelial cells, BMP-4 did not stimulate cell proliferation by itself. However, when added in combination with suboptimal concentrations of fibroblast growth factor (FGF)-2, FGF-7, FGF-10, epidermal growth factor (EGF) or hepatocyte growth factor (HGF), BMP-4 potently enhanced growth factor-induced cell proliferation. These results reveal a hitherto unsuspected interplay between BMP-4 and growth factors in the regulation of mammary epithelial cell proliferation. We suggest that the ability of BMP-4 to potentiate the mitogenic activity of multiple growth factors may contribute to mammary gland ductal morphogenesis as well as to breast cancer progression.

Montesano, Roberto [Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Rue-Michel-Servet, 1, CH-1211 Geneva 4 (Switzerland)], E-mail: Roberto.Montesano@unige.ch; Sarkoezi, Rita; Schramek, Herbert [Department of Internal Medicine IV, Nephrology and Hypertensiology, Innsbruck Medical University, Innsbruck (Austria)

2008-09-12

300

Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases  

PubMed Central

Adipocytes are important but underappreciated components of bone marrow microenvironment, and their numbers greatly increase with age, obesity, and associated metabolic pathologies. Age and obesity are also significant risk factors for development of metastatic prostate cancer. Adipocytes are metabolically active cells that secrete adipokines, growth factors, and inflammatory mediators; influence behavior and function of neighboring cells; and have a potential to disturb local milleu and dysregulate normal bone homeostasis. Increased marrow adiposity has been linked to bone marrow inflammation and osteoporosis of the bone, but its effects on growth and progression of prostate tumors that have metastasized to the skeleton are currently not known. This review focuses on fat-bone relationship in a context of normal bone homeostasis and metastatic tumor growth in bone. We discuss effects of marrow fat cells on bone metabolism, hematopoiesis, and inflammation. Special attention is given to CCL2- and COX-2-driven pathways and their potential as therapeutic targets for bone metastatic disease. PMID:24398857

Hardaway, Aimalie L.; Herroon, Mackenzie K.; Rajagurubandara, Erandi

2014-01-01

301

Mouse Bone Marrow-Derived Endothelial Progenitor Cells Do Not Restore Radiation-Induced Microvascular Damage  

PubMed Central

Background. Radiotherapy is commonly used to treat breast and thoracic cancers but it also causes delayed microvascular damage and increases the risk of cardiac mortality. Endothelial cell proliferation and revascularization are crucial to restore microvasculature damage and maintain function of the irradiated heart. We have therefore examined the potential of bone marrow-derived endothelial progenitor cells (BM-derived EPCs) for restoration of radiation-induced microvascular damage. Material & Methods. 16?Gy was delivered to the heart of adult C57BL/6 mice. Mice were injected with BM-derived EPCs, obtained from Eng+/+ or Eng+/? mice, 16 weeks and 28 weeks after irradiation. Morphological damage was evaluated at 40 weeks in transplanted mice, relative to radiation only and age-matched controls. Results. Cardiac irradiation decreased microvascular density and increased endothelial damage in surviving capillaries (decrease alkaline phosphatase expression and increased von Willebrand factor). Microvascular damage was not diminished by treatment with BM-derived EPCs. However, BM-derived EPCs from both Eng+/+ and Eng+/? mice diminished radiation-induced collagen deposition. Conclusion. Treatment with BM-derived EPCs did not restore radiation-induced microvascular damage but it did inhibit fibrosis. Endoglin deficiency did not impair this process. PMID:25101181

Seemann, Ingar; te Poele, Johannes A. M.; Hoving, Saske; Stewart, Fiona A.

2014-01-01

302

Bone morphogenetic protein-6 induces castration resistance in prostate cancer cells through tumor infiltrating macrophages.  

PubMed

Bone morphogenetic protein (BMP) is a pleiotropic growth factor that has been implicated in inflammation and prostate cancer (CaP) progression. We investigated the potential role of BMP-6 in the context of macrophages and castration-resistant prostate cancer. When the androgen-responsive murine (Tramp-C1 and PTENCaP8) and human (LNCaP) CaP cell lines were cocultured with macrophages in the presence of dihydrotestosterone, BMP-6 increased androgen-responsive promoter activity and cell count significantly. Subsequent studies revealed that BMP-6 increased the expression level of androgen receptor (AR) mRNA and protein in CaP cell lines only in the presence of macrophages. Simultaneously, the AR antagonists bicalutamide and MDV3100 partially or completely blocked BMP-6-induced macrophage-mediated androgen hypersensitivity in CaP cells. Abolishing interleukin-6 signaling with neutralizing antibody in CaP/macrophage cocultures inhibited the BMP-6-mediated AR upregulation in CaP cells. Using Tramp-C1 and PTENCaP8 cells with a tetracycline-inducible expression of BMP-6, the induction of BMP-6 in vivo resulted in a significant resistance to castration. However, this resistance was blocked after the removal of macrophages with clodronate liposomes. Taken together, these results show that BMP-6 induces castration resistance by increasing the expression of AR through macrophage-derived interleukin-6. PMID:23710822

Lee, Geun Taek; Jung, Yeon Suk; Ha, Yun-Sok; Kim, Jeong Hyun; Kim, Wun-Jae; Kim, Isaac Y

2013-08-01

303

Bone morphogenetic protein 4 inhibits liposaccharide-induced inflammation in the airway.  

PubMed

Bone morphogenetic protein 4 (BMP4) is a multifunctional growth factor that belongs to the TGF-? superfamily. The role of BMP4 in lung diseases is not fully understood. Here, we demonstrate that BMP4 was upregulated in lungs undergoing lipopolysaccharide (LPS)-induced inflammation, and in airway epithelial cells treated with LPS or TNF-?. BMP4 mutant (BMP4(+/-) ) mice presented with more severe lung inflammation in response to LPS or Pseudomonas aeruginosa, and lower bacterial load compared with that in BMP4(+/+) mice. Knockdown of BMP4 by siRNA increased LPS and TNF-?-induced IL-8 expression in 16HBE human airway epithelial cells and in primary human bronchial epithelial cells. Similarly, peritoneal macrophages from BMP4(+/-) mice produced greater levels of TNF-? and keratinocyte chemoattractant (KC) upon LPS treatment compared with cells from BMP4(+/+) mice. Administration of exogenous BMP4 attenuated the upregulation of TNF-?, IL-8, or KC induced by LPS and/or TNF-? in airway epithelial cells, and peritoneal macrophages. Finally, partial deficiency of BMP4 in BMP4(+/-) mice protected the animals from restrictive lung function reduction upon chronic LPS exposure. These results indicate that BMP4 plays an important anti-inflammatory role, controlling the strength and facilitating the resolution of acute lung inflammation; yet, BMP4 also contributes to lung function impairment during chronic lung inflammation. PMID:25142202

Li, Zhengtu; Wang, Jian; Wang, Yan; Jiang, Hua; Xu, Xiaoming; Zhang, Chenting; Li, Defu; Xu, Chuyi; Zhang, Kedong; Qi, Yafei; Gong, Xuefang; Tang, Chun; Zhong, Nanshan; Lu, Wenju

2014-11-01

304

The mitigating effect of Citrullus colocynthis (L.) fruit extract against genotoxicity induced by cyclophosphamide in mice bone marrow cells.  

PubMed

Possible genoprotective effect of Citrullus colocynthis (L.) (CCT) fruits extract against cyclophosphamide- (CP-)induced DNA damage in mice bone marrow cells was evaluated using micronucleus assay, as an index of induced chromosomal damage. Mice were preadministered with different doses of CCT via intraperitoneal injection for 7 consecutive days followed by injection with CP (70?mg/kg b.w.) 1?hr after the last injection of CCT. After 24?hr, mice were scarified to evaluate the frequency of micronucleated polychromatic erythrocytes (MnPCEs). In addition, the number of polychromatic erythrocytes (PCEs) among 1000 normochromatic erythrocytes (NCEs) per animal was recorded to evaluate bone marrow. Pretreatment with CCT significantly reduced the number of MnPCEs induced by CP in bone marrow cells (P < 0.0001). At 200 mg/kg, CCT had a maximum chemoprotective effect and reduced the number of MnPCEs by 6.37-fold and completely normalized the mitotic activity. CCT also led to marked proliferation and hypercellularity of immature myeloid elements after mice were treated with CP and mitigated the bone marrow suppression. Our study revealed that CCT has an antigenotoxic effect against CP-induced oxidative DNA damage in mice. Therefore, it could be used concomitantly as a supplement to protect people undergoing chemotherapy. PMID:24324391

Shokrzadeh, Mohammad; Chabra, Aroona; Naghshvar, Farshad; Ahmadi, Amirhossein

2013-01-01

305

The Mitigating Effect of Citrullus colocynthis (L.) Fruit Extract against Genotoxicity Induced by Cyclophosphamide in Mice Bone Marrow Cells  

PubMed Central

Possible genoprotective effect of Citrullus colocynthis (L.) (CCT) fruits extract against cyclophosphamide- (CP-)induced DNA damage in mice bone marrow cells was evaluated using micronucleus assay, as an index of induced chromosomal damage. Mice were preadministered with different doses of CCT via intraperitoneal injection for 7 consecutive days followed by injection with CP (70?mg/kg b.w.) 1?hr after the last injection of CCT. After 24?hr, mice were scarified to evaluate the frequency of micronucleated polychromatic erythrocytes (MnPCEs). In addition, the number of polychromatic erythrocytes (PCEs) among 1000 normochromatic erythrocytes (NCEs) per animal was recorded to evaluate bone marrow. Pretreatment with CCT significantly reduced the number of MnPCEs induced by CP in bone marrow cells (P < 0.0001). At 200?mg/kg, CCT had a maximum chemoprotective effect and reduced the number of MnPCEs by 6.37-fold and completely normalized the mitotic activity. CCT also led to marked proliferation and hypercellularity of immature myeloid elements after mice were treated with CP and mitigated the bone marrow suppression. Our study revealed that CCT has an antigenotoxic effect against CP-induced oxidative DNA damage in mice. Therefore, it could be used concomitantly as a supplement to protect people undergoing chemotherapy. PMID:24324391

Chabra, Aroona; Naghshvar, Farshad; Ahmadi, Amirhossein

2013-01-01

306

G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4  

Microsoft Academic Search

Granulocyte colony-stimulating factor (G-CSF)–induced hematopoietic stem cell mobilization is widely used for clinical transplantation; however, the mechanism is poorly understood. We report here that G-CSF induced a reduction of the chemokine stromal cell–derived factor 1 (SDF-1) and an increase in its receptor CXCR4 in the bone marrow (BM), whereas their protein expression in the blood was less affected. The gradual

Isabelle Petit; Martine Szyper-Kravitz; Arnon Nagler; Meir Lahav; Amnon Peled; Liliana Habler; Tanya Ponomaryov; Russell S. Taichman; Fernando Arenzana-Seisdedos; Nobutaka Fujii; Judith Sandbank; Dov Zipori; Tsvee Lapidot

2002-01-01

307

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

NASA Technical Reports Server (NTRS)

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

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

1976-01-01

308

Influence of proprioceptive information on space orientation on the ground and in orbital weightlessness  

NASA Astrophysics Data System (ADS)

Conscious space orientation depends on afferent information from different sense organs including the labyrinth, the eyes, tactile cues from the skin, joint receptors, muscle spindles, tendon organs and possibly viscera. An important role is played by impulses from the cervical position receptors in interaction with concomitant information from the otolith system. In order to isolate the effect of cervical position receptors from that of the otolith system, space experiments in orbital weightlessness and in parabolic aircraft flight were performed. It was found that stimulation of the neck receptors in weightlessness markedly influences the perception of the subjective vertical and horizontal and in addition has a weak effect on ocular torsion.

von Baumgarten, R.; Kass, J.; Vogel, H.; Wetzig, J.

309

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

NASA Technical Reports Server (NTRS)

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

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

2009-01-01

310

Effect of Formononetin on Mechanical Properties and Chemical Composition of Bones in Rats with Ovariectomy-Induced Osteoporosis  

PubMed Central

Formononetin is a naturally occurring isoflavone, which can be found in low concentrations in many dietary products, but the greatest sources of this substance are Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata, which all belong to Fabaceae family. Due to its structural similarity to 17?-estradiol, it can mimic estradiol's effect and therefore is considered as a “phytoestrogen.” The aim of this study was to examine the effect of formononetin on mechanical properties and chemical composition of bones in rats with ovariectomy-induced osteoporosis. 12-week-old female rats were divided into 4 groups: sham-operated, ovariectomized, ovariectomized treated with estradiol (0.2?mg/kg) and ovariectomized treated with formononetin (10?mg/kg). Analyzed substances were administered orally for 4 weeks. Ovariectomy caused osteoporotic changes, which can be observed in bone biomechanical features (decrease of maximum load and fracture load and increase of displacements for maximum and fracture loads) and bone chemical composition (increase of water and organic fraction content, while a decrease of minerals takes place). Supplementation with formononetin resulted in slightly enhanced bone mechanical properties and bone chemistry improvement (significantly lower water content and insignificantly higher mineral fraction content). To summarize, administration of formononetin to ovariectomized rats shows beneficial effect on bone biomechanical features and chemistry; thus, it can prevent osteoporosis development. PMID:23762138

Kaczmarczyk-Sedlak, Ilona; Wojnar, Weronika; Zych, Maria; Ozimina-Kami?ska, Ewa; Taranowicz, Joanna; Siwek, Agata

2013-01-01

311

Effect of formononetin on mechanical properties and chemical composition of bones in rats with ovariectomy-induced osteoporosis.  

PubMed

Formononetin is a naturally occurring isoflavone, which can be found in low concentrations in many dietary products, but the greatest sources of this substance are Astragalus membranaceus, Trifolium pratense, Glycyrrhiza glabra, and Pueraria lobata, which all belong to Fabaceae family. Due to its structural similarity to 17 ? -estradiol, it can mimic estradiol's effect and therefore is considered as a "phytoestrogen." The aim of this study was to examine the effect of formononetin on mechanical properties and chemical composition of bones in rats with ovariectomy-induced osteoporosis. 12-week-old female rats were divided into 4 groups: sham-operated, ovariectomized, ovariectomized treated with estradiol (0.2?mg/kg) and ovariectomized treated with formononetin (10?mg/kg). Analyzed substances were administered orally for 4 weeks. Ovariectomy caused osteoporotic changes, which can be observed in bone biomechanical features (decrease of maximum load and fracture load and increase of displacements for maximum and fracture loads) and bone chemical composition (increase of water and organic fraction content, while a decrease of minerals takes place). Supplementation with formononetin resulted in slightly enhanced bone mechanical properties and bone chemistry improvement (significantly lower water content and insignificantly higher mineral fraction content). To summarize, administration of formononetin to ovariectomized rats shows beneficial effect on bone biomechanical features and chemistry; thus, it can prevent osteoporosis development. PMID:23762138

Kaczmarczyk-Sedlak, Ilona; Wojnar, Weronika; Zych, Maria; Ozimina-Kami?ska, Ewa; Taranowicz, Joanna; Siwek, Agata

2013-01-01

312

Bone morphogenetic protein 4: Potential regulator of shear stress-induced graft neointimal atrophy  

PubMed Central

Objective Placement in baboons of a distal femoral arteriovenous fistula increases shear stress through aortoiliac polytetrafluoroethylene (PTFE) grafts and induces regression of a preformed neointima. Atrophy of the neointima might be controlled by shear stress-induced genes, including the bone morphogenetic proteins (BMPs). We have investigated the expression and function of BMPs 2, 4, and 5 in the graft neointima and in cultured baboon smooth muscle cells (SMCs). Methods Baboons received bilateral aortoiliac PTFE grafts and 8 weeks later, a unilateral femoral arteriovenous fistula. Results Quantitative polymerase chain reaction showed that high shear stress increased BMP2, 4, and 5 messenger RNA (mRNA) in graft intima between 1 and 7 days, while noggin (a BMP inhibitor) mRNA was decreased. BMP4 most potently (60% inhibition) inhibited platelet-derived growth factor-stimulated SMC proliferation compared with BMP2 and BMP5 (31% and 26%, respectively). BMP4 also increased SMC death by 190% ±10%. Noggin reversed the antiproliferative and proapoptotic effects of BMP4. Finally, Western blotting confirmed BMP4 protein upregulation by high shear stress at 4 days. BMP4 expression demonstrated by in situ hybridization was confined to endothelial cells. Conclusions Increased BMPs (particularly BMP4) coupled with decreased noggin may promote high shear stress-mediated graft neointimal atrophy by inhibiting SMC proliferation and increasing SMC death. Clinical Relevance Pharmacologic therapy to prevent luminal stenosis or restenosis after vascular reconstruction is directed at inhibiting intimal hyperplasia and smooth muscle cell growth. An alternative approach might be to induce intimal atrophy after luminal narrowing has developed. This approach would be particularly useful for treating stenosis in stented vessels or synthetic bypass grafts because intimal hyperplasia is the only mechanism for luminal narrowing. Furthermore, it would permit the physician to treat the population of patients (about 30%) who actually develop a problem with stenosis or restenosis. We have previously provided proof of principle that an established neointima can be induced to atrophy in baboon polytetrafluoroethylene grafts, but not in normal artery, by simply switching from normal to high blood flow and shear stress. In this study, we provide evidence that members of the bone morphogenetic protein family may play a role in this neointimal atrophy. PMID:16414402

Hsieh, Patrick C. H.; Kenagy, Richard D.; Mulvihill, Eileen R.; Jeanette, Joseph P.; Wang, Xi; Chang, Cindy M. C.; Yao, Zizhen; Ruzzo, Walter L.; Justice, Suzanne; Hudkins, Kelly L.; Alpers, Charles E.; Berceli, Scott; Clowes, Alexander W.

2006-01-01

313

Comparison of bone scan and radiograph sensitivity in the detection of steroid-induced ischemic necrosis of bone  

SciTech Connect

A prospective study of bone scanning for detection of ischemic necrosis of bone (INB) was performed in 36 patients (97% female, age range 16-36 yrs.) with systemic lupus erythematosis (SLE). Since the hips, knees, and shoulders are usually affected by INB in patients with SLE, 300 K converging collimator images of these joints were obtained on film and in digital format 2 to 3 hours after the injection of 20 mCi (740 MBq) of Tc-99m methylene diphosphonate. All patients underwent radiography of the joints, and 10 had intraosseous pressure determinations in the marrow space of affected joints (n . 31) for independent assessment of INB. Scans showed abnormally increased joint activity in 28 of the 36 patients. A total of 97 joints showed abnormalities, 19% in the hips, 34% in the knees, and 47% in the shoulders. Twenty-four of 27 joints with elevated bone marrow pressure (BMP) had abnormal scans (sensitivity . 89%), and scans were abnormal in 2 of 4 joints with normal pressures (specificity . 50%). The positive predictive value of the scans compared with BMP measurements was 92% (24/26). Eleven of 27 joints with abnormal BMP had abnormal radiographs, a sensitivity of 41%.

Conklin, J.J.; Alderson, P.O.; Zizic, T.M.; Hungerford, D.S.; Densereaux, J.Y.; Gober, A.; Wagner, H.N.

1983-04-01

314

Comparison of bone scan and radiograph sensitivity in the detection of steroid-induced ischemic necrosis of bone  

SciTech Connect

A prospective study of bone scanning for detection of ischemic necrosis of bone (INB) was performed in 36 patients (97% female, age range 16-36 yrs.) with systemic lupus erythematosis (SLE). Since the hips, knees, and shoulders are usually affected by INB in patients with SLE, 300 K converging collimator images of these joints were obtained on film and in digital format 2 to 3 hours after the injection of 20 mCi (740 MBq) of Tc-99m methylene diphosphonate. All patients underwent radiography of the joints, and 10 had intraosseous pressure determinations in the marrow space of affected joints (n=31) for independent assessment of INB. Scans showed abnormally increased joint activity in 28 of the 36 patients. A total of 97 joints showed abnormalities, 19% in the hips, 34% in the knees, and 47% in the shoulders. Twenty-four of 27 joints with elevated bone marrow pressure (BMP) had abnormal scans (sensitivity = 89%), and scans were abnormal in 2 of 4 joints with normal pressures (specificity = 50%). The positive predicitive value of the scans compared with BMP measurements was 92% (24/26). Eleven of 27 joints with abnormal BMP had abnormal radiographs, a sensitivity of 41%.

Conklin, J.J.; Alderson, P.O.; Zizic, T.M.; Hungerford, D.S.; Densereaux, J.Y.; Gober, A.; Wagner, H.N.

1983-04-01

315

A soluble activin type IIA receptor induces bone formation and improves skeletal integrity  

PubMed Central

Diseases that affect the regulation of bone turnover can lead to skeletal fragility and increased fracture risk. Members of the TGF-? superfamily have been shown to be involved in the regulation of bone mass. Activin A, a TGF-? signaling ligand, is present at high levels in bone and may play a role in the regulation of bone metabolism. Here we demonstrate that pharmacological blockade of ligand signaling through the high affinity receptor for activin, type II activin receptor (ActRIIA), by administration of the soluble extracellular domain of ActRIIA fused to a murine IgG2a-Fc, increases bone formation, bone mass, and bone strength in normal mice and in ovariectomized mice with established bone loss. These observations support the development of this pharmacological strategy for the treatment of diseases with skeletal fragility. PMID:18460605

Pearsall, R. Scott; Canalis, Ernesto; Cornwall-Brady, Milton; Underwood, Kathryn W.; Haigis, Brendan; Ucran, Jeffrey; Kumar, Ravindra; Pobre, Eileen; Grinberg, Asya; Werner, Eric D.; Glatt, Vaida; Stadmeyer, Lisa; Smith, Deanna; Seehra, Jasbir; Bouxsein, Mary L.

2008-01-01

316

Bone Marrow Transplantation Transfers Age-Related Susceptibility to Neovascular Remodeling in Murine Laser-Induced Choroidal Neovascularization  

PubMed Central

Purpose. Neovascular remodeling (NVR), the progression of small capillaries into large-caliber arterioles with perivascular fibrosis, represents a major therapeutic challenge in neovascular age-related macular degeneration (AMD). Neovascular remodeling occurs after laser-induced choroidal neovascularization (CNV) in aged but not young mice. Additionally, bone marrow–derived cells, including macrophages, endothelial precursor cells, and mesenchymal precursor cells, contribute to CNV severity. In this study, we investigated the impact of aged bone marrow transplantation (BMT) on the degree of fibrosis, size, and vascular morphology of CNV lesions in a mouse model of laser-induced CNV. Methods. Young (2 months) and old (16 months) mice were transplanted with green fluorescent protein (GFP)-labeled bone marrow isolated from either young or old donors. Laser CNV was induced 1 month following transplant, and eyes were analyzed via choroidal flat mounts and immunohistochemistry 1 month postlaser. The identity of cells infiltrating CNV lesions was determined using specific markers for the labeled transplanted cells (GFP+), macrophages (F4/80+), perivascular mesenchymal-derived cells (smooth muscle actin, SMA+), and endothelial cells (CD31+). Results. Bone marrow transplantation from aged mice transferred susceptibility to NVR into young recipients. Inversely, transplantation of young marrow into old mice prevented NVR, preserving small size and minimal fibrosis. Mice with NVR demonstrated a greater relative contribution of marrow-derived SMA+ perivascular mesenchymal cells as compared to other cells. Conclusions. Our findings indicate that the status of bone marrow is an important determining factor of neovascular severity. Furthermore, we find that perivascular mesenchymal cells, rather than endothelial cells, derived from aged bone marrow may contribute to increased CNV severity in this murine model of experimental neovascularization. PMID:24135751

Espinosa-Heidmann, Diego G.; Malek, Goldis; Mettu, Priyatham S.; Caicedo, Alejandro; Saloupis, Peter; Gach, Sarah; Dunnon, Askia K.; Hu, Peng; Spiga, Maria-Grazia; Cousins, Scott W.

2013-01-01

317

Bone Markers, Calcium Metabolism, and Calcium Kinetics During Extended-Duration Space Flight on the Mir Space Station  

NASA Technical Reports Server (NTRS)

Bone loss is a current limitation for long-term space exploration. Bone markers, calcitropic hormones, and calcium kinetics of crew members on space missions of 4-6 months were evaluated. Spaceflight-induced bone loss was associated with increased bone resorption and decreased calcium absorption. INTRODUCTION: Bone loss is a significant concern for the health of astronauts on long-duration missions. Defining the time course and mechanism of these changes will aid in developing means to counteract these losses during space flight and will have relevance for other clinical situations that impair weight-bearing activity. MATERIALS AND METHODS: We report here results from two studies conducted during the Shuttle-Mir Science Program. Study 1 was an evaluation of bone and calcium biochemical markers of 13 subjects before and after long-duration (4-6 months) space missions. In study 2, stable calcium isotopes were used to evaluate calcium metabolism in six subjects before, during, and after flight. Relationships between measures of bone turnover, biochemical markers, and calcium kinetics were examined. RESULTS: Pre- and postflight study results confirmed that, after landing, bone resorption was increased, as indicated by increases in urinary calcium (p < 0.05) and collagen cross-links (N-telopeptide, pyridinoline, and deoxypyridinoline were all increased >55% above preflight levels, p < 0.001). Parathyroid hormone and vitamin D metabolites were unchanged at landing. Biochemical markers of bone formation were unchanged at landing, but 2-3 weeks later, both bone-specific alkaline phosphatase and osteocalcin were significantly (p < 0.01) increased above preflight levels. In studies conducted during flight, bone resorption markers were also significantly higher than before flight. The calcium kinetic data also validated that bone resorption was increased during flight compared with preflight values (668 +/- 130 versus 427 +/- 153 mg/day; p < 0.001) and clearly documented that true intestinal calcium absorption was significantly lower during flight compared with preflight values (233 +/- 87 versus 460 +/- 47 mg/day; p < 0.01). Weightlessness had a detrimental effect on the balance in bone turnover such that the daily difference in calcium retention during flight compared with preflight values approached 300 mg/day (-234 +/- 102 versus 63 +/- 75 mg/day; p < 0.01). CONCLUSIONS: These bone marker and calcium kinetic studies indicated that the bone loss that occurs during space flight is a consequence of increased bone resorption and decreased intestinal calcium absorption.

Smith, Scott M.; Wastney, Meryl E.; O'Brien, Kimberly O.; Morukov, Boris V.; Larina, Irina M.; Abrams, Steven A.; Davis-Street, Janis E.; Oganov, Victor; Shackelford, Linda C.

2005-01-01

318

Growth factor-induced osteogenesis in a novel radiolucent bone chamber.  

PubMed

Treatment of large bone defects is currently performed using mainly autograft or allograft bone. There are important drawbacks to bone grafting, such as limited availability, donor site morbidity in the case of autograft and inferior performance of allografts. Therefore, there is a great need for a suitable bone graft substitute. In order to evaluate efficiently newly developed biomaterials and factors intended for orthopaedic surgery, the bone chamber is a very suitable model. To allow longitudinal investigation of bone growth with ?CT, a new bone chamber made of radiolucent polyether ether ketone (PEEK) was developed and studied for its feasibility. Therefore, PEEK bone chambers were placed on rat tibiae, and filled with vehicle (Matrigel without growth factors, negative controls), with bone morphogenetic protein 2 (BMP-2, positive controls), or a mix of growth factors combining BMP-2, vascular endothelial growth factor and the chemokine stromal cell-derived factor 1?, all laden on gelatin microspheres for controlled release (combined growth factors). Growth factor presence led to a significant increase in bone formation after 8 weeks, which subsided after 12 weeks, underlining the importance of longitudinal analysis. We conclude that the PEEK-bone chamber is a suitable translational animal model to assess orthotopic bone formation in a longitudinal manner. PMID:25552427

Poldervaart, M T; van der Stok, J; de Haas, M F; 't Hart, M C; Öner, F C; Dhert, W J; Weinans, H; Alblas, J

2015-01-01

319

Surgically induced endometriosis attenuates accrual of bone mineral density in growing rats  

Microsoft Academic Search

Objective: A possible association of endometriosis with decreased bone mineral density in women has been proposed. It has been reported that cortical and trabecular bone mass of the distal portion of the radius is decreased in patients with endometriosis. The objective of this study was to investigate the relationship between endometriosis and bone mineral density with the use of a

Rhonda M. Hearns-Stokes; Nannette F. Santoro; James A. Simon

2001-01-01

320

Effect of beta-carotene on spontaneous and X-ray-induced chromosomal damage in bone marrow cells of mice.  

PubMed

The effect of beta-carotene on spontaneous and X-ray-induced chromosomal damage in bone marrow cells of mice was studied. As a source of beta-carotene, dried Dunaliella bardawil (containing 6% beta-carotene) or oil suspension of Dunaliella beta-carotene was used. In Experiment 1, mice were given a basal diet, a 0.5% Dunaliella diet, or a 4% Dunaliella diet for four weeks. In Experiment 2, mice were given an oil suspension of Dunaliella beta-carotene (300 mg/kg body wt) by gavage for seven days while being fed a fat-rich diet. After beta-carotene treatment for the indicated time, spontaneous and X-ray (0.3 Gy, whole-body)-induced chromosomal damage in bone marrow cells was evaluated in terms of the percentages of micronucleated reticulocytes in their peripheral blood. The beta-carotene treatment slightly lowered the spontaneous and X-ray-induced chromosomal damage in bone marrow cells. Despite the higher doses of beta-carotene, the concentrations of beta-carotene in bone marrow, liver, and serum were much lower than those of vitamin E. In addition, the beta-carotene treatment markedly lowered the concentration of vitamin E in the tissues. PMID:7877897

Umegaki, K; Takeuchi, N; Ikegami, S; Ichikawa, T

1994-01-01

321

Protective effect of zinc supplementation against cadmium-induced oxidative stress and the RANK/RANKL/OPG system imbalance in the bone tissue of rats  

SciTech Connect

It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-?? (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/antioxidative status, and Cd and Zn were determined in the distal femur of the rats administered Zn (30 and 60 mg/l) or/and Cd (5 and 50 mg/l) for 6 months. Soluble RANKL (sRANKL) and OPG were measured in the bone and serum. Zn supplementation importantly protected from Cd-induced oxidative stress preventing protein, DNA, and lipid oxidation in the bone. Moreover, Zn protected from the Cd-induced increase in sRANKL concentration and the sRANKL/OPG ratio, and decrease in OPG concentration in the bone and serum. Numerous correlations were noted between indices of the oxidative/antioxidative bone status, concentrations of sRANKL and OPG in the bone and serum, as well as the bone concentrations of Zn and Cd, and previously reported by us in these animals (Brzóska et al., 2007) indices of bone turnover and bone mineral density. The results allow us to conclude that the ability of Zn to prevent from oxidative stress and the RANK/RANKL/OPG system imbalance may be implicated in the mechanisms of its protective impact against Cd-induced bone damage. This paper is the first report from an in vivo study providing evidence that beneficial Zn impact on the skeleton under exposure to Cd is related to the improvement of the bone tissue oxidative/antioxidative status and mediating the RANK/RANKL/OPG system. - Highlights: • Cd induces oxidative stress in the bone tissue. • Cd disturbs bone metabolism via disorder of the RANK/RANKL/OPG system balance. • Zn supplementation protects from Cd-induced oxidative stress in the bone tissue. • Zn protects from the RANK/RANKL/OPG system imbalance caused by Cd in the bone tissue. • Enhanced Zn intake protects from Cd-induced disorders in bone metabolism.

Brzóska, Malgorzata M., E-mail: Malgorzata.Brzoska@umb.edu.pl; Rogalska, Joanna

2013-10-01

322

Transfusion Induced Bone Marrow Transplant Rejection Due to Minor Histocompatibility Antigens  

PubMed Central

Traditionally, alloimmunization to transfused blood products has focused exclusively upon recipient antibodies recognizing donor alloantigens present on the cell surface. Accordingly, the immunological sequelae of alloimmunization have been antibody mediated effects (i.e. hemolytic transfusion reactions, platelet refractoriness, anti-HLA and anti-HNA effects, etc.). However, in addition to the above sequelae, there is also a correlation between the number of antecedent transfusions in humans and the rate of bone marrow transplant (BMT) rejection - under reduced intensity conditioning with HLA matched or HLA identical marrow. BMT of this nature is the only existing cure for a series of non-malignant hematological diseases (e.g. sickle cell disease, thalassemias, etc.); however, rejection remains a clinical problem. It has been hypothesized that transfusion induces subsequent BMT rejection through immunization. Studies in animal models have observed the same effect and have demonstrated that transfusion induced BMT rejection can occur in response to alloimmunization. However, unlike traditional antibody responses, sensitization in this case results in cellular immune effects, involving populations such as T cell or NK cells. In this case, rejection occurs in the absence of alloantibodies, and would not be detected by existing immune-hematological methods. We review human and animal studies in light of the hypothesis that, for distinct clinical populations, enhanced rejection of BMT may be an unappreciated adverse consequence of transfusion which current blood bank methodologies are unable to detect. PMID:24090731

Patel, Seema R; Zimring, James C

2014-01-01

323

Bone marrow-derived clonal mesenchymal stem cells inhibit ovalbumin-induced atopic dermatitis.  

PubMed

Mesenchymal stem cells (MSCs) possess immunomodulatory activities, including suppression of T- and B-cell activation. However, their effects on atopic dermatitis (AD) have not yet been studied. Using an ovalbumin-induced AD mouse model, we investigated whether MSCs can be used as therapeutics in AD. We isolated both allogeneic and syngeneic clonal MSCs (cMSCs) from mouse bone marrow according to the subfractionation culturing method. Our cMSCs suppressed both T- and B-cell activation. T-cell proliferation and cytokine production, including interferon (IFN)-? and interleukin (IL)-4, were suppressed by inhibition of transcription factors, such as T-bet, GATA-3, and c-Maf. Those transcription factors were nitric oxide dependent. Immunoglobulin E (IgE) suppression occurred through downregulation of AID and BLIMP-1, important regulators for isotype class switch and B-cell differentiation. The cMSCs were injected intravenously into ovalbumin-induced AD mouse model, and the therapeutic effects were analyzed. Injection of both allogeneic and syngeneic cMSCs in an AD mouse model inhibited cell infiltration in skin lesions and decreased the serum level of IgE. IL-4 expression was also suppressed by cMSCs in both the lymph node and skin. The cMSCs migrated to skin lesions and draining lymph nodes. Taken together, these data demonstrated that cMSCs, which suppressed T- and B-cell functions, can be used for the treatment of AD in mice. PMID:25032868

Na, K; Yoo, H S; Zhang, Y X; Choi, M-S; Lee, K; Yi, T G; Song, S U; Jeon, M-S

2014-01-01

324

Hematopoietic stem cell senescence and cancer therapy-induced long-term bone marrow injury  

PubMed Central

Due to improvements in early detection and treatment of cancer, the number of long-term cancer survivors is increasing. Unfortunately, these survivors are at increased risk for developing cancer treatment-related late effects, including ionizing radiation (IR)- and chemotherapy-induced long-term bone marrow (LT-BM) injury. Because LT-BM injury can deteriorate over time or after the patients receiving additional cancer treatment or undergoing autologous BM transplantation, it may eventually lead to the development of hypoplastic anemia or myelodysplastic syndrome. This review is to provide a survey of some of these recent findings regarding the underlying mechanisms by which IR and chemotherapy cause LT-BM injury. Particularly, we will highlight the discoveries of the role of reactive oxygen species in regulating HSC self-renewal and the role of oxidative stress in mediating IR- and chemotherapy-induced HSC senescence and LT-BM injury. These discoveries may lead to the development of new therapeutic strategies that have the potential to reduce the late adverse effects of conventional cancer therapy on the hematopoietic system in long-term cancer survivors. PMID:24605290

Shao, Lijian; Wang, Yingying; Chang, Jianhui; Luo, Yi; Meng, Aimin; Zhou, Daohong

2014-01-01

325

Smad6 Recruits Transcription Corepressor CtBP To Repress Bone Morphogenetic Protein-Induced Transcription  

PubMed Central

Smad6 and Smad7 are inhibitory Smads induced by transforming growth factor ?-Smad signal transduction pathways in a negative-feedback mechanism. Previously it has been thought that inhibitory Smads bind to the type I receptor and block the phosphorylation of receptor-activated Smads, thereby inhibiting the initiation of Smad signaling. Conversely, few studies have suggested the possible nuclear functions of inhibitory Smads. Here, we present compelling evidence demonstrating that Smad6 repressed bone morphogenetic protein-induced Id1 transcription through recruiting transcriptional corepressor C-terminal binding protein (CtBP). A consensus CtBP-binding motif, PLDLS, was identified in the linker region of Smad6. Our findings show that mutation in the motif abolished the Smad6 binding to CtBP and subsequently its repressor activity of transcription. We conclude that the nuclear functions and physical interaction of Smad6 and CtBP provide a novel mechanism for the transcriptional regulation by inhibitory Smads. PMID:14645520

Lin, Xia; Liang, Yao-Yun; Sun, Baohua; Liang, Min; Shi, Yujiang; Brunicardi, F. Charles; Shi, Yang; Feng, Xin-Hua

2003-01-01

326

c-Abl-dependent Molecular Circuitry Involving Smad5 and Phosphatidylinositol 3-Kinase Regulates Bone Morphogenetic Protein-2-induced Osteogenesis*  

PubMed Central

Skeletal remodeling consists of timely formation and resorption of bone by osteoblasts and osteoclasts in a quantitative manner. Patients with chronic myeloid leukemia receiving inhibitors of c-Abl tyrosine kinase often show reduced bone remodeling due to impaired osteoblast and osteoclast function. BMP-2 plays a significant role in bone generation and resorption by contributing to the formation of mature osteoblasts and osteoclasts. The effects of c-Abl on BMP-2-induced bone remodeling and the underlying mechanisms are not well studied. Using a pharmacological inhibitor and expression of a dominant negative mutant of c-Abl, we show an essential role of this tyrosine kinase in the development of bone nodules containing mature osteoblasts and formation of multinucleated osteoclasts in response to BMP-2. Calvarial osteoblasts prepared from c-Abl null mice showed the absolute requirement of this tyrosine kinase in maturation of osteoblasts and osteoclasts. Activation of phosphatidylinositol 3-kinase (PI 3-kinase)/Akt signaling by BMP-2 leads to osteoblast differentiation. Remarkably, inhibition of c-Abl significantly suppressed BMP-2-stimulated PI 3-kinase activity and its downstream Akt phosphorylation. Interestingly, c-Abl regulated BMP-2-induced osteoclastogenic CSF-1 expression. More importantly, we identified the requirements of c-Abl in BMP-2 autoregulation and the expressions of alkaline phosphatase and osterix that are necessary for osteoblast differentiation. c-Abl contributed to BMP receptor-specific Smad-dependent transcription of CSF-1, osterix, and BMP-2. Finally, c-Abl associates with BMP receptor IA and regulates phosphorylation of Smad in response to BMP-2. We propose that activation of c-Abl is an important step, which induces into two signaling pathways involving noncanonical PI 3-kinase and canonical Smads to integrate BMP-2-induced osteogenesis. PMID:23821550

Ghosh-Choudhury, Nandini; Mandal, Chandi C.; Das, Falguni; Ganapathy, Suthakar; Ahuja, Seema; Ghosh Choudhury, Goutam

2013-01-01

327

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

PubMed Central

Background: Whole-body vibration (WBV) induces reflex muscle activity and leads to increased muscle strength. However, little is known about the physiological mechanisms underlying the effects of whole-body vibration on muscular performance. Tonic vibration reflex is the most commonly cited mechanism to explain the effects of whole-body vibration on muscular performance, although there is no conclusive evidence that tonic vibration reflex occurs. The bone myoregulation reflex is another neurological mechanism used to explain the effects of vibration on muscular performance. Bone myoregulation reflex is defined as a reflex mechanism in which osteocytes exposed to cyclic mechanical loading induce muscle activity. Aims: The aim of this study was to assess whether bone tissue affected vibration-induced reflex muscle activity and vibration-induced muscle strength gain. Study Design: A prospective, randomised, controlled, double-blind, parallel-group clinical trial. Methods: Thirty-four participants were randomised into two groups. High-magnitude whole-body vibration was applied in the exercise group, whereas low-magnitude whole-body vibration exercises were applied in the control group throughout 20 sessions. Hip bone mineral density, isokinetic muscle strength, and plasma sclerostin levels were measured. The surface electromyography data were processed to obtain the Root Mean Squares, which were normalised by maximal voluntarily contraction. Results: In the exercise group, muscle strength increased in the right and left knee flexors (23.9%, p=0.004 and 27.5%, p<0.0001, respectively). However, no significant change was observed in the knee extensor muscle strength. There was no significant change in the knee muscle strength in the control group. The vibration-induced corrected Root Mean Squares of the semitendinosus muscle was decreased by 2.8 times (p=0.005) in the exercise group, whereas there was no change in the control group. Sclerostin index was decreased by 15.2% (p=0.031) in the exercise group and increased by 20.8% (p=0.028) in the control group. A change in the sclerostin index was an important predictor of a change in the vibration-induced normalised Root Mean Square of the semitendinosus muscle (R2=0.7, p=0.0001). Femoral neck bone mineral density was an important predictor of muscle strength gain (R2=0.26, p=0.035). Conclusion: This study indicates that bone tissue may have an effect on vibration-induced muscle strength gain and vibration-induced reflex muscle activity. Trial registration: ClinicalTrials.gov: NCT01310348. PMID:25207162

Cidem, Muharrem; Karacan, ?lhan; Diraço?lu, Demirhan; Y?ld?z, Aysel; Küçük, Suat Hayri; Uluda?, Murat; Gün, Kerem; Özkaya, Murat; Karamehmeto?lu, ?afak Sahir

2014-01-01

328

Space Radiation and Bone Loss  

PubMed Central

Exposure to ionizing radiation may negatively impact skeletal integrity during extended spaceflight missions to the moon, Mars, or near-Earth asteroids. However, our understanding of the effects of radiation on bone is limited when compared to the effects of weightlessness. In addition to microgravity, astronauts will be exposed to space radiation from solar and cosmic sources. Historically, radiation exposure has been shown to damage both osteoblast precursors and local vasculature within the irradiated volume. The resulting suppression of bone formation and a general state of low bone-turnover is thought to be the primary contributor to bone loss and eventual fracture. Recent investigations using mouse models have identified a rapid, but transient, increase in osteoclast activity immediately after irradiation with both spaceflight and clinically-relevant radiation qualities and doses. Together with a chronic suppression of bone formation after radiation exposure, this acute skeletal damage may contribute to long-term deterioration of bone quality, potentially increasing fracture risk. Direct evidence for the damaging effects of radiation on human bone are primarily demonstrated by the increased incidence of fractures at sites that absorb high doses of radiation during cancer therapy: exposures are considerably higher than what could be expected during spaceflight. However, both the rapidity of bone damage and the chronic nature of the changes appear similar between exposure scenarios. This review will outline our current knowledge of space and clinical exploration exposure to ionizing radiation on skeletal health. PMID:22826632

Willey, Jeffrey S.; Lloyd, Shane A.J.; Nelson, Gregory A.; Bateman, Ted A.

2011-01-01

329

Antimutagenic effect of Origanum majorana L. essential oil against prallethrin-induced genotoxic damage in rat bone marrow cells.  

PubMed

This study aimed to investigate the genotoxic and cytotoxic potential of prallethrin in rat bone marrow cells and the protective effect of Origanum majorana L. essential oil (EO). Our results demonstrated that prallethrin at dose 64.0 mg/kg body weight (b.wt.) (1/10 LD50), has a clastogenic/genotoxic potential as shown by the high percentage of chromosomal aberration (CA) and micronucleus (MN) in the bone marrow cells of male rats, whereas the combined treatment of prallethrin and O. majorana EO resulted in the reduction of the CA (54.54%). The combined treatment also reduced the micronuclei formation significantly. In conclusion, prallethrin can be considered clastogenic/genotoxic and may carry a risk to human health. The study revealed the antigenotoxic and anticytotoxic potential of O. majorana EO against prallethrin-induced genotoxic and cytotoxic effects in rat bone marrow cells. PMID:24195751

Mossa, Abdel-Tawab H; Refaie, Amel A; Ramadan, Amal; Bouajila, Jalloul

2013-12-01

330

Reversible bone marrow aplasia induced by pegylated interferon-?-2a therapy in a patient with primary myelofibrosis.  

PubMed

Interferon has been widely used in the management of patients with hematological malignancies such as polycythemia vera, myelofibrosis, chronic myeloid leukemia and viral infections such as chronic hepatitis C. Hematological adverse effects such as cytopenias have been observed, particularly in patients who receive a combination of interferon-?-2a and ribavirin for hepatitis C. Mild myelosuppression can be seen with pegylated interferon; however, bone marrow aplasia in patients with myelofibrosis has not been reported. It is important to be aware of such a serious complication since persistent bone marrow aplasia can be fatal. We describe a case of pegylated interferon-induced reversible bone marrow aplasia in a patient with primary myelofibrosis. PMID:24067929

Mainali, Naba R; Bhatt, Vijaya R; Kedia, Shiksha; Krishnamurthy, Jairam; Wake, Laura M; Akhtari, Mojtaba

2014-10-01

331

An Analysis of Hardware Configurations for an Adaptive Weightless Neural Network  

Microsoft Academic Search

123 Abstract - This paper examines the potential offered by adaptive hardware configurations of a class of weightless neural architecture called the Enhanced Probabilistic Convergent Network targeted on a Virtex-II pro FPGA which is re configurable. The reconfiguration and adaptive capability of the Enhanced Probabilistic Convergent Network is a highly adaptive architecture offering a very fast, automated, uninterrupted responses in

P. Lorrentz; W. G. J. Howells; K. D. McDonald-Maier

332

Effects of weightlessness on the development of the vestibular apparatus and ocular nystagmus in the rat  

NASA Technical Reports Server (NTRS)

The chronic 2g centrifuge was constructed for testing weightlessness effects on development of vestibular apparatus and ocular nystagmus in the rat. Both the stationary and rotating rail tests were performed. A physiological review is presented on vestibular apparatus, along with a system analysis. Time constants and input threshold level of the system are also considered.

Clark, D. L.

1972-01-01

333

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

NASA Technical Reports Server (NTRS)

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

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

1988-01-01

334

A Pathologist's view on the effects of very long exposure to weightlessness  

NASA Technical Reports Server (NTRS)

Speculations concerning the probable consequences of exposure to weightlessness during periods of one year or more and how these effects compare with aging are made. Orthostatic and excercise intolerance, neurological and muscular effects, cell division and DNA synthesis, tissue hypoxia, and edema are discussed in reference to the in-space and return-to-Earth situations.

Bensch, K. G.

1982-01-01

335

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

NASA Technical Reports Server (NTRS)

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

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

1993-01-01

336

[Bone and androgens].  

PubMed

Sexual steroids are major determinants of skeletal maturation and steady state. Estrogens are mandatory in both sexes. They induce endochondral bone formation and growth plate knitting. Androgens are mainly active in male. They increase length and radial bone growth. These differences explain the duality of biomechanics in both sexes. Deep androgen deficiency induces rapid bone loss and increases bone fracture risk. The androgen treatment of andropause has weak rationale. Androgens interact with bone metabolism within the medulla-bone unit. They activate the whole osteoblastic lineage and interact with preosteoclastic regulation. Androgens found their place in bone metabolism regulation through RANK/osteoprotegerin and Wnt/sclerostin pathways. PMID:24332181

Weryha, Georges; Angelousi, Anna; Diehdiou, Demba; Cuny, Thomas

2014-02-01

337

Bone Turnover Markers Correlate with Implant fixation in a Rat Model Using LPS Doped Particles to Induced Implant Loosening1  

PubMed Central

Revision surgery for particle-induced implant loosening in total joint replacement is expected to increase dramatically over the next few decades. This study was designed to investigate if local tissue and serum markers of bone remodeling reflect implant fixation following administration of lipopolysaccharide (LPS)-doped polyethylene (PE) particles in a rat model. 24 rats received bilateral implantation of intramedullary titanium rods in the distal femur, followed by weekly bilateral intra-articular injection of either LPS-doped PE particles (n = 12) or vehicle which contained no particles (n= 12) for 12 weeks. The group in which the particles were injected had increased serum C-terminal telopeptide of type I collagen, decreased serum osteocalcin, increased peri-implant eroded surface, decreased peri-implant bone volume, and decreased mechanical pull-out strength compared to the controls. Implant fixation strength was positively correlated with peri-implant bone volume and serum osteocalcin and inversely correlated with serum C-terminal telopeptide of type I collagen, while energy to yield was positively correlated with serum osteocalcin and inversely correlated with the number of tartrate resistant acid phosphatase positive cells at the interface and the amount of peri-implant eroded surface. There was no effect on trabecular bone volume at a remote site. Thus, the particle-induced impaired fixation in this rat model was directly associated with local and serum markers of elevated bone resorption and depressed bone formation, supporting the rationale of exploring both anti-catabolic and anabolic strategies to treat and prevent particle-related implant osteolysis and loosening and indicating that serum markers may prove useful in tracking implant fixation. PMID:22275163

Liu, Shuo; Virdi, Amarjit S.; Sena, Kotaro; Hughes, W. Frank; Sumner, Dale R.

2011-01-01

338

Transcriptomic profile induced in bone marrow mesenchymal stromal cells after interaction with multiple myeloma cells: implications in myeloma progression and myeloma bone disease  

PubMed Central

Despite evidence about the implication of the bone marrow (BM) stromal microenvironment in multiple myeloma (MM) cell growth and survival, little is known about the effects of myelomatous cells on BM stromal cells. Mesenchymal stromal cells (MSCs) from healthy donors (dMSCs) or myeloma patients (pMSCs) were co-cultured with the myeloma cell line MM.1S, and the transcriptomic profile of MSCs induced by this interaction was analyzed. Deregulated genes after co-culture common to both d/pMSCs revealed functional involvement in tumor microenvironment cross-talk, myeloma growth induction and drug resistance, angiogenesis and signals for osteoclast activation and osteoblast inhibition. Additional genes induced by co-culture were exclusively deregulated in pMSCs and predominantly associated to RNA processing, the ubiquitine-proteasome pathway, cell cycle regulation, cellular stress and non-canonical Wnt signaling. The upregulated expression of five genes after co-culture (CXCL1, CXCL5 and CXCL6 in d/pMSCs, and Neuregulin 3 and Norrie disease protein exclusively in pMSCs) was confirmed, and functional in vitro assays revealed putative roles in MM pathophysiology. The transcriptomic profile of pMSCs co-cultured with myeloma cells may better reflect that of MSCs in the BM of myeloma patients, and provides new molecular insights to the contribution of these cells to MM pathophysiology and to myeloma bone disease. PMID:25268740

Garcia-Gomez, Antonio; Las Rivas, Javier De; Ocio, Enrique M.; Díaz-Rodríguez, Elena; Montero, Juan C.; Martín, Montserrat; Blanco, Juan F.; Sanchez-Guijo, Fermín M.; Pandiella, Atanasio; San Miguel, Jesús F.; Garayoa, Mercedes

2014-01-01

339

Bone grafts in dentistry  

PubMed Central

Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation. PMID:23946565

Kumar, Prasanna; Vinitha, Belliappa; Fathima, Ghousia

2013-01-01

340

Secreted Phosphoprotein 24 kD (Spp24) and Spp14 Affect TGF-? Induced Bone Formation Differently  

PubMed Central

Transforming growth factor-? (TGF-?) and bone morphogenetic proteins (BMPs) have opposing but complementary functions in directing bone growth, repair, and turnover. Both are found in the bone matrix. Proteins that bind to and affect the activity of these growth factors will determine the relative abundance of the growth factors and, therefore, regulate bone formation. Secreted phosphoprotein 24 kD (Spp24) is a bone matrix protein that has been demonstrated to bind to and affect the activity of BMPs. The arginine-rich carboxy terminus of Spp24 is proteolytically processed to produce three other predictable truncation products (Spp18.1, Spp16.0, and Spp14.5). In this work, we report that kinetic data obtained by surface plasmon resonance demonstrate that Spp24 and the three C-terminal truncation products all bind to TGF-?1 and TGF-?2 with a similar but somewhat less affinity than they bind BMP-2; that, as in the case of BMP-2, the full-length (FL) form of Spp24 binds TGF-? with greater affinity than do the truncation products; that FL-Spp24 inhibits TGF-?2 induced bone formation in vivo, but Spp14.5 does not; and that co-administration of FL-Spp24 or Spp14.5 with TGF-?2 in vivo is associated with a reduction in the amount of cartilage, relative to new bone, present at the site of injection. This finding is consistent with the observation that low-dose TGF-? administration in vivo is associated with greater bone formation than high-dose TGF-? administration, and suggests that one function of Spp24 and its truncation products is to down-regulate local TGF-? activity or availability during bone growth and development. The similarities and differences of the interactions between Spp24 proteins and TGF-? compared to the interaction of the Spp24 proteins and BMPs have significant implications with respect to the regulation of bone metabolism and with respect to engineering therapeutic proteins for skeletal disorders. PMID:23991133

Tian, Haijun; Bi, Xiaoda; Li, Chen-Shuang; Zhao, Ke-Wei; Brochmann, Elsa J.; Montgomery, Scott R.; Aghdasi, Bayan; Chen, Deyu; Daubs, Michael D.; Wang, Jeffrey C.; Murray, Samuel S.

2013-01-01

341

Repeated Autologous Bone Marrow-Derived Mesenchymal Stem Cell Injections Improve Radiation-Induced Proctitis in Pigs  

PubMed Central

The management of proctitis in patients who have undergone very-high-dose conformal radiotherapy is extremely challenging. The fibrosis-necrosis, fistulae, and hemorrhage induced by pelvic overirradiation have an impact on morbidity. Augmenting tissue repair by the use of mesenchymal stem cells (MSCs) may be an important advance in treating radiation-induced toxicity. Using a preclinical pig model, we investigated the effect of autologous bone marrow-derived MSCs on high-dose radiation-induced proctitis. Irradiated pigs received repeated intravenous administrations of autologous bone marrow-derived MSCs. Immunostaining and real-time polymerase chain reaction analysis were used to assess the MSCs' effect on inflammation, extracellular matrix remodeling, and angiogenesis, in radiation-induced anorectal and colon damages. In humans, as in pigs, rectal overexposure induces mucosal damage (crypt depletion, macrophage infiltration, and fibrosis). In a pig model, repeated administrations of MSCs controlled systemic inflammation, reduced in situ both expression of inflammatory cytokines and macrophage recruitment, and augmented interleukin-10 expression in rectal mucosa. MSC injections limited radiation-induced fibrosis by reducing collagen deposition and expression of col1a2/col3a1 and transforming growth factor-?/connective tissue growth factor, and by modifying the matrix metalloproteinase/TIMP balance. In a pig model of proctitis, repeated injections of MSCs effectively reduced inflammation and fibrosis. This treatment represents a promising therapy for radiation-induced severe rectal damage. PMID:24068742

Busson, Elodie; Holler, Valerie; Strup-Perrot, Carine; Lacave-Lapalun, Jean-Victor; Lhomme, Bruno; Prat, Marie; Devauchelle, Patrick; Sabourin, Jean-Christophe; Simon, Jean-Marc; Bonneau, Michel; Lataillade, Jean-Jacques; Benderitter, Marc

2013-01-01

342

Directed Differentiation of Human Induced Pluripotent Stem Cells Toward Bone and Cartilage: In Vitro Versus In Vivo Assays  

PubMed Central

The ability to differentiate induced pluripotent stem cells (iPSCs) into committed skeletal progenitors could allow for an unlimited autologous supply of such cells for therapeutic uses; therefore, we attempted to create novel bone-forming cells from human iPSCs using lines from two distinct tissue sources and methods of differentiation that we previously devised for osteogenic differentiation of human embryonic stem cells, and as suggested by other publications. The resulting cells were assayed using in vitro methods, and the results were compared with those obtained from in vivo transplantation assays. Our results show that true bone was formed in vivo by derivatives of several iPSC lines, but that the successful cell lines and differentiation methodologies were not predicted by the results of the in vitro assays. In addition, bone was formed equally well from iPSCs originating from skin or bone marrow stromal cells (also known as bone marrow-derived mesenchymal stem cells), suggesting that the iPSCs did not retain a “memory” of their previous life. Furthermore, one of the iPSC-derived cell lines formed verifiable cartilage in vivo, which likewise was not predicted by in vitro assays. PMID:24855277

Phillips, Matthew D.; Kuznetsov, Sergei A.; Cherman, Natasha; Park, Kyeyoon; Chen, Kevin G.; McClendon, Britney N.; Hamilton, Rebecca S.; McKay, Ronald D.G.; Chenoweth, Josh G.; Mallon, Barbara S.

2014-01-01

343

Pharmacologic inhibition of bone resorption prevents cancer-induced osteolysis but enhances soft tissue metastasis in a mouse model of osteolytic breast cancer.  

PubMed

Osteoprotegerin (OPG) is a secreted member of the TNF receptor superfamily, which binds to the receptor activator of nuclear factor ?B ligand (RANKL) and inhibits osteoclast activity and bone resorption. Systemic administration of recombinant OPG was previously shown to inhibit tumor growth in bone and to prevent cancer-induced osteolysis. In this study, we examined the effect of OPG, when produced locally by breast cancer cells located within bone, using a mouse model of osteolytic breast cancer. MDA-MB-231-TXSA breast cancer cells, tagged with a luciferase reporter gene construct and engineered to overexpress full-length human OPG, were transplanted directly into the tibial marrow cavity of nude mice. Overexpression of OPG by breast cancer cells protected the bone from breast cancer-induced osteolysis and diminished intra-osseous tumor growth but had no effect on extra-skeletal tumor growth. This effect was associated with a significant reduction in the number of osteoclasts that lined the bone surface, resulting in a net increase in bone volume. Despite limiting breast cancer-mediated bone loss, OPG overexpression resulted in a significant increase in the incidence of pulmonary metastasis. Our results demonstrate that inhibition of osteoclastic bone resorption by OPG when secreted locally by tumors in bone may affect the behaviour of cancer cells within the bone microenvironment and their likelihood of spreading and establishing metastasis elsewhere in the body. PMID:24865346

Zinonos, Irene; Luo, Ke-Wang; Labrinidis, Agatha; Liapis, Vasilios; Hay, Shelley; Panagopoulos, Vasilios; Denichilo, Mark; Ko, Chun-Hay; Yue, Grace Gar-Lee; Lau, Clara Bik-San; Ingman, Wendy; Ponomarev, Vladimir; Atkins, Gerald J; Findlay, David M; Zannettino, Andrew C W; Evdokiou, Andreas

2014-08-01

344

Weightlessness alters up/down asymmetries in the perception of self-motion.  

PubMed

In the present study, we investigated the effect of weightlessness on the ability to perceive and remember self-motion when passing through virtual 3D tunnels that curve in different direction (up, down, left, right). We asked cosmonaut subjects to perform the experiment before, during and after long-duration space flight aboard the International Space Station (ISS), and we manipulated vestibular versus haptic cues by having subjects perform the task either in a rigidly fixed posture with respect to the space station or during free-floating, in weightlessness. Subjects were driven passively at constant speed through the virtual 3D tunnels containing a single turn in the middle of a linear segment, either in pitch or in yaw, in increments of 12.5°. After exiting each tunnel, subjects were asked to report their perception of the turn's angular magnitude by adjusting, with a trackball, the angular bend in a rod symbolizing the outside view of the tunnel. We demonstrate that the strong asymmetry between downward and upward pitch turns observed on Earth showed an immediate and significant reduction when free-floating in weightlessness and a delayed reduction when the cosmonauts were firmly in contact with the floor of the station. These effects of weightlessness on the early processing stages (vestibular and optokinetics) that underlie the perception of self-motion did not stem from a change in alertness or any other uncontrolled factor in the ISS, as evidenced by the fact that weightlessness had no effect on the perception of yaw turns. That the effects on the perception of pitch may be partially overcome by haptic cues reflects the fusion of multisensory cues and top-down influences on visual perception. PMID:23397113

De Saedeleer, Caty; Vidal, Manuel; Lipshits, Mark; Bengoetxea, Ana; Cebolla, Ana Maria; Berthoz, Alain; Cheron, Guy; McIntyre, Joseph

2013-04-01

345

Raman spectroscopy delineates radiation-induced injury and partial rescue by amifostine in bone: a murine mandibular model.  

PubMed

Despite its therapeutic role in head and neck cancer, radiation administration degrades the biomechanical properties of bone and can lead to pathologic fracture and osteoradionecrosis. Our laboratories have previously demonstrated that prophylactic amifostine administration preserves the biomechanical properties of irradiated bone and that Raman spectroscopy accurately evaluates bone composition ex vivo. As such, we hypothesize that Raman spectroscopy can offer insight into the temporal and mechanical effects of both irradiation and amifostine administration on bone to potentially predict and even prevent radiation-induced injury. Male Sprague-Dawley rats (350-400 g) were randomized into control, radiation exposure (XRT), and amifostine pre-treatment/radiation exposure groups (AMF-XRT). Irradiated animals received fractionated 70 Gy radiation to the left hemi-mandible, while AMF-XRT animals received amifostine just prior to radiation. Hemi-mandibles were harvested at 18 weeks after radiation, analyzed via Raman spectroscopy, and compared with specimens previously harvested at 8 weeks after radiation. Mineral (?958) and collagen (?1665) depolarization ratios were significantly lower in XRT specimens than in AMF-XRT and control specimens at both 8 and 18 weeks. amifostine administration resulted in a full return of mineral and collagen depolarization ratios to normal levels at 18 weeks. Raman spectroscopy demonstrates radiation-induced damage to the chemical composition and ultrastructure of bone while amifostine prophylaxis results in a recovery towards normal, native mineral and collagen composition and orientation. These findings have the potential to impact on clinical evaluations and interventions by preventing or detecting radiation-induced injury in patients requiring radiotherapy as part of a treatment regimen. PMID:25319554

Felice, Peter A; Gong, Bo; Ahsan, Salman; Deshpande, Sagar S; Nelson, Noah S; Donneys, Alexis; Tchanque-Fossuo, Catherine; Morris, Michael D; Buchman, Steven R

2014-10-16

346

Estradiol protects against ethanol-induced bone loss by inhibiting up-regulation of receptor activator of nuclear factor-kB ligand in osteoblasts  

Technology Transfer Automated Retrieval System (TEKTRAN)

To investigate the effects of sex hormones on ethanol (EtOH)-induced bone loss, female Sprague-Dawley rats were fed control or EtOH-containing diets (12 g/kg/day) by intragastric infusion. After 3 weeks, rats receiving EtOH had significant decreases in tibial trabecular and total bone mineral densit...

347

Inhibition of megakaryocyte development in the bone marrow underlies dengue virus-induced thrombocytopenia in humanized mice.  

PubMed

A characteristic clinical feature of dengue virus infection is thrombocytopenia, though its underlying mechanism is not definitively determined. By adoptive transfer of human CD34(+) fetal liver cells into immunodeficient mice, we have constructed humanized mice with significant levels of human platelets, monocytes/macrophages, and hepatocytes. Infection of these mice with both lab-adapted and clinical strains of dengue virus induces characteristic human hematological changes, including transient leukopenia and thrombocytopenia. We show that the specific depletion of human platelets is not mediated by antibodies in the periphery or reduced production of human thrombopoietin in the liver but reduction of human megakaryocytes and megakaryocyte progenitors in the bone marrow of the infected mice. These findings identify inhibition of platelet production in the bone marrow as a key mechanism underlying dengue-induced thrombocytopenia and suggest the utility of the improved humanized mouse model in studying dengue virus infection and pathogenesis in a human cell context. PMID:23966397

Sridharan, Aishwarya; Chen, Qingfeng; Tang, Kin Fai; Ooi, Eng Eong; Hibberd, Martin L; Chen, Jianzhu

2013-11-01

348

Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells on Laser-Induced Retinal Injury in Mice  

PubMed Central

Stem cell therapy has shown encouraging results for neurodegenerative diseases. The retina provides a convenient locus to investigate stem cell functions and distribution in the nervous system. In the current study, we investigated the therapeutic potential of bone marrow mesenchymal stem cells (MSCs) by systemic transplantation in a laser-induced retinal injury model. MSCs from C57BL/6 mice labeled with green fluorescent protein (GFP) were injected via the tail vein into mice after laser photocoagulation. We found that the average diameters of laser spots and retinal cell apoptosis were decreased in the MSC-treated group. Interestingly, GFP-MSCs did not migrate to the injured retina. Further examination revealed that the mRNA expression levels of glial fibrillary acidic protein and matrix metalloproteinase-2 were lower in the injured eyes after MSC transplantation. Our results suggest that intravenously injected MSCs have the ability to inhibit retinal cell apoptosis, reduce the inflammatory response and limit the spreading of damage in the laser-injured retina of mice. Systemic MSC therapy might play a role in neuroprotection, mainly by regulation of the intraocular microenvironment. PMID:24871366

Jiang, Yuanfeng; Zhang, Yan; Zhang, Lingjun; Wang, Meiyan; Zhang, Xiaomin; Li, Xiaorong

2014-01-01

349

Human Bone Marrow Mesenchymal Stem Cells Induce Collagen Production and Tongue Cancer Invasion  

PubMed Central

Tumor microenvironment (TME) is an active player in carcinogenesis and changes in its composition modify cancer growth. Carcinoma-associated fibroblasts, bone marrow-derived multipotent mesenchymal stem cells (BMMSCs), and inflammatory cells can all affect the composition of TME leading to changes in proliferation, invasion and metastasis formation of carcinoma cells. In this study, we confirmed an interaction between BMMSCs and oral tongue squamous cell carcinoma (OTSCC) cells by analyzing the invasion progression and gene expression pattern. In a 3-dimensional myoma organotypic invasion model the presence of BMMSCs inhibited the proliferation but increased the invasion of OTSCC cells. Furthermore, the signals originating from OTSCC cells up-regulated the expression of inflammatory chemokines by BMMSCs, whereas BMMSC products induced the expression of known invasion linked molecules by carcinoma cells. Particularly, after the cell-cell interactions, the chemokine CCL5 was abundantly secreted from BMMSCs and a function blocking antibody against CCL5 inhibited BMMSC enhanced cancer invasion area. However, CCL5 blocking antibody did not inhibit the depth of invasion. Additionally, after exposure to BMMSCs, the expression of type I collagen mRNA in OTSCC cells was markedly up-regulated. Interestingly, also high expression of type I collagen N-terminal propeptide (PINP) in vivo correlated with the cancer-specific mortality of OTSCC patients, whereas there was no association between cancer tissue CCL5 levels and the clinical parameters. In conclusion, our results suggest that the interaction between BMMSC and carcinoma cells induce cytokine and matrix molecule expression, of which high level of type I collagen production correlates with the prognosis of OTSCC patients. PMID:24204919

Merkku, Kalle; Nyberg, Pia; Bello, Ibrahim O.; Vuoristo, Jussi; Sutinen, Meeri; Vähänikkilä, Hannu; Costea, Daniela E.; Kauppila, Joonas; Lehenkari, Petri; Dayan, Dan; Vered, Marilena; Risteli, Juha; Salo, Tuula

2013-01-01

350

Brain-mediated dysregulation of the bone marrow activity in angiotensin II-induced hypertension.  

PubMed

Oxidative stress in the brain is implicated in increased sympathetic drive, inflammatory status, and vascular dysfunctions, associated with development and establishment of hypertension. However, little is known about the mechanism of this impaired brain-vascular communication. Here, we tested the hypothesis that increased oxidative stress in the brain cardioregulatory areas, such as the paraventricular nucleus of the hypothalamus, is driven by mitochondrial reactive oxygen species and leads to increased inflammatory cells (ICs) and decreased/dysfunctional endothelial progenitor cells (EPCs), thereby compromising vasculature repair and accelerating hypertension. Chronic angiotensin II infusion resulted in elevated blood pressure and sympathetic vasomotor drive, decreased spontaneous baroreflex gain, and increased microglia activation in the paraventricular nucleus. This was associated with 46% decrease in bone marrow (BM)-derived EPCs and 250% increase in BM ICs, resulting in 5-fold decrease of EPC/IC ratio in the BM. Treatment with mitochondrial-targeted antioxidant, a scavenger of mitochondrial O(2)(-·), intracerebroventricularly but not subcutaneously attenuated angiotensin II-induced hypertension, decreased activation of microglia in the paraventricular nucleus, and normalized EPCs/ICs. This functional communication between the brain and BM was confirmed by retrograde neuronal labeling from the BM with green fluorescent protein-tagged pseudorabies virus. Administration of green fluorescent protein-tagged pseudorabies virus into the BM resulted in predominant labeling of paraventricular nucleus neurons within 3 days, with some fluorescence in the nucleus tractus solitarius, the rostral ventrolateral medulla, and subfornical organ. Taken together, these data demonstrate that inhibition of mitochondrial reactive oxygen species attenuates angiotensin II-induced hypertension and corrects the imbalance in EPCs/ICs in the BM. They suggest that an imbalance in vascular reparative and ICs may perpetuate vascular pathophysiology in this model of hypertension. PMID:23045460

Jun, Joo Yun; Zubcevic, Jasenka; Qi, Yanfei; Afzal, Aqeela; Carvajal, Jessica Marulanda; Thinschmidt, Jeffrey S; Grant, Maria B; Mocco, J; Raizada, Mohan K

2012-11-01

351

Recovery From Radiation-induced Bone Marrow Damage by HSP25 Through Tie2 Signaling  

SciTech Connect

Purpose: Whole-body radiation therapy can cause severe injury to the hematopoietic system, and therefore it is necessary to identify a novel strategy for overcoming this injury. Methods and Materials: Mice were irradiated with 4.5 Gy after heat shock protein 25 (HSP25) gene transfer using an adenoviral vector. Then, peripheral blood cell counts, histopathological analysis, and Western blotting on bone marrow (BM) cells were performed. The interaction of HSP25 with Tie2 was investigated with mouse OP9 and human BM-derived mesenchymal stem cells to determine the mechanism of HSP25 in the hematopoietic system. Results: HSP25 transfer increased BM regeneration and reduced apoptosis following whole-body exposure to ionizing radiation (IR). The decrease in Tie2 protein expression that followed irradiation of the BM was blocked by HSP25 transfer, and Tie2-positive cells were more abundant among the BM cells of HSP25-transferred mice, even after IR exposure. Following systemic RNA interference of Tie2 before IR, HSP25-mediated radioprotective effects were partially blocked in both mice and cell line systems. Stability of Tie2 was increased by HSP25, a response mediated by the interaction of HSP25 with Tie2. IR-induced tyrosine phosphorylation of Tie2 was augmented by HSP25 overexpression; downstream events in the Tie2 signaling pathway, including phosphorylation of AKT and EKR1/2, were also activated. Conclusions: HSP25 protects against radiation-induced BM damage by interacting with and stabilizing Tie2. This may be a novel strategy for HSP25-mediated radioprotection in BM.

Lee, Hae-June [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)] [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kwon, Hee-Chung [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)] [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Chung, Hee-Yong [College of Medicine, Hanyang University, Seoul (Korea, Republic of)] [College of Medicine, Hanyang University, Seoul (Korea, Republic of); Lee, Yoon-Jin [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)] [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yun-Sil, E-mail: yslee0425@ewha.ac.kr [College of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Woman's University, Seoul (Korea, Republic of)] [College of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Woman's University, Seoul (Korea, Republic of)

2012-09-01

352

Celastrol attenuates bone erosion in collagen-Induced arthritis mice and inhibits osteoclast differentiation and function in RANKL-induced RAW264.7.  

PubMed

Recently, the traditional Chinese medicine Tripterygium wilfordii Hook f (TwHF) of the Celastraceae family has attracted increasing attention for its potential therapeutic application in patients with rheumatoid arthritis (RA). It is well accepted that TwHF exerts the antirheumatic activity and mainly depends on its potent anti-inflammatory property. To further explore the therapeutic potential of the well-defined TwHF-derived single compound - celastrol in RA, we study the therapeutic efficacy of celastrol on bone erosion in collagen-induced arthritis (CIA) mice and delineate its effects on osteoclast differentiation and functions in RANKL-induced osteoclast precursors RAW264.7 cell line. In CIA mice, daily injection of celastrol (beginning on day 28 after arthritis induction) markedly suppressed arthritis, and reduced bone damage in the joints as demonstrated by histology and bone micro-computed tomography (CT). The effects were accompanied by reductions of osteoclast cells in joints, serum tartrate-resistant acid phosphatase (TRAP) 5b, and expression of osteoclastic genes (Trap, Ctsk, Ctr, Mmp-9) and transcriptional factors (c-Fos, c-Jun and NFATc1). When RAW264.7 cells were treated with RANKL, celastrol inhibited the formation of TRAP+ multinucleated cells and the bone-resorbing activity in dose-dependent manners. Furthermore, celastrol reduced the RANKL-induced expression of osteoclastic genes and transcriptional factors, as well as phosphorylation of NF-kB and mitogen-activated protein kinases (MAPK). These findings show that celastrol could directly inhibit osteoclast formation and function, suggesting a novel therapeutic strategy of celastrol for managing RA, especially in preventing bone destruction. PMID:25529994

Gan, Ke; Xu, Lingxiao; Feng, Xiaoke; Zhang, Qiande; Wang, Fang; Zhang, Miaojia; Tan, Wenfeng

2015-02-01

353

Calcineurin/NFAT pathway mediates wear particle-induced TNF-? release and osteoclastogenesis from mice bone marrow macrophages in vitro  

PubMed Central

Aim: To investigate the roles of the calcineurin/nuclear factor of activated T cells (NFAT) pathway in regulation of wear particles-induced cytokine release and osteoclastogenesis from mouse bone marrow macrophages in vitro. Methods: Osteoclasts were induced from mouse bone marrow macrophages (BMMs) in the presence of 100 ng/mL receptor activator of NF-?B ligand (RANKL). Acridine orange staining and MTT assay were used to detect the cell viability. Osteoclastogenesis was determined using TRAP staining and RT-PCR. Bone pit resorption assay was used to examine osteoclast phenotype. The expression and cellular localization of NFATc1 were examined using RT-PCR and immunofluorescent staining. The production of TNF? was analyzed with ELISA. Results: Titanium (Ti) or polymethylmethacrylate (PMMA) particles (0.1 mg/mL) did not significantly change the viability of BMMs, but twice increased the differentiation of BMMs into mature osteoclasts, and markedly increased TNF-? production. The TNF-? level in the PMMA group was significantly higher than in the Ti group (96 h). The expression of NFATc1 was found in BMMs in the presence of the wear particles and RANKL. In bone pit resorption assay, the wear particles significantly increased the resorption area and total number of resorption pits in BMMs-seeded ivory slices. Addition of 11R-VIVIT peptide (a specific inhibitor of calcineurin-mediated NFAT activation, 2.0 ?mol/L) did not significantly affect the viability of BMMs, but abolished almost all the wear particle-induced alterations in BMMs. Furthermore, VIVIT reduced TNF-? production much more efficiently in the PMMA group than in the Ti group (96 h). Conclusion: Calcineurin/NFAT pathway mediates wear particles-induced TNF-? release and osteoclastogenesis from BMMs. Blockade of this signaling pathway with VIVIT may provide a promising therapeutic modality for the treatment of periprosthetic osteolysis. PMID:24056707

Liu, Feng-xiang; Wu, Chuan-long; Zhu, Zhen-an; Li, Mao-qiang; Mao, Yuan-qing; Liu, Ming; Wang, Xiao-qing; Yu, De-gang; Tang, Ting-ting

2013-01-01

354

Aging diminishes lamellar and woven bone formation induced by tibial compression in adult C57BL/6.  

PubMed

Aging purportedly diminishes the ability of the skeleton to respond to mechanical loading, but recent data show that old age did not impair loading-induced accrual of bone in BALB/c mice. Here, we hypothesized that aging limits the response of the tibia to axial compression over a range of adult ages in the commonly used C57BL/6. We subjected the right tibia of old (22 month), middle-aged (12 month) and young-adult (5 month) female C57BL/6 mice to peak periosteal strains (measured near the mid-diaphysis) of -2200 ?? and -3000 ?? (n=12-15/age/strain) via axial tibial compression (4 Hz, 1200 cycles/day, 5 days/week, 2 weeks). The left tibia served as a non-loaded, contralateral control. In mice of every age, tibial compression that engendered a peak strain of -2200 ?? did not alter cortical bone volume but loading to a peak strain of -3000 ?? increased cortical bone volume due in part to woven bone formation. Both loading magnitudes increased total volume, medullary volume and periosteal bone formation parameters (MS/BS, BFR/BS) near the cortical midshaft. Compared to the increase in total volume and bone formation parameters of 5-month mice, increases were less in 12- and 22-month mice by 45-63%. Moreover, woven bone incidence was greatest in 5-month mice. Similarly, tibial loading at -3000 ?? increased trabecular BV/TV of 5-month mice by 18% (from 0.085 mm3/mm3), but trabecular BV/TV did not change in 12- or 22-month mice, perhaps due to low initial BV/TV (0.032 and 0.038 mm3/mm3, respectively). In conclusion, these data show that while young-adult C57BL/6 mice had greater periosteal bone formation following loading than middle-aged or old mice, aging did not eliminate the ability of the tibia to accrue cortical bone. PMID:24836737

Holguin, Nilsson; Brodt, Michael D; Sanchez, Michelle E; Silva, Matthew J

2014-08-01

355

Biodegradable chitosan particles induce chemokine release and negligible arginase-1 activity compared to IL-4 in murine bone marrow-derived macrophages  

E-print Network

Biodegradable chitosan particles induce chemokine release and negligible arginase-1 activity January 2011 Available online xxxx Keywords: Chitosan Bone marrow-derived macrophages Macrophage implicated in the therapeutic activity of biodegradable chitosan on wound healing, however, the mechanisms

Buschmann, Michael

356

Effect of spaceflight on the non-weight-bearing bones of rat skeleton  

NASA Technical Reports Server (NTRS)

The effects of weightlessness on the integrated growth and remodeling of nonweight-bearing bones (the mandibles, teeth, and ribs) were studied. Rats prelabeled with tetracycline to mark the surfaces of bone and tooth formation were subjected to spaceflight conditions for 18.5 days, followed by further injections of tetracycline on days 6 and 29 postflight.Results show that spaceflight conditions did not alter the rate of periosteal bone formation in the ribs and regions of the mandibles covered by masticatory muscles, although bone formation-calcification rates were found to be impaired at those sites in the jaw that had no contiguous muscle (molar region). The remodeling activity on the alveolar bone around the buccal roots of the molar teeth was found to be significantly reduced. While total Ca, P, and hydroxyproline concentrations in the jaws, incisors, and ribs were normal after spaceflight, it was determined that weightless conditions caused a delay in the maturation of bone mineral and matrix in the jaws. These anomalies were found to be corrected by 29 days postflight. These results indicate that most of the nonweight-bearing bones of the rat skeleton are at risk to the effects of weightlessness.

Simmons, D. J.; Russell, J. E.; Winter, F.; Tran Van, P.; Vignery, A.; Baron, R.; Rosenberg, G. D.; Walker, W. V.

1983-01-01

357

Hip, thigh and calf muscle atrophy and bone loss after 5-week bedrest inactivity.  

PubMed

Unloaded inactivity induces atrophy and functional deconditioning of skeletal muscle, especially in the lower extremities. Information is scarce, however, regarding the effect of unloaded inactivity on muscle size and function about the hip. Regional bone loss has been demonstrated in hips and knees of elderly orthopaedic patients, as quantified by computerized tomography (CT). This method remains to be validated in healthy individuals rendered inactive, including real or simulated weightlessness. In this study, ten healthy males were subjected to 5 weeks of experimental bedrest and five matched individuals served as ambulatory controls. Maximum voluntary isometric hip and knee extension force were measured using the strain gauge technique. Cross-sectional area (CSA) of hip, thigh and calf muscles, and radiological density (RD) of the proximal tibial bone were measured using CT. Bedrest decreased (P < 0.05) average (SD) muscle strength by 20 (8)% in knee extension, and by 22 (12)% in hip extension. Bedrest induced atrophy (P < 0.05) of extensor muscles in the gluteal region, thigh and calf, ranging from 2 to 12%. Atrophy was more pronounced in the knee extensors [9 (4)%] and ankle plantar flexors [12 (3)%] than in the gluteal extensor muscles [2 (2)%]. Bone density of the proximal tibia decreased (P < 0.05) by 3 (2)% during bedrest. Control subjects did not show any temporal changes in muscle or bone indices (P > 0.05), when examined at similar time intervals. The present findings of a substantial loss in hip extensor strength and a smaller, yet significant atrophy of these muscles, demonstrate that hip muscle deconditioning accompanies losses in thigh and calf muscle mass after bedrest. This suggests that comprehensive quantitative studies on impaired locomotor function after inactivity should include all joints of the lower extremity. Our results also demonstrate that a decreased RD, indicating bone mineral loss, can be shown already after 5 weeks of unloaded bedrest, using a standard CT technique. PMID:17186305

Berg, Hans E; Eiken, Ola; Miklavcic, Lucijan; Mekjavic, Igor B

2007-02-01

358

Inhibitors of glutamate release from breast cancer cells; new targets for cancer-induced bone-pain  

PubMed Central

Glutamate is an important signaling molecule in a wide variety of tissues. Aberrant glutamatergic signaling disrupts normal tissue homeostasis and induces several disruptive pathological conditions including pain. Breast cancer cells secrete high levels of glutamate and often metastasize to bone. Exogenous glutamate can disrupt normal bone turnover and may be responsible for cancer-induced bone pain (CIBP). CIBP is a significant co-morbidity that affects quality of life for many advanced-stage breast cancer patients. Current treatment options are commonly accompanied by serious side-effects that negatively impact patient care. Identifying small molecule inhibitors of glutamate release from aggressive breast cancer cells advances a novel, mechanistic approach to targeting CIBP that could advance treatment for several pathological conditions. Using high-throughput screening, we investigated the ability of approximately 30,000 compounds from the Canadian Compound Collection to reduce glutamate release from MDA-MB-231 breast cancer cells. This line is known to secrete high levels of glutamate and has been demonstrated to induce CIBP by this mechanism. Positive chemical hits were based on the potency of each molecule relative to a known pharmacological inhibitor of glutamate release, sulfasalazine. Efficacy was confirmed and drug-like molecules were identified as potent inhibitors of glutamate secretion from MDA-MB-231, MCF-7 and Mat-Ly-Lu cells. PMID:25670024

Fazzari, Jennifer; Lin, Hanxin; Murphy, Cecilia; Ungard, Robert; Singh, Gurmit

2015-01-01

359

Black rice (Oryza sativa L.) extracts induce osteoblast differentiation and protect against bone loss in ovariectomized rats.  

PubMed

Osteoporosis, an age associated skeletal disease, exhibits increased adipogenesis at the expense of osteogenesis from common osteoporotic bone marrow cells. In this study, black rice (Oryza sativa L.) extracts (BRE) were identified as osteogenic inducers. BRE stimulated the alkaline phosphatase (ALP) activity in both C3H10T1/2 and primary bone marrow cells. Similarly, BRE increased mRNA expression of ALP and osterix. Oral administration of BRE in OVX rats prevented decreases in bone density and strength. By contrast, BRE inhibited adipocyte differentiation of mesenchymal C3H10T1/2 cells and prevented increases in body weight and fat mass in high fat diet fed obese mice, further suggesting the dual effects of BRE on anti-adipogenesis and pro-osteogenesis. UPLC analysis identified cyanidin-3-O-glucoside and peonidin-3-O-glucoside as main anti-adipogenic effectors but not for pro-osteogenic induction. In mechanism studies, BRE selectively stimulated Wnt-driven luciferase activities. BRE treatment also induced Wnt-specific target genes such as Axin2, WISP2, and Cyclin D1. Taken together, these data suggest that BRE is a potentially useful ingredient to protect against age related osteoporosis and diet induced obesity. PMID:25428526

Jang, Woo-Seok; Seo, Cho-Rong; Jang, Hwan Hee; Song, No-Joon; Kim, Jong-Keun; Ahn, Jee-Yin; Han, Jaejoon; Seo, Woo Duck; Lee, Young Min; Park, Kye Won

2015-01-24

360

Inhibitors of glutamate release from breast cancer cells; new targets for cancer-induced bone-pain.  

PubMed

Glutamate is an important signaling molecule in a wide variety of tissues. Aberrant glutamatergic signaling disrupts normal tissue homeostasis and induces several disruptive pathological conditions including pain. Breast cancer cells secrete high levels of glutamate and often metastasize to bone. Exogenous glutamate can disrupt normal bone turnover and may be responsible for cancer-induced bone pain (CIBP). CIBP is a significant co-morbidity that affects quality of life for many advanced-stage breast cancer patients. Current treatment options are commonly accompanied by serious side-effects that negatively impact patient care. Identifying small molecule inhibitors of glutamate release from aggressive breast cancer cells advances a novel, mechanistic approach to targeting CIBP that could advance treatment for several pathological conditions. Using high-throughput screening, we investigated the ability of approximately 30,000 compounds from the Canadian Compound Collection to reduce glutamate release from MDA-MB-231 breast cancer cells. This line is known to secrete high levels of glutamate and has been demonstrated to induce CIBP by this mechanism. Positive chemical hits were based on the potency of each molecule relative to a known pharmacological inhibitor of glutamate release, sulfasalazine. Efficacy was confirmed and drug-like molecules were identified as potent inhibitors of glutamate secretion from MDA-MB-231, MCF-7 and Mat-Ly-Lu cells. PMID:25670024

Fazzari, Jennifer; Lin, Hanxin; Murphy, Cecilia; Ungard, Robert; Singh, Gurmit

2015-01-01

361

The effect of purified compared with nonpurified diet on bone changes induced by hindlimb suspension of female rats  

NASA Technical Reports Server (NTRS)

The purpose of this study was to compare the bone changes induced by unloading in rats fed different diets, because space flight studies use a semipurified diet, whereas space flight simulation studies typically use nonpurified diets. Female Sprague-Dawley rats were fed a purified American Institute of Nutrition (AIN) 93G diet or a standard nonpurified diet and kept ambulatory or subjected to unloading by hindlimb suspension (HLS) for 38 days. Bone mineral content (BMC), mechanical strength, and factors related to the diet that affect bone (i.e., urinary calcium excretion, estradiol, and corticosterone) were measured. Average food intakes (grams per day) differed for diets, but caloric intake (kilocalories per day) and the final body masses of treatment groups were similar. The HLS-induced decrease in femoral BMC was not statistically different for rats fed a nonpurified diet (-8.6%) compared with a purified AIN-93G diet (-11.4%). The HLS-induced decrease in femoral mechanical strength was not statistically different for rats fed a nonpurified diet (-24%) compared with a purified AIN-93G diet (-31%). However, bone lengths were decreased (P < 0.05) in rats fed a nonpurified diet compared with a purified diet. Plasma estradiol levels were lower (P < 0.05) in the HLS/AIN-93G group but similar in the HLS and ambulatory rats fed a nonpurified diet. Plasma estradiol was related to femoral BMC (r = 0.85, P < 0.01). Urinary calcium excretion was higher (P < 0.05) in rats fed a nonpurified diet than those fed a purified AIN-93G diet, which is consistent with the higher level of calcium in the nonpurified diet. Urinary corticosterone levels were higher (P < 0.05) in rats fed a nonpurified diet than rats fed the AIN-93G diet. Although the osteopenia induced by unloading was similar in both diet groups, there were differences in longitudinal bone growth, calcium excretion, plasma estradiol levels, and urinary corticosterone levels. Results indicate that the type of standard diet used is an important factor to consider when measuring bone end points.

Tou, Janet C L.; Arnaud, Sara B.; Grindeland, Richard; Wade, Charles

2005-01-01

362

Inflammatory Bone Loss in Experimental Periodontitis Induced by Aggregatibacter actinomycetemcomitans in Interleukin-1 Receptor Antagonist Knockout Mice  

PubMed Central

The interleukin-1 receptor antagonist (IL-1Ra) binds to IL-1 receptors and inhibits IL-1 activity. However, it is not clear whether IL-1Ra plays a protective role in periodontal disease. This study was undertaken to compare experimental periodontitis induced by Aggregatibacter actinomycetemcomitans in IL-1Ra knockout (KO) mice and wild-type (WT) mice. Computed tomography (CT) analysis and hematoxylin-and-eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining were performed. In addition, osteoblasts were isolated; the mRNA expression of relevant genes was assessed by real-time quantitative PCR (qPCR); and calcification was detected by Alizarin Red staining. Infected IL-1Ra KO mice exhibited elevated (P, <0.05) levels of antibody against A. actinomycetemcomitans, bone loss in furcation areas, and alveolar fenestrations. Moreover, protein for tumor necrosis factor alpha (TNF-?) and IL-6, mRNA for macrophage colony-stimulating factor (M-CSF), and receptor activator of NF-?B ligand (RANKL) in IL-1Ra KO mouse osteoblasts stimulated with A. actinomycetemcomitans were increased (P, <0.05) compared to in WT mice. Alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN)/bone gla protein (BGP), and runt-related gene 2 (Runx2) mRNA levels were decreased (P, <0.05). IL-1? mRNA expression was increased, and calcification was not observed, in IL-1 Ra KO mouse osteoblasts. In brief, IL-1Ra deficiency promoted the expression of inflammatory cytokines beyond IL-1 and altered the expression of genes involved in bone resorption in A. actinomycetemcomitans-infected osteoblasts. Alterations consistent with rapid bone loss in infected IL-Ra KO mice were also observed for genes expressed in bone formation and calcification. In short, these data suggest that IL-1Ra may serve as a potential therapeutic drug for periodontal disease. PMID:24566623

Izawa, A.; Mizutani, H.; Kobayashi, S.; Goto, H.; Okabe, E.; Takeda, H.; Ozawa, Y.; Kamiya, Y.; Sugita, Y.; Kubo, K.; Kamei, H.; Kikuchi, T.; Mitani, A.; Hayashi, J.; Nishihara, T.; Maeda, H.; Noguchi, T.

2014-01-01

363

Laser-perforated membranous biomaterials induced pore size-dependent bone induction when used as a new BMP carrier.  

PubMed

Previously we found that laser perforation of a collagen membrane (35 microm thickness, Koken Co., Tokyo) produced an effective bone morphogenetic protein (BMP) carrier, if the created pore sizes were larger than 0.5 mm. In this study we applied the same technique to create pores of 0.2 and 1.0 mm in a thicker (1.2 mm thickness) porous biodegradable membrane made of polylactic acid and an epsilon-caprolactone copolymer (PLA-CL) to obtain an effective membranous BMP carrier with higher mechanical strength. Pieces of PLA-CL (0.5 x 1.0 x 0.12 cm) combined with rhBMP-2 (5 microg) were implanted subcutaneously into rats and processed for analyses at 1-3 weeks. The laser-perforated PLA-CL membranes equipped with 1.0 mm pores induced mineralization beginning from the margins of the pores judging from the X-ray patterns, but bone formation seemed to proceed irregularly inside the pores. In the perforated PLA-CL membrane with 1.0-mm pores bone formation did not significantly increase compared with the nonperforated one. This was due to the fact that the PLA-CL membrane was already a porous structure (85% porosity). In contrast with laser-perforated PLA-CL 0.2 mm pores, bone was induced on the collagen fibers and fiber bundles inside the pores. The different patterns of bone formation between the PLA-CL membranes with 1.0 and 0.2 mm pores seemed to be related to the active formation of perpendicular collagen fibers through the 0.2 mm pores. PMID:12952216

Kuboki, Y; Kikuchi, M; Takita, H; Yoshimoto, R; Nakayama, Y; Matsuda, T; Ikada, Y

2003-01-01

364

Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system  

PubMed Central

Background Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC), satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that support neuronal survival and axonal growth following peripheral nerve injury. Fibroblast growth factor-2 (FGF-2) is the main mitogenic factor for SCs and is released in large amounts by bone marrow-derived cells, as well as by growing axons and endoneurial fibroblasts during development and regeneration of the peripheral nervous system (PNS). Results Here we show that bone marrow-derived cell treatment induce an increase in the expression of FGF-2 in the sciatic nerve, dorsal root ganglia and the dorsolateral (DL) region of the lumbar spinal cord (LSC) in a model of sciatic nerve transection and connection into a hollow tube. SCs in culture in the presence of bone marrow derived conditioned media (CM) resulted in increased proliferation and migration. This effect was reduced when FGF-2 was neutralized by pretreating BMMC or CM with a specific antibody. The increased expression of FGF-2 was validated by RT-PCR and immunocytochemistry in co-cultures of bone marrow derived cells with sciatic nerve explants and regenerating nerve tissue respectivelly. Conclusion We conclude that FGF-2 secreted by BMMC strongly increases early glial proliferation, which can potentially improve PNS regeneration. PMID:22793996

2012-01-01

365

Granulocytosis-inducing tumor inhibits the production of B lymphocytes in murine bone marrow  

Microsoft Academic Search

Mice bearing a transplantable CE mammary carcinoma have been shown to have greatly augmented rates of neutrophil production coupled with a marked diminution of bone marrow lymphocytes. The objective the present study was to test whether the loss of lymphocytes, and especially of B cells, from the bone marrow and spleen of tumor-bearing animals was due to a reduced rate

G. Fueloep; M. Y. Lee; C. Rosse

1985-01-01

366

Osteogenesis induced by autologous bone marrow cells transplant in the pediatric skull  

Microsoft Academic Search

Background and purpose  The ability of cranial bone to repair defects of continuity is limited and it is mostly dependent on the age of the patient. In infancy and in early pediatric age, the scarce thickness of the calvarial bones and the need for a harmonic development of the child’s skull limit the application of most of the surgical procedures usually

Francesco Velardi; Paolina R. Amante; Maurizio Caniglia; Giulio De Rossi; PierPaolo Gaglini; Giancarlo Isacchi; Paolo Palma; Emidio Procaccini; Francesco Zinno

2006-01-01

367

Castor oil polymer induces bone formation with high matrix metalloproteinase-2 expression.  

PubMed

The aim of this study was to evaluate the modulation of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) expression in newly formed bone tissue at the interface between implants derived from castor oil (Ricinus communis) polymer and the tibia medullary canal. Forty-four rabbits were assigned to either Group 1 (n?=?12; control) or Group 2 (n?=?30), which had the tibial medullary canals reamed bilaterally and filled with polymer. CT scans showed no space between the material surface and the bone at the implant/bone marrow interface, and the density of the tissues at this interface was similar to the density measured of other regions of the bone. At 90 days postimplantation, the interface with the polymer presented a thick layer of newly formed bone tissue rich in osteocytes. This tissue exhibited ongoing maturation at 120 and 150 days postimplantation. Overall, bone remodeling process was accompanied by positive modulation of MMP-2 and low MMP-9 expression. Differently, in control group, the internal surface close to the medullary canal was lined by osteoblasts, followed by a bone tissue zone with few lacunae filled with osteocytes. Maturation of the tissue of the medullary internal surface occurred in the inner region, with the bone being nonlamellar. PMID:23670892

Saran, Wallace Rocha; Chierice, Gilberto Orivaldo; da Silva, Raquel Assed Bezerra; de Queiroz, Alexandra Mussolino; Paula-Silva, Francisco Wanderley Garcia; da Silva, Léa Assed Bezerra

2014-02-01

368

A superior semicircular canal dehiscence induced air-bone gap in chinchilla  

PubMed Central

An SCD is a pathologic hole (or dehiscence) in the bone separating the superior semicircular canal from the cranial cavity that has been associated with a conductive hearing loss in patients with SCD syndrome. The conductive loss is defined by an audiometrically determined air-bone gap that results from the combination of a decrease in sensitivity to air-conducted sound and an increase in sensitivity to bone-conducted sound. Our goal is to demonstrate, through physiological measurements in an animal model, that mechanically altering the superior semicircular canal (SC) by introducing a hole (dehiscence) is sufficient to cause such an air-bone gap. We surgically introduced holes into the SC of chinchilla ears and evaluated auditory sensitivity (cochlear potential) in response to both air- and bone-conducted stimuli. The introduction of the SC hole led to a low-frequency (< 2000 Hz) decrease in sensitivity to air-conducted stimuli and a low-frequency (< 1000 Hz) increase in sensitivity to bone-conducted stimuli resulting in an air-bone gap. This result was consistent and reversible. The air-bone gaps in the animal results are qualitatively consistent with findings in patients with SCD syndrome. PMID:20638462

Songer, Jocelyn E.; Rosowski, John J.

2010-01-01

369

A mechanism for sympathectomy-induced bone resorption in the middle ear  

Microsoft Academic Search

BACKGROUND: Recent investigations have demonstrated a link between sympathectomy and osteoclast-mediated bone resorption. The exact nature of this link, however, is unknown. We hypothesize that substance P, a potent vasoconstrictive neuropeptide found in peripheral sensory fibers, including those innervating bone, is the mediator of this phenomenon. To test this theory, the effects of substance P on in vitro calcium release

BRET E. SHERMAN; RICHARD A. CHOLE

1995-01-01

370

A New Piezoelectric Actuator Induces Bone Formation In Vivo: A Preliminary Study  

PubMed Central

This in vivo study presents the preliminary results of the use of a novel piezoelectric actuator for orthopedic application. The innovative use of the converse piezoelectric effect to mechanically stimulate bone was achieved with polyvinylidene fluoride actuators implanted in osteotomy cuts in sheep femur and tibia. The biological response around the osteotomies was assessed through histology and histomorphometry in nondecalcified sections and histochemistry and immunohistochemistry in decalcified sections, namely, through Masson's trichrome, and labeling of osteopontin, proliferating cell nuclear antigen, and tartrate-resistant acid phosphatase. After one-month implantation, total bone area and new bone area were significantly higher around actuators when compared to static controls. Bone deposition rate was also significantly higher in the mechanically stimulated areas. In these areas, osteopontin increased expression was observed. The present in vivo study suggests that piezoelectric materials and the converse piezoelectric effect may be used to effectively stimulate bone growth. PMID:22701304

Reis, Joana; Frias, Clara; Canto e Castro, Carlos; Botelho, Maria Luísa; Marques, António Torres; Simões, José António Oliveira; Capela e Silva, Fernando; Potes, José

2012-01-01

371

A new piezoelectric actuator induces bone formation in vivo: a preliminary study.  

PubMed

This in vivo study presents the preliminary results of the use of a novel piezoelectric actuator for orthopedic application. The innovative use of the converse piezoelectric effect to mechanically stimulate bone was achieved with polyvinylidene fluoride actuators implanted in osteotomy cuts in sheep femur and tibia. The biological response around the osteotomies was assessed through histology and histomorphometry in nondecalcified sections and histochemistry and immunohistochemistry in decalcified sections, namely, through Masson's trichrome, and labeling of osteopontin, proliferating cell nuclear antigen, and tartrate-resistant acid phosphatase. After one-month implantation, total bone area and new bone area were significantly higher around actuators when compared to static controls. Bone deposition rate was also significantly higher in the mechanically stimulated areas. In these areas, osteopontin increased expression was observed. The present in vivo study suggests that piezoelectric materials and the converse piezoelectric effect may be used to effectively stimulate bone growth. PMID:22701304

Reis, Joana; Frias, Clara; Canto e Castro, Carlos; Botelho, Maria Luísa; Marques, António Torres; Simões, José António Oliveira; Capela e Silva, Fernando; Potes, José

2012-01-01

372

Spaceflight-induced Bone Loss: Is there a Risk for Accelerated Osteoporosis after Return?  

NASA Technical Reports Server (NTRS)

The evidence-to to-date suggests that the rapid rate of site-specific bone loss in space, due to the unbalanced stimulation of bone resorption, may predispose crew members to irreversible changes in bone structure and microarchitecture. No analyses conducted in the postflight period to assess microarchitectural changes. There is no complete analysis of skeletal recovery in the postflight period to evaluate the structural changes that accompany increases in DXA aBMD. Postflight analyses based upon QCT scans performed on limited crew members indicate reductions in hip bone strength and incomplete recovery at 1 year. No recovery of trabecular vBMD after 1 year return (HRP IWG). Time course of bone loss in space unknown.

Sibonga, Jean

2008-01-01

373