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Sample records for human bone lead

  1. The analysis of lead, cadmium, zinc, copper and nickel content in human bones from the upper Silesian industrial district.

    Science.gov (United States)

    Baranowska, I; Czernicki, K; Aleksandrowicz, R

    1995-01-10

    The concentration of lead, cadmium, zinc, copper and nickel in autopsy samples of bones from adults living in the Upper Silesian industrial district (Poland)--an ecological disaster region--was determined by atomic absorption spectrometry (flame and flameless GF AAS). Lead concentrations ranged from 20 micrograms/g to 200 micrograms/g bone wet weight, cadmium from 0.4 microgram/g to 1.5 micrograms/g bone wet weight. About one-fourth of the bones examined from Silesia, contained lead in the range from 100 micrograms/g to 200 micrograms/g. The were no significant differences in zinc, copper and nickel concentration between the control groups. The samples were mineralized in a microwave digestion system. To avoid anomalous results caused by the influence of the matrix Ca3 (PO4)2--the procedure of lead determination was carried out at a temperature of 2000 degrees C, the cadmium determination at a temperature of about 1200 degrees C.

  2. Modeling of Blood Lead Levels in Astronauts Exposed to Lead from Microgravity-Accelerated Bone Loss

    Science.gov (United States)

    Garcia, H.; James, J.; Tsuji, J.

    2014-01-01

    Human exposure to lead has been associated with toxicity to multiple organ systems. Studies of various population groups with relatively low blood lead concentrations (adults. Cognitive effects are considered by regulatory agencies to be the most sensitive endpoint at low doses. Although 95% of the body burden of lead is stored in the bones, the adverse effects of lead correlate with the concentration of lead in the blood better than with that in the bones. NASA has found that prolonged exposure to microgravity during spaceflight results in a significant loss of bone minerals, the extent of which varies from individual to individual and from bone to bone, but generally averages about 0.5% per month. During such bone loss, lead that had been stored in bones would be released along with calcium. The effects on the concentration of lead in the blood (PbB) of various concentrations of lead in drinking water (PbW) and of lead released from bones due to accelerated osteoporosis in microgravity, as well as changes in exposure to environmental lead before, during, and after spaceflight were evaluated using a physiologically based pharmacokinetic (PBPK) model that incorporated exposure to environmental lead both on earth and in flight and included temporarily increased rates of osteoporosis during spaceflight.

  3. A new anthropometric phantom of the human leg for calibrating in vivo measurements of stable lead in bone using x-ray fluorescence

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    Spitz, Henry; Jenkins, Mark; Lodwick, Jeffrey [Cincinnati Univ., OH (United States). Dept. of Mechanical, Industrial and Nuclear Engineering

    1997-12-31

    Full text. A new anthropometric phantom of the human leg has been developed for calibrating in vivo measurements of stable lead in the bone using x-ray fluorescence. The phantom reproduces the shape and radiological characteristics of the midshaft of the human leg and includes tissue substitutes for cortical bone, bone marrow, and muscle which have been formulated using polyurethanes and calcium carbonate to provide the desired characteristics of density x-ray attenuation, and calcium content. The phantom includes a set of simulated tibia bones, each containing a precisely known concentration of stable lead, that can be easily inserted into the leg. Formerly, of a set of plexiglas cylinders filled with plaster of-paris, each containing a known lead content, was the consensus standard calibration phantom. Tissue substitute materials used in the new anthropometric calibration phantom are much more uniform in density and composition than the plaster-of-paris phantoms and its realistic appearance provides a practical means of evaluating the variability in measurements results due to the changes in subject-detector positioning. Use of the new anthropometric calibration phantom results in a energy spectrum that closely resembles the spectrum observed when measuring a human subject. The energy spectrum produced by the plaster-of-paris phantom lacks the substantial Compton Scattering component produced by the leg muscle mass which leads to unrealistic estimates of in vivo measurement sensitivity. The minimum detection limit (MDL) for in vivo measurement of stable lead in bone, using an efficiency derived from the new anthropometric phantom, ranges from 18,6 parts per million (ppm) to 26,3 ppm using the K{sub {beta}1,3}/Elastic ratio or the K{sup 1}/Elastic ratio, respectively. These values are significantly greater than the MDL cited in the literature obtained using a efficiency derived the conventional cylindrical plaster-of-paris phantom. Likewise, the realistic shape of

  4. Microdistribution of lead in bone: A new approach

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    Jones, K.W. [Brookhaven National Lab., Upton, NY (United States); Bockman, R.S. [Cornell Univ., New York, NY (United States). Medical Coll.; Bronner, F. [Connecticut Univ. Health Center, Farmington, CT (United States)

    1991-12-31

    A knowledge of the microdistribution of lead in bone is important in order to understand the mechanisms for accumulation and release of lead. The availability of the synchrotron x-ray microscope for sensitive measurements of bone content and distribution of lead provides a valuable tool which, when combined with kinetic, balance, and tissue measurements, can lead to better evaluation of lead toxicity. It may also provide the basis for the development of a suitable model of how lead behaves in the human body. An outline of an experimental protocol for exploitation of the x-ray microscope is given, along with synchrotron x-ray microscope measurements of the distribution of gallium in rat bone that demonstrate the feasibility of the experimental approach.

  5. Microdistribution of lead in bone: A new approach

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    Jones, K.W. (Brookhaven National Lab., Upton, NY (United States)); Bockman, R.S. (Cornell Univ., New York, NY (United States). Medical Coll.); Bronner, F. (Connecticut Univ. Health Center, Farmington, CT (United States))

    1991-01-01

    A knowledge of the microdistribution of lead in bone is important in order to understand the mechanisms for accumulation and release of lead. The availability of the synchrotron x-ray microscope for sensitive measurements of bone content and distribution of lead provides a valuable tool which, when combined with kinetic, balance, and tissue measurements, can lead to better evaluation of lead toxicity. It may also provide the basis for the development of a suitable model of how lead behaves in the human body. An outline of an experimental protocol for exploitation of the x-ray microscope is given, along with synchrotron x-ray microscope measurements of the distribution of gallium in rat bone that demonstrate the feasibility of the experimental approach.

  6. Comparative investigations on the lead content of human bones from prehistoric and historical times from Bavaria and Peru. Vergleichende Untersuchungen zum Bleigehalt praehistorischer und historischer menschlicher Knochen aus Bayern und Peru

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    Brabender von Lossberg, I.

    1982-05-25

    The lead content of human bones of 129 individuals from different prehistoric and historical populations of Bavaria and Peru was determined by means of flameless absorption spectroscopy. By the same method the lead content of human tissue was determined in 12 Peruvian mummy heads, and that of the hair in two individuals. The results were compared with each other and with those of other investigations on prehistoric, historical and modern populations and were interpreted. The comparative investigation confirmed the assumption that intensive exposure to lead in a population leads to higher lead concentration in the bones. The lead concentration in the bones of the late mediaeval series of Niedermuenster 4 was comparable to the one in the bones of modern populations and amounted to about 10 times the average one in prehistoric Peruvians. The lead accumulation was not found to be sex-dependent. The chronic lead intoxication of the late Middle Ages described by the history of medicine was confirmed by the relatively high lead contents in bones of Niedermuenster 4. In the framework of an epidemiological survey the problem of chronic lead intoxication was traced back to pre and early history.

  7. The effect of lead in bone densitometry

    Science.gov (United States)

    Popovic, Marija; McNeill, Fiona E.; Webber, Colin E.; Chettle, David R.

    2004-01-01

    Dual energy X-ray absorptiometry (DXA) is presently considered the standard technique for diagnosis of osteoporosis. It has been suggested that the presence of lead interferes with the accurate measurement of bone mineral density (BMD) by DXA because of the increased attenuation and that an accurate measurement of BMD cannot be determined unless the patient's bone lead content of patients is known. We performed DXA measurements on plaster of Paris phantoms and a Hologic Spine phantom in combination with polyester resin doped with various concentrations of lead. At lead levels which correspond to bone concentrations in occupationally exposed individuals, the suggested increase in densitometric BMD was not detected. Numerical calculations show that the effect of the lead depends upon the two energies of the X-ray beam of a particular device. The discrepancy between the actual and the densitometric BMD increases linearly and is about 0.3% at 100 ppm. Such change cannot be detected by the Hologic QDR 4500A, the device used for this experiment.

  8. Individual variability in human tibia lead concentration.

    OpenAIRE

    Todd, A. C.; Parsons, P J; Tang, S.; Moshier, E L

    2001-01-01

    Our aims in this study were to determine proximal-distal variability in adult human tibia lead concentration via electrothermal atomization atomic absorption spectrometry (ETAAS) and to determine whether there were any differences between core and surface tibia lead concentrations. We analyzed duplicate core and surface tibia samples for lead at multiple proximal-distal sections on 10 adult human cadaver legs. Dried bone samples were digested in nitric acid using microwave-assisted heating, a...

  9. Lead and osteoporosis: Mobilization of lead from bone in postmenopausal women

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    Silbergeld, E.K. (Environmental Defense Fund, WA (USA)); Schwartz, J. (Environmental Protection Agency, Washington, DC (USA)); Mahaffey, K. (National Institute of Environmental Health Sciences, Research Triangle Park, NC (USA))

    1988-10-01

    Although it has been known that humans accumulate lead in bone, mineralized tissue has been considered primarily as a sequestering compartment and not as a site of toxic action for lead. However, experimental data indicate that bone lead can be released during conditions of demineralization, such as pregnancy and lactation. We have examined lead status in women, before and after menopause, using the NHANES II dataset compiled between 1976 and 1980. In 2981 black and white women there was a highly significant increase in both whole blood and calculated plasma lead concentrations after menopause. The results indicate that bone lead is not an inert storage site for absorbed lead. Moreover, lead may interact with other factors in the course of postmenopausal osteoporosis, to aggravate the course of the disease, since lead is known to inhibit activation of vitamin D, uptake of dietary calcium, and several regulatory aspects of bone cell function. The consequences of this mobilization may also be of importance in assessing the risks of maternal lead exposure to fetal and infant health.

  10. Increased bone calcium dissociation in lead-exposed rats

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    Eko Suhartono

    2012-12-01

    Full Text Available Background Lead is still a major environmental and occupational health hazard, since it is extensively used in the production of paints, gasoline and cosmetics. This causes the metal to be ubiquitous in the environment, being found in the air, soil, and water, from which it can enter the human body by inhalation or ingestion. Absorbed lead is capable of altering the calcium levels in bone. The aim of this study was to demonstrate the effect of lead on bone calcium levels by measuring the reaction constant, Gibbs free energy, and enthalpy. Methods This study was of pure experimental design using 100 male albino rats (Rattus norvegicus. The experimental animals were assigned by simple randomization to two groups, one group receiving lead acetate orally at a dosage of 100 mg/kgBW, while the other group did not receive lead acetate. The intervention was given for 4 weeks and the rats were observed weekly for measurement of bone calcium levels by the permanganometric method. Results This study found that k1 (hydroxyapatite dissociation rate constant was 0.90 x 10-3 dt-1, and that k2 (hydroxyapatite association rate constant was 6.16 x 10-3 dt-1 for the control group, whereas for the intervention group k1 = 26.20 x 10-3 dt-1 and k2 = 16.75 x 10-3 dt-1. Thermodynamically, the overall reaction was endergonic and endothermic (DG > 0 and DH > 0. ConclusionS Lead exposure results in increased dissociation rate of bone in comparison with its association rate. Overall, the reaction was endergonic and endothermic (DG > 0 and DH > 0.

  11. Increased bone calcium dissociation in lead-exposed rats

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    Eko Suhartono

    2015-12-01

    Full Text Available BACKGROUND Lead is still a major environmental and occupational health hazard, since it is extensively used in the production of paints, gasoline and cosmetics. This causes the metal to be ubiquitous in the environment, being found in the air, soil, and water, from which it can enter the human body by inhalation or ingestion. Absorbed lead is capable of altering the calcium levels in bone. The aim of this study was to demonstrate the effect of lead on bone calcium levels by measuring the reaction constant, Gibbs free energy, and enthalpy. METHODS This study was of pure experimental design using 100 male albino rats (Rattus norvegicus. The experimental animals were assigned by simple randomization to two groups, one group receiving lead acetate orally at a dosage of 100 mg/ kgBW, while the other group did not receive lead acetate. The intervention was given for 4 weeks and the rats were observed weekly for measurement of bone calcium levels by the permanganometric method. RESULTS This study found that k1 (hydroxyapatite dissociation rate constant was 0.90 x 10-3 dt-1, and that k2 (hydroxyapatite association rate constant was 6.16 x 10-3 dt-1 for the control group, whereas for the intervention group k1 = 26.20 x 10-3 dt-1 and k2 = 16.75 x 10-3 dt-1. Thermodynamically, the overall reaction was endergonic and endothermic (ΔG > 0 and ΔH > 0. CONCLUSIONS Lead exposure results in increased dissociation rate of bone in comparison with its association rate. Overall, the reaction was endergonic and endothermic (ΔG > 0 and ΔH > 0.

  12. RNA Amplification Protocol Leads to Biased Polymerase Chain Reaction Results Especially for Low-Copy Transcripts of Human Bone Marrow-Derived Stromal Cells.

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    Carolin Coenen

    Full Text Available The amplification of RNA is becoming increasingly important, as often only limited amounts of cells are available for gene expression analysis. In this study, the gene expression profile of the 39 human homeobox (HOX genes was analyzed in bone marrow-derived multipotent stromal cells (BM-MSCs by reverse transcription (RT- and quantitative polymerase chain reaction (qPCR. For further unlimited gene expression analysis, Whole Transcriptome Amplification (WTA was used to amplify RNA from human BM-MSCs. However, WTA led to biased RT- and qPCR results, and even non-detectability of HOX transcripts compared to non-amplified BM-MSC samples which instead revealed transcription. It is important to note that the same RNA of the respective human BM-MSC line was used for normal cDNA synthesis by standard reverse transcription (non-amplified RT samples and for cDNA synthesis by WTA (amplified WTA samples. On this account, the different RT- and qPCR results were unexpected applying WTA. The significantly reduced detection of HOX transcripts after WTA has been demonstrated for numerous BM-MSC lines (n = 26 by RT-PCR analysis. Furthermore, undetectable HOX transcripts meaning HOX transcripts of human BM-MSCs that were detected after normal cDNA synthesis, but were no longer detectable after WTA, were consistently observed by qPCR analysis. Finally, qPCR experiments revealed a possible explanation for the differences between amplified and non-amplified BM-MSC samples: an inverse correlation between the biased qPCR results and the low expression level of the respective HOX gene. The PCR analysis of high-copy transcripts like GAPDH or RPL13A revealed unchanged qPCR results after WTA compared to corresponding non-amplified BM-MSC samples. In contrast, WTA led to biased qPCR results for medium-copy HOX transcripts, and even non-detectability of low-copy HOX transcripts of human BM-MSCs resulting in false negative RT- and qPCR data applying WTA.

  13. Bone regeneration with cultured human bone grafts

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    Yoshikawa, T.; Nakajima, H. [Nara Medical Univ., Kashihara City (Japan). Dept. of Pathology; Nara Medical Univ., Kashihara City (Japan). Dept. of Orthopedic Surgery; Ohgushi, H.; Ueda, Y.; Takakura, Y. [Nara Medical Univ., Kashihara City (Japan). Dept. of Orthopedic Surgery; Uemura, T.; Tateishi, T. [National Inst. for Advanced Interdisciplinary Research (NAIR), Ibaraki (Japan). Tsukuba Research Center; Enomoto, Y.; Ichijima, K. [Nara Medical Univ., Kashihara City (Japan). Dept. of Pathology

    2001-07-01

    From 73 year old female patient, 3 ml of bone marrow was collected from the ilium. The marrow was cultured to concentrate and expand the marrow mesenchymal cells on a culture dish. The cultured cells were then subculturedeither on another culture dish or in porous areas of hydroxyapatite ceramics in the presence of dexamethasone and beta-glycerophosphate (osteo genic medium). The subculturedtissues on the dishes were analyzed by scanning electron microscopy (SEM), and subculturedtissues in the ceramics were implanted intraperitoneally into athymic nude mice. Vigorous growth of spindle-shaped cells and a marked formation of bone matrix beneath the cell layers was observed on the subculture dishes by SEM. The intraperitoneally implanted ceramics with cultured tissues revealed thick layer of lamellar bone together with active osteoblasts lining in many pore areas of the ceramics after 8 weeks. The in vitro bone formations on the culture dishes and in vivo bone formation in porous ceramics were detected. These results indicate that we can assemble an in vitro bone/ceramic construct, and due to the porous framework of the ceramic, the construct has osteogenic potential similar to that of autologous cancellous bone. A significant benefit of this method is that the construct can be made with only a small amount of aspirated marrow cells from aged patients with little host morbidity. (orig.)

  14. Prenatal lead exposure and bone growth. Doctoral thesis

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    Hamilton, J.D.; O' Flaherty, E.J.

    1990-07-24

    An experimental system of lead (7439921) related prenatal and postnatal growth retardation in rats was developed. Sprague-Dawley-rats and Long-Evans-rats were used in these studies. Rats were exposed to lead in their drinking water at up to 1000 parts per million. A significant effect on fetal bone mineralization could not be excluded and there was a definite effect on fetal body weight following maternal lead exposure. Reduced food intake during the first week of lead exposure was the primary determinant of reduced body and skeletal growth in the lead exposed weanling female rats. When maternal lead exposure was continued during lactation a greater degree of lead related growth retardation in rat offspring occurred than when maternal lead exposure was terminated at parturition. Combined prenatal and postnatal lead exposure impaired bone resorption and increased growth plate widths. In studies using matrix induced endochondral bone plaques, locally applied lead enhanced plaque mineralization through comineralization of lead with calcium. When lead was administered in drinking water, plaque mineralization was also enhanced through the comineralization of lead with calcium.

  15. Nuclear microprobe analysis of lead profile in crocodile bones

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    Orlic, I.; Siegele, R.; Hammerton, K.; Jeffree, R. A.; Cohen, D. D.

    2003-09-01

    Elevated concentrations of lead were found in Australian free ranging saltwater crocodile ( Crocodylus porosus) bone and flesh. Lead shots were found as potential source of lead in these animals. ANSTO's heavy ion nuclear microprobe was used to measure the distribution of Pb in a number of bones and osteoderms. The aim was to find out if elevated Pb concentration remains in growth rings and if the concentration is correlated with the blood levels recorded at the time. Results of our study show a very distinct distribution of accumulated Pb in bones and osteoderms as well as good correlation with the level of lead concentration in blood. To investigate influence of ion species on detection limits measurements of the same sample were performed by using 3 MeV protons, 9 MeV He ions and 20 MeV carbon ions. Peak to background ratios, detection limits and the overall 'quality' of obtained spectra are compared and discussed.

  16. Localized accumulation of lead within and among bones from lead-dosed goats

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    Cretacci, Yan [Laboratory of Inorganic and Nuclear Chemistry, Wadsworth Center, New York State Department of Health, P.O. Box 509, Albany, NY 12201-0509 (United States); Department of Environmental Health Sciences, School of Public Health, The University at Albany, P.O. Box 509, Albany, NY 12201-0509 (United States); Parsons, Patrick J., E-mail: pparsons@wadsworth.org [Laboratory of Inorganic and Nuclear Chemistry, Wadsworth Center, New York State Department of Health, P.O. Box 509, Albany, NY 12201-0509 (United States); Department of Environmental Health Sciences, School of Public Health, The University at Albany, P.O. Box 509, Albany, NY 12201-0509 (United States)

    2010-01-15

    The principal aim of this study was to gain a better understanding of where lead (Pb) accumulates and how it is distributed, within the bones of dosed goats. Adult goats were periodically dosed with Pb over a number of years for the primary purpose of producing blood pools containing endogenously bound Pb, for the New York State Blood Lead Proficiency Testing Program. Bone samples (e.g., primarily tibia, femur, humerus, and radius) were collected post-mortem from 11 animals and were analyzed for Pb content by acid digestion and electrothermal atomic absorption spectrometry (ETAAS or GFAAS). Average tibia Pb levels were found to correlate strongly with the cumulative Pb dose (r{sup 2}=0.81). However, the concentration of Pb in different bones and even within a small area of the same bone varied tremendously. Blood-rich trabecular (spongy) bone, such as the patella and calcaneus, were much more enriched in Pb than was cortical (compact) bone. In some dosed animals, the Pb concentration in the tibia was markedly higher at the proximal and distal ends of the bone compared to the mid-shaft. The implications of these findings with regard to the noninvasive measurement of lead in bone by XRF methods are discussed.

  17. The influence of lead on the biomechanical properties of bone tissue in rats

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    Grazyna Olchowik

    2014-06-01

    Full Text Available introduction and objective. Environmental lead (Pb is a serious public health problem. At high levels, Pb is devastating to almost all organs. On the other hand, it is difficult to determine a safe level of exposure to Pb. More than 90% of the Pb in the adult human body and 70% in a child’s body is stored in the bones. In the presented study, the effects of lead exposure on bones were studied for rats treated orally with Pb acetate in drinking water for 14 days. The hypothesis was tested that lead exposure negatively affects bone structure. materials and methods. Femur strength was measured in a three-point bending test, whereas infrared spectroscopy (FTIR was used to measure molecular structural changes. results. Lead significantly decreased the ratio of area of two types of vibrational transitions, which are highly specific to mineral to matrix ratio. The results of the biomechanical study show that femurs of rats treated by Pb-acetate appeared to be weaker than bones of the control group, and may produce a condition for the development of higher risk of fractures. Additionally, a great difference in body mass was observed between control and the Pb acetate-treated groups. conclusions. The lower bone mineral content and the weaker mechanical properties of bones from Pb-treated rats are associated with the pathologic state dependent of the exposure of lead.

  18. Toxicity of uranium and lead on osteoblastic bone cells

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    Milgram, S.; Thiebault, C.; Carriere, M.; Gouget, B. [CEA Saclay, CNRS, UMR9956, Lab Pierre Sue, F-91191 Gif Sur Yvette, (France); Malaval, L. [INSERM, 42023 Saint Etienne (France)

    2007-07-01

    Bone is one of the main retention organs affected by uranium (U) and lead (Pb). Intoxications have been documented to inhibit bone formation and impair bone modeling and remodeling. However, only few studies dealt with cellular and molecular mechanisms of their toxicity. The purpose of this study was to investigate the acute cytotoxicity of U and Pb and their phenotypic effects on ROS17/2.8 osteoblastic cells. The most likely forms of the toxics in contact with cells after blood contamination were selected for cell exposure. Results show that whatever their speciation, bone cells are always more sensitive to Pb than to U. Moreover, Pb is toxic when it is left free in the exposure medium or when it is complexed with bicarbonate, cysteine or citrate, but not with albumin or phosphate. U is more cytotoxic when it is complexed with transferrin than with bicarbonate. A direct correlation between toxicity and cellular accumulation could be observed. Beside, exposure of U or Pb to bone cells induces a speciation-dependant variation of RNA expression of two markers of bone formation and mineralization: osteocalcin (OCN) and bone sialoprotein (BSP). OCN and BSP-expression could be activated in sub-toxic condition, respectively, by Pb-albumin (1.6-fold) and U-bicarbonate (2.3-fold). In the meantime, U-transferrin and Pb-citrate lead to an inhibition of the two markers. This study shows a complex mechanism of toxicity of two heavy metals with a significant phenotypic impact on osteoblastic cells highly dependant on metal speciation which controls cell accumulation. (authors)

  19. Atomic scale chemical tomography of human bone

    Science.gov (United States)

    Langelier, Brian; Wang, Xiaoyue; Grandfield, Kathryn

    2017-01-01

    Human bone is a complex hierarchical material. Understanding bone structure and its corresponding composition at the nanometer scale is critical for elucidating mechanisms of biomineralization under healthy and pathological states. However, the three-dimensional structure and chemical nature of bone remains largely unexplored at the nanometer scale due to the challenges associated with characterizing both the structural and chemical integrity of bone simultaneously. Here, we use correlative transmission electron microscopy and atom probe tomography for the first time, to our knowledge, to reveal structures in human bone at the atomic level. This approach provides an overlaying chemical map of the organic and inorganic constituents of bone on its structure. This first use of atom probe tomography on human bone reveals local gradients, trace element detection of Mg, and the co-localization of Na with the inorganic-organic interface of bone mineral and collagen fibrils, suggesting the important role of Na-rich organics in the structural connection between mineral and collagen. Our findings provide the first insights into the hierarchical organization and chemical heterogeneity in human bone in three-dimensions at its smallest length scale – the atomic level. We demonstrate that atom probe tomography shows potential for new insights in biomineralization research on bone.

  20. Human fetal bone cells in delivery systems for bone engineering.

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    Tenorio, Diene M H; Scaletta, Corinne; Jaccoud, Sandra; Hirt-Burri, Nathalie; Pioletti, Dominique P; Jaques, Bertrand; Applegate, Lee Ann

    2011-11-01

    The aim of this study was to culture human fetal bone cells (dedicated cell banks of fetal bone derived from 14 week gestation femurs) within both hyaluronic acid gel and collagen foam, to compare the biocompatibility of both matrices as potential delivery systems for bone engineering and particularly for oral application. Fetal bone cell banks were prepared from one organ donation and cells were cultured for up to 4 weeks within hyaluronic acid (Mesolis®) and collagen foams (TissueFleece®). Cell survival and differentiation were assessed by cell proliferation assays and histology of frozen sections stained with Giemsa, von Kossa and ALP at 1, 2 and 4 weeks of culture. Within both materials, fetal bone cells could proliferate in three-dimensional structure at ∼70% capacity compared to monolayer culture. In addition, these cells were positive for ALP and von Kossa staining, indicating cellular differentiation and matrix production. Collagen foam provides a better structure for fetal bone cell delivery if cavity filling is necessary and hydrogels would permit an injectable technique for difficult to treat areas. In all, there was high biocompatibility, cellular differentiation and matrix deposition seen in both matrices by fetal bone cells, allowing for easy cell delivery for bone stimulation in vivo. Copyright © 2011 John Wiley & Sons, Ltd.

  1. Bone invading NSCLC cells produce IL-7: mice model and human histologic data

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    Quarto Rodolfo

    2010-01-01

    Full Text Available Abstract Background Bone metastases are a common and dismal consequence of lung cancer that is a leading cause of death. The role of IL-7 in promoting bone metastases has been previously investigated in NSCLC, but many aspects remain to be disclosed. To further study IL-7 function in bone metastasis, we developed a human-in-mice model of bone aggression by NSCLC and analyzed human bone metastasis biopsies. Methods We used NOD/SCID mice implanted with human bone. After bone engraftment, two groups of mice were injected subcutaneously with A549, a human NSCLC cell line, either close or at the contralateral flank to the human bone implant, while a third control group did not receive cancer cells. Tumor and bone vitality and IL-7 expression were assessed in implanted bone, affected or not by A549. Serum IL-7 levels were evaluated by ELISA. IL-7 immunohistochemistry was performed on 10 human bone NSCLC metastasis biopsies for comparison. Results At 12 weeks after bone implant, we observed osteogenic activity and neovascularization, confirming bone vitality. Tumor aggressive cells implanted close to human bone invaded the bone tissue. The bone-aggressive cancer cells were positive for IL-7 staining both in the mice model and in human biopsies. Higher IL-7 serum levels were found in mice injected with A549 cells close to the bone implant compared to mice injected with A549 cells in the flank opposite to the bone implant. Conclusions We demonstrated that bone-invading cells express and produce IL-7, which is known to promote osteoclast activation and osteolytic lesions. Tumor-bone interaction increases IL-7 production, with an increase in IL-7 serum levels. The presented mice model of bone invasion by contiguous tumor is suitable to study bone-tumor cell interaction. IL-7 plays a role in the first steps of metastatic process.

  2. Osteoradionecrosis of the Temporal Bone Leading to Cerebellar Abscess.

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    Layton, Thomas B

    2017-01-01

    Squamous cell carcinoma of the temporal bone is a rare and destructive malignancy and represents both diagnostic and therapeutic challenge. The complex regional anatomy of the temporal bone requires equally intricate surgical techniques to adequately resect the tumour mass during surgical excision. Adjuvant radiotherapy is offered to patients with advanced disease and has been showed to confer a survival benefit in carefully selected patients. One feared complication of radiotherapy is osteoradionecrosis and is a major obstacle faced in the treatment of head and neck cancers. The case presented here is a rare example of a patient who was successfully treated for SCC of the temporal with both surgical resection and adjuvant radiotherapy who subsequently developed two major complications: first, osteoradionecrosis of the temporal bone that leads to penetrating osteomyelitis; second, the formation of a large cerebellar abscess that required surgical drainage. This case is a rare example of the complications that are possible following radiotherapy to the head and the close follow-up that is required in patients.

  3. Lower Bone Mass and Higher Bone Resorption in Pheochromocytoma: Importance of Sympathetic Activity on Human Bone.

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    Kim, Beom-Jun; Kwak, Mi Kyung; Ahn, Seong Hee; Kim, Hyeonmok; Lee, Seung Hun; Song, Kee-Ho; Suh, Sunghwan; Kim, Jae Hyeon; Koh, Jung-Min

    2017-08-01

    Despite the apparent biological importance of sympathetic activity on bone metabolism in rodents, its role in humans remains questionable. To clarify the link between the sympathetic nervous system and the skeleton in humans. Among 620 consecutive subjects with newly diagnosed adrenal incidentaloma, 31 patients with histologically confirmed pheochromocytoma (a catecholamine-secreting neuroendocrine tumor) and 280 patients with nonfunctional adrenal incidentaloma were defined as cases and controls, respectively. After adjustment for confounders, subjects with pheochromocytoma had 7.2% lower bone mass at the lumbar spine and 33.5% higher serum C-terminal telopeptide of type 1 collagen (CTX) than those without pheochromocytoma (P = 0.016 and 0.001, respectively), whereas there were no statistical differences between groups in bone mineral density (BMD) at the femur neck and total hip and in serum bone-specific alkaline phosphatase (BSALP) level. The odds ratio (OR) for lower BMD at the lumbar spine in the presence of pheochromocytoma was 3.31 (95% confidence interval, 1.23 to 8.56). However, the ORs for lower BMD at the femur neck and total hip did not differ according to the presence of pheochromocytoma. Serum CTX level decreased by 35.2% after adrenalectomy in patients with pheochromocytoma, whereas serum BSALP level did not change significantly. This study provides clinical evidence showing that sympathetic overstimulation in pheochromocytoma can contribute to adverse effects on human bone through the increase of bone loss (especially in trabecular bone), as well as bone resorption.

  4. Age changes in human bone: an overview

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    Sharpe, W.D.

    1977-12-03

    The human skeleton steadily changes structure and mass during life because of a variety of internal and external factors. Extracellular substance and bone cells get old, characteristic structural remodeling occurs with age and these age-related changes are important in the discrimination between pathological and physiological changes. Perhaps 20 percent of the bone mass is lost between the fourth and the ninth decades, osteoblasts function less efficiently and gradual loss of bone substance is enhanced by delayed mineralization of an increased surface area of thin and relatively less active osteoid seams. After the fifth decade, osteoclasia and the number of Howship's lacunae increase, and with age, the number of large osteolytic osteocytes increases as the number of small osteocytes declines and empty osteocyte lacunae become more common. The result is greater liability to fracture and diminished healing or replacement of injured bone.

  5. [Thermo-elastic stress analysis of human bones].

    Science.gov (United States)

    Krüger-Franke, M; Heiland, A; Plitz, W; Refior, H J

    1995-01-01

    The Thermoelastic Stress Analysis (THESA) is a widely used procedure in motorcar- and airplane engineering. This study investigated the reliability of THESA for stress analysis of human bone. A human femur was cyclic stressed and the resulting stress pattern was scanned from the surface of the bone by means of the thermoelastic stress measuring instrument SPATE 9000. To proof whether the scan of SPATE 9000 is equivalent to the stress distribution of human femur surface, strain gauges are used to control the results at two different regions of the femur diaphysis under equal but static conditions. It could be shown, that both measuring methods lead to corresponding results of stress pattern on human femur surface.

  6. Analysis of lead toxicity in human cells

    Directory of Open Access Journals (Sweden)

    Gillis Bruce S

    2012-07-01

    Full Text Available Abstract Background Lead is a metal with many recognized adverse health side effects, and yet the molecular processes underlying lead toxicity are still poorly understood. Quantifying the injurious effects of lead is also difficult because of the diagnostic limitations that exist when analyzing human blood and urine specimens for lead toxicity. Results We analyzed the deleterious impact of lead on human cells by measuring its effects on cytokine production and gene expression in peripheral blood mononuclear cells. Lead activates the secretion of the chemokine IL-8 and impacts mitogen-dependent activation by increasing the secretion of the proinflammatory cytokines IL-6 and TNF-α and of the chemokines IL-8 and MIP1-α in the presence of phytohemagglutinin. The recorded changes in gene expression affected major cellular functions, including metallothionein expression, and the expression of cellular metabolic enzymes and protein kinase activity. The expression of 31 genes remained elevated after the removal of lead from the testing medium thereby allowing for the measurement of adverse health effects of lead poisoning. These included thirteen metallothionein transcripts, three endothelial receptor B transcripts and a number of transcripts which encode cellular metabolic enzymes. Cellular responses to lead correlated with blood lead levels and were significantly altered in individuals with higher lead content resultantly affecting the nervous system, the negative regulation of transcription and the induction of apoptosis. In addition, we identified changes in gene expression in individuals with elevated zinc protoporphyrin blood levels and found that genes regulating the transmission of nerve impulses were affected in these individuals. The affected pathways were G-protein mediated signaling, gap junction signaling, synaptic long-term potentiation, neuropathic pain signaling as well as CREB signaling in neurons. Cellular responses to lead were

  7. Diagnostic dry bone histology in human paleopathology.

    Science.gov (United States)

    de Boer, H H Hans; Van der Merwe, A E Lida

    2016-10-01

    Paleopathology is the study of trauma and disease as may be observed in ancient (human) remains. In contrast to its central role in current medical practice, microscopy plays a rather modest role in paleopathology. This is at least partially due to the differences between fresh and decomposed (i.e., skeletonized or "dry bone") tissue samples. This review discusses these differences and describes how they affect the histological analysis of paleopathological specimens. First, we provide a summary of some general challenges related to the histological analysis of palaeopathological specimens. Second, the reader is introduced in bone tissue histology and bone tissue dynamics. The remainder of the paper is dedicated to the diagnostic value of dry bone histology. Its value and limitations are illustrated by comparing several well-studied paleopathological cases with similar contemporary, clinical cases. This review illustrates that due to post-mortem loss of soft tissue, a limited number of disorders display pathognomonic features during histological analysis of skeletonized human remains. In the remainder of cases, histology may help to narrow down the differential diagnosis or is diagnostically unspecific. A comprehensive, multidisciplinary diagnostic approach therefore remains essential. Clin. Anat. 29:831-843, 2016. © 2016 Wiley Periodicals, Inc.

  8. Peripheral blood and bone marrow cell status of white rats with long-term lead exposure

    Energy Technology Data Exchange (ETDEWEB)

    Sudakova, A.I.; Shevchenko, Z.H.T.; Nosova, L.I.

    Blood test and bone marrow examination in experiments with albino rats weighing 100-110 g subjected to long-term lead influence (1% lead acetate per os) showed availability of reticulocytosis with thrombocytopenia (on the 62d day) and thrombocytosis on the 92d day of the experiment) in peripheral blood. Reduction of the bone marrow neutrophil index and leuko-erythroblastic ration due to an increase of an erythroblastic radicle was recorded in the bone marrow.

  9. Osteoblast recruitment routes in human cancellous bone remodeling

    DEFF Research Database (Denmark)

    Kristensen, Helene B; Levin Andersen, Thomas; Marcussen, Niels

    2014-01-01

    It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling......-terminal peptide versus osterix, and (ii) canopy cell densities, found to decline with age, and canopy-capillary contacts above eroded surfaces correlated positively with osteoblast density on bone-forming surfaces. Furthermore, we showed that bone remodeling compartment canopies arise from a mesenchymal envelope...

  10. A negative bone scan leads to an unusual diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    O`Brien, L. [Royal Brisbane Hospital, Herston, QLD (Australia). Department of Nuclear Medicine

    1998-03-01

    Full text: A bone scan looking for osteomyelitis or a more sinister pathology was performed on a 7-year-old boy with Von Willebrand``s disease. He presented with symptoms of pain in the left groin and a lump, although there had been no history of direct trauma, and an X-ray report stating that there was an irregular ill-defined area of bony destruction seen in the lower aspect of the left ischium. Blood pool images of the pelvis were acquired soon after an injection of MDP and three hours later a whole body bone scan was done. Results of the bone scan showed that the radiolucent lesion in the left ilium seen on the plain radiographs was not metabolically active on the technetium MDP study. Features compatible with a response to an intraosseous or sub-periosteal haematoma were seen when reviewing the original X-rays and, as there was a spontaneous resolution of the patient``s symptoms, this was considered to be the diagnosis. This study shows that a negative bone scan, which rules out an active bone lesion, is of value in making a diagnosis when used in conjunction with X-rays and a knowledge of the patient``s history.

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

    Science.gov (United States)

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

  12. Dissociation of bone resorption and bone formation in adult mice with a non-functional V-ATPase in osteoclasts leads to increased bone strength.

    Directory of Open Access Journals (Sweden)

    Kim Henriksen

    Full Text Available Osteopetrosis caused by defective acid secretion by the osteoclast, is characterized by defective bone resorption, increased osteoclast numbers, while bone formation is normal or increased. In contrast the bones are of poor quality, despite this uncoupling of formation from resorption.To shed light on the effect of uncoupling in adult mice with respect to bone strength, we transplanted irradiated three-month old normal mice with hematopoietic stem cells from control or oc/oc mice, which have defective acid secretion, and followed them for 12 to 28 weeks.Engraftment levels were assessed by flow cytometry of peripheral blood. Serum samples were collected every six weeks for measurement of bone turnover markers. At termination bones were collected for µCT and mechanical testing. An engraftment level of 98% was obtained. From week 6 until termination bone resorption was significantly reduced, while the osteoclast number was increased when comparing oc/oc to controls. Bone formation was elevated at week 6, normalized at week 12, and reduced onwards. µCT and mechanical analyses of femurs and vertebrae showed increased bone volume and bone strength of cortical and trabecular bone.In conclusion, these data show that attenuation of acid secretion in adult mice leads to uncoupling and improves bone strength.

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

    Science.gov (United States)

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

    1999-01-01

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

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

    Science.gov (United States)

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

    1999-01-01

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

  15. Current issues in human lead exposure and regulation of lead.

    Science.gov (United States)

    Davis, J M; Elias, R W; Grant, L D

    1993-01-01

    Concern about lead as a significant public health problem has increased as epidemiological and experimental evidence has mounted regarding adverse health effects at successively lower levels of lead exposure. This concern has led to downward revision of criteria for acceptable blood lead concentrations to the 10 micrograms/dL mark now designated by EPA as a target level for regulatory development and enforcement/clean-up purposes. Much progress has been made in reducing lead exposures during the past 10-15 years, with marked declines evident both in air lead and blood lead concentrations in parallel to the phase-down of lead in gasoline and notable decreases in food lead exposure due to elimination of lead soldered cans by U.S. food processors. With the lessening of exposure from these sources, the importance of other components of multimedia exposure pathways has grown and stimulated increasing regulatory attention and abatement efforts to reduce health risks associated with lead exposure from drinking water, from lead-based paint, and from household dust and soil contaminated by deteriorating paint, smelter emissions, or various other sources. Increasing attention is also being accorded to reduction of occupational lead exposures (including those related to lead abatement activities), with particular concern for protection of men and women during their reproductive years.

  16. Mechanistic fracture criteria for the failure of human cortical bone

    Energy Technology Data Exchange (ETDEWEB)

    Nalla, Ravi K.; Kinney, John H.; Ritchie, Robert O.

    2002-12-13

    A mechanistic understanding of fracture in human bone is critical to predicting fracture risk associated with age and disease. Despite extensive work, a mechanistic framework for describing how the underlying microstructure affects the failure mode in bone is lacking.

  17. Creep of trabecular bone from the human proximal tibia

    Energy Technology Data Exchange (ETDEWEB)

    Novitskaya, Ekaterina, E-mail: eevdokim@ucsd.edu [Mechanical and Aerospace Engineering, UC, San Diego, La Jolla, CA 92093 (United States); Materials Science and Engineering Program, UC, San Diego, La Jolla, CA 92093 (United States); Zin, Carolyn [Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218 (United States); Chang, Neil; Cory, Esther; Chen, Peter [Departments of Bioengineering and Orthopaedic Surgery, UC, San Diego, La Jolla, CA 92093 (United States); D’Lima, Darryl [Shiley Center for Orthopaedic Research and Education, Scripps Health, La Jolla, CA 92037 (United States); Sah, Robert L. [Materials Science and Engineering Program, UC, San Diego, La Jolla, CA 92093 (United States); Departments of Bioengineering and Orthopaedic Surgery, UC, San Diego, La Jolla, CA 92093 (United States); McKittrick, Joanna [Mechanical and Aerospace Engineering, UC, San Diego, La Jolla, CA 92093 (United States); Materials Science and Engineering Program, UC, San Diego, La Jolla, CA 92093 (United States)

    2014-07-01

    Creep is the deformation that occurs under a prolonged, sustained load and can lead to permanent damage in bone. Creep in bone is a complex phenomenon and varies with type of loading and local mechanical properties. Human trabecular bone samples from proximal tibia were harvested from a 71-year old female cadaver with osteoporosis. The samples were initially subjected to one cycle load up to 1% strain to determine the creep load. Samples were then loaded in compression under a constant stress for 2 h and immediately unloaded. All tests were conducted with the specimens soaked in phosphate buffered saline with proteinase inhibitors at 37 °C. Steady state creep rate and final creep strain were estimated from mechanical testing and compared with published data. The steady state creep rate correlated well with values obtained from bovine tibial and human vertebral trabecular bone, and was higher for lower density samples. Tissue architecture was analyzed by micro-computed tomography (μCT) both before and after creep testing to assess creep deformation and damage accumulated. Quantitative morphometric analysis indicated that creep induced changes in trabecular separation and the structural model index. A main mode of deformation was bending of trabeculae. - Highlights: • Compressive creep tests of human trabecular bone across the tibia were performed. • The creep rate was found to be inversely proportional to the density of the samples. • μ-computed tomography before and after testing identified regions of deformation. • Bending of the trabeculae was found to be the main deformation mode.

  18. Comparison of bone lead in pre-Hispanic, 18th century and modern population of Tenerife.

    Science.gov (United States)

    Arnay-De-La-Rosa, M; Gonzalez-Reimers, E; Velasco-Vazquez, J; Galindo-Martin, L; Delgado-Ureta, E; Santolaria-Fernandez, F; Barros-Lopez, N

    1998-01-19

    The present study has been performed in order to determine concentrations of lead in the bone of 14 individuals who were interred towards the beginning of the 18th century at the church 'La Concepción' (Santa Cruz de Tenerife) of 15 Pre-Hispanic individuals of Tenerife and a modern sample for Tenerife, composed of 25 individuals. We have observed higher bone lead values in the modern population than in the ancient one (P = 0.0022), although Pre-Hispanic individuals and those of the 18th century showed similar bone lead values.

  19. Obesity induced by high dietary fat leads to increased bone resorption marker, TRAP, and decreased bone mass in mice

    Science.gov (United States)

    Obesity, which is growing in prevalence, is a risk factor for such chronic health disorders as diabetes and cardiovascular diseases. However, it is thought to be a protective factor for osteoporosis and bone fractures in humans. Accumulating data in humans suggest that fat mass has a negative effect...

  20. Dissolution of the inorganic phase of bone leading to release of calcium regulates osteoclast survival

    DEFF Research Database (Denmark)

    Nielsen, Rasmus H; Karsdal, Morten A; Sørensen, Mette G

    2007-01-01

    Osteoclasts are the sole cells possessing the ability to resorb calcified bone matrix. This occurs via secretion of hydrochloric acid mediated by the V-ATPase and the chloride channel ClC-7. Loss of acidification leads to osteopetrosis characterized by ablation of bone resorption and increased os...

  1. Aging, human immunodeficiency virus, and bone health

    Directory of Open Access Journals (Sweden)

    Kim C Mansky

    2010-09-01

    Full Text Available Kim C ManskyDivision of Orthodontics, Department of Developmental and Surgical Sciences, School of Dentistry, University of Minnesota, Minneapolis, MN, USAAbstract: Highly active antiretroviral therapy (HAART has had a profound impact on improving the long-term prognosis for individuals infected with human immunodeficiency virus (HIV. HAART has been available for close to two decades, and now a significant number of patients with access to HAART are over the age of 50 years. Many clinical studies have indicated that HIV infection, as well as components of HAART, can increase the risk in these individuals to a variety of noninfectious complications, including a risk to bone health. There is a significant need for detailed mechanistic analysis of the aging, HIV-infected population regarding the risk of HIV infection and therapy in order to maintain bone health. Insights from basic mechanistic studies will help to shed light on the role of HIV infection and the components of HAART that impact bone health, and will help in identifying preventative countermeasures, particularly for individuals 50 years of age and older.Keywords: osteopenia, osteomalacia, osteoporosis, bisphosphonates, tenofovir, osteoimmunology

  2. Effects of chronic lead exposure on bone mineral properties in femurs of growing rats.

    Science.gov (United States)

    Álvarez-Lloret, Pedro; Lee, Ching Ming; Conti, María Inés; Terrizzi, Antonela Romina; González-López, Santiago; Martínez, María Pilar

    2017-02-15

    Lead exposure has been associated with several defective skeletal growth processes and bone mineral alterations. The aim of the present study is to make a more detailed description of the toxic effects of lead intoxication on bone intrinsic material properties as mineral composition, morphology and microstructural characteristics. For this purpose, Wistar rats were exposed (n=12) to 1000ppm lead acetate in drinking water for 90days while control group (n=8) were treated with sodium acetate. Femurs were examined using inductively coupled plasma optical emission spectrometry (ICP-OES), Attenuated Total Reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), and micro-Computed Tomography (μCT). Results showed that femur from the lead-exposed rats had higher carbonate content in bone mineral and (Ca(2+)+Mg(2+)+ Na(+))/P ratio values, although no variations were observed in crystal maturity and crystallite size. From morphological analyses, lead exposure rats showed a decreased in trabecular bone surface and distribution while trabecular thickness and cortical area increased. These overall effects indicate a similar mechanism of bone maturation normally associated to age-related processes. These responses are correlated with the adverse actions induced by lead on the processes regulating bone turnover mechanism. This information may explain the osteoporosis diseases associated to lead intoxication as well as the risk of fracture observed in populations exposed to this toxicant. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Long-term effects of lead poisoning on bone mineralization in vultures exposed to ammunition sources

    Energy Technology Data Exchange (ETDEWEB)

    Gangoso, Laura [Department of Conservation Biology, Estacion Biologica de Donana, C.S.I.C., Avda Ma Luisa s/n, 41013 Sevilla (Spain)], E-mail: laurag@ebd.csic.es; Alvarez-Lloret, Pedro [Department of Mineralogy and Petrology, University of Granada, Avda Fuentenueva s/n, 18002 Granada (Spain)], E-mail: pedalv@ugr.es; Rodriguez-Navarro, Alejandro A.B. [Department of Mineralogy and Petrology, University of Granada, Avda Fuentenueva s/n, 18002 Granada (Spain)], E-mail: anava@ugr.es; Mateo, Rafael [Instituto de Investigacion en Recursos Cinegeticos, IREC (CSIC, UCLM, JCCM), Ronda de Toledo s/n, 13071 Ciudad Real (Spain)], E-mail: Rafael.Mateo@uclm.es; Hiraldo, Fernando [Department of Conservation Biology, Estacion Biologica de Donana, C.S.I.C., Avda Ma Luisa s/n, 41013 Sevilla (Spain)], E-mail: hiraldo@ebd.csic.es; Donazar, Jose Antonio [Department of Conservation Biology, Estacion Biologica de Donana, C.S.I.C., Avda Ma Luisa s/n, 41013 Sevilla (Spain)], E-mail: donazar@ebd.csic.es

    2009-02-15

    Long-lived species are particularly susceptible to bioaccumulation of lead in bone tissues. In this paper we gain insights into the sublethal effects of lead contamination on Egyptian vultures (Neophron percnopterus). Our approach was done on the comparison of two populations (Canary Islands and Iberian Peninsula) differing in exposures to the ingestion of lead ammunition. Blood lead levels were higher in the island population (Canary Islands range: 5.10-1780 {mu}g L{sup -1}n = 137; Iberian Peninsula range: 5.60-217.30 {mu}g L{sup -1}n = 32) showing clear seasonal trends, peaking during the hunting season. Moreover, males were more susceptible to lead accumulation than females. Bone lead concentration increased with age, reflecting a bioaccumulation effect. The bone composition was significantly altered by this contaminant: the mineralization degree decreased as lead concentration levels increased. These results demonstrate the existence of long-term effects of lead poisoning, which may be of importance in the declines of threatened populations of long-lived species exposed to this contaminant. - Bone lead accumulation decreases the degree of bone mineralization in vultures exposed to ammunition sources.

  4. In vitro induction of alkaline phosphatase levels predicts in vivo bone forming capacity of human bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    Henk-Jan Prins

    2014-03-01

    Full Text Available One of the applications of bone marrow stromal cells (BMSCs that are produced by ex vivo expansion is for use in in vivo bone tissue engineering. Cultured stromal cells are a mixture of cells at different stages of commitment and expansion capability, leading to a heterogeneous cell population that each time can differ in the potential to form in vivo bone. A parameter that predicts for in vivo bone forming capacity is thus far lacking. We employed single colony-derived BMSC cultures to identify such predictive parameters. Using limiting dilution, we have produced sixteen single CFU-F derived BMSC cultures from human bone marrow and found that only five of these formed bone in vivo. The single colony-derived BMSC strains were tested for proliferation, osteogenic-, adipogenic- and chondrogenic differentiation capacity and the expression of a variety of associated markers. The only robust predictors of in vivo bone forming capacity were the induction of alkaline phosphatase, (ALP mRNA levels and ALP activity during in vitro osteogenic differentiation. The predictive value of in vitro ALP induction was confirmed by analyzing “bulk-cultured” BMSCs from various bone marrow biopsies. Our findings show that in BMSCs, the additional increase in ALP levels over basal levels during in vitro osteogenic differentiation is predictive of in vivo performance.

  5. The determination of low lead levels in the bone of lead-depleted mice by graphite furnace atomic absorption spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Iavicoli, I.; Carelli, G.; Castellino, N. [Univ. Cattolica del Sacro Cuore, Roma (Italy). Inst. of Occupational Health; Schlemmer, G. [Bodenseewerk Perkin-Elmer und Co. GmbH, Ueberlingen (Germany)

    2001-08-01

    Low lead levels in the femurs of mice fed with a lead-depleted diet have been determined by use of electrothermal atomic absorption spectrometry with Zeeman-effect background correction. The method is based on the use of Mg(NO{sub 3}){sub 2}/Pd as matrix modifier which enables significant reduction of the spectral interferences prevalent if chemical modifiers based on NH{sub 4}H{sub 2}PO{sub 4} with either Ca or Mg are used for samples rich in Ca{sub 3}(PO{sub 4}){sub 2} matrix. The method was developed and validated by use of the NIST standard reference material 1486 bone. Bones were decomposed in a pressurized microwave-heated system using 70% nitric acid. Forty-three mice femurs, with a mass of 74.62 {+-} 12.54 mg, were dissolved in concentrated nitric acid. The lead results found in SRM 1486 (1.25 {+-} 0.15 {mu}g g{sup -1}, n = 9) were in good agreement with the certificate (1.335 {+-} 0.014 {mu}g g{sup -1}). Recoveries of 200 ng lead added to the SRM before or after digestion were 99.0 {+-} 1.4% and 98.5 {+-} 1.6%, respectively. The lead detection limit in bone samples is 0.06 {mu}g g{sup -1} dry mass. This method is, therefore, suitable for the determination of very low lead levels (0.06-0.20 {mu}g Pb kg{sup -1} bone) in the femurs of mice fed a diet with lead level of < 20 {mu}g kg{sup -1}. (orig.)

  6. Chronic lead poisoning magnifies bone detrimental effects in an ovariectomized rat model of postmenopausal osteoporosis.

    Science.gov (United States)

    Lee, Ching Ming; Terrizzi, Antonela Romina; Bozzini, Clarisa; Piñeiro, Adriana Emilce; Conti, María Inés; Martínez, María Pilar

    2016-01-01

    Lead (Pb) is a persistent environmental contaminant that is mainly stored in bones being an important source of endogenous lead exposure during periods of increased bone resorption as occurs in menopause. As no evidence exists of which bone biomechanical properties are impaired in those elderly women who had been exposed to Pb during their lifetime, the aim of the present study is to discern whether chronic lead poisoning magnifies the deterioration of bone biology that occurs in later stages of life. We investigated the effect of Pb in the femora of ovariectomized (OVX) female Wistar rats who had been intoxicated with 1000 ppm of Pb acetate in drinking water for 8 months. Structural properties were determined using a three-point bending mechanical test, and geometrical and material properties were evaluated after obtaining the load/deformation curve. Areal Bone Mineral Density (BMD) was estimated using a bone densitometer. Femoral histomorphometry was carried out on slices dyed with H&E (Hematoxylin and Eosin). Pb and OVX decreased all structural properties with a higher effect when both treatments were applied together. Medullar and cortical area of femurs under OVX increased, allowing the bone to accommodate its architecture, which was not observed under Pb intoxication. Pb and OVX significantly decreased BMD, showing lead treated ovariectomized rats (PbOVX) animals the lowest BMD levels. Trabecular bone volume per total volume (BV/TV%) was decreased in OVX and PbOVX animals in 54% compared to the control animals (pbone biomechanics of OVX rats with a consequent enhancement of the risk of fracture. These results enable the discussion of the detrimental effects of lead intoxication in bone biology in elderly women. Copyright © 2015 Elsevier GmbH. All rights reserved.

  7. Effect of lead toxicity on bone calcium content and morphometric parameters

    Directory of Open Access Journals (Sweden)

    Payal Bhardwaj

    2016-01-01

    Results: Our study revealed that Lead significantly reduced calcium concentration in both femur (p<0.001 and tibia (p<0.001 in lead intoxicated rats. Furthermore, morphometric parameters showed significant reduction in the femoral head width upon lead intoxication. Significant decrease in the ash content of both the bones was observed upon lead intoxication for both the age groups, no significant change observed in the length of the femur as well as tibia of all the treated groups. Conclusions: From this study we can conclude that the lead has induced bone toxicity and has deteriorated the development of bone tissue in the case of growing animals, is the consequence of oxidative stress. [Int J Res Med Sci 2016; 4(1.000: 177-180

  8. Stable lead isotopes in environmental health with emphasis on human investigations

    Energy Technology Data Exchange (ETDEWEB)

    Gulson, Brian [Graduate School of the Environment, Macquarie University, Sydney NSW 2109 (Australia); CSIRO Exploration and Mining North Ryde NSW 1670 (Australia)], E-mail: bgulson@gse.mq.edu.au

    2008-08-01

    There has been widespread use of stable lead isotopes in the earth sciences for more than 40 years focussed on the origin and age of rocks and minerals with lesser application in environmental investigations where the emphasis has been directed typically to the source of lead in environmental media such as air, water and soils. In contrast, the number of environmental health investigations focussed on humans (and primates) is limited in spite of the demonstrated utility of the approach in pioneering studies in the early 1970's. This paper reviews the status of lead isotopes in human investigations especially over the past 2 decades, the period over which most activity has taken place. Following a brief introduction to the method, examples are provided illustrating the use of lead isotopes in a wide spectrum of activities including sources and pathways of lead in diverse environments from urban to mining communities, various applications associated with pregnancy, the contribution of bone lead to blood lead including in the elderly, the half-life of lead in blood, and lead in bones and other media. A brief outline of critical research on non-human primates is also given. The lead isotope method is a powerful technique for tracing lead and could be employed more widely in human investigations.

  9. Alveolar bone loss associated to periodontal disease in lead intoxicated rats under environmental hypoxia.

    Science.gov (United States)

    Terrizzi, Antonela R; Fernandez-Solari, Javier; Lee, Ching M; Bozzini, Clarisa; Mandalunis, Patricia M; Elverdin, Juan C; Conti, María Ines; Martínez, María Pilar

    2013-10-01

    Previously reported studies from this laboratory revealed that rats chronically intoxicated with lead (Pb) under hypoxic conditions (HX) impaired growth parameters and induced damages on femoral and mandibular bones predisposing to fractures. We also described periodontal inflammatory processes under such experimental conditions. Periodontitis is characterised by inflammation of supporting tissues of the teeth that result in alveolar bone loss. The existence of populations living at high altitudes and exposed to lead contamination aimed us to establish the macroscopic, biochemical and histological parameters consistent with a periodontal disease in the same rat model with or without experimental periodontitis (EP). Sixty female rats were divided into: Control; Pb (1000ppm of lead acetate in drinking water); HX (506mbar) and PbHX (both treatments simultaneously). EP was induced by placing ligatures around the molars of half of the rats during the 14 days previous to the autopsy. Hemi-mandibles were extracted to evaluate bone loss by histomorphometrical techniques. TNFα plasmatic concentration was greater (palveolar bone loss, while Pb showed spontaneous bone loss also. In conclusion, these results show that lead intoxication under hypoxic environment enhanced not only alveolar bone loss but also systemic and oral tissues inflammatory parameters, which could aggravate the physiopathological alterations produced by periodontal disease.

  10. Human Placenta-Derived Adherent Cells Prevent Bone loss, Stimulate Bone formation, and Suppress Growth of Multiple Myeloma in Bone

    Science.gov (United States)

    Li, Xin; Ling, Wen; Pennisi, Angela; Wang, Yuping; Khan, Sharmin; Heidaran, Mohammad; Pal, Ajai; Zhang, Xiaokui; He, Shuyang; Zeitlin, Andy; Abbot, Stewart; Faleck, Herbert; Hariri, Robert; Shaughnessy, John D.; van Rhee, Frits; Nair, Bijay; Barlogie, Bart; Epstein, Joshua; Yaccoby, Shmuel

    2011-01-01

    Human placenta has emerged as a valuable source of transplantable cells of mesenchymal and hematopoietic origin for multiple cytotherapeutic purposes, including enhanced engraftment of hematopoietic stem cells, modulation of inflammation, bone repair, and cancer. Placenta-derived adherent cells (PDACs) are mesenchymal-like stem cells isolated from postpartum human placenta. Multiple myeloma is closely associated with induction of bone disease and large lytic lesions, which are often not repaired and are usually the sites of relapses. We evaluated the antimyeloma therapeutic potential, in vivo survival, and trafficking of PDACs in the severe combined immunodeficiency (SCID)–rab model of medullary myeloma-associated bone loss. Intrabone injection of PDACs into non-myelomatous and myelomatous implanted bone in SCID-rab mice promoted bone formation by stimulating endogenous osteoblastogenesis, and most PDACs disappeared from bone within 4 weeks. PDACs inhibitory effects on myeloma bone disease and tumor growth were dose-dependent and comparable with those of fetal human mesenchymal stem cells (MSCs). Intrabone, but not subcutaneous, engraftment of PDACs inhibited bone disease and tumor growth in SCID-rab mice. Intratumor injection of PDACs had no effect on subcutaneous growth of myeloma cells. A small number of intravenously injected PDACs trafficked into myelomatous bone. Myeloma cell growth rate in vitro was lower in coculture with PDACs than with MSCs from human fetal bone or myeloma patients. PDACs also promoted apoptosis in osteoclast precursors and inhibited their differentiation. This study suggests that altering the bone marrow microenvironment with PDAC cytotherapy attenuates growth of myeloma and that PDAC cytotherapy is a promising therapeutic approach for myeloma osteolysis. PMID:21732484

  11. Tea flavonoids for bone health: from animals to humans.

    Science.gov (United States)

    Shen, Chwan-Li; Chyu, Ming-Chien

    2016-10-01

    Osteoporosis is a skeletal disease characterized by a deterioration of bone mass and bone quality that predisposes an individual to a higher risk of fragility fractures. Emerging evidence has shown that the risk for low bone mass and osteoporosis-related fractures can be reduced by nutritional approaches aiming to improve bone microstructure, bone mineral density, and strength. Tea and its flavonoids, especially those of black tea and green tea, have been suggested to protect against bone loss and to reduce risk of fracture, due to tea's antioxidant and anti-inflammatory properties. Based on the results of animal studies, moderate intake of tea has shown to benefit bone health as shown by mitigation of bone loss and microstructural deterioration as well as improvement of bone strength and quality. Epidemiological studies have reported positive, insignificant, and negative impacts on bone mineral density at multiple skeletal sites and risk of fracture in humans with habitual tea consumption. There are limited human clinical trials that objectively and quantitatively assessed tea consumption and bone efficacy using validated outcome measures in a population at high risk for osteoporosis, along with safety monitoring approach. This review summarizes the current state of knowledge of laboratory animal research, epidemiological observational studies, and clinical trials assessing the skeletal effects of tea and its active flavonoids, along with discussion of relevant future directions in translational research.

  12. Fundamental ratios and logarithmic periodicity in human limb bones.

    Science.gov (United States)

    Pietak, Alexis; Ma, Siyan; Beck, Caroline W; Stringer, Mark D

    2013-05-01

    Fundamental mathematical relationships are widespread in biology yet there is little information on this topic with regard to human limb bone lengths and none related to human limb bone volumes. Forty-six sets of ipsilateral upper and lower limb long bones and third digit short bones were imaged by computed tomography. Maximum bone lengths were measured manually and individual bone volumes calculated from computed tomography images using a stereologic method. Length ratios of femur : tibia and humerus : ulna were remarkably similar (1.21 and 1.22, respectively) and varied little (bone volume ratios varied much more than upper limb ratios. The relationship between bone length and volume was found to be well described by power laws, with R(2) values ranging from 0.983 to 0.995. The most striking finding was a logarithmic periodicity in bone length moving from distal to proximal up the limb (upper limb λ = 0.72, lower limb λ = 0.93). These novel data suggest that human limb bone lengths and volumes follow fundamental and highly conserved mathematical relationships, which may contribute to our understanding of normal and disordered growth, stature estimation, and biomechanics.

  13. Bone dosimetry using synthetic images to represent trabecular bones of five regions of the human body

    Energy Technology Data Exchange (ETDEWEB)

    Lima Filho, Jose de M. [Instituto Federal de Educacao, Ciencia e Tecnologia de Pernambuco (IFPE), Recife, PE (Brazil); Vieira, Jose W. [Escola Politecnica de Pernambuco (POLI). Universidade de Pernambuco (UPE), Recife, PE (Brazil); Lima, Vanildo J. de M., E-mail: vjr@ufpe.br [Departamento de Anatomia. Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Lima, Lindeval F., E-mail: lindeval@dmat.ufrr.br [Departamento de Matematica (DMAT). Universidade Federal de Roraima (UFRR), Boa Vista, RR (Brazil); Lima, Fernando R.A., E-mail: falima@cnen.gov.br [Centro Regional de Ciencias Nucleares (CRCN/NE-CNEN-PE), Recife, PE (Brazil); Vasconcelos, Wagner E. de [Departamento de Energia Nuclear (DEN). Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil)

    2011-07-01

    One of the greatest challenges in numerical dosimetry of ionizing radiation is to estimate the absorbed dose by bone tissue in the human body. The bone tissues of greater radiosensitivity are the red bone marrow (RBM), that consist of the hematopoietic cells, located within the trabecular bones, and the bone surface cells (BSC), called osteogenic cells. The report 70 of the ICRP lists five spongiosa regions with their respective volume percent of trabecular bone: ribs (also contemplating the clavicles and sternum), spine, long bones, pelvis and skull (also contemplating mandible). The Grupo de Pesquisa em Dosimetria Numerica (GDN/CNPq) has been built exposure computational models (ECMs) based on voxel phantoms and EGSnrc Monte Carlo code. To estimate the energy deposited in the RBM and in the BSC of a phantom, the GDN/CNPq has used a method based on micro-CT images of the five trabecular regions mentioned above. These images were provided by other research institutes and were obtained from scan of bone samples of adult. Here is the greatest difficulty in reproducing this method: besides the need for bone images of real people with micrometer resolution, the distribution of bone marrow in the human body, according to ICRP 70, varies with age. This article presents some proposals of the GDN/CNPQ for replacing in the ECMs the micro-CT images by images synthesized by the computer, based on Monte Carlo sampling. (author)

  14. Influence of Lead on the Interpretation of Bone Samples with Laser-Induced Breakdown Spectroscopy

    Directory of Open Access Journals (Sweden)

    Abdolhamed Shahedi

    2016-01-01

    Full Text Available This study is devoted to tracing and identifying the elements available in bone sample using Laser-Induced Breakdown Spectroscopy (LIBS. The bone samples were prepared from the thigh of laboratory rats, which consumed 325.29 g/mol lead acetate having 4 mM concentration in specified time duration. About 76 atomic lines have been analyzed and we found that the dominant elements are Ca I, Ca II, Mg I, Mg II, Fe I, and Fe II. Temperature curve and bar graph were drawn to compare bone elements of group B which consumed lead with normal group, group A, in the same laboratory conditions. Plasma parameters including plasma temperature and electron density were determined by considering Local Thermodynamic Equilibrium (LTE condition in the plasma. An inverse relationship has been detected between lead absorption and elements like Calcium and Magnesium absorption comparing elemental values for both the groups.

  15. Soil is an important pathway of human lead exposure.

    OpenAIRE

    Mielke, H W; Reagan, P L

    1998-01-01

    This review shows the equal or greater importance of leaded gasoline-contaminated dust compared to lead-based paint to the child lead problem, and that soil lead, resulting from leaded gasoline and pulverized lead-based paint, is at least or more important than lead-based paint (intact and not pulverized) as a pathway of human lead exposure. Because lead-based paint is a high-dose source, the biologically relevant dosage is similar to lead in soil. Both lead-based paint and soil lead are asso...

  16. Soil is an important pathway of human lead exposure.

    OpenAIRE

    Mielke, H W; Reagan, P L

    1998-01-01

    This review shows the equal or greater importance of leaded gasoline-contaminated dust compared to lead-based paint to the child lead problem, and that soil lead, resulting from leaded gasoline and pulverized lead-based paint, is at least or more important than lead-based paint (intact and not pulverized) as a pathway of human lead exposure. Because lead-based paint is a high-dose source, the biologically relevant dosage is similar to lead in soil. Both lead-based paint and soil lead are asso...

  17. Cross-correlative 3D micro-structural investigation of human bone processed into bone allografts

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Atul Kumar [Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Mumbai 400076 (India); Gajiwala, Astrid Lobo [Tissue Bank, Tata Memorial Hospital, Parel, Mumbai 400012 (India); Rai, Ratan Kumar [Centre of Biomedical Research, SGPGIMS Campus, Lucknow 226014 (India); Khan, Mohd Parvez [Division of Endocrinology, Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI) CSIR-Central Drug Research Institute, Lucknow 226031 (India); Singh, Chandan [Centre of Biomedical Research, SGPGIMS Campus, Lucknow 226014 (India); Barbhuyan, Tarun [Division of Endocrinology, Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI) CSIR-Central Drug Research Institute, Lucknow 226031 (India); Vijayalakshmi, S. [Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Mumbai 400076 (India); Chattopadhyay, Naibedya [Division of Endocrinology, Center for Research in Anabolic Skeletal Targets in Health and Illness (ASTHI) CSIR-Central Drug Research Institute, Lucknow 226031 (India); Sinha, Neeraj, E-mail: neerajcbmr@gmail.com [Centre of Biomedical Research, SGPGIMS Campus, Lucknow 226014 (India); Kumar, Ashutosh, E-mail: ashutoshk@iitb.ac.in [Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076 (India); Bellare, Jayesh R., E-mail: jb@iitb.ac.in [Centre for Research in Nanotechnology & Science, Indian Institute of Technology Bombay, Mumbai 400076 (India); Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai 400076 (India)

    2016-05-01

    Bone allografts (BA) are a cost-effective and sustainable alternative in orthopedic practice as they provide a permanent solution for preserving skeletal architecture and function. Such BA however, must be processed to be disease free and immunologically safe as well as biologically and clinically useful. Here, we have demonstrated a processing protocol for bone allografts and investigated the micro-structural properties of bone collected from osteoporotic and normal human donor samples. In order to characterize BA at different microscopic levels, a combination of techniques such as Solid State Nuclear Magnetic Resonance (ssNMR), Scanning Electron Microscope (SEM), micro-computed tomography (μCT) and Thermal Gravimetric Analysis (TGA) were used for delineating the ultra-structural property of bone. ssNMR revealed the extent of water, collagen fine structure and crystalline order in the bone. These were greatly perturbed in the bone taken from osteoporotic bone donor. Among the processing methods analyzed, pasteurization at 60 °C and radiation treatment appeared to substantially alter the bone integrity. SEM study showed a reduction in Ca/P ratio and non-uniform distribution of elements in osteoporotic bones. μ-CT and MIMICS® (Materialize Interactive Medical Image Control System) demonstrated that pasteurization and radiation treatment affects the BA morphology and cause a shift in the HU unit. However, the combination of all these processes restored all-important parameters that are critical for BA integrity and sustainability. Cross-correlation between the various probes we used quantitatively demonstrated differences in morphological and micro-structural properties between BA taken from normal and osteoporotic human donor. Such details could also be instrumental in designing an appropriate bone scaffold. For the best restoration of bone microstructure and to be used as a biomaterial allograft, a step-wise processing method is recommended that preserves all

  18. Lead sources in human diet in Greenland

    DEFF Research Database (Denmark)

    Bjerregaard, Peter; Johansen, Poul; Mulvad, Gert

    2004-01-01

    Although blood lead levels have declined in Greenland, they are still elevated despite the fact that lead levels in the Greenland environment are very low. Fragments of lead shot in game birds have been suggested as an important source of dietary exposure, and meals of sea birds, particularly eid...

  19. Dosimetry study for a new in vivo X-ray fluorescence (XRF) bone lead measurement system

    Science.gov (United States)

    Nie, Huiling; Chettle, David; Luo, Liqiang; O'Meara, Joanne

    2007-10-01

    A new 109Cd γ-ray induced bone lead measurement system has been developed to reduce the minimum detectable limit (MDL) of the system. The system consists of four 16 mm diameter detectors. It requires a stronger source compared to the "conventional" system. A dosimetry study has been performed to estimate the dose delivered by this system. The study was carried out by using human-equivalent phantoms. Three sets of phantoms were made to estimate the dose delivered to three age groups: 5-year old, 10-year old and adults. Three approaches have been applied to evaluate the dose: calculations, Monte Carlo (MC) simulations, and experiments. Experimental results and analytical calculations were used to validate MC simulation. The experiments were performed by placing Panasonic UD-803AS TLDs at different places in phantoms that representing different organs. Due to the difficulty of obtaining the organ dose and the whole body dose solely by experiments and traditional calculations, the equivalent dose and effective dose were calculated by MC simulations. The result showed that the doses delivered to the organs other than the targeted lower leg are negligibly small. The total effective doses to the three age groups are 8.45/9.37 μSv (female/male), 4.20 μSv, and 0.26 μSv for 5-year old, 10-year old and adult, respectively. An approval to conduct human measurements on this system has been received from the Research Ethics Board based on this research.

  20. Lead sources in human diet in Greenland

    DEFF Research Database (Denmark)

    Bjerregaard, Peter; Johansen, Poul; Mulvad, Gert

    2004-01-01

    Although blood lead levels have declined in Greenland, they are still elevated despite the fact that lead levels in the Greenland environment are very low. Fragments of lead shot in game birds have been suggested as an important source of dietary exposure, and meals of sea birds, particularly eider......, contain high concentrations of lead. In a cross-sectional population survey in Greenland in 1993-1994, blood lead adjusted for age and sex was found to be associated with the reported consumption of sea birds. Participants reporting less than weekly intake of sea birds had blood lead concentrations...... of approximately 75 microg/L, whereas those who reported eating sea birds several times a week had concentrations of approximately 110 microg/L, and those who reported daily intake had concentrations of 170 microg/L (p = 0.01). Blood lead was not associated with dietary exposure to other local or imported food...

  1. Morphological Study of Wormian Bones in Dried Human Skulls

    OpenAIRE

    Divyesh Patel; Ketan Chauhan; Dhananjay Patil

    2015-01-01

    Background: Wormian bones may be defined as a those accidental bones found in the cranium having no regular relation to their normal ossification centre. They are assocated with cranial and central nervous system abnormalities. Knowledge of these bones is important for anthropo-logists, forensic experts, radiologists, orthopedic and neurosurgeons to avoid misleading for multiple fractures of the skull. Materials and Methods: Adult dry human skulls (n= 27) of unknown age and sex availablei...

  2. Comparative cortical bone thickness between the long bones of humans and five common non-human mammal taxa.

    Science.gov (United States)

    Croker, Sarah L; Reed, Warren; Donlon, Denise

    2016-03-01

    The task of identifying fragments of long bone shafts as human or non-human is difficult but necessary, for both forensic and archaeological cases, and a fast simple method is particularly useful. Previous literature suggests there may be differences in the thickness of the cortical bone between these two groups, but this has not been tested thoroughly. The aim of this study was not only to test this suggestion, but also to provide data that could be of practical assistance for future comparisons. The major limb bones (humerus, radius, femur and tibia) of 50 Caucasoid adult skeletons of known age and sex were radiographed, along with corresponding skeletal elements from sheep, pigs, cattle, large dogs and kangaroos. Measurements were taken from the radiographs at five points along the bone shaft, of shaft diameter, cortical bone thickness, and a cortical thickness index (sum of cortices divided by shaft diameter) in both anteroposterior and mediolateral orientations. Each variable for actual cortical bone thickness as well as cortical thickness indices were compared between the human group (split by sex) and each of the non-human groups in turn, using Student's t-tests. Results showed that while significant differences did exist between the human groups and many of the non-human groups, these were not all in the same direction. That is, some variables in the human groups were significantly greater than, and others were significantly less than, the corresponding variable in the non-human groups, depending on the particular non-human group, sex of the human group, or variable under comparison. This was the case for measurements of both actual cortical bone thickness and cortical thickness index. Therefore, for bone shaft fragments for which the skeletal element is unknown, the overlap in cortical bone thickness between different areas of different bones is too great to allow identification using this method alone. However, by providing extensive cortical bone

  3. A simplified procedure for preparation of undecalcified human bone sections

    DEFF Research Database (Denmark)

    Wallin, J A; Tkocz, I; Levinsen, J

    1985-01-01

    A new type of apparatus for sectioning samples of hard, undecalcified bone is described. Slices of fresh or archeological human bone 4-5 mm thick are dehydrated and then embedded in epoxy resin. The apparatus used to prepare sections from the resulting blocks consists of a low-speed rim-type diam...

  4. A simplified procedure for preparation of undecalcified human bone sections

    DEFF Research Database (Denmark)

    Wallin, J A; Tkocz, I; Levinsen, J

    1985-01-01

    A new type of apparatus for sectioning samples of hard, undecalcified bone is described. Slices of fresh or archeological human bone 4-5 mm thick are dehydrated and then embedded in epoxy resin. The apparatus used to prepare sections from the resulting blocks consists of a low-speed rim...

  5. Role of purinergic receptor polymorphisms in human bone

    DEFF Research Database (Denmark)

    Wesselius, Anke; Bours, Martijn J L; Agrawal, Ankita

    2011-01-01

    in the mechanotransductory process, where mechanical stimulation on bone leads to anabolic responses in the skeleton. A number of single nucleotide polymorphisms have been identified in the P2 receptor genes, where especially the P2X7 subtype has been the focus of extensive investigation where several polymorphisms have......Osteoporosis is a multifactorial disease with a strong genetic component. Variations in a number of genes have been shown to associate with bone turnover and risk of osteoporosis. P2 purinergic receptors are proteins that have ATP or other nucleotides as their natural ligands. Various P2Y and P2X...... receptor subtypes have been identified on bone cells. Several cellular functions in bone tissue are coupled to P2-receptor activation, including bone resorption, cytokine release, apoptosis, bone formation, and mineral deposition. Furthermore, ATP release and P2 purinergic signalling is a key pathway...

  6. Bioreactor cultivation of anatomically shaped human bone grafts.

    Science.gov (United States)

    Temple, Joshua P; Yeager, Keith; Bhumiratana, Sarindr; Vunjak-Novakovic, Gordana; Grayson, Warren L

    2014-01-01

    In this chapter, we describe a method for engineering bone grafts in vitro with the specific geometry of the temporomandibular joint (TMJ) condyle. The anatomical geometry of the bone grafts was segmented from computed tomography (CT) scans, converted to G-code, and used to machine decellularized trabecular bone scaffolds into the identical shape of the condyle. These scaffolds were seeded with human bone marrow-derived mesenchymal stem cells (MSCs) using spinner flasks and cultivated for up to 5 weeks in vitro using a custom-designed perfusion bioreactor system. The flow patterns through the complex geometry were modeled using the FloWorks module of SolidWorks to optimize bioreactor design. The perfused scaffolds exhibited significantly higher cellular content, better matrix production, and increased bone mineral deposition relative to non-perfused (static) controls after 5 weeks of in vitro cultivation. This technology is broadly applicable for creating patient-specific bone grafts of varying shapes and sizes.

  7. Ethanol inhibits human bone cell proliferation and function in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Friday, K.E.; Howard, G.A. (University of Washington, Seattle (USA))

    1991-06-01

    The direct effects of ethanol on human bone cell proliferation and function were studied in vitro. Normal human osteoblasts from trabecular bone chips were prepared by collagenase digestion. Exposure of these osteoblasts to ethanol in concentrations of 0.05% to 1% for 22 hours induced a dose-dependent reduction in bone cell DNA synthesis as assessed by incorporation of 3H-thymidine. After 72 hours of ethanol exposure in concentrations of 0.01% to 1%, protein synthesis as measured by 3H-proline incorporation into trichbroacetic acid (TCA)-precipitable material was reduced in a dose-dependent manner. Human bone cell protein concentrations and alkaline phosphatase total activity were significantly reduced after exposure to 1% ethanol for 72 hours, but not with lower concentrations of ethanol. This reduction in osteoblast proliferation and activity may partially explain the development of osteopenia in humans consuming excessive amounts of ethanol.

  8. Bone lead (Pb) content at the tibia is associated with thinner distal tibia cortices and lower volumetric bone density in postmenopausal women.

    Science.gov (United States)

    Wong, Andy K O; Beattie, Karen A; Bhargava, Aakash; Cheung, Marco; Webber, Colin E; Chettle, David R; Papaioannou, Alexandra; Adachi, Jonathan D

    2015-10-01

    Conflicting evidence suggests that bone lead or blood lead may reduce areal bone mineral density (BMD). Little is known about how lead at either compartment affects bone structure. This study examined postmenopausal women (N=38, mean age 76 ± 8, body mass index (BMI): 26.74 ± 4.26 kg/m(2)) within the Hamilton cohort of the Canadian Multicentre Osteoporosis Study (CaMos), measuring bone lead at 66% of the non-dominant leg and at the calcaneus using (109)Cadmium X-ray fluorescence. Volumetric BMD and structural parameters were obtained from peripheral quantitative computed tomography images (200 μm in-plane resolution, 2.3 ± 0.5mm slice thickness) of the same 66% site and of the distal 4% site of the tibia length. Blood lead was measured using atomic absorption spectrometry and blood-to-bone lead partition coefficients (PBB, log ratio) were computed. Multivariable linear regression examined each of bone lead at the 66% tibia, calcaneus, blood lead and PBB as related to each of volumetric BMD and structural parameters, adjusting for age and BMI, diabetes or antiresorptive therapy. Regression coefficients were reported along with 95% confidence intervals. Higher amounts of bone lead at the tibia were associated with thinner distal tibia cortices (-0.972 (-1.882, -0.061) per 100 μg Pb/g of bone mineral) and integral volumetric BMD (-3.05 (-6.05, -0.05) per μg Pb/g of bone mineral). A higher PBB was associated with larger trabecular separation (0.115 (0.053, 0.178)), lower trabecular volumetric BMD (-26.83 (-50.37, -3.29)) and trabecular number (-0.08 (-0.14, -0.02)), per 100 μg Pb/g of bone mineral after adjusting for age and BMI, and remained significant while accounting for diabetes or use of antiresorptives. Total lead exposure activities related to bone lead at the calcaneus (8.29 (0.11, 16.48)) and remained significant after age and antiresorptives-adjustment. Lead accumulated in bone can have a mild insult on bone structure; but greater partitioning of lead

  9. Bone blood flow and metabolism in humans

    DEFF Research Database (Denmark)

    Heinonen, Ilkka; Kemppainen, Jukka; Kaskinoro, Kimmo

    2012-01-01

    in femoral bone at rest and during one leg intermittent isometric exercise with increasing exercise intensities. In nine men, blood flow in femur was determined at rest and during dynamic one leg exercise, and two other physiological perturbations: moderate systemic hypoxia (14 O(2) ) at rest and during...... leg. In conclusion, resting femoral bone blood flow increases by physical exercise, but appears to level off with increasing exercise intensities. Moreover, while moderate systemic hypoxia does not change bone blood flow at rest or during exercise, intra-arterially administered adenosine during...

  10. Bone mineral density, Bone mineral contents, MMP-8 and MMP-9 levels in Human Mandible and alveolar bone: Simulated microgravity

    Science.gov (United States)

    Rai, Balwant; Kaur, Jasdeep; Catalina, Maria

    Exposure to microgravity has been associated with several physiological changes in astronauts and cosmonauts, including an osteoporosis-like loss of bone mass. It has been reported that head-down tilt bed-rest studies mimic many of the observations seen in flights. There is no study on the correlation on effects of mandibular bone and alveolar bone loss in both sex in simulating microgravity. This study was designed to determine the Bone mineral density and GCF MMP-8 MMP-9 in normal healthy subject of both sexes in simulated microgravity condition of -6 head-down-tilt (HDT) bed rest. The subjects of this investigation were 10 male and 10 female volunteers participated in three weeks 6 HDT bed-rest exposure. The Bone density and bone mineral contents were measured by dual energy X-ray absorptiometry before and in simulated microgravity. The GCF MMP-8 MMP-8 were measured by Enzyme-linked immunosorbent assays (Human Quantikine MMP-8,-9 ELISA kit). The bone mineral density and bone mineral contents levels were significantly decreased in simulated microgravity condition in both genders, although insignificantly loss was higher in females as compared to males. MMP-8 MMP-9 levels were significantly increased in simulated microgravity as compared to normal condition although insignificantly higher in females as compared to males. Further study is required on large samples size including all factors effecting in simulated microgravity and microgravity. Keys words-Simulated microgravity condition, head-down-tilt, Bone loss, MMP-8, MMP-9, Bone density, Bone mineral contents.

  11. Reduced Bone and Body Mass in Young Male Rats Exposed to Lead

    Directory of Open Access Journals (Sweden)

    Fellipe Augusto Tocchini de Figueiredo

    2014-01-01

    Full Text Available The aim of this study was to see whether there would be differences in whole blood versus tibia lead concentrations over time in growing rats prenatally. Lead was given in the drinking water at 30 mg/L from the time the dams were pregnant until offspring was 28- or 60-day-old. Concentrations of lead were measured in whole blood and in tibia after 28 (28D and 60 days (60D in control (C and in lead-exposed animals (Pb. Lead measurements were made by GF-AAS. There was no significant difference (P>0.05 in the concentration of whole blood lead between Pb-28D (8.0±1.1 μg/dL and Pb-60D (7.2±0.89 μg/dL, while both significantly varied (P<0.01 from controls (0.2 μg/dL. Bone lead concentrations significantly varied between the Pb-28D (8.02±1.12 μg/g and the Pb-60D (43.3±13.26 μg/g lead-exposed groups (P<0.01, while those exposed groups were also significantly higher (P<0.0001 than the 28D and 60D control groups (Pb < 1 μg/g. The Pb-60D group showed a 25% decrease in tibia mass as compared to the respective control. The five times higher amount of lead found in the bone of older animals (Pb-60D versus Pb-28D, which reinforces the importance of using bone lead as an exposure biomarker.

  12. No effect of Osteoset, a bone graft substitute, on bone healing in humans: a prospective randomized double-blind study

    DEFF Research Database (Denmark)

    Petruskevicius, Juozas; Nielsen, Mette Strange; Kaalund, Søren;

    2002-01-01

    We studied the effects of a newly marketed bone substitute, Osteoset, on bone healing in a tibial defect in humans. 20 patients undergoing an ACL (anterior cruciate ligament) reconstruction with bone-patella tendon-bone graft were block-randomized into 2 groups of 10 each. In the treatment group...

  13. Osteochondrosis Can Lead to Formation of Pseudocysts and True Cysts in the Subchondral Bone of Horses.

    Science.gov (United States)

    Olstad, K; Østevik, L; Carlson, C S; Ekman, S

    2015-09-01

    Osteochondrosis arises as a result of focal failure of the blood supply to growth cartilage. The current aim was to examine the pathogenesis of pseudocysts and true cysts in subchondral bone following failure of the blood supply to the articular-epiphyseal cartilage complex in horses. Cases were recruited based on identification of lesions (n = 17) that were considered likely to progress to or to represent pseudocysts or true cysts in epiphyseal bone in histological sections and included 10 horses ranging in age from 48 days to 5 years old. Cases comprised 3 warmbloods, 3 Standardbreds, 1 Quarter horse and 1 Arabian with spontaneous lesions and 2 Fjord ponies with experimentally induced lesions. Seven lesions consisted of areas of ischemic chondronecrosis and were compatible with pseudocysts. Two lesions were located at intermediate depth in epiphyseal growth cartilage, 2 lesions were located in the ossification front, 2 lesions were located in epiphyseal bone and 1 lesion was located in the metaphyseal growth plate (physis). Ten lesions contained dilated blood vessels and were compatible with true cysts. In 2 lesions the dilated blood vessels were located within the lumina of failed cartilage canals. In the 8 remaining lesions areas of ischemic chondronecrosis were associated with granulation tissue in the subjacent bone and dilated vessels were located within this granulation tissue. Failure of the blood supply and ischemic chondronecrosis can lead to formation of pseudocysts or dilatation of blood vessels and formation of true cysts in the epiphyseal bone of horses. © The Author(s) 2014.

  14. Bone density and tissue lead accretion in growing rats fed low high calcium with or without supplemental clinoptilolite

    Energy Technology Data Exchange (ETDEWEB)

    Pond, W.G.; Ho, H.; Su, D.R. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1996-12-31

    The toxicity of lead in animals and humans is well documented. The naturally occurring zeolite, clinoptilolite, is known to offer protection against ammonium ion toxicity in rats and sheep and to counteract cadmium-induced iron deficiency anemia in rats and swine. The cation-exchange and adsorption properties of clinoptilolite suggest is possible role in reducing tissue uptake of ingested lead by animals. Evidence supporting this role was reported in growing pigs whose liver and kidney concentrations of lead were significantly reduced by the addition of 1.0% clinoptilolite to diets containing 500 or 1000ppm of lead. The basal diet was a highly fortified milk-replacer containing about 1% calcium supplied by milk constituents. High dietary calcium is known to reduce tissue uptake of lead and protect the pig from the tissue pathology associated with lead ingestion. The objective of this experiment was to test the hypothesis that dietary clinoptilolite and calcium levels affect the growth, tissue uptake and bone morphology of growing rats fed diets containing toxic levels of lead. 20 refs., 3 tabs.

  15. Effects of lead shot ingestion on bone mineralization in a population of red-legged partridge (Alectoris rufa)

    Energy Technology Data Exchange (ETDEWEB)

    Álvarez-Lloret, Pedro, E-mail: pedroalvarez@geol.uniovi.es [Department of Mineralogy and Petrology, University of Granada, Avd. Fuentenueva s/n, 18002 Granada (Spain); Departament of Geology, University of Oviedo, C/Jesús Arias de Velasco, s/n, 33005 Oviedo (Spain); Rodríguez-Navarro, Alejandro B. [Department of Mineralogy and Petrology, University of Granada, Avd. Fuentenueva s/n, 18002 Granada (Spain); Romanek, Christopher S. [Department of Earth and Environmental Sciences, University of Kentucky, Lexington, KY (United States); Ferrandis, Pablo [Department of Plant Production and Agricultural Technology, E.T.S. Ingenieros Agrónomos, University of Castilla-La Mancha, Campus Universitario s/n, 02071 Albacete (Spain); Martínez-Haro, Mónica [Instituto de Investigación en Recursos Cinegéticos, IREC (CSIC, UCLM, JCCM), Ronda de Toledo s/n, 13005 Ciudad Real (Spain); IMAR-Instituto do Mar, Department of Life Sciences, University of Coimbra, 3004-517 Coimbra (Portugal); Mateo, Rafael [Instituto de Investigación en Recursos Cinegéticos, IREC (CSIC, UCLM, JCCM), Ronda de Toledo s/n, 13005 Ciudad Real (Spain)

    2014-01-01

    The effect of lead (Pb) toxicity on bone mineralization was investigated in a wild population of red-legged partridge (Alectoris rufa) inhabiting a farmland area contaminated with Pb-shot from recreational hunting activities in Albacete, a southeastern province of Spain. Femora from 40 specimens of red-legged partridge were analyzed for Pb by graphite furnace atomic absorption spectroscopy (GF-AAS), and for bone composition by Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD). The FTIR and DRX data of bone were analyzed in detail to determine possible alterations in bone mineral chemistry and crystallinity due to Pb toxicity. Results showed a marked decrease in the degree of mineralization as Pb concentrations in bone tissue increased while XRD analyses showed that the crystallinity of apatite crystals increased with the Pb load in bone. These load-dependent effects are indicative that Pb contamination altered bone remodeling by reducing new bone mineral formation and demonstrate that bone quality is a sensitive indicator of adverse effects on wild bird populations exposed to Pb pollution. - Highlights: •The effect of Pb toxicity on bone mineralization was investigated in partridges. •Lead exposure decreased bone mineralization degree. •Demonstrated usefulness of FTIR and DRX to evaluate alterations in bone chemistry and crystallinity by Pb exposure.

  16. MicroCT evaluation of bone mineral density loss in human bones

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, Liebert P.; Braz, Delson; Lopes, Ricardo T. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia (COPPE). Lab. de Instrumentacao Nuclear]. E-mails: lnogueira@con.ufrj.br; Barroso, Regina C.; Oliveira, Luis F. [Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ (Brazil). Inst. de Fisica]. E-mail: cely@uerj.br

    2007-07-01

    Bone is a connective tissue largely composed of an organic protein, collagen and the inorganic mineral hydroxyapatite [Ca{sub 10}(PO{sub 4}){sub 6}OH{sub 2}], which combine to provide a mechanical and supportive role in the body. Depending on the orientation of collagen fibers, two types of bone can be distinguished: trabecular and cortical bone. Degree of mineralization is considered an important feature of bone quality. Changes in the degree of mineralization is generally due to osteoporosis, but many recent studies have already shown that alterations in degree of mineralization can occur due to a large variety of factors. The transmission X-ray microtomography is one of the most popular methods, which provides the spatial distribution of the total absorption coefficient inside the sample. The aim of this study was to investigate the suitability of using microCT as a supplementary tool for the diagnosis of the health status of human bones. Eleven samples were constructed simulating the physiological range of bone mineral density (BMD) found in cortical human bone. The samples represent healthy mixtures of swine compact bone dried at room temperature, powdered and mixed with fat (0 - 100 % by mass). The samples were imaged by a microfocus tube (Fein-Focus) with focal size of about 60 {mu}m ({+-}5%), and a CCD camera (0.143 mm pixel size) coupled with an intensifier tube with fluoroscope screen at the Nuclear Instrumentation Laboratory (COPPE/UFRJ), Brazil. The images were reconstructed and treated with suitable software developed at the Nuclear Instrumentation Laboratory. The mineral content in cortical bone is defined by the volume of dry, fat-free bone per unit bulk volume of the bone. The volumes were calculated from the bone density using the relationship between volume and density. The densities of fat and bone were taken to be 0.95 g.cm{sup -3} and 1.92 g.cm{sup -3} respectively. The correlation of the measured absorption coefficient with the mineral content

  17. Early reversal cells in adult human bone remodeling

    DEFF Research Database (Denmark)

    Abdelgawad, Mohamed Essameldin; Delaissé, Jean-Marie; Hinge, Maja

    2016-01-01

    The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter...... of debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts...... demonstrates that reversal cells colonizing bone surfaces right after resorption are osteoblast-lineage cells, and extends to adult human bone remodeling their role in rendering eroded surfaces osteogenic....

  18. Morphological Study of Wormian Bones in Dried Human Skulls

    Directory of Open Access Journals (Sweden)

    Divyesh Patel

    2015-09-01

    Full Text Available Background: Wormian bones may be defined as a those accidental bones found in the cranium having no regular relation to their normal ossification centre. They are assocated with cranial and central nervous system abnormalities. Knowledge of these bones is important for anthropo-logists, forensic experts, radiologists, orthopedic and neurosurgeons to avoid misleading for multiple fractures of the skull. Materials and Methods: Adult dry human skulls (n= 27 of unknown age and sex availablein the Department of Anatomy, Govt. Medical College, Surat were included in the study. Result: Overall incidence of wormian bone was 44.4%. They occurred more frequently at lambdoid suture (48.14%.Wormian bones were also presentat asterion (18.5%, along the coronal suture (0.03%, along the parito-temporal suture (0.07%, along the occipito-mastoid suture (0.03%,andat pterion (0.03 %. Wormain bones were found 48.1% on left half of skull and 37.03% on right half of skull. Conclusion: The Wormian bones were more frequent at the lambdoid suture. The clinical importances of these variant bones were emphasized with relevant review of literature. [Natl J Med Res 2015; 5(3.000: 222-225

  19. Determinants of microdamage in elderly human vertebral trabecular bone.

    Directory of Open Access Journals (Sweden)

    Hélène Follet

    Full Text Available Previous studies have shown that microdamage accumulates in bone as a result of physiological loading and occurs naturally in human trabecular bone. The purpose of this study was to determine the factors associated with pre-existing microdamage in human vertebral trabecular bone, namely age, architecture, hardness, mineral and organic matrix. Trabecular bone cores were collected from human L2 vertebrae (n = 53 from donors 54-95 years of age (22 men and 30 women, 1 unknown and previous cited parameters were evaluated. Collagen cross-link content (PYD, DPD, PEN and % of collagen was measured on surrounding trabecular bone. We found that determinants of microdamage were mostly the age of donors, architecture, mineral characteristics and mature enzymatic cross-links. Moreover, linear microcracks were mostly associated with the bone matrix characteristics whereas diffuse damage was associated with architecture. We conclude that linear and diffuse types of microdamage seemed to have different determinants, with age being critical for both types.

  20. DNA and bone structure preservation in medieval human skeletons.

    Science.gov (United States)

    Coulson-Thomas, Yvette M; Norton, Andrew L; Coulson-Thomas, Vivien J; Florencio-Silva, Rinaldo; Ali, Nadir; Elmrghni, Samir; Gil, Cristiane D; Sasso, Gisela R S; Dixon, Ronald A; Nader, Helena B

    2015-06-01

    Morphological and ultrastructural data from archaeological human bones are scarce, particularly data that have been correlated with information on the preservation of molecules such as DNA. Here we examine the bone structure of macroscopically well-preserved medieval human skeletons by transmission electron microscopy and immunohistochemistry, and the quantity and quality of DNA extracted from these skeletons. DNA technology has been increasingly used for analyzing physical evidence in archaeological forensics; however, the isolation of ancient DNA is difficult since it is highly degraded, extraction yields are low and the co-extraction of PCR inhibitors is a problem. We adapted and optimised a method that is frequently used for isolating DNA from modern samples, Chelex(®) 100 (Bio-Rad) extraction, for isolating DNA from archaeological human bones and teeth. The isolated DNA was analysed by real-time PCR using primers targeting the sex determining region on the Y chromosome (SRY) and STR typing using the AmpFlSTR(®) Identifiler PCR Amplification kit. Our results clearly show the preservation of bone matrix in medieval bones and the presence of intact osteocytes with well preserved encapsulated nuclei. In addition, we show how effective Chelex(®) 100 is for isolating ancient DNA from archaeological bones and teeth. This optimised method is suitable for STR typing using kits aimed specifically at degraded and difficult DNA templates since amplicons of up to 250bp were successfully amplified.

  1. Non-invasive photo acoustic approach for human bone diagnosis.

    Science.gov (United States)

    Thella, Ashok Kumar; Rizkalla, James; Helmy, Ahdy; Suryadevara, Vinay Kumar; Salama, Paul; Rizkalla, Maher

    2016-12-01

    The existing modalities of bone diagnosis including X-ray and ultrasound may cite drawback in some cases related to health issues and penetration depth, while the ultrasound modality may lack image quality. Photo acoustic approach however, provides light energy to the acoustic wave, enabling it to activate and respond according to the propagating media (which is type of bones in this case). At the same time, a differential temperature change may result in the bio heat response, resulting from the heat absorbed across the multiple materials under study. In this work, we have demonstrated the features of using photo acoustic modality in order to non-invasively diagnose the type of human bones based on their electrical, thermal, and acoustic properties that differentiate the output response of each type. COMSOL software was utilized to combine both acoustic equations and bio heat equations, in order to study both the thermal and acoustic responses through which the differential diagnosis can be obtained. In this study, we solved both the acoustic equation and bio heat equations for four types of bones, bone (cancellous), bone (cortical), bone marrow (red), and bone marrow (yellow). 1 MHz acoustic source frequency was chosen and 10(5) W/m(2) power source was used in the simulation. The simulation tested the dynamic response of the wave over a distance of 5 cm from each side for the source. Near 2.4 cm was detected from simulation from each side of the source with a temperature change of within 0.5 K for various types of bones, citing a promising technique for a practical model to detect the type of bones via the differential temperature as well as the acoustic was response via the multiple materials associated with the human bones (skin and blood). The simulation results suggest that the PA technique may be applied to non-invasive diagnosis for the different types of bones, including cancerous bones. A practical model for detecting both the temperature change via

  2. Study of lead accumulation in bones of Wistar rats by X-ray fluorescence analysis: aging effect.

    Science.gov (United States)

    Guimarães, Diana; Carvalho, Maria Luísa; Geraldes, Vera; Rocha, Isabel; Santos, José Paulo

    2012-01-01

    The accumulation of lead in several bones of Wistar rats with time was determined and compared for the different types of bones. Two groups were studied: a control group (n = 20), not exposed to lead and a contaminated group (n = 30), exposed to lead from birth, first indirectly through mother's milk, and then directly through a diet containing lead acetate in drinking water (0.2%). Rats age ranged from 1 to 11 months, with approximately 1 month intervals and each of the collections had 3 contaminated rats and 2 control rats. Iliac, femur, tibia-fibula and skull have been analysed by Energy Dispersive X-ray Fluorescence Technique (EDXRF). Samples of formaldehyde used to preserve the bone tissues were also analysed by Electrothermal Atomic Absorption (ETAAS), showing that there was no significant loss of lead from the tissue to the preservative. The bones mean lead concentration of exposed rats range from 100 to 300 μg g(-1) while control rats never exceeded 10 μg g(-1). Mean bone lead concentrations were compared and the concentrations were higher in iliac, femur and tibia-fibula and after that skull. However, of all the concentrations in the different collections, only those in the skull were statistically significantly different (p bones. Analysis of a radar chart also allowed us to say that these differences tend to diminish with age. The Spearman correlation test applied to mean lead concentrations showed strong and very strong positive correlations between all different types of bones. This test also showed that mean lead concentrations in bones are negatively correlated with the age of the animals. This correlation is strong in iliac and femur and very strong in tibia-fibula and skull. It was also shown that the decrease of lead accumulation with age is made by three plateaus of accumulation, which coincide, in all analysed bones, between 2nd-3rd and 9th-10th months.

  3. Estrogen Deficiency Leads to Further Bone Loss in the Mandible of CKD Mice.

    Directory of Open Access Journals (Sweden)

    Yuchen Guo

    Full Text Available Chronic kidney disease (CKD has been regarded as a grave public health problem. Estrogen is a critical factor for both renal protection and bone remodeling. Our previous study demonstrated that CKD impairs the healing of titanium implants. The aim of this study was to investigate the effects of estrogen deficiency on the mandibular bone in CKD mice.Forty eleven-week-old female C57BL mice were used in this study. Uremia and estrogen deficiency were induced by 5/6 nephrectomy and ovariectomy (OVX, respectively. After 8 weeks, the mice were sacrificed, and their mandibles were collected for micro-CT analysis and histological examination.All the mice survived the experimental period. Serum measurements confirmed a significant increase in BUN in the CKD group that was further increased by OVX. OVX led to significant decreases in both the BV/TV and cortical thickness of the mandibular bone in CKD mice.In summary, our findings indicate that estrogen deficiency leads to further mandibular bone loss in CKD mice.

  4. Effect of boundary conditions on yield properties of human femoral trabecular bone.

    Science.gov (United States)

    Panyasantisuk, J; Pahr, D H; Zysset, P K

    2016-10-01

    Trabecular bone plays an important mechanical role in bone fractures and implant stability. Homogenized nonlinear finite element (FE) analysis of whole bones can deliver improved fracture risk and implant loosening assessment. Such simulations require the knowledge of mechanical properties such as an appropriate yield behavior and criterion for trabecular bone. Identification of a complete yield surface is extremely difficult experimentally but can be achieved in silico by using micro-FE analysis on cubical trabecular volume elements. Nevertheless, the influence of the boundary conditions (BCs), which are applied to such volume elements, on the obtained yield properties remains unknown. Therefore, this study compared homogenized yield properties along 17 load cases of 126 human femoral trabecular cubic specimens computed with classical kinematic uniform BCs (KUBCs) and a new set of mixed uniform BCs, namely periodicity-compatible mixed uniform BCs (PMUBCs). In stress space, PMUBCs lead to 7-72 % lower yield stresses compared to KUBCs. The yield surfaces obtained with both KUBCs and PMUBCs demonstrate a pressure-sensitive ellipsoidal shape. A volume fraction and fabric-based quadric yield function successfully fitted the yield surfaces of both BCs with a correlation coefficient [Formula: see text]. As expected, yield strains show only a weak dependency on bone volume fraction and fabric. The role of the two BCs in homogenized FE analysis of whole bones will need to be investigated and validated with experimental results at the whole bone level in future studies.

  5. Overexpression of Human Bone Alkaline Phosphatase in Pichia Pastoris

    Science.gov (United States)

    Karr, Laurel; Malone, Christine, C.; Rose, M. Franklin (Technical Monitor)

    2000-01-01

    The Pichiapastoris expression system was utilized to produce functionally active human bone alkaline phosphatase in gram quantities. Bone alkaline phosphatase is a key enzyme in bone formation and biomineralization, yet important questions about its structural chemistry and interactions with other cellular enzymes in mineralizing tissues remain unanswered. A soluble form of human bone alkaline phosphatase was constructed by deletion of the 25 amino acid hydrophobic C-terminal region of the encoding cDNA and inserted into the X-33 Pichiapastoris strain. An overexpression system was developed in shake flasks and converted to large-scale fermentation. Alkaline phosphatase was secreted into the medium to a level of 32mgAL when cultured in shake flasks. Enzyme activity was 12U/mg measured by a spectrophotometric assay. Fermentation yielded 880mgAL with enzymatic activity of 968U/mg. Gel electrophoresis analysis indicates that greater than 50% of the total protein in the fermentation is alkaline phosphatase. A purification scheme has been developed using ammonium sulfate precipitation followed by hydrophobic interaction chromatography. We are currently screening crystallization conditions of the purified recombinant protein for subsequent X-ray diffraction analyses. Structural data should provide additional information on the role of alkaline phosphatase in normal bone mineralization and in certain bone mineralization anomalies.

  6. Lead--the toxic metal to stay with human.

    Science.gov (United States)

    Srianujata, S

    1998-07-01

    Lead has been known to be toxic to most living things at high dose. It is found naturally in earth and present in almost all parts of the environment, such as foods, air, water, dust, soil, paint, and tissues of living organisms including human. This metal is being used in various aspects including the manufacturing of storage batteries, production of chemicals, paints and gasoline additives. It is also used to make various metal products, e.g. sheet lead, solder, and pipes. Human exposure to lead is mainly from foods and other environments. However, it is expected that exposure to environmental lead is normally excessive and produces toxic effects. The well-known and excessive environmental exposures are air of industrial and heavy traffic areas. Use of leaded gasoline has caused the main lead pollution for years in almost every big city. Therefore, city inhabitants normally exposed to lead much more than those who live in the rural area. The most vulnerable groups at risk to lead exposure are fetuses and preschool age children. Young children in the 2-3 year-old age may be the most at risk for exposure to contaminated soil. Adults are affected when exposure is excessive in the working place and causing lead poisoning. Toxicities are mainly on heme biosynthesis, neurological effects including encepharopathy, peripheral neuropathy, and most importantly on I.Q. deficits. It also affects renal tissues to produce acute and chronic nephropathy and elevated blood pressure. There are studies of lead exposure of various means and the effects on human health, both in children and adults. Lead in environment and human exposure are expected to stay with us for long to come, due the still required lead use in many fields, particularly the use of lead in storage batteries and others. The magnitude of exposure will depend solely on the control of use by not allowing the contamination of lead in our environment to be excessive.

  7. A comprehensive clinical review of recombinant human bone morphogenetic protein-2 (INFUSE® Bone Graft)

    Science.gov (United States)

    Peckham, Steven M.; Badura, Jeffrey M.

    2007-01-01

    The combination of recombinant human bone morphogenetic protein-2 (rhBMP-2) on an absorbable collagen sponge (ACS) carrier has been shown to induce bone formation in a number of preclinical and clinical investigations. In 2002, rhBMP-2/ACS at a 1.5-mg/cc concentration (INFUSE® Bone Graft, Medtronic Spinal and Biologics, Memphis, TN) was FDA-approved as an autograft replacement for certain interbody spinal fusion procedures. In 2004, INFUSE® Bone Graft was approved for open tibial fractures with an intermedullary (IM) nail fixation. Most recently, in March 2007, INFUSE® Bone Graft was approved as an alternative to autogenous bone grafts for sinus augmentations, and for localised alveolar ridge augmentations for defects associated with extraction sockets. The culmination of extensive preclinical and clinical research and three FDA approvals makes rhBMP-2 one of the most studied, published and significant advances in orthopaedics. This review article summarises a number of clinical findings of rhBMP-2/ACS, including the FDA-approved investigational device exemption (IDE) studies used in gaining the aforementioned approvals. PMID:17639384

  8. Lead shot from hunting as a source of lead in human blood

    Energy Technology Data Exchange (ETDEWEB)

    Johansen, Poul [National Environmental Research Institute, Frederiksborgvej 399, DK-4000 Roskilde (Denmark)]. E-mail: poj@dmu.dk; Pedersen, Henning Sloth [Primary Health Care Center, DK-3900 Nuuk (Greenland); Asmund, Gert [National Environmental Research Institute, Frederiksborgvej 399, DK-4000 Roskilde (Denmark); Riget, Frank [National Environmental Research Institute, Frederiksborgvej 399, DK-4000 Roskilde (Denmark)

    2006-07-15

    This study investigates the relationship between the intake of birds hunted with lead shot and the lead concentration in human blood. Fifty adult men from Nuuk, Greenland took part in the study. From September 2003 to June 2004 they regularly gave blood samples and recorded how many birds they ate. We found a clear relationship between the number of bird meals and blood lead and also a clear seasonal variation. The concentration was highest in mid-winter when bird consumption is at its highest. Blood lead was low (15 {mu}g/L, mean concentration) among the participants reporting not eating birds. Among those reporting to eat birds regularly, blood lead was significantly higher, up to 128 {mu}g/L (mean concentration). Concentrations depended on the frequency of bird meals: the more the bird meals, the higher the resulting blood lead. This clear relationship points to lead shot as the dominating lead source to people in Greenland. - Birds hunted with lead shot and consumed are a source of lead in human blood.

  9. Microscopic residues of bone from dissolving human remains in acids.

    Science.gov (United States)

    Vermeij, Erwin; Zoon, Peter; van Wijk, Mayonne; Gerretsen, Reza

    2015-05-01

    Dissolving bodies is a current method of disposing of human remains and has been practiced throughout the years. During the last decade in the Netherlands, two cases have emerged in which human remains were treated with acid. In the first case, the remains of a cremated body were treated with hydrofluoric acid. In the second case, two complete bodies were dissolved in a mixture of hydrochloric and sulfuric acid. In both cases, a great variety of evidence was collected at the scene of crime, part of which was embedded in resin, polished, and investigated using SEM/EDX. Apart from macroscopic findings like residual bone and artificial teeth, in both cases, distinct microscopic residues of bone were found as follows: (partly) digested bone, thin-walled structures, and recrystallized calcium phosphate. Although some may believe it is possible to dissolve a body in acid completely, at least some of these microscopic residues will always be found. © 2015 American Academy of Forensic Sciences.

  10. Age variations in the properties of human tibial trabecular bone

    DEFF Research Database (Denmark)

    Ding, Ming; Dalstra, M; Danielsen, CC;

    1997-01-01

    We tested in compression specimens of human proximal tibial trabecular bone from 31 normal donors aged from 16 to 83 years and determined the mechanical properties, density and mineral and collagen content. Young's modulus and ultimate stress were highest between 40 and 50 years, whereas ultimate...

  11. Ancient DNA in human bone remains from Pompeii archaeological site.

    Science.gov (United States)

    Cipollaro, M; Di Bernardo, G; Galano, G; Galderisi, U; Guarino, F; Angelini, F; Cascino, A

    1998-06-29

    aDNA extraction and amplification procedures have been optimized for Pompeian human bone remains whose diagenesis has been determined by histological analysis. Single copy genes amplification (X and Y amelogenin loci and Y specific alphoid repeat sequences) have been performed and compared with anthropometric data on sexing.

  12. [Microdetermination of fluoride in human bones (author's transl)].

    Science.gov (United States)

    Hanocq, M; Helson-Cambier, M

    1979-01-15

    A spectrophotometric method (cerium(III)-alizarin complexan-fluoride in presence of 25% dimethylsulfoxyde) is described for the determination of fluoride in human bones. The anion is determined after separation by microdiffusion as hydrofluoric acid using Petri boxes without any mineralization. This analytical method is selective, accurate and rapid.

  13. Training human mesenchymal stromal cells for bone tissue engineering applications

    NARCIS (Netherlands)

    Doorn, J.

    2012-01-01

    Human mesenchymal stromal cells (hMSCs) are an interesting source for cell therapies and tissue engineering applications, because these cells are able to differentiate into various target tissues, such as bone, cartilage, fat and endothelial cells. In addition, they secrete a wide array of growth fa

  14. Ex Vivo Behaviour of Human Bone Tumor Endothelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Infante, Teresa [SDN-Foundation, Institute of Diagnostic and Nuclear Development, IRCCS, 80143 Naples (Italy); Cesario, Elena [Department of Biochemistry and Biophysics, Second University of Naples, 80138 Naples (Italy); Gallo, Michele; Fazioli, Flavio [Division of Skeletal Muscles Oncology Surgery, National Cancer Institute, Pascale Foundation, 80131 Naples (Italy); De Chiara, Annarosaria [Anatomic Pathology Unit, National Cancer Institute, Pascale Foundation, 80131 Naples (Italy); Tutucci, Cristina; Apice, Gaetano [Medical Oncology of Bone and Soft Sarcoma tissues Unit, National Cancer Institute, Pascale Foundation, 80131 Naples (Italy); Nigris, Filomena de, E-mail: filomena.denigris@unina2.it [Department of Biochemistry and Biophysics, Second University of Naples, 80138 Naples (Italy)

    2013-04-11

    Cooperation between endothelial cells and bone in bone remodelling is well established. In contrast, bone microvasculature supporting the growth of primary tumors and metastasis is poorly understood. Several antiangiogenic agents have recently been undergoing trials, although an extensive body of clinical data and experimental research have proved that angiogenic pathways differ in each tumor type and stage. Here, for the first time, we characterize at the molecular and functional level tumor endothelial cells from human bone sarcomas at different stages of disease and with different histotypes. We selected a CD31{sup +} subpopulation from biopsies that displayed the capability to grow as adherent cell lines without vascular endothelial growth factor (VEGF). Our findings show the existence in human primary bone sarcomas of highly proliferative endothelial cells expressing CD31, CD44, CD105, CD146 and CD90 markers. These cells are committed to develop capillary-like structures and colony formation units, and to produce nitric oxide. We believe that a better understanding of tumor vasculature could be a valid tool for the design of an efficacious antiangiogenic therapy as adjuvant treatment of sarcomas.

  15. Stable isotopic analysis on ancient human bones in Jiahu site

    Institute of Scientific and Technical Information of China (English)

    HU YaoWu; S.H.AMBROSE; WANG ChangSui

    2007-01-01

    Palaeodietary analysis is one of important topics in bioarchaeology field and has been paid great attention to by Chinese archaeometrists recently. Ancient human bones in Jiahu Site were analyzed by means of stable isotopes of C, N and 0.13 human bones were excluded from 28 bones for dietary reconstruction due to their unusual collagen contents, C and N contents, and C/N atomic ratios especially.δ13C(-20.37±0.53‰)in collagen of remaining samples showed that C3 food were consumed mainly, which is consistent of the archaeological findings that rice was the staple in Jiahu. According to the difference of δ15N and δ13C values in bone collagen, the samples can be classified into four clusters. The changes of δ15N values in bone collagen and δ13C values in hydroxylapatite through whole cultural phases indicated the transition from hunting to gathering and fishing to rice agriculture and animal domestication ultimately. Meanwhile, the δ18O change in hydroxylapatite showed that palaeoclimate was relatively constant during Jiahu culture.

  16. Stable isotopic analysis on ancient human bones in Jiahu site

    Institute of Scientific and Technical Information of China (English)

    S.H.AMBROSE

    2007-01-01

    Palaeodietary analysis is one of important topics in bioarchaeology field and has been paid great at- tention to by Chinese archaeometrists recently. Ancient human bones in Jiahu Site were analyzed by means of stable isotopes of C, N and O. 13 human bones were excluded from 28 bones for dietary re- construction due to their unusual collagen contents, C and N contents, and C/N atomic ratios espe- cially. δ 13C (-20.37±0.53‰) in collagen of remaining samples showed that C3 food were consumed mainly, which is consistent of the archaeological findings that rice was the staple in Jiahu. According to the difference of δ 15N and δ 13C values in bone collagen, the samples can be classified into four clusters. The changes of δ 15N values in bone collagen and δ 13C values in hydroxylapatite through whole cultural phases indicated the transition from hunting to gathering and fishing to rice agriculture and animal domestication ultimately. Meanwhile, the δ 18O change in hydroxylapatite showed that pa- laeoclimate was relatively constant during Jiahu culture.

  17. Regional distribution of lead in human milk from Egypt.

    Science.gov (United States)

    Saleh, M A; Ragab, A A; Kamel, A; Jones, J; el-Sebae, A K

    1996-05-01

    Bioaccumulation of lead during chronic exposure and its mobilization and secretion with mother's milk constitute a serious health hazard to the newly born children. Lead levels in human breast milk of 120 Egyptian women representing 20 different governorates throughout Egypt were determined using a graphite furnace Atomic Absorption spectrometer. According to the daily permissible intake (DPI) value established by the WHO of 5.0 micrograms/kg/d in mother's milk, the mean values of lead were around the permissible level in most of the Egyptian governorates. However, lead levels in mother's milk from Alexandria, Assiut and Cairo were significantly higher than the permissible value. Higher lead levels in mother's milk from these governorates may be attributed to heavy automobile traffic using leaded gasoline in addition to the use of lead water pipelines in these areas.

  18. How Tough is Human Cortical Bone? In-Situ Measurements on Realistically Short Cracks

    Energy Technology Data Exchange (ETDEWEB)

    Ritchie, Robert O; Koester, K. J.; Ager III, J. W.; Ritchie, R.O.

    2008-05-10

    Bone is more difficult to break than to split. Although this is well known, and many studies exist on the behavior of long cracks in bone, there is a need for data on the orientation-dependent crack-growth resistance behavior of human cortical bone which accurately assesses its toughness at appropriate size-scales. Here we use in-situ mechanical testing in the scanning electron microscope and x-ray computed tomography to examine how physiologically-pertinent short (<600 mu m) cracks propagate in both the transverse and longitudinal orientations in cortical bone, using both crack-deflection/twist mechanics and nonlinear-elastic fracture mechanics to determine crack-resistance curves. We find that after only 500 mu m of cracking, the driving force for crack propagation was more than five times higher in the transverse (breaking) direction than in the longitudinal (splitting) direction due to major crack deflections/twists principally at cement sheathes. Indeed, our results show that the true transverse toughness of cortical bone is far higher than previously reported. However, the toughness in the longitudinal orientation, where cracks tend to follow the cement lines, is quite low at these small crack sizes; it is only when cracks become several millimeters in length that bridging mechanisms can develop leading to the (larger-crack) toughnesses generally quoted for bone.

  19. Recent origin of low trabecular bone density in modern humans.

    Science.gov (United States)

    Chirchir, Habiba; Kivell, Tracy L; Ruff, Christopher B; Hublin, Jean-Jacques; Carlson, Kristian J; Zipfel, Bernhard; Richmond, Brian G

    2015-01-13

    Humans are unique, compared with our closest living relatives (chimpanzees) and early fossil hominins, in having an enlarged body size and lower limb joint surfaces in combination with a relatively gracile skeleton (i.e., lower bone mass for our body size). Some analyses have observed that in at least a few anatomical regions modern humans today appear to have relatively low trabecular density, but little is known about how that density varies throughout the human skeleton and across species or how and when the present trabecular patterns emerged over the course of human evolution. Here, we test the hypotheses that (i) recent modern humans have low trabecular density throughout the upper and lower limbs compared with other primate taxa and (ii) the reduction in trabecular density first occurred in early Homo erectus, consistent with the shift toward a modern human locomotor anatomy, or more recently in concert with diaphyseal gracilization in Holocene humans. We used peripheral quantitative CT and microtomography to measure trabecular bone of limb epiphyses (long bone articular ends) in modern humans and chimpanzees and in fossil hominins attributed to Australopithecus africanus, Paranthropus robustus/early Homo from Swartkrans, Homo neanderthalensis, and early Homo sapiens. Results show that only recent modern humans have low trabecular density throughout the limb joints. Extinct hominins, including pre-Holocene Homo sapiens, retain the high levels seen in nonhuman primates. Thus, the low trabecular density of the recent modern human skeleton evolved late in our evolutionary history, potentially resulting from increased sedentism and reliance on technological and cultural innovations.

  20. Emerging bone problems in patients infected with human immunodeficiency virus.

    Science.gov (United States)

    Mondy, Kristin; Tebas, Pablo

    2003-04-01

    Recently, a high incidence of osteopenia and osteoporosis has been observed in individuals infected with human immunodeficiency virus (HIV). This problem appears to be more frequent in patients receiving potent antiretroviral therapy. Other bone-related complications in HIV-infected individuals, including avascular necrosis of the hip and compression fracture of the lumbar spine, have also been reported. People living with HIV have significant alterations in bone metabolism, regardless of whether they are receiving potent antiretroviral therapy. The underlying mechanisms to account for these observations remain unknown, although studies are underway to examine the relationship between the bone abnormalities and other complications associated with HIV and antiretroviral therapy. HIV-infected patients with osteopenia or osteoporosis should be treated similarly to HIV-seronegative patients with appropriate use of nutritional supplements (calcium and vitamin D) and exercise. Hormone replacement and antiresorptive therapies might be also indicated.

  1. Human Bone Marrow Stromal Cells: A Reliable, Challenging Tool for In Vitro Osteogenesis and Bone Tissue Engineering Approaches

    Directory of Open Access Journals (Sweden)

    Ute Hempel

    2016-01-01

    Full Text Available Adult human bone marrow stromal cells (hBMSC are important for many scientific purposes because of their multipotency, availability, and relatively easy handling. They are frequently used to study osteogenesis in vitro. Most commonly, hBMSC are isolated from bone marrow aspirates collected in clinical routine and cultured under the “aspect plastic adherence” without any further selection. Owing to the random donor population, they show a broad heterogeneity. Here, the osteogenic differentiation potential of 531 hBMSC was analyzed. The data were supplied to correlation analysis involving donor age, gender, and body mass index. hBMSC preparations were characterized as follows: (a how many passages the osteogenic characteristics are stable in and (b the influence of supplements and culture duration on osteogenic parameters (tissue nonspecific alkaline phosphatase (TNAP, octamer binding transcription factor 4, core-binding factor alpha-1, parathyroid hormone receptor, bone gla protein, and peroxisome proliferator-activated protein γ. The results show that no strong prediction could be made from donor data to the osteogenic differentiation potential; only the ratio of induced TNAP to endogenous TNAP could be a reliable criterion. The results give evidence that hBMSC cultures are stable until passage 7 without substantial loss of differentiation potential and that established differentiation protocols lead to osteoblast-like cells but not to fully authentic osteoblasts.

  2. Strategies For Human Exploration Leading To Human Colonization of Space

    Science.gov (United States)

    Smitherman, David; Everett, Harmon

    2009-01-01

    Enabling the commercial development of space is key to the future colonization of space and key to a viable space exploration program. Without commercial development following in the footsteps of exploration it is difficult to justify and maintain public interest in the efforts. NASA's exploration program has suffered from the lack of a good commercial economic strategy for decades. Only small advances in commercial space have moved forward, and only up to Earth orbit with the commercial satellite industry. A way to move beyond this phase is to begin the establishment of human commercial activities in space in partnership with the human exploration program. In 2007 and 2008, the authors researched scenarios to make space exploration and commercial space development more feasible as part of their graduate work in the Space Architecture Program at the Sasakawa International Center for Space Architecture at the University of Houston, Houston, Texas. Through this research it became apparent that the problems facing future colonization are much larger than the technology being developed or the international missions that our space agencies are pursuing. These issues are addressed in this paper with recommendations for space exploration, commercial development, and space policy that are needed to form a strategic plan for human expansion into space. In conclusion, the authors found that the current direction in space as carried out by our space agencies around the world is definitely needed, but is inadequate and incapable of resolving all of the issues that inhibit commercial space development. A bolder vision with strategic planning designed to grow infrastructures and set up a legal framework for commercial markets will go a long way toward enabling the future colonization of space.

  3. Characterization of Human Bone Alkaline Phosphatase in Pichia Pastoris

    Science.gov (United States)

    Malone, Christine C.; Ciszak, Eva; Karr, Laurel J.

    1999-01-01

    A soluble form of human bone alkaline phosphatase has been expressed in a recombinant strain of the methylotrophic yeast Pichia pastoris. We constructed a plasmid containing cDNA encoding for human bone alkaline phosphatase, with the hydrophobic carboxyl terminal portion deleted. Alkaline phosphatase was secreted into the medium to a level of 32mg/L when cultured in shake flasks, and enzyme activity was 12U/mg, as measured by a spectrophotometric assay. By conversion to a fermentation system, a yield of 880mg/L has been achieved with an enzyme activity of 968U/mg. By gel electrophoresis analysis, it appears that greater than 50% of the total protein in the fermentation media is alkaline phosphatase. Although purification procedures are not yet completely optimized, they are expected to include filtration, ion exchange and affinity chromatography. Our presentation will focus on the purification and crystallization results up to the time of the conference. Structural data should provide additional information on the role of alkaline phosphatase in normal bone mineralization and in certain bone mineralization anomalies.

  4. Calcium isotope ratios in animal and human bone

    Science.gov (United States)

    Reynard, L. M.; Henderson, G. M.; Hedges, R. E. M.

    2010-07-01

    Calcium isotopes in tissues are thought to be influenced by an individual's diet, reflecting parameters such as trophic level and dairy consumption, but this has not been carefully assessed. We report the calcium isotope ratios (δ 44/42Ca) of modern and archaeological animal and human bone ( n = 216). Modern sheep raised at the same location show 0.14 ± 0.08‰ higher δ 44/42Ca in females than in males, which we attribute to lactation by the ewes. In the archaeological bone samples the calcium isotope ratios of the herbivorous fauna vary by location. At a single site, the archaeological fauna do not show a trophic level effect. Humans have lower δ 44/42Ca than the mean site fauna by 0.22 ± 0.22‰, and the humans have a greater δ 44/42Ca range than the animals. No effect of sex or age on the calcium isotope ratios was found, and intra-individual skeletal δ 44/42Ca variability is negligible. We rule out dairy consumption as the main cause of the lower human δ 44/42Ca, based on results from sites pre-dating animal domestication and dairy availability, and suggest instead that individual physiology and calcium intake may be important in determining bone calcium isotope ratios.

  5. Lead bullet fragments in venison from rifle-killed deer: potential for human dietary exposure.

    Directory of Open Access Journals (Sweden)

    W Grainger Hunt

    Full Text Available Human consumers of wildlife killed with lead ammunition may be exposed to health risks associated with lead ingestion. This hypothesis is based on published studies showing elevated blood lead concentrations in subsistence hunter populations, retention of ammunition residues in the tissues of hunter-killed animals, and systemic, cognitive, and behavioral disorders associated with human lead body burdens once considered safe. Our objective was to determine the incidence and bioavailability of lead bullet fragments in hunter-killed venison, a widely-eaten food among hunters and their families. We radiographed 30 eviscerated carcasses of White-tailed Deer (Odocoileus virginianus shot by hunters with standard lead-core, copper-jacketed bullets under normal hunting conditions. All carcasses showed metal fragments (geometric mean = 136 fragments, range = 15-409 and widespread fragment dispersion. We took each carcass to a separate meat processor and fluoroscopically scanned the resulting meat packages; fluoroscopy revealed metal fragments in the ground meat packages of 24 (80% of the 30 deer; 32% of 234 ground meat packages contained at least one fragment. Fragments were identified as lead by ICP in 93% of 27 samples. Isotope ratios of lead in meat matched the ratios of bullets, and differed from background lead in bone. We fed fragment-containing venison to four pigs to test bioavailability; four controls received venison without fragments from the same deer. Mean blood lead concentrations in pigs peaked at 2.29 microg/dL (maximum 3.8 microg/dL 2 days following ingestion of fragment-containing venison, significantly higher than the 0.63 microg/dL averaged by controls. We conclude that people risk exposure to bioavailable lead from bullet fragments when they eat venison from deer killed with standard lead-based rifle bullets and processed under normal procedures. At risk in the U.S. are some ten million hunters, their families, and low

  6. An Upper Palaeolithic engraved human bone associated with ritualistic cannibalism.

    Science.gov (United States)

    Bello, Silvia M; Wallduck, Rosalind; Parfitt, Simon A; Stringer, Chris B

    2017-01-01

    Cut-marked and broken human bones are a recurrent feature of Magdalenian (~17-12,000 years BP, uncalibrated dates) European sites. Human remains at Gough's Cave (UK) have been modified as part of a Magdalenian mortuary ritual that combined the intensive processing of entire corpses to extract edible tissues and the modification of skulls to produce skull-cups. A human radius from Gough's Cave shows evidence of cut marks, percussion damage and human tooth marks, indicative of cannibalism, as well as a set of unusual zig-zagging incisions on the lateral side of the diaphysis. These latter incisions cannot be unambiguously associated with filleting of muscles. We compared the macro- and micro-morphological characteristics of these marks to over 300 filleting marks on human and non-human remains and to approximately 120 engraved incisions observed on two artefacts from Gough's Cave. The new macro- and micro-morphometric analyses of the marks, as well as further comparisons with French Middle Magdalenian engraved artefacts, suggest that these modifications are the result of intentional engraving. The engraved motif comfortably fits within a Magdalenian pattern of design; what is exceptional in this case, however, is the choice of raw material (human bone) and the cannibalistic context in which it was produced. The sequence of the manipulations suggests that the engraving was a purposeful component of the cannibalistic practice, implying a complex ritualistic funerary behaviour that has never before been recognized for the Palaeolithic period.

  7. The detrimental effects of lead on human and animal health

    Science.gov (United States)

    Assi, Mohammed Abdulrazzaq; Hezmee, Mohd Noor Mohd; Haron, Abd Wahid; Sabri, Mohd Yusof Mohd; Rajion, Mohd Ali

    2016-01-01

    Lead, a chemical element in the carbon group with symbol Pb (from Latin: Plumbum, meaning “the liquid silver”) and has an atomic number 82 in the periodic table. It was the first element that was characterized by its kind of toxicity. In animal systems, lead (Pb) has been incriminated in a wide spectrum of toxic effects and it is considered one of the persistent ubiquitous heavy metals. Being exposed to this metal could lead to the change of testicular functions in human beings as well as in the wildlife. The lead poising is a real threat to the public health, especially in the developing countries. Accordingly, great efforts on the part of the occupational and public health have been taken to curb the dangers of this metal. Hematopoietic, renal, reproductive, and central nervous system are among the parts of the human body and systems that are vulnerable toward the dangers following exposure to high level of Pb. In this review, we discussed the massive harmful impact that leads acetate toxicity has on the animals and the worrying fact that this harmful toxicant can be found quite easily in the environment and abundance. Highlighting its (Pb) effects on various organs in the biological systems, its economic, as well as scientific importance, with the view to educate the public/professionals who work in this area. In this study, we focus on the current studies and research related to lead toxicity in animals and also to a certain extent toward human as well. PMID:27397992

  8. The detrimental effects of lead on human and animal health

    Directory of Open Access Journals (Sweden)

    Mohammed Abdulrazzaq Assi

    2016-06-01

    Full Text Available Lead, a chemical element in the carbon group with symbol Pb (from Latin: Plumbum, meaning “the liquid silver” and has an atomic number 82 in the periodic table. It was the first element that was characterized by its kind of toxicity. In animal systems, lead (Pb has been incriminated in a wide spectrum of toxic effects and it is considered one of the persistent ubiquitous heavy metals. Being exposed to this metal could lead to the change of testicular functions in human beings as well as in the wildlife. The lead poising is a real threat to the public health, especially in the developing countries. Accordingly, great efforts on the part of the occupational and public health have been taken to curb the dangers of this metal. Hematopoietic, renal, reproductive, and central nervous system are among the parts of the human body and systems that are vulnerable toward the dangers following exposure to high level of Pb. In this review, we discussed the massive harmful impact that leads acetate toxicity has on the animals and the worrying fact that this harmful toxicant can be found quite easily in the environment and abundance. Highlighting its (Pb effects on various organs in the biological systems, its economic, as well as scientific importance, with the view to educate the public/professionals who work in this area. In this study, we focus on the current studies and research related to lead toxicity in animals and also to a certain extent toward human as well.

  9. Aged human bone marrow stromal cells maintaining bone forming capacity in vivo evaluated using an improved method of visualization

    DEFF Research Database (Denmark)

    Stenderup, Karin; Rosada, Cecilia; Justesen, J;

    2004-01-01

    an in vivo assay for quantifying the bone forming capacity (BFC) and we compared the BFC of osteoblastic cells obtained from young and old donors. Osteoblasts were obtained from human bone marrow stromal cell cultures and implanted subcutaneously in immuno-deficient mice (NOD/LtSz- Prkdc(scid)). After 8...... weeks, the implants were removed and embedded un-decalcified in methyl methacrylate (MMA). Sections were stained histochemically with Goldner's Trichrome stain and immuno-histochemically using human-specific antibodies against known osteogenic markers. Implanted human marrow stromal cells (hMSC) were...... able to form bone in vivo. The donor origin of bone was verified using several human-specific antibodies. Dose-response experiments demonstrated that 5 x 10(5) hMSC per implant gave the maximal bone formation after 8 weeks. No difference in BFC was observed between cells obtained from young (24...

  10. Longitudinal evolution of bone mineral density and bone markers in human immunodeficiency virus-infected individuals.

    Science.gov (United States)

    Mondy, Kristin; Yarasheski, Kevin; Powderly, William G; Whyte, Michael; Claxton, Sherry; DeMarco, Debra; Hoffmann, Mary; Tebas, Pablo

    2003-02-15

    The underlying mechanisms of several bone disorders in human immunodeficiency virus (HIV)-infected persons and any relation to antiretroviral therapy have yet to be defined. A longitudinal study was conducted to estimate the prevalence of osteopenia or osteoporosis in HIV-infected persons; to assess bone mineralization, metabolism, and histomorphometry over time; and to evaluate predisposing factors. A total of 128 patients enrolled the study, and 93 were observed for 72 weeks. "Classic" risk factors (low body mass index, history of weight loss, steroid use, and smoking) for low bone mineral density (BMD) and duration of HIV infection were strongly associated with osteopenia. There was a weak association between low BMD and receipt of treatment with protease inhibitors; this association disappeared after controlling for the above factors. Markers of bone turnover tended to be elevated in the whole cohort but were not associated with low BMD. BMD increased slightly during follow-up. Traditional risk factors and advanced HIV infection play a more significant pathogenic role in the development of osteopenia and osteoporosis associated with HIV infection than do treatment-associated factors.

  11. Subchondral bone density distribution in the human femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Wright, David A.; Meguid, Michael; Lubovsky, Omri; Whyne, Cari M. [Sunnybrook Research Institute, Orthopaedic Biomechanics Laboratory, Toronto, Ontario (Canada)

    2012-06-15

    This study aims to quantitatively characterize the distribution of subchondral bone density across the human femoral head using a computed tomography derived measurement of bone density and a common reference coordinate system. Femoral head surfaces were created bilaterally for 30 patients (14 males, 16 females, mean age 67.2 years) through semi-automatic segmentation of reconstructed CT data and used to map bone density, by shrinking them into the subchondral bone and averaging the greyscale values (linearly related to bone density) within 5 mm of the articular surface. Density maps were then oriented with the center of the head at the origin, the femoral mechanical axis (FMA) aligned with the vertical, and the posterior condylar axis (PCA) aligned with the horizontal. Twelve regions were created by dividing the density maps into three concentric rings at increments of 30 from the horizontal, then splitting into four quadrants along the anterior-posterior and medial-lateral axes. Mean values for each region were compared using repeated measures ANOVA and a Bonferroni post hoc test, and side-to-side correlations were analyzed using a Pearson's correlation. The regions representing the medial side of the femoral head's superior portion were found to have significantly higher densities compared to other regions (p < 0.05). Significant side-to-side correlations were found for all regions (r {sup 2} = 0.81 to r {sup 2} = 0.16), with strong correlations for the highest density regions. Side-to-side differences in measured bone density were seen for two regions in the anterio-lateral portion of the femoral head (p < 0.05). The high correlation found between the left and right sides indicates that this tool may be useful for understanding 'normal' density patterns in hips affected by unilateral pathologies such as avascular necrosis, fracture, developmental dysplasia of the hip, Perthes disease, and slipped capital femoral head epiphysis. (orig.)

  12. A Crust-based Method of Reconstructing Human Bone

    Institute of Scientific and Technical Information of China (English)

    MA Shu-chao; LIU Yi

    2014-01-01

    We present a crust-based procedure for modeling human being’s bone, which is based on voronoi diagram and its dual, Delaunay triangulation. In three-dimensional space, the crust algorithm can generate a 3D-model using a set of sample points. The purposes of this paper is to extract precise contour from CT series, then refer to these contours as sample points, and then apply the crust algorithm to these sample points to get three dimensional mesh.

  13. Aging and Fracture of Human Cortical Bone and Tooth Dentin

    Energy Technology Data Exchange (ETDEWEB)

    Ager, Joel; Koester, Kurt J.; Ager III, Joel W.; Ritchie, Robert O.

    2008-05-07

    Mineralized tissues, such as bone and tooth dentin, serve as structural materials in the human body and, as such, have evolved to resist fracture. In assessing their quantitative fracture resistance or toughness, it is important to distinguish between intrinsic toughening mechanisms which function ahead of the crack tip, such as plasticity in metals, and extrinsic mechanisms which function primarily behind the tip, such as crack bridging in ceramics. Bone and dentin derive their resistance to fracture principally from extrinsic toughening mechanisms which have their origins in the hierarchical microstructure of these mineralized tissues. Experimentally, quantification of these toughening mechanisms requires a crack-growth resistance approach, which can be achieved by measuring the crack-driving force, e.g., the stress intensity, as a function of crack extension ("R-curve approach"). Here this methodology is used to study of the effect of aging on the fracture properties of human cortical bone and human dentin in order to discern the microstructural origins of toughness in these materials.

  14. Uncertainty calculations for the measurement of in vivo bone lead by x-ray fluorescence.

    Science.gov (United States)

    O'Meara, J M; Fleming, D E B

    2009-04-21

    In order to quantify the bone lead concentration from an in vivo x-ray fluorescence measurement, typically two estimates of the lead concentration are determined by comparing the normalized x-ray peak amplitudes from the Kalpha(1) and Kbeta(1) features to those of the calibration phantoms. In each case, the normalization consists of taking the ratio of the x-ray peak amplitude to the amplitude of the coherently scattered photon peak in the spectrum. These two Pb concentration estimates are then used to determine the weighted mean lead concentration of that sample. In calculating the uncertainties of these measurements, it is important to include any covariance terms where appropriate. When determining the uncertainty of the lead concentrations from each x-ray peak, the standard approach does not include covariance between the x-ray peaks and the coherently scattered feature. These spectral features originate from two distinct physical processes, and therefore no covariance between these features can exist. Through experimental and simulated data, we confirm that there is no observed covariance between the detected Pb x-ray peaks and the coherently scattered photon signal, as expected. This is in direct contrast to recent work published by Brito (2006 Phys. Med. Biol. 51 6125-39). There is, however, covariance introduced in the calculation of the weighted mean lead concentration due to the common coherent normalization. This must be accounted for in calculating the uncertainty of the weighted mean lead concentration, as is currently the case. We propose here an alternative approach to calculating the weighted mean lead concentration in such a way as to eliminate the covariance introduced by the common coherent normalization. It should be emphasized that this alternative approach will only apply in situations in which the calibration line intercept is not included in the calculation of the Pb concentration from the spectral data: when the source of the intercept is

  15. Demineralized bone matrix and human cancellous bone enhance fixation of titanium implants

    DEFF Research Database (Denmark)

    Babiker, Hassan; Ding, Ming; Overgaard, Søren

    Denmark, DenmarkAbstractReplacement of extensive local bone loss especially in revision joint arthroplasty and spine fusion is a significant clinical challenge. Allograft and autograft have been considered as gold standard for bone replacement. However, there are several disadvantages such as donor site...... from human tissue were included (IsoTis OrthoBiologics, Inc. USA). Both materials are commercially available. Titanium alloy implants (Biomet Inc.) of 10 mm in length and 10 mm in diameter were inserted bilaterally into the femoral condyles of 8 skeletally mature sheep. Thus four implants...... with a concentric gap of 2 mm were implanted in each sheep. The gap was filled with: DBM; DBM/CB with ratio of 1/3; DBM/allograft with ratio of 1/3; or allograft (Gold standard), respectively. Standardised surgical procedure was used1. At sacrifice, 6 weeks after surgery, both distal femurs were harvested...

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

    Science.gov (United States)

    Anderson, H C; Coulter, P R

    1967-04-01

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

  17. Building bones in babies: can and should we exceed the human milk-fed infant's rate of bone calcium accretion?

    Science.gov (United States)

    Increasing calcium absorption and bone calcium accretion to levels above those achieved by human milk-fed, full-term infants is possible with infant formulas. However, no data support such a goal or suggest that it is beneficial to short- or long-term bone health. Small differences in the bioavailab...

  18. The SK-N-AS human neuroblastoma cell line develops osteolytic bone metastases with increased angiogenesis and COX-2 expression

    Directory of Open Access Journals (Sweden)

    Takahiro Tsutsumimoto

    2014-11-01

    Full Text Available Neuroblastoma (NB, which arises from embryonic neural crest cells, is the most common extra-cranial solid tumor of childhood. Approximately half of NB patients manifest bone metastasis accompanied with bone pain, fractures and bone marrow failure, leading to disturbed quality of life and poor survival. To study the mechanism of bone metastasis of NB, we established an animal model in which intracardiac inoculation of the SK-N-AS human NB cells in nude mice developed osteolytic bone metastases with increased osteoclastogenesis. SK-N-AS cells induced the expression of receptor activator of NF-κB ligand and osteoclastogenesis in mouse bone marrow cells in the co-culture. SK-N-AS cells expressed COX-2 mRNA and produced substantial amounts of prostaglandin E2 (PGE2. In contrast, the SK-N-DZ and SK-N-FI human NB cells failed to develop bone metastases, induce osteoclastogenesis, express COX-2 mRNA and produce PGE2. Immunohistochemical examination of SK-N-AS bone metastasis and subcutaneous tumor showed strong expression of COX-2. The selective COX-2 inhibitor NS-398 inhibited PGE2 production and suppressed bone metastases with reduced osteoclastogenesis. NS-398 also inhibited subcutaneous SK-N-AS tumor development with decreased angiogenesis and vascular endothelial growth factor-A expression. Of interest, metastasis to the adrenal gland, a preferential site for NB development, was also diminished by NS-398. Our results suggest that COX2/PGE2 axis plays a critical role in the pathophysiology of osteolytic bone metastases and tumor development of the SK-NS-AS human NB. Inhibition of angiogenesis by suppressing COX-2/PGE2 may be an effective therapeutic approach for children with NB.

  19. Tissue engineered humanized bone supports human hematopoiesis in vivo.

    Science.gov (United States)

    Holzapfel, Boris M; Hutmacher, Dietmar W; Nowlan, Bianca; Barbier, Valerie; Thibaudeau, Laure; Theodoropoulos, Christina; Hooper, John D; Loessner, Daniela; Clements, Judith A; Russell, Pamela J; Pettit, Allison R; Winkler, Ingrid G; Levesque, Jean-Pierre

    2015-08-01

    Advances in tissue-engineering have resulted in a versatile tool-box to specifically design a tailored microenvironment for hematopoietic stem cells (HSCs) in order to study diseases that develop within this setting. However, most current in vivo models fail to recapitulate the biological processes seen in humans. Here we describe a highly reproducible method to engineer humanized bone constructs that are able to recapitulate the morphological features and biological functions of the HSC niches. Ectopic implantation of biodegradable composite scaffolds cultured for 4 weeks with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone organ including a large number of human mesenchymal cells which were shown to be metabolically active and capable of establishing a humanized microenvironment supportive of the homing and maintenance of human HSCs. A syngeneic mouse-to-mouse transplantation assay was used to prove the functionality of the tissue-engineered ossicles. We predict that the ability to tissue engineer a morphologically intact and functional large-volume bone organ with a humanized bone marrow compartment will help to further elucidate physiological or pathological interactions between human HSCs and their native niches. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  20. Non-severe burn injury leads to depletion of bone volume that can be ameliorated by inhibiting TNF-α.

    Science.gov (United States)

    O'Halloran, Emily; Kular, Jasreen; Xu, Jiake; Wood, Fiona; Fear, Mark

    2015-05-01

    Bone loss after severe burn injury is well established, and is thought to be a consequence of the severe hyper-metabolic response as well as changes in cytokine and glucocorticoid levels that decrease bone synthesis and increase rate of loss. However, 90% of presentations are for non-severe burns which do not elicit this response. Little is known about whether these non-severe injuries may also affect bone tissue, and whether other mechanisms may be involved. To investigate whether bone loss occurs after a non-severe burn injury we used a mouse model of an approximately 8% total body surface area (TBSA) full-thickness burn and micro-CT. We also assessed whether blocking TNF-α after a burn injury by administration of an antibody could modulate the impacts of the burn on bone tissue. There was a significant loss of trabecular bone volume of (3.27% compared to 5.27%, p=0.0051) after non-severe burn injury. Trabecular number was significantly decreased (0.57/mm after injury compared to 1.02/mm controls, p=0.0051) and spacing increased after burn injury (0.40 compared to 0.28, p=0.0083). Anti-TNF-α antibodies significantly improved trabecular bone volume (8.53%, p=0.0034) and number after burn injury (1.28/mm, p=0.0034). There was no significant change observed in cortical bone after burn injury or administration of anti-TNF-α antibodies. These findings show that non-severe burn injury can lead to changes in bone metabolism. Monitoring bone density in patients with non-severe injuries and interventions to limit the impacts of the inflammatory storm may benefit patient recovery and outcomes.

  1. Elastic Comparison Between Human and Bovine Femural Bone

    Directory of Open Access Journals (Sweden)

    Mohamed S. Gaith

    2012-12-01

    Full Text Available In this study, the elastic stiffness and the degree of anisotropy will be compared for the femur human and bovine bones are presented. A scale for measuring the overall elastic stiffness of the bone at different locations is introduced and its correlation with the calculated bulk modulus is analyzed. Based on constructing orthonormal tensor basis elements using the form-invariant expressions, the elastic stiffness for orthotropic system materials is decomposed into two parts; isotropic (two terms and anisotropic parts. The overall elastic stiffness is calculated and found to be directly proportional to bulk modulus. A scale quantitative comparison of the contribution of the anisotropy to the elastic stiffness and to measure the degree of anisotropy in an anisotropic material is proposed using the Norm Ratio Criteria (NRC. It is found that bovine femure plexiform has the largest overall elastic stiffness and bovine has the most isotropic (least anisotropic symmetry.

  2. In-vivo generation of bone via endochondral ossification by in-vitro chondrogenic priming of adult human and rat mesenchymal stem cells

    LENUS (Irish Health Repository)

    Farrell, Eric

    2011-01-31

    Abstract Background Bone grafts are required to repair large bone defects after tumour resection or large trauma. The availability of patients\\' own bone tissue that can be used for these procedures is limited. Thus far bone tissue engineering has not lead to an implant which could be used as alternative in bone replacement surgery. This is mainly due to problems of vascularisation of the implanted tissues leading to core necrosis and implant failure. Recently it was discovered that embryonic stem cells can form bone via the endochondral pathway, thereby turning in-vitro created cartilage into bone in-vivo. In this study we investigated the potential of human adult mesenchymal stem cells to form bone via the endochondral pathway. Methods MSCs were cultured for 28 days in chondrogenic, osteogenic or control medium prior to implantation. To further optimise this process we induced mineralisation in the chondrogenic constructs before implantation by changing to osteogenic medium during the last 7 days of culture. Results After 8 weeks of subcutaneous implantation in mice, bone and bone marrow formation was observed in 8 of 9 constructs cultured in chondrogenic medium. No bone was observed in any samples cultured in osteogenic medium. Switch to osteogenic medium for 7 days prevented formation of bone in-vivo. Addition of β-glycerophosphate to chondrogenic medium during the last 7 days in culture induced mineralisation of the matrix and still enabled formation of bone and marrow in both human and rat MSC cultures. To determine whether bone was formed by the host or by the implanted tissue we used an immunocompetent transgenic rat model. Thereby we found that osteoblasts in the bone were almost entirely of host origin but the osteocytes are of both host and donor origin. Conclusions The preliminary data presented in this manuscript demonstrates that chondrogenic priming of MSCs leads to bone formation in vivo using both human and rat cells. Furthermore, addition of

  3. Comparative study on seeding methods of human bone marrow stromal cells in bone tissue engineering

    Institute of Scientific and Technical Information of China (English)

    齐欣; 刘建国; 常颖; 徐莘香

    2004-01-01

    Background In general the traditional static seeding method has its limitation while the dynamic seeding method reveals its advantages over traditional static method. We compared static and dynamic seeding method for human bone marrow stromal cells (hBMSCs) in bone tissue engineering.Methods DNA assay was used for detecting the maximal initial seeding concentration for static seeding. Dynamic and static seeding methods were compared, when scaffolds were loaded with hBMSCs at this maximal initial cell seeding concentration. Histology and scanning electron microscope (SEM) were examined to evaluate the distribution of cells inside the constructs. Markers encoding osteogenic genes were measured by fluorescent RT-PCR. The protocol for dynamic seeding of hBMSCs was also investigated.Results DNA assay showed that the static maximal initial seeding concentration was lower than that in dynamic seeding. Histology and SEM showed even distribution and spread of cells in the dynamically seeded constructs, while their statically seeded counterparts showed cell aggregation.Fluorescent RT-PCR again showed stronger osteogenic potential of dynamically seeded constructs.Conclusion dynamic seeding of hBMSCs is a promising technique in bone tissue engineering.

  4. Omission of bone scanning according to staging guidelines leads to futile therapy in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schirrmeister, Holger [Department of Nuclear Medicine, University of Kiel, Kiel (Germany); Arslandemir, Coskun; Hetzel, Martin [Department of Internal Medicine II, University of Ulm, Robert-Koch-Strasse 8, 89081, Ulm (Germany); Glatting, Gerhard; Buck, Andreas [Department of Nuclear Medicine, University of Ulm, Ulm (Germany); Mayer-Steinacker, Regine; Bommer, Martin [Department of Hematology and Oncology, University of Ulm, Ulm (Germany); Dreinhoefer, Karsten [Department of Orthopedics, University of Ulm, Ulm (Germany)

    2004-07-01

    The leading European and American professional societies recommend that bone scans (BS) should be performed in the staging of lung cancer only in those patients with bone pain. This prospective study investigated the sensitivity of conventional skeletal scintigraphy in detecting osseous metastases in patients with lung cancer and addressed the potential consequences of failure to use this method in the work-up of asymptomatic patients. Subsequent to initial diagnosis of non-small cell lung cancer, 100 patients were examined and questioned regarding skeletal complaints. Two specialists in internal medicine decided whether they would recommend a bone scan on the basis of the clinical evaluation. Skeletal scintigraphy was then performed blinded to the findings of history and physical examination. The combined results of magnetic resonance imaging (MRI) of the vertebral column, positron emission tomography (PET) of skeletal bone and the subsequent clinical course served as the gold standard for the identification of osseous metastases. Bone scintigraphy showed an 87% sensitivity in the detection of bone metastases. Failure to perform skeletal scintigraphy in asymptomatic patients reduced the sensitivity of the method, depending on the interpretation of the symptoms, to 19-39%. Without the findings of skeletal scintigraphy and the gold standard methods, 14-22% of patients would have undergone unnecessary surgery or neoadjuvant therapy. On this basis it is concluded that bone scans should not be omitted in asymptomatic patients. (orig.)

  5. Development of a Human Cranial Bone Surrogate for Impact Studies.

    Science.gov (United States)

    Roberts, Jack C; Merkle, Andrew C; Carneal, Catherine M; Voo, Liming M; Johannes, Matthew S; Paulson, Jeff M; Tankard, Sara; Uy, O Manny

    2013-01-01

    In order to replicate the fracture behavior of the intact human skull under impact it becomes necessary to develop a material having the mechanical properties of cranial bone. The most important properties to replicate in a surrogate human skull were found to be the fracture toughness and tensile strength of the cranial tables as well as the bending strength of the three-layer (inner table-diplöe-outer table) architecture of the human skull. The materials selected to represent the surrogate cranial tables consisted of two different epoxy resins systems with random milled glass fiber to enhance the strength and stiffness and the materials to represent the surrogate diplöe consisted of three low density foams. Forty-one three-point bending fracture toughness tests were performed on nine material combinations. The materials that best represented the fracture toughness of cranial tables were then selected and formed into tensile samples and tested. These materials were then used with the two surrogate diplöe foam materials to create the three-layer surrogate cranial bone samples for three-point bending tests. Drop tower tests were performed on flat samples created from these materials and the fracture patterns were very similar to the linear fractures in pendulum impacts of intact human skulls, previously reported in the literature. The surrogate cranial tables had the quasi-static fracture toughness and tensile strength of 2.5 MPa√ m and 53 ± 4.9 MPa, respectively, while the same properties of human compact bone were 3.1 ± 1.8 MPa√ m and 68 ± 18 MPa, respectively. The cranial surrogate had a quasi-static bending strength of 68 ± 5.7 MPa, while that of cranial bone was 82 ± 26 MPa. This material/design is currently being used to construct spherical shell samples for drop tower and ballistic tests.

  6. Can experimental data in humans verify the finite element-based bone remodeling algorithm?

    DEFF Research Database (Denmark)

    Wong, C.; Gehrchen, P.M.; Kiaer, T.

    2008-01-01

    STUDY DESIGN: A finite element analysis-based bone remodeling study in human was conducted in the lumbar spine operated on with pedicle screws. Bone remodeling results were compared to prospective experimental bone mineral content data of patients operated on with pedicle screws. OBJECTIVE......: The validity of 2 bone remodeling algorithms was evaluated by comparing against prospective bone mineral content measurements. Also, the potential stress shielding effect was examined using the 2 bone remodeling algorithms and the experimental bone mineral data. SUMMARY OF BACKGROUND DATA: In previous studies......, in the human spine, the bone remodeling algorithms have neither been evaluated experimentally nor been examined by comparing to unsystematic experimental data. METHODS: The site-specific and nonsite-specific iterative bone remodeling algorithms were applied to a finite element model of the lumbar spine...

  7. Lead

    Science.gov (United States)

    ... found? Who is at risk? What are the health effects of lead? Get educational material about lead Get certified as a Lead Abatement Worker, or other abatement discipline Lead in drinking water Lead air pollution Test your child Check and maintain your home ...

  8. Antinociceptive Effect of Intrathecal Microencapsulated Human Pheochromocytoma Cell in a Rat Model of Bone Cancer Pain

    Directory of Open Access Journals (Sweden)

    Xiao Li

    2014-07-01

    Full Text Available Human pheochromocytoma cells, which are demonstrated to contain and release met-enkephalin and norepinephrine, may be a promising resource for cell therapy in cancer-induced intractable pain. Intrathecal injection of alginate-poly (l lysine-alginate (APA microencapsulated human pheochromocytoma cells leads to antinociceptive effect in a rat model of bone cancer pain, and this effect was blocked by opioid antagonist naloxone and alpha 2-adrenergic antagonist rauwolscine. Neurochemical changes of cerebrospinal fluid are in accordance with the analgesic responses. Taken together, these data support that human pheochromocytoma cell implant-induced antinociception was mediated by met-enkephalin and norepinephrine secreted from the cell implants and acting at spinal receptors. Spinal implantation of microencapsulated human pheochromocytoma cells may provide an alternative approach for the therapy of chronic intractable pain.

  9. Glycation of human cortical and cancellous bone captures differences in the formation of Maillard reaction products between glucose and ribose.

    Science.gov (United States)

    Sroga, Grażyna E; Siddula, Alankrita; Vashishth, Deepak

    2015-01-01

    To better understand some aspects of bone matrix glycation, we used an in vitro glycation approach. Within two weeks, our glycation procedures led to the formation of advanced glycation end products (AGEs) at the levels that corresponded to approx. 25-30 years of the natural in vivo glycation. Cortical and cancellous bones from human tibias were glycated in vitro using either glucose (glucosylation) or ribose (ribosylation). Both glucosylation and ribosylation led to the formation of higher levels of AGEs and pentosidine (PEN) in cancellous than cortical bone dissected from all tested donors (young, middle-age and elderly men and women). More efficient glycation of bone matrix proteins in cancellous bone most likely depended on the higher porosity of this tissue, which facilitated better accessibility of the sugars to the matrix proteins. Notably, glycation of cortical bone from older donors led to much higher AGEs levels as compared to young donors. Such efficient in vitro glycation of older cortical bone could result from aging-related increase in porosity caused by the loss of mineral content. In addition, more pronounced glycation in vivo would be driven by elevated oxidation processes. Interestingly, the levels of PEN formation differed pronouncedly between glucosylation and ribosylation. Ribosylation generated very high levels of PEN (approx. 6- vs. 2.5-fold higher PEN level than in glucosylated samples). Kinetic studies of AGEs and PEN formation in human cortical and cancellous bone matrix confirmed higher accumulation of fluorescent crosslinks for ribosylation. Our results suggest that in vitro glycation of bone using glucose leads to the formation of lower levels of AGEs including PEN, whereas ribosylation appears to support a pathway toward PEN formation. Our studies may help to understand differences in the progression of bone pathologies related to protein glycation by different sugars, and raise awareness for excessive sugar supplementation in food and

  10. Nanoscale Bonding between Human Bone and Titanium Surfaces: Osseohybridization

    Directory of Open Access Journals (Sweden)

    Jun-Sik Kim

    2015-01-01

    Full Text Available Until now, the chemical bonding between titanium and bone has been examined only through a few mechanical detachment tests. Therefore, in this study, a sandblasted and acid-etched titanium mini-implant was removed from a human patient after 2 months of placement in order to identify the chemical integration mechanism for nanoscale osseointegration of titanium implants. To prepare a transmission electron microscopy (TEM specimen, the natural state was preserved as much as possible by cryofixation and scanning electron microscope/focused ion beam (SEM-FIB milling without any chemical treatment. High-resolution TEM (HRTEM, energy dispersive X-ray spectroscopy (EDS, and scanning TEM (STEM/electron energy loss spectroscopic analysis (EELS were used to investigate the chemical composition and structure at the interface between the titanium and bone tissue. HRTEM and EDS data showed evidence of crystalline hydroxyapatite and intermixing of bone with the oxide layer of the implant. The STEM/EELS experiment provided particularly interesting results: carbon existed in polysaccharides, calcium and phosphorus existed as tricalcium phosphate (TCP, and titanium existed as oxidized titanium. In addition, the oxygen energy loss near edge structures (ELNESs showed a possibility of the presence of CaTiO3. These STEM/EELS results can be explained by structures either with or without a chemical reaction layer. The possible existence of the osseohybridization area and the form of the carbon suggest that reconsideration of the standard definition of osseointegration is necessary.

  11. SYNCHROTRON RADIATION XRF MICROPROBE STUDY OF HUMAN BONE TUMOR SLICE

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The experimental apparatus of X-ray fluorescence (XRF) microprobe analysis at Beijing Synchrotron Radiation Facility (BSRF) is described Using the bovine liver as the standard reference.the minimum detection limit(MDL) of trace element was measured to determine the capability of biological sample analysis by synchrotron radiation XRF microprobe.The relative change of the content of the major or trace element in the normal and tumor part of human bone tissue slice was investigated The experimental result relation to the clinical medicine was also discussed.

  12. The relationship between bone health and plasma zinc, copper lead and cadmium concentration in osteoporotic women.

    Science.gov (United States)

    Sadeghi, Naficeh; Oveisi, Mohammad Reza; Jannat, Behrooz; Hajimahmoodi, Mannan; Behzad, Masoomeh; Behfar, Abdolazim; Sadeghi, Fatemeh; Saadatmand, Sahereh

    2014-01-01

    Osteoporosis is a multi factorial disease with dimension of genetic and nutritional considerations. The aim of this study was to present data from the association of plasma zinc, copper and toxic elements of lead and cadmium levels with bone mineral density in Iranian women. 135 women gave their information and enrolled. Fasting plasma was used for measurement of trace elements and heavy metals by Differential Pulse Anodic Stripping Voltammetry. Control group (n = 51) were normal in both lumbar spine (L1-L4) and femoral neck density (T-score ≥ -1), but just femoral neck T-score was considered as criterion in selection of patient group (n = 49, Tscore T-score > -1.7), 1.463 ± 0.174, 1.327 ± 0.147 μg/ml in Severe patient group (T-score < -1.7); respectively. Mean ± SD plasma level of lead and cadmium was 168.42 ± 9.61 ng/l, 2.91 ± 0.18 ng/ml in control group, 176.13 ± 8.64 ng/l, 2.97 ± 0.21 ng/ml in TP, 176.43 ± 13.2 ng/l, 2.99 ± 0.1 ng/ml in mild patients, 221.44 ± 20 ng/l and 3.80 ± 0.70 ng/ml in severe patient group, respectively. In this study plasma zinc, copper, lead & cadmium concentrations were higher in the patients than in the control, though differences were not significant. However, differences were higher between the controls and patients with severe disease (T-score < -1.7). In addition adjusted T-score of femur with age and BMI showed negative significant correlation with plasma levels of zinc and lead in total participants (p < 0.05, r = -0.201, p = 0.044, r = -0.201). It seems that more extensive study with larger ample size might supply definite results about this association for copper and cadmium.

  13. Lead and stable lead isotope ratios in soil, earthworms, and bones of American woodcock (Scolopax minor) from eastern Canada.

    Science.gov (United States)

    Scheuhammer, Anton M; Bond, Della E; Burgess, Neil M; Rodrigue, Jean

    2003-11-01

    A study to discriminate among different possible sources of elevated Pb exposure for American woodcock (Scolopax minor) in eastern Canada is described. Undamaged wing bones excised from young-of-the-year woodcock collected from several locations in southern Ontario, southern Quebec, New Brunswick, and Nova Scotia, Canada, along with soil and earthworm (Aporrectodea tuberculata and Lumbricus rubellus) samples from the same sites, were analyzed for total Pb, and stable Pb isotopes. Ignoring six soil samples with high (> 60 microg/g) Pb concentration from the vicinity of Montreal (QC, Canada), the mean soil-Pb concentration for all sites combined was 19 microg/g (dry wt; n = 64), with a mean 206Pb:207Pb ratio of 1.19, values typical for uncontaminated rural soils in eastern North America. In earthworms, Pb concentrations ranged from 2.4 to 865 (microg/g [dry wt], mean = 24 microg/g). Concentrations of Pb in worms and soils were positively correlated (r = 0.71; p 20 microg/g) had 206Pb:207Pb ratios substantially different from worms and soils sampled from the same areas, even though woodcock feed extensively on soil invertebrates, especially earthworms. The range of 206Pb:207Pb ratios in wing bones of woodcock with elevated Pb exposure was not consistent with exposure to environmental Pb from past gasoline combustion nor Precambrian mining wastes but was consistent with ingestion of spent Pb shotgun pellets.

  14. Methods and theory in bone modeling drift: comparing spatial analyses of primary bone distributions in the human humerus.

    Science.gov (United States)

    Maggiano, Corey M; Maggiano, Isabel S; Tiesler, Vera G; Chi-Keb, Julio R; Stout, Sam D

    2016-01-01

    This study compares two novel methods quantifying bone shaft tissue distributions, and relates observations on human humeral growth patterns for applications in anthropological and anatomical research. Microstructural variation in compact bone occurs due to developmental and mechanically adaptive circumstances that are 'recorded' by forming bone and are important for interpretations of growth, health, physical activity, adaptation, and identity in the past and present. Those interpretations hinge on a detailed understanding of the modeling process by which bones achieve their diametric shape, diaphyseal curvature, and general position relative to other elements. Bone modeling is a complex aspect of growth, potentially causing the shaft to drift transversely through formation and resorption on opposing cortices. Unfortunately, the specifics of modeling drift are largely unknown for most skeletal elements. Moreover, bone modeling has seen little quantitative methodological development compared with secondary bone processes, such as intracortical remodeling. The techniques proposed here, starburst point-count and 45° cross-polarization hand-drawn histomorphometry, permit the statistical and populational analysis of human primary tissue distributions and provide similar results despite being suitable for different applications. This analysis of a pooled archaeological and modern skeletal sample confirms the importance of extreme asymmetry in bone modeling as a major determinant of microstructural variation in diaphyses. Specifically, humeral drift is posteromedial in the human humerus, accompanied by a significant rotational trend. In general, results encourage the usage of endocortical primary bone distributions as an indicator and summary of bone modeling drift, enabling quantitative analysis by direction and proportion in other elements and populations.

  15. Beneficial use of meat and bone meal combustion residue: "an efficient low cost material to remove lead from aqueous effluent".

    Science.gov (United States)

    Deydier, Eric; Guilet, Richard; Sharrock, Patrick

    2003-07-04

    Meat and bone meal (MBM) combustion residues, a natural apatite-rich substance, was evaluated as a low cost substitute for hydroxyapatite in lead sequestration from water effluents. The thermal behaviour of crude meat and bone meal was followed by TGA and 24% inorganic residue was collected. The resulting ashes were characterised by powder X-ray diffraction (XRD), particle size distribution, specific surface area (BET), and elemental analysis confirming apatite contents, with high level of phosphate (56.3%) and calcium (36.8%). Mechanism and kinetics of lead removal by this bioinorganic material were investigated and compared to mechanisms and kinetics involved with synthetic apatite. Batch metal removal experiments were carried out with 500 and 1500ppm (mg/kg) Pb(2+) solutions. Lead concentration, calcium and pH were monitored. We observed that the mechanism is similar to that occurring for pure apatite, and involved both surface complexation and calcium hydroyapatite (CaHA), Ca(10)(PO(4))(6)(OH)(2), dissolution followed by less soluble Pb(10)(PO(4))(6)(OH)(2) precipitation, as confirmed by XRD analysis of ashes after incubation with lead solution. Our results show that this natural apatite-rich material removes in a few minutes a large quantity of lead (275mg/g capacity) which remains however lower than the theoretical maximum capacity (if calcium were totally substituted by lead). Meat and bone meal combustion residues represent a valuable alternative apatite source for environmental application.

  16. A re-evaluation of the premaxillary bone in humans.

    Science.gov (United States)

    Barteczko, K; Jacob, M

    2004-03-01

    The discovery of the premaxillary bone (os incisivum, os intermaxillare or premaxilla) in humans has been attributed to Goethe, and it has also been named os Goethei. However, Broussonet (1779) and Vicq d'Azyr (1780) came to the same result with different methods. The first anatomists described this medial part of the upper jaw as a separate bone in the vertebrate skull, and, as we know, Coiter (1573) was the first to present an illustration of the sutura incisiva in the human. This fact, and furthermore its development from three parts:-(1) the alveolar part with the facial process, (2) the palatine process, and (3) the processus Stenonianus-can no longer be found in modern textbooks of developmental biology. At the end of the nineteenth and in the early twentieth century a vehement discussion focused on the number and position of its ossification centers and its sutures. Therefore, it is hard to believe that the elaborate work of the old embryologists is ignored and that the existence of a premaxillary bone in humans is even denied by many authors. Therefore this re-evaluation was done to demonstrate the early development of the premaxillary bone using the reconstructions of Felber (1919), Jarmer (1922) and data from our own observations on SEM micrographs and serial sections from 16 mm embryo to 68 mm fetus. Ossification of a separate premaxilla was first observed in a 16 mm embryo. We agree with Jarmer (1922), Peter (1924), and Shepherd and McCarthy (1955) that it develops from three anlagen, which are, however, not fully separated. The predominant sutura incisiva (rudimentarily seen on the facial side in a prematurely born child) and a shorter sutura intraincisiva argue in this sense. The later growth of this bone and its processes establish an important structure in the middle of the facial skull. Its architecture fits well with the functional test of others. We also focused on the relation of the developing premaxilla to the forming nasal septum moving from

  17. Development of a strain rate dependent material model of human cortical bone for computer-aided reconstruction of injury mechanisms.

    Science.gov (United States)

    Asgharpour, Zahra; Zioupos, Peter; Graw, Matthias; Peldschus, Steffen

    2014-03-01

    Computer-aided methods such as finite-element simulation offer a great potential in the forensic reconstruction of injury mechanisms. Numerous studies have been performed on understanding and analysing the mechanical properties of bone and the mechanism of its fracture. Determination of the mechanical properties of bones is made on the same basis used for other structural materials. The mechanical behaviour of bones is affected by the mechanical properties of the bone material, the geometry, the loading direction and mode and of course the loading rate. Strain rate dependency of mechanical properties of cortical bone has been well demonstrated in literature studies, but as many of these were performed on animal bones and at non-physiological strain rates it is questionable how these will apply in the human situations. High strain-rates dominate in a lot of forensic applications in automotive crashes and assault scenarios. There is an overwhelming need to a model which can describe the complex behaviour of bone at lower strain rates as well as higher ones. Some attempts have been made to model the viscoelastic and viscoplastic properties of the bone at high strain rates using constitutive mathematical models with little demonstrated success. The main objective of the present study is to model the rate dependent behaviour of the bones based on experimental data. An isotropic material model of human cortical bone with strain rate dependency effects is implemented using the LS-DYNA material library. We employed a human finite element model called THUMS (Total Human Model for Safety), developed by Toyota R&D Labs and the Wayne State University, USA. The finite element model of the human femur is extracted from the THUMS model. Different methods have been employed to develop a strain rate dependent material model for the femur bone. Results of one the recent experimental studies on human femur have been employed to obtain the numerical model for cortical femur. A

  18. Bone regenerative properties of rat, goat and human platelet-rich plasma.

    NARCIS (Netherlands)

    Plachokova, A.S.; Dolder, J. van den; Beucken, J.J.J.P. van den; Jansen, J.A.

    2009-01-01

    To explore the reported contradictory osteogenic capacity of platelet-rich plasma (PRP), the aim of the study was to examine and compare the bone regenerative effect of: PRPs of different species (rat, goat, human); human bone graft (HB) vs. HB combined with human PRP (HB+hPRP); and HB+hPRP vs. synt

  19. [Effects of lead exposure on the human body and health implications].

    Science.gov (United States)

    Moreira, Fátima Ramos; Moreira, Josino Costa

    2004-02-01

    To review the literature concerning the risks associated with exposure to lead and lead compounds, especially in children and in populations that are occupationally exposed. Using "chumbo" [lead] and "efeitos" [effects] as search terms, two large databases, namely PubMed (United States National Library of Medicine) and LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde [Latin American and Caribbean Literature in the Health Sciences]), were searched for studies on lead toxicity from 1988 to 2002. Other sources used to conduct the search include the web page of the United States Agency for Toxic Substances and Disease Registry, in Atlanta, Georgia, and the library of the Toxicology Laboratory of the Center for Workers' Health and Human Ecology at the National School of Public Health [Centro de Estudos da Saúde de Trabalhador e Ecologia Humana, Escola Nacional de Saúde Pública], Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. The toxic effects of lead and lead compounds have been extensively studied for over a century. In recent years, epidemiologic studies have focused primarily on the neurotoxic effects of lead on children, particularly in terms of impaired intellectual ability and behavioral problems. However, there is still insufficient information on the mechanisms of action that account for such toxicity. More in-depth studies are also needed on the effects of lead exposure on bone, the central nervous system, the cardiovascular system, the kidneys, the liver, the male and female reproductive systems, and the endocrine system. The potential teratogenicity and carcinogenicity of lead, as well as its effect on pregnancy outcomes and neonatal growth and development, also require further study.

  20. Can experimental data in humans verify the finite element-based bone remodeling algorithm?

    DEFF Research Database (Denmark)

    Wong, Christian; Gehrchen, P Martin; Kiaer, Thomas

    2008-01-01

    A finite element analysis-based bone remodeling study in human was conducted in the lumbar spine operated on with pedicle screws. Bone remodeling results were compared to prospective experimental bone mineral content data of patients operated on with pedicle screws....

  1. Recombinant human bone morphogenic protein-2-enhanced anterior spine fusion without bone encroachment into the spinal canal: a histomorphometric study in a thoracoscopically instrumented porcine model.

    Science.gov (United States)

    Zhang, Hong; Sucato, Daniel J; Welch, Robert D

    2005-03-01

    A thoracoscopically assisted 5-level anterior spinal fusion and instrumentation model analyzing new bone formation when using recombinant human bone morphogenic protein-2 (rhBMP-2) with a collagen hydroxyapatite-tricalcium phosphate (HA/TCP) composite sponge carrier. To determine whether new bone formation extends beyond the posterior confines of the vertebral body encroaching into the spinal canal when rhBMP-2 is used to enhance anterior fusion. A possible concern regarding the use of rhBMP-2 to enhance spinal fusion is the risk of unwanted bone formation leading to inadvertent fusion of adjacent levels or compression of neural elements. The safety of rhBMP-2 in one spinal application does not ensure similar results in other applications. Therefore, the expanded use of rhBMP-2 should occur only after carefully monitored preclinical and clinical studies for each new application. Eighteen pigs underwent thoracoscopically-assisted instrumentation and fusion of 5 contiguous levels (T5-T10) and randomly assigned to 4 treatment groups: group 1 (n = 6): rh-BMP-2 on a HA/TCP-collagen sponge (Medtronic Sofamor Danek, Memphis, TN); group 2 (n = 4): iliac crest autograft; group 3 (n = 4): empty; group 4 (n = 4): HA/TCP-collagen sponge (Medtronic Sofamor Danek) only. In groups 1 and 4, the HA/TCP collagen sponge was morselized into small granules and pushed through a bone delivery funnel for implantation into the disc. At 4 months after surgery, spines were sectioned longitudinally through the midsagittal plane and underwent undecalcified processing. Bone formation extending beyond the margins of the original discectomy and the confines of vertebral body were evaluated histomorphometrically at each operative level. Recombinant human bone morphogenic protein-2 on a HA/TCP-collagen sponge induced significant new bone formation extending anterior to the confines of the vertebral body compared with the other treatment groups (P fusion area and beyond the discectomy area (P fusion

  2. Age variations in the properties of human tibial trabecular bone and cartilage

    DEFF Research Database (Denmark)

    Ding, Ming

    2000-01-01

    ) to investigate the age-related and osteoarthrosis-related changes in the mechanical properties of the human tibial cartilage-bone complex; and 3) to evaluate mutual associations among various properties. Normal specimens from human autopsy proximal tibiae were used for investigation of age variations...... in the properties of trabecular bone and the cartilage-bone complex, and osteoarthrotic specimens were used for the investigation of changes in the mechanical properties of the cartilage-bone complex induced by this disease process. The mechanical properties and physical/compositional properties of trabecular bone...... is parallel to the longitudinal loading axis of the tibia. The mechanical properties of the normal cartilage and bone vary with age and respond simultaneously to mechanical loading. Both cartilage and bone in early-stage OA are mechanically inferior to normal, and OA cartilage and bone have lost their unit...

  3. The relevance of mouse models for investigating age-related bone loss in humans.

    Science.gov (United States)

    Jilka, Robert L

    2013-10-01

    Mice are increasingly used for investigation of the pathophysiology of osteoporosis because their genome is easily manipulated, and their skeleton is similar to that of humans. Unlike the human skeleton, however, the murine skeleton continues to grow slowly after puberty and lacks osteonal remodeling of cortical bone. Yet, like humans, mice exhibit loss of cancellous bone, thinning of cortical bone, and increased cortical porosity with advancing age. Histologic evidence in mice and humans alike indicates that inadequate osteoblast-mediated refilling of resorption cavities created during bone remodeling is responsible. Mouse models of progeria also show bone loss and skeletal defects associated with senescence of early osteoblast progenitors. Additionally, mouse models of atherosclerosis, which often occurs in osteoporotic participants, also suffer bone loss, suggesting that common diseases of aging share pathophysiological pathways. Knowledge of the causes of skeletal fragility in mice should therefore be applicable to humans if inherent limitations are recognized.

  4. Secondary lead poisoning a projectile housed in the human body

    Directory of Open Access Journals (Sweden)

    Juan Bernardo Gerstner Garcés

    2012-09-01

    Full Text Available 72 1024x768 Normal 0 21 false false false ES X-NONE X-NONE With the increase of violence and use of firearms in Colombia, we may see more cases of lead poisoning in our environment, and must be prepared to diagnose and treat them. Subtle signs and symptoms as unexplained anemia, gastro-intestinal discomfort and abdominal cramps, and severe as changes in behavior and neurological status, nephropathy, and unexplained death, may be associated with a history of gunshot wounds and projectiles in the human body, and must offer the patient knowledge and management strategies of pathology.

  5. Bone

    Science.gov (United States)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

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

  6. Building bones in babies: can and should we exceed the human milk-fed infant's rate of bone calcium accretion?

    Science.gov (United States)

    Abrams, Steven A

    2006-11-01

    Increasing calcium absorption and bone calcium accretion to levels above those achieved by human milk-fed, full-term infants is possible with infant formulas. However, no data support such a goal or suggest that it is beneficial to short- or long-term bone health. Small differences in the bioavailability of calcium between infant formulas are unlikely to have long-term consequences. Long-term studies of the effects of infant feeding type on ultimate bone mass are needed. For now, the vitamin-replete breast-fed infant's rate of calcium accretion during the first year of life should be the standard targeted for infant formulas.

  7. Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2−/− mice

    Science.gov (United States)

    Gil-Henn, Hava; Destaing, Olivier; Sims, Natalie A.; Aoki, Kazuhiro; Alles, Neil; Neff, Lynn; Sanjay, Archana; Bruzzaniti, Angela; De Camilli, Pietro; Baron, Roland; Schlessinger, Joseph

    2007-01-01

    The protein tyrosine kinase Pyk2 is highly expressed in osteoclasts, where it is primarily localized in podosomes. Deletion of Pyk2 in mice leads to mild osteopetrosis due to impairment in osteoclast function. Pyk2-null osteoclasts were unable to transform podosome clusters into a podosome belt at the cell periphery; instead of a sealing zone only small actin rings were formed, resulting in impaired bone resorption. Furthermore, in Pyk2-null osteoclasts, Rho activity was enhanced while microtubule acetylation and stability were significantly reduced. Rescue experiments by ectopic expression of wild-type or a variety of Pyk2 mutants in osteoclasts from Pyk2−/− mice have shown that the FAT domain of Pyk2 is essential for podosome belt and sealing zone formation as well as for bone resorption. These experiments underscore an important role of Pyk2 in microtubule-dependent podosome organization, bone resorption, and other osteoclast functions. PMID:17846174

  8. Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(-/-) mice.

    Science.gov (United States)

    Gil-Henn, Hava; Destaing, Olivier; Sims, Natalie A; Aoki, Kazuhiro; Alles, Neil; Neff, Lynn; Sanjay, Archana; Bruzzaniti, Angela; De Camilli, Pietro; Baron, Roland; Schlessinger, Joseph

    2007-09-10

    The protein tyrosine kinase Pyk2 is highly expressed in osteoclasts, where it is primarily localized in podosomes. Deletion of Pyk2 in mice leads to mild osteopetrosis due to impairment in osteoclast function. Pyk2-null osteoclasts were unable to transform podosome clusters into a podosome belt at the cell periphery; instead of a sealing zone only small actin rings were formed, resulting in impaired bone resorption. Furthermore, in Pyk2-null osteoclasts, Rho activity was enhanced while microtubule acetylation and stability were significantly reduced. Rescue experiments by ectopic expression of wild-type or a variety of Pyk2 mutants in osteoclasts from Pyk2(-/-) mice have shown that the FAT domain of Pyk2 is essential for podosome belt and sealing zone formation as well as for bone resorption. These experiments underscore an important role of Pyk2 in microtubule-dependent podosome organization, bone resorption, and other osteoclast functions.

  9. Comparison between lead levels in blood and bone tissue of rock doves (Columba livia) treated with lead acetate or exposed to the environment of Alcala de Henares

    Energy Technology Data Exchange (ETDEWEB)

    Tejedor, M.C.; Gonzalez, M. [Universidad de Alcala de Henares, Madrid (Spain)

    1992-06-01

    The increase in the amount of lead released into the environment in developed countries during the last two to three decades has resulted in a significant increase in lead levels in organisms from completely different environments. Several surveys have been made in urban areas with high traffic densities in an attempt to identify plant and animal species that might reflect environmental metal concentrations so that those species could be used as sensitive biological indicators of heavy metal contamination. Studies of lead accumulation in U.K. rock doves imply that use of this species as a pollution indicator would facilitate periodic monitoring of chronic lead exposure conditions in the urban environment. Laboratory investigations cannot readily reflect environmental conditions since the validity of extrapolating laboratory results, where high doses are administered over short-time periods, to the natural environment has been seriously questioned. The present study was made on four rock dove (Columbia livia) populations: two groups (males and females) were dosed with lead acetate in the laboratory and two groups of males were housed in different parts of the city of Alcala de Henares. Data on lead bioaccumulation were collected in two situations: the first was in a laboratory with controlled amounts of lead, while in the second situation the amounts reflected the actual environmental levels in Alcala de Henares. Lead levels were determined in two tissues: blood, which is the target of first impact in possible acute situations; and bone, which is the main tissue where lead accumulates and, therefore, very important during chronic exposure. The study focused on the following three items: (1) lead tissue distribution; (2) variation with habitat; and (3) an evaluation of the levels of lead contamination in the city of Alcala de Henares. 19 refs., 3 figs., 1 tab.

  10. Incorporation of Trace Elements in Ancient and Modern Human Bone: An X-Ray Absorption Spectroscopy Study

    Science.gov (United States)

    Pingitore, N. E.; Cruz-Jimenez, G.; Price, T. D.

    2001-12-01

    X-ray absorption spectroscopy (XAS) affords the opportunity to probe the atomic environment of trace elements in human bone. We are using XAS to investigate the mode(s) of incorporation of Sr, Zn, Pb, and Ba in both modern and ancient (and thus possibly altered) human and animal bone. Because burial and diagenesis may add trace elements to bone, we performed XAS analysis on samples of pristine contemporary and ancient, buried human and animal bone. We assume that deposition of these elements during burial occurs by processes distinct from those in vivo, and this will be reflected in their atomic environments. Archaeologists measure strontium in human and animal bone as a guide to diet. Carnivores show lower Sr/Ca ratios than their herbivore prey due to discrimination against Sr relative to Ca up the food chain. In an initial sample suite no difference was observed between modern and buried bone. Analysis of additional buried samples, using a more sensitive detector, revealed significant differences in the distance to the second and third neighbors of the Sr in some of the buried samples. Distances to the first neighbor, oxygen, were similar in all samples. Zinc is also used in paleo-diet studies. Initial x-ray absorption spectroscopy of a limited suite of bones did not reveal any differences between modern and buried samples. This may reflect the limited number of samples examined or the low levels of Zn in typical aqueous solutions in soils. Signals from barium and lead were too low to record useful XAS spectra. Additional samples will be studied for Zn, Ba, and Pb. We conducted our XAS experiments on beam lines 4-1 and 4-3 at the Stanford Synchrotron Radiation Laboratory. Data were collected in the fluorescence mode, using a Lytle detector and appropriate filter, and a solid state, 13-element Ge-detector.

  11. Microtomography of the human tooth-alveolar bone complex

    Science.gov (United States)

    Dalstra, Michel; Cattaneo, Paolo M.; Beckmann, Felix; Sakima, Maurício T.; Lemor, Carsten; Laursen, Morten G.; Melsen, Birte

    2006-08-01

    In this study the structure of the adult human dentoalveolar process is examined using conventional and synchrotron radiation-based microtomography (SRμCT). Mandibular and maxillary segments containing two to five adjacent teeth were harvested at autopsy from 49 adult donors. These segments were embedded in blocks of methylmetacrylate and scanned using a conventional table-top μCT-scanner at a pixel size and slice thickness of 35 μm. A few segments were also scanned at a synchrotron facility at an initial pixel size of 16.4 μm, which was binned by a factor 2 to result in an effective voxel size of almost 32.8 μm. The three-dimensional reconstructions revealed how intricately the teeth are supported by the alveolar bone. Furthermore, this support is highly inhomogeneous with respect to the buccal, mesial, lingual and distal quadrants. Reflecting their various degrees of mineralization, tissues like bone, dentine, enamel and cementum, could well be identified, especially in the scans made with SRμCT. Despite comparable voxel sizes, the reconstructed data-sets obtained with conventional μCT were less detailed and somewhat fuzzy in appearance compared to the data-sets of SRμCT. However, for quantification of macroscopical features like the thickness of the alveolar wall or the presence of dehiscences/fenestrations this seemed sufficient.

  12. Inner ear contribution to bone conduction hearing in the human.

    Science.gov (United States)

    Stenfelt, Stefan

    2015-11-01

    Bone conduction (BC) hearing relies on sound vibration transmission in the skull bone. Several clinical findings indicate that in the human, the skull vibration of the inner ear dominates the response for BC sound. Two phenomena transform the vibrations of the skull surrounding the inner ear to an excitation of the basilar membrane, (1) inertia of the inner ear fluid and (2) compression and expansion of the inner ear space. The relative importance of these two contributors were investigated using an impedance lumped element model. By dividing the motion of the inner ear boundary in common and differential motion it was found that the common motion dominated at frequencies below 7 kHz but above this frequency differential motion was greatest. When these motions were used to excite the model it was found that for the normal ear, the fluid inertia response was up to 20 dB greater than the compression response. This changed in the pathological ear where, for example, otosclerosis of the stapes depressed the fluid inertia response and improved the compression response so that inner ear compression dominated BC hearing at frequencies above 400 Hz. The model was also able to predict experimental and clinical findings of BC sensitivity in the literature, for example the so called Carhart notch in otosclerosis, increased BC sensitivity in superior semicircular canal dehiscence, and altered BC sensitivity following a vestibular fenestration and RW atresia.

  13. Human foot bones from Klasies River main site, South Africa.

    Science.gov (United States)

    Rightmire, G Philip; Deacon, H J; Schwartz, Jeffrey H; Tattersall, Ian

    2006-01-01

    The caves at Klasies River contain abundant archaeological evidence relating to human evolution in the late Pleistocene of southern Africa. Along with Middle Stone Age artifacts, animal bones, and other food waste, there are hominin cranial fragments, mandibles with teeth, and a few postcranial remains. Three foot bones can now be added to this inventory. An adult first metatarsal is similar in size and discrete anatomical features to those from Holocene burials in the Cape Province. A complete and well-preserved second metatarsal is especially long and heavy at midshaft in comparison to all Holocene and more recent South African homologues. A large fifth metatarsal is highly distinctive in its morphology. In overall size, these pedal elements resemble specimens from late Pleistocene sites in western Asia, but there are some differences in proportions. The fossils support earlier suggestions concerning a relatively high level of sexual dimorphism in the African Middle Stone Age population. Squatting facets on the two lateral metatarsals appear to indicate a high frequency of kneeling among members of this group. The new postcranial material also underlines the fact that the morphology of particular skeletal elements of some of the 100,000-year-old Klasies River individuals falls outside the range of modern variation.

  14. Scanning electron microscopy of human cortical bone failure surfaces.

    Science.gov (United States)

    Braidotti, P; Branca, F P; Stagni, L

    1997-02-01

    Undecalcified samples extracted from human femoral shafts are fractured by bending and the fracture surfaces are examined with a scanning electron microscope (SEM). The investigation is performed on both dry and wet (hydrated with a saline solution) specimens. SEM micrographs show patterns in many respects similar to those observed in fractography studies of laminated fiber-reinforced synthetic composites. In particular, dry and wet samples behave like brittle and ductile matrix laminates, respectively. An analysis carried out on the basis of the mechanisms that dominate the fracture process of laminates shows that a reasonable cortical bone model is that of a laminated composite material whose matrix is composed of extracellular noncollagenous calcified proteins, and the reinforcement is constituted by the calcified collagen fiber system.

  15. Animal Models and Bone Histomorphometry: Translational Research for the Human Research Program

    Science.gov (United States)

    Sibonga, Jean D.

    2010-01-01

    This slide presentation reviews the use of animal models to research and inform bone morphology, in particular relating to human research in bone loss as a result of low gravity environments. Reasons for use of animal models as tools for human research programs include: time-efficient, cost-effective, invasive measures, and predictability as some model are predictive for drug effects.

  16. A physical mechanism for coupling bone resorption and formation in adult human bone

    DEFF Research Database (Denmark)

    Andersen, Thomas Levin; Sondergaard, Teis Esben; Skorzynska, Katarzyna Ewa

    2009-01-01

    During skeletal remodeling, pre-osteoclasts and pre-osteoblasts are targeted to critical sites of the bone to resorb and reconstruct bone matrix, respectively. Coordination of site-specific recruitment of these two cell types is a prerequisite to maintain the specific architecture of each bone...... within strict limits throughout adult life. Here, we determined that the bone marrow microanatomy adjacent to remodeling areas is a central player in this process. By using histomorphometry and multiple immunostainings, we demonstrated in biopsies exhibiting coupled bone resorption and formation...... that osteoclasts and osteoblasts on the bone surface were always covered by a canopy of flat cells expressing osteoblast markers. In contrast, in biopsies in which this canopy was disrupted, bone formation was deficient. Three-dimensional visualizations revealed that this canopy covered the entire remodeling site...

  17. Relationship between mechanical properties and bone mineral density of human femoral bone retrieved from patients with osteoarthritis.

    Science.gov (United States)

    Haba, Yvonne; Lindner, Tobias; Fritsche, Andreas; Schiebenhöfer, Ann-Kristin; Souffrant, Robert; Kluess, Daniel; Skripitz, Ralf; Mittelmeier, Wolfram; Bader, Rainer

    2012-01-01

    The objective of this study was to analyse retrieved human femoral bone samples using three different test methods, to elucidate the relationship between bone mineral density and mechanical properties. Human femoral heads were retrieved from 22 donors undergoing primary total hip replacement due to hip osteoarthritis and stored for a maximum of 24 hours postoperatively at + 6 °C to 8 °C.Analysis revealed an average structural modulus of 232±130 N/mm(2) and ultimate compression strength of 6.1±3.3 N/mm(2) with high standard deviations. Bone mineral densities of 385±133 mg/cm(2) and 353±172 mg/cm(3) were measured using thedual energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT), respectively. Ashing resulted in a bone mineral density of 323±97 mg/cm(3). In particular, significant linear correlations were found between DXA and ashing with r = 0.89 (p < 0.01, n = 22) and between structural modulus and ashing with r = 0.76 (p < 0.01, n = 22).Thus, we demonstrated a significant relationship between mechanical properties and bone density. The correlations found can help to determine the mechanical load capacity of individual patients undergoing surgical treatments by means of noninvasive bone density measurements.

  18. Lead

    Science.gov (United States)

    ... Chapter 6 Chapter 7 Chapter 8 Chapter 9 Appendix I Appendix II Tables Figures State Programs Alabama Alaska Arizona ... Tool Kit Resources Healthy Homes and Lead Poisoning Prevention Training Center (HHLPPTC) Training Tracks File Formats Help: ...

  19. Human bone hardness seems to depend on tissue type but not on anatomical site in the long bones of an old subject.

    Science.gov (United States)

    Ohman, Caroline; Zwierzak, Iwona; Baleani, Massimiliano; Viceconti, Marco

    2013-02-01

    It has been hypothesised that among different human subjects, the bone tissue quality varies as a function of the bone segment morphology. The aim of this study was to assess and compare the quality, evaluated in terms of hardness of packages of lamellae, of cortical and trabecular bones, at different anatomical sites within the human skeleton. The contralateral six long bones of an old human subject were indented at different levels along the diaphysis and at both epiphyses of each bone. Hardness value, which is correlated to the degree of mineralisation, of both cortical and trabecular bone tissues was calculated for each indentation location. It was found that the cortical bone tissue was harder (+18%) than the trabecular one. In general, the bone hardness was found to be locally highly heterogeneous. In fact, considering one single slice obtained for a bone segment, the coefficient of variation of the hardness values was up to 12% for cortical bone and up to 17% for trabecular bone. However, the tissue hardness was on average quite homogeneous within and among the long bones of the studied donor, although differences up to 9% among levels and up to 7% among bone segments were found. These findings seem not to support the mentioned hypothesis, at least not for the long bones of an old subject.

  20. Demineralized bone matrix and human cancellous bone enhance fixation of porous-coated titanium implants in sheep

    DEFF Research Database (Denmark)

    Babiker, Hassan; Ding, Ming; Overgaard, Søren

    2016-01-01

    Allogenic bone graft has been considered the gold standard in connection with bone graft material in revision joint arthroplasty. However, the lack of osteogenic potential and the risk of disease transmission are clinical challenges. The use of osteoinductive materials, such as demineralized bone...... of DBM alone, DBM with CB, or allograft on the fixation of porous-coated titanium implants. DBM100 and CB produced from human tissue were included. Both materials are commercially available. DBM granules are placed in pure DBM and do not contain any other carrier. Titanium alloy implants, 10 mm long × 10...... (gold standard), respectively. A standardized surgical procedure was used. At sacrifice 6 weeks after implantation, both distal femurs were harvested. The implant fixation was evaluated by mechanical push-out testing to test shear mechanical properties between implant and the host bone...

  1. A lead isotopic study of the human bioaccessibility of lead in urban soils from Glasgow, Scotland

    Energy Technology Data Exchange (ETDEWEB)

    Farmer, John G., E-mail: J.G.Farmer@ed.ac.uk [School of GeoSciences, University of Edinburgh, Edinburgh, EH9 3JN, Scotland (United Kingdom); Broadway, Andrew [School of GeoSciences, University of Edinburgh, Edinburgh, EH9 3JN, Scotland (United Kingdom); Cave, Mark R.; Wragg, Joanna [British Geological Survey, Keyworth, Nottingham NG12 5GG, England (United Kingdom); Fordyce, Fiona M. [British Geological Survey, Edinburgh, EH9 3LA, Scotland (United Kingdom); Graham, Margaret C.; Ngwenya, Bryne T. [School of GeoSciences, University of Edinburgh, Edinburgh, EH9 3JN, Scotland (United Kingdom); Bewley, Richard J.F. [URS Corporation Ltd, Manchester, M1 6HS, England (United Kingdom)

    2011-11-01

    The human bioaccessibility of lead (Pb) in Pb-contaminated soils from the Glasgow area was determined by the Unified Bioaccessibility Research Group of Europe (BARGE) Method (UBM), an in vitro physiologically based extraction scheme that mimics the chemical environment of the human gastrointestinal system and contains both stomach and intestine compartments. For 27 soils ranging in total Pb concentration from 126 to 2160 mg kg{sup -1} (median 539 mg kg{sup -1}), bioaccessibility as determined by the 'stomach' simulation (pH {approx} 1.5) was 46-1580 mg kg{sup -1}, equivalent to 23-77% (mean 52%) of soil total Pb concentration. The corresponding bioaccessibility data for the 'stomach + intestine' simulation (pH {approx} 6.3) were 6-623 mg kg{sup -1} and 2-42% (mean 22%) of soil Pb concentration. The soil {sup 206}Pb/{sup 207}Pb ratios ranged from 1.057 to 1.175. Three-isotope plots of {sup 208}Pb/{sup 206}Pb against {sup 206}Pb/{sup 207}Pb demonstrated that {sup 206}Pb/{sup 207}Pb ratios were intermediate between values for source end-member extremes of imported Australian Pb ore (1.04) - used in the manufacture of alkyl Pb compounds (1.06-1.10) formerly added to petrol - and indigenous Pb ores/coal (1.17-1.19). The {sup 206}Pb/{sup 207}Pb ratios of the UBM 'stomach' extracts were similar (< 0.01 difference) to those of the soil for 26 of the 27 samples (r = 0.993, p < 0.001) and lower in 24 of them. A slight preference for lower {sup 206}Pb/{sup 207}Pb ratio was discernible in the UBM. However, the source of Pb appeared to be less important in determining the extent of UBM-bioaccessible Pb than the overall soil total Pb concentration and the soil phases with which the Pb was associated. The significant phases identified in a subset of samples were carbonates, manganese oxides, iron-aluminium oxyhydroxides and clays. - Highlights: {yields} We determined the human bioaccessibility of Pb in urban soils by in vitro extraction. {yields} We

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

    Science.gov (United States)

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

    2015-05-01

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

  3. Engineering new bone via a minimally invasive route using human bone marrow-derived stromal cell aggregates, microceramic particles, and human platelet-rich plasma gel.

    Science.gov (United States)

    Chatterjea, Anindita; Yuan, Huipin; Fennema, Eelco; Burer, Ruben; Chatterjea, Supriyo; Garritsen, Henk; Renard, Auke; van Blitterswijk, Clemens A; de Boer, Jan

    2013-02-01

    There is a rise in the popularity of arthroscopic procedures in orthopedics. However, the majority of cell-based bone tissue-engineered constructs (TECs) rely on solid preformed scaffolding materials, which require large incisions and extensive dissections for placement at the defect site. Thus, they are not suitable for minimally invasive techniques. The aim of this study was to develop a clinically relevant, easily moldable, bone TEC, amenable to minimally invasive techniques, using human mesenchymal stromal cells (hMSCs) and calcium phosphate microparticles in combination with an in situ forming platelet-rich plasma gel obtained from human platelets. Most conventional TECs rely on seeding and culturing single-cell suspensions of hMSCs on scaffolds. However, for generating TECs amenable to the minimally invasive approach, it was essential to aggregate the hMSCs in vitro before seeding them on the scaffolds as unaggregated MSCs did not generate any bone. Twenty four hours of in vitro aggregation was determined to be optimal for maintaining cell viability in vitro and bone formation in vivo. Moreover, no statistically significant difference was observed in the amount of bone formed when the TECs were implanted via an open approach or a minimally invasive route. TECs generated using MSCs from three different human donors generated new bone through the minimally invasive route in a reproducible manner, suggesting that these TECs could be a viable alternative to preformed scaffolds employed through an open surgery for treating bone defects.

  4. Aging Leads to a Dysregulation in Mechanically Driven Bone Formation and Resorption.

    Science.gov (United States)

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

    2015-10-01

    Physical activity is essential to maintain skeletal mass and structure, but its effect seems to diminish with age. To test the hypothesis that bone becomes less sensitive to mechanical strain with age, we used a combined in vivo/in silico approach. We investigated how maturation and aging influence the mechanical regulation of bone formation and resorption to 2 weeks of noninvasive in vivo controlled loading in mice. Using 3D in vivo morphometrical assessment of longitudinal microcomputed tomography images, we quantified sites in the mouse tibia where bone was deposited or resorbed in response to controlled in vivo loading. We compared the (re)modeling events (formation/resorption/quiescent) to the mechanical strains induced at these sites (predicted using finite element analysis). Mice of all age groups (young, adult, and elderly) responded to loading with increased formation and decreased resorption, preferentially at high strains. Low strains were associated with no anabolic response in adult and elderly mice, whereas young animals showed a strong response. Adult animals showed a clear separation between strain ranges where formation and resorption occurred but without an intermediate quiescent "lazy zone". This strain threshold disappeared in elderly mice, as mechanically induced (re)modeling became dysregulated, apparent in an inability to inhibit resorption or initiate formation. Contrary to what is generally believed until now, aging does not shift the mechanical threshold required to initiate formation or resorption, but rather blurs its specificity. These data suggest that pharmaceutical strategies augmenting physical exercise should consider this dysfunction in the mechanical regulation of bone (re)modeling to more effectively combat age-related bone loss.

  5. Bone grafting: An overview

    Directory of Open Access Journals (Sweden)

    D. O. Joshi

    2010-08-01

    Full Text Available Bone grafting is the process by which bone is transferred from a source (donor to site (recipient. Due to trauma from accidents by speedy vehicles, falling down from height or gunshot injury particularly in human being, acquired or developmental diseases like rickets, congenital defects like abnormal bone development, wearing out because of age and overuse; lead to bone loss and to replace the loss we need the bone grafting. Osteogenesis, osteoinduction, osteoconduction, mechanical supports are the four basic mechanisms of bone graft. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. An ideal bone graft material is biologically inert, source of osteogenic, act as a mechanical support, readily available, easily adaptable in terms of size, shape, length and replaced by the host bone. Except blood, bone is grafted with greater frequency. Bone graft indicated for variety of orthopedic abnormalities, comminuted fractures, delayed unions, non-unions, arthrodesis and osteomyelitis. Bone graft can be harvested from the iliac crest, proximal tibia, proximal humerus, proximal femur, ribs and sternum. By adopting different procedure of graft preservation its antigenicity can be minimized. The concept of bone banking for obtaining bone grafts and implants is very useful for clinical application. Absolute stability require for successful incorporation. Ideal bone graft must possess osteogenic, osteoinductive and osteocon-ductive properties. Cancellous bone graft is superior to cortical bone graft. Usually autologous cancellous bone graft are used as fresh grafts where as allografts are employed as an alloimplant. None of the available type of bone grafts possesses all these properties therefore, a single type of graft cannot be recomm-ended for all types of orthopedic abnormalities. Bone grafts and implants can be selected as per clinical problems, the equipments available and preference of

  6. Three-dimensional microstructure of human alveolar trabecular bone: a micro-computed tomography study

    Science.gov (United States)

    2017-01-01

    Purpose The microstructural characteristics of trabecular bone were identified using micro-computed tomography (micro-CT), in order to develop a potential strategy for implant surface improvement to facilitate osseointegration. Methods Alveolar bone specimens from the cadavers of 30 humans were scanned by high-resolution micro-CT and reconstructed. Volumes of interest chosen within the jaw were classified according to Hounsfield units into 4 bone quality categories. Several structural parameters were measured and statistically analyzed. Results Alveolar bone specimens with D1 bone quality had significantly higher values for all structural parameters than the other bone quality categories, except for trabecular thickness (Tb.Th). The percentage of bone volume, trabecular separation (Tb.Sp), and trabecular number (Tb.N) varied significantly among bone quality categories. Tb.Sp varied markedly across the bone quality categories (D1: 0.59±0.22 mm, D4: 1.20±0.48 mm), whereas Tb.Th had similar values (D1: 0.30±0.08 mm, D4: 0.22±0.05 mm). Conclusions Bone quality depended on Tb.Sp and number—that is, endosteal space architecture—rather than bone surface and Tb.Th. Regardless of bone quality, Tb.Th showed little variation. These factors should be taken into account when developing individualized implant surface topographies. PMID:28261521

  7. Is the corticomedullary index valid to distinguish human from nonhuman bones: a multislice computed tomography study.

    Science.gov (United States)

    Rérolle, Camille; Saint-Martin, Pauline; Dedouit, Fabrice; Rousseau, Hervé; Telmon, Norbert

    2013-09-10

    The first step in the identification process of bone remains is to determine whether they are of human or nonhuman origin. This issue may arise when only a fragment of bone is available, as the species of origin is usually easily determined on a complete bone. The present study aims to assess the validity of a morphometric method used by French forensic anthropologists to determine the species of origin: the corticomedullary index (CMI), defined by the ratio of the diameter of the medullary cavity to the total diameter of the bone. We studied the constancy of the CMI from measurements made on computed tomography images (CT scans) of different human bones, and compared our measurements with reference values selected in the literature. The measurements obtained on CT scans at three different sites of 30 human femurs, 24 tibias, and 24 fibulas were compared between themselves and with the CMI reference values for humans, pigs, dogs and sheep. Our results differed significantly from these reference values, with three exceptions: the proximal quarter of the femur and mid-fibular measurements for the human CMI, and the proximal quarter of the tibia for the sheep CMI. Mid-tibial, mid-femoral, and mid-fibular measurements also differed significantly between themselves. Only 22.6% of CT scans of human bones were correctly identified as human. We concluded that the CMI is not an effective method for determining the human origin of bone remains.

  8. Acumulación de plomo en hueso y sus efectos en la salud Lead storage in bone and its effects on health

    Directory of Open Access Journals (Sweden)

    Luz Helena Sanín

    1998-07-01

    Full Text Available Los efectos nocivos del plomo han sido conocidos desde tiempos antiguos por su amplia gama; este metal afecta prácticamente todos los órganos y sistemas del cuerpo humano. Recientemente se han documentado efectos tóxicos crónicos en los sistemas cardiovascular y nervioso, con niveles que antes se consideraban seguros. El sitio primario de almacenamiento de plomo en el organismo es el hueso, pero sólo hasta fechas recientes se ha clarificado la significancia toxicológica de este hecho. En este artículo se analiza el papel del plomo en hueso como fuente de exposición endógena, como biomarcador de exposición crónica y como tejido blanco. Se presentan además los avances recientes para la medición de plomo en hueso mediante los rayos X-fluorescentes (XRF. Finalmente se revisa la importancia, para la salud pública, de estudiar y medir el plomo en hueso en lugares con una historia de exposición crónica como la Ciudad de México y en los ambientes ocupacionales, especialmente como fuente remanente de exposición. Se analiza especialmente el caso de mujeres en edad reproductiva, quienes pueden convertirse en fuentes de exposición para el feto y para el niño amamantado.The adverse effects of lead have been known for long since the metal affects practically all organs and systems of the human body. Recently, toxic effects have been reported in the cardiovascular and nervous systems at lead levels previously considered to be secure. The main lead storage site in the body is bone. The toxicologic significance of this fact has been clarified only recently. The present study analyzes the role of lead as an endogenous source of exposure, as a chronic exposure biomarker and as a target organ. Recent advances to measure bone lead through fluorescent X-Rays are discussed. Additionally, the importance of bone lead from a public health perspective in places with a chronic history of exposure such as Mexico City, and in some occupational

  9. Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis.

    Science.gov (United States)

    Jafari, Abbas; Qanie, Diyako; Andersen, Thomas L; Zhang, Yuxi; Chen, Li; Postert, Benno; Parsons, Stuart; Ditzel, Nicholas; Khosla, Sundeep; Johansen, Harald Thidemann; Kjærsgaard-Andersen, Per; Delaisse, Jean-Marie; Abdallah, Basem M; Hesselson, Daniel; Solberg, Rigmor; Kassem, Moustapha

    2017-02-14

    Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.

  10. The three-dimensional microstructure of trabecular bone: Analysis of site-specific variation in the human jaw bone

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jo Eun; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul; Huh, Kyung Hoe [Dept. of Oral and Maxillofacial Radiology and Dental Research Institute, School of Dentistry, Seoul National University, Seoul (Korea, Republic of); Shin, Jae Myung [Dept. of Oral and Maxillofacial Surgery, Ilsan Paik Hospital, Inje University College of Medicine, Goyang (Korea, Republic of); Oh, Sung Ook [A Plus Dental Clinic, Seoul (Korea, Republic of)

    2013-12-15

    This study was performed to analyze human maxillary and mandibular trabecular bone using the data acquired from micro-computed tomography (micro-CT), and to characterize the site-specific microstructures of trabeculae. Sixty-nine cylindrical bone specimens were prepared from the mandible and maxilla. They were divided into 5 groups by region: the anterior maxilla, posterior maxilla, anterior mandible, posterior mandible, and mandibular condyle. After the specimens were scanned using a micro-CT system, three-dimensional microstructural parameters such as the percent bone volume, bone specific surface, trabecular thickness, trabecular separation, trabecular number, structure model index, and degrees of anisotropy were analyzed. Among the regions other than the condylar area, the anterior mandibular region showed the highest trabecular thickness and the lowest value for the bone specific surface. On the other hand, the posterior maxilla region showed the lowest trabecular thickness and the highest value for the bone specific surface. The degree of anisotropy was lowest at the anterior mandible. The condyle showed thinner trabeculae with a more anisotropic arrangement than the other mandibular regions. There were microstructural differences between the regions of the maxilla and mandible. These results suggested that different mechanisms of external force might exist at each site.

  11. Trace determination of heavy metals in human bones - problems in their analysis and result interpretation

    Energy Technology Data Exchange (ETDEWEB)

    Liese, T.; Simon, J.

    1984-02-01

    An investigation of the lead and cadmium contents of rib-bones of patients suffering from bronchial cancer was carried out with the aid of electrothermal AAS and DPASV. An analysis of the anamnesis data indicated a significant correlation between the bone-cadmium content and the patient's smoking history.

  12. Crestal bone resorption in augmented bone using mineralized freeze-dried bone allograft or pristine bone during submerged implant healing: a prospective study in humans.

    Science.gov (United States)

    Huang, Hsiang-yun; Ogata, Yumi; Hanley, James; Finkelman, Matthew; Hur, Yong

    2016-02-01

    There is limited evidence on the crestal bone level changes around implants placed in bone augmented by guided bone regeneration (GBR) during submerged healing. The purpose of this study was to prospectively compare radiographic crestal bone changes around implants placed in augmented bone with changes around implants placed in pristine bone. Patients receiving dental implants in the augmented or pristine mandibular posterior edentulous ridge were included in the study. The digital standardized radiographs from the implant placement procedure were compared to the radiographs from the second-stage procedure to evaluate the peri-implant marginal bone level changes. The soft tissue thickness (ST), width of keratinized mucosa (wKM), and early cover screw exposure (eIE) were measured at the time of the second-stage procedure. A total of 29 implants in 26 patients, 11 in augmented bone (test group) and 18 in pristine bone (control group), were analyzed. The mean peri-implant bone loss (ΔBL) was 0.74 ± 0.74 mm (mean ± SD) in the test group and 0.25 ± 0.55 mm (mean ± SD) in the control group. The differences between the test and control groups in the mesial, distal, and mean peri-implant crestal bone level changes were statistically significant (P = 0.009, P = 0.004, and P = 0.001, respectively). The confounding factors (ST, wKM, and eIE) were adjusted. More peri-implant crestal bone loss during the submerged healing period was observed in augmented bone than in pristine bone. Augmented bone may not exhibit the same characteristics as pristine bone during the implant submerged healing period. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Ancient Human Bone Microstructure in Medieval England: Comparisons between Two Socio-Economic Groups

    OpenAIRE

    Miszkiewicz, Justyna J.; Mahoney, Patrick

    2016-01-01

    Understanding the links between bone microstructure and human lifestyle is critical for clinical and anthropological research into skeletal\\ud growth and adaptation. The present study is the first to report correspondence between socio-economic status and variation in bone microstructure\\ud in ancient humans. Products of femoral cortical remodeling were assessed using histological methods in a large human medieval\\ud sample (N:450) which represented two distinct socio-economic groups. Osteona...

  14. Modeling the effect of levothyroxine therapy on bone mass density in postmenopausal women: a different approach leads to new inference

    Directory of Open Access Journals (Sweden)

    Tavangar Seyed

    2007-06-01

    Full Text Available Abstract Background The diagnosis, treatment and prevention of osteoporosis is a national health emergency. Osteoporosis quietly progresses without symptoms until late stage complications occur. Older patients are more commonly at risk of fractures due to osteoporosis. The fracture risk increases when suppressive doses of levothyroxine are administered especially in postmenopausal women. The question is; "When should bone mass density be tested in postmenopausal women after the initiation of suppressive levothyroxine therapy?". Standard guidelines for the prevention of osteoporosis suggest that follow-up be done in 1 to 2 years. We were interested in predicting the level of bone mass density in postmenopausal women after the initiation of suppressive levothyroxine therapy with a novel approach. Methods The study used data from the literature on the influence of exogenous thyroid hormones on bone mass density. Four cubic polynomial equations were obtained by curve fitting for Ward's triangle, trochanter, spine and femoral neck. The behaviors of the models were investigated by statistical and mathematical analyses. Results There are four points of inflexion on the graphs of the first derivatives of the equations with respect to time at about 6, 5, 7 and 5 months. In other words, there is a maximum speed of bone loss around the 6th month after the start of suppressive L-thyroxine therapy in post-menopausal women. Conclusion It seems reasonable to check bone mass density at the 6th month of therapy. More research is needed to explain the cause and to confirm the clinical application of this phenomenon for osteoporosis, but such an approach can be used as a guide to future experimentation. The investigation of change over time may lead to more sophisticated decision making in a wide variety of clinical problems.

  15. One Million Bones: Measuring the Effect of Human Rights Participation in the Social Work Classroom

    Science.gov (United States)

    McPherson, Jane; Cheatham, Leah P.

    2015-01-01

    This article describes the integration of human rights content and a national arts-activism initiative--One Million Bones--into a bachelor's-level macro practice class as a human rights teaching strategy. Two previously validated scales, the Human Rights Exposure (HRX) in Social Work and the Human Rights Engagement (HRE) in Social Work (McPherson…

  16. One Million Bones: Measuring the Effect of Human Rights Participation in the Social Work Classroom

    Science.gov (United States)

    McPherson, Jane; Cheatham, Leah P.

    2015-01-01

    This article describes the integration of human rights content and a national arts-activism initiative--One Million Bones--into a bachelor's-level macro practice class as a human rights teaching strategy. Two previously validated scales, the Human Rights Exposure (HRX) in Social Work and the Human Rights Engagement (HRE) in Social Work (McPherson…

  17. Determination of Lead in Human Calculi and Its Effects on Renal Function of Lead Occupational Workers

    Directory of Open Access Journals (Sweden)

    F. Memon

    2016-06-01

    Full Text Available Seventy five samples of renal and eighteen samples of supra gingival calculi of lead recycling workers were collected over the period of seven years (2008-2014 and studied for the accumulation of lead. The results were compared with those of non exposed subjects. The lead content of calculi was investigated for its dependence on type and composition of calculi, blood lead, job status and duration of exposure. The effect of blood lead and renal calculi was also investigated in relation to kidney function of respective subjects. The mean lead levels of various types of calculi were found to follow the order as phosphate > oxalate > urate .> cystine while single principal group of supra gingival calculi resulted in lower levels of metal. The lead content of calculi positively correlated with phosphate content of both of the renal (r = 0.655 and supra gingival calculi (r= 0.866, Impaired renal function was more pronounced in active workers and depended on blood lead levels in addition to presence of metal in renal calculi

  18. The identification of proteoglycans and glycosaminoglycans in archaeological human bones and teeth.

    Science.gov (United States)

    Coulson-Thomas, Yvette M; Coulson-Thomas, Vivien J; Norton, Andrew L; Gesteira, Tarsis F; Cavalheiro, Renan P; Meneghetti, Maria Cecília Z; Martins, João R; Dixon, Ronald A; Nader, Helena B

    2015-01-01

    Bone tissue is mineralized dense connective tissue consisting mainly of a mineral component (hydroxyapatite) and an organic matrix comprised of collagens, non-collagenous proteins and proteoglycans (PGs). Extracellular matrix proteins and PGs bind tightly to hydroxyapatite which would protect these molecules from the destructive effects of temperature and chemical agents after death. DNA and proteins have been successfully extracted from archaeological skeletons from which valuable information has been obtained; however, to date neither PGs nor glycosaminoglycan (GAG) chains have been studied in archaeological skeletons. PGs and GAGs play a major role in bone morphogenesis, homeostasis and degenerative bone disease. The ability to isolate and characterize PG and GAG content from archaeological skeletons would unveil valuable paleontological information. We therefore optimized methods for the extraction of both PGs and GAGs from archaeological human skeletons. PGs and GAGs were successfully extracted from both archaeological human bones and teeth, and characterized by their electrophoretic mobility in agarose gel, degradation by specific enzymes and HPLC. The GAG populations isolated were chondroitin sulfate (CS) and hyaluronic acid (HA). In addition, a CSPG was detected. The localization of CS, HA, three small leucine rich PGs (biglycan, decorin and fibromodulin) and glypican was analyzed in archaeological human bone slices. Staining patterns were different for juvenile and adult bones, whilst adolescent bones had a similar staining pattern to adult bones. The finding that significant quantities of PGs and GAGs persist in archaeological bones and teeth opens novel venues for the field of Paleontology.

  19. The identification of proteoglycans and glycosaminoglycans in archaeological human bones and teeth.

    Directory of Open Access Journals (Sweden)

    Yvette M Coulson-Thomas

    Full Text Available Bone tissue is mineralized dense connective tissue consisting mainly of a mineral component (hydroxyapatite and an organic matrix comprised of collagens, non-collagenous proteins and proteoglycans (PGs. Extracellular matrix proteins and PGs bind tightly to hydroxyapatite which would protect these molecules from the destructive effects of temperature and chemical agents after death. DNA and proteins have been successfully extracted from archaeological skeletons from which valuable information has been obtained; however, to date neither PGs nor glycosaminoglycan (GAG chains have been studied in archaeological skeletons. PGs and GAGs play a major role in bone morphogenesis, homeostasis and degenerative bone disease. The ability to isolate and characterize PG and GAG content from archaeological skeletons would unveil valuable paleontological information. We therefore optimized methods for the extraction of both PGs and GAGs from archaeological human skeletons. PGs and GAGs were successfully extracted from both archaeological human bones and teeth, and characterized by their electrophoretic mobility in agarose gel, degradation by specific enzymes and HPLC. The GAG populations isolated were chondroitin sulfate (CS and hyaluronic acid (HA. In addition, a CSPG was detected. The localization of CS, HA, three small leucine rich PGs (biglycan, decorin and fibromodulin and glypican was analyzed in archaeological human bone slices. Staining patterns were different for juvenile and adult bones, whilst adolescent bones had a similar staining pattern to adult bones. The finding that significant quantities of PGs and GAGs persist in archaeological bones and teeth opens novel venues for the field of Paleontology.

  20. Inca - interparietal bones in neurocranium of human skulls in central India.

    Science.gov (United States)

    Marathe, Rr; Yogesh, As; Pandit, Sv; Joshi, M; Trivedi, Gn

    2010-01-01

    Inca bones are accessory bones found in neurocranium of human skulls. Occurrence of Inca bones is rare as compared to other inter sutural bones such as wormian bones. These Inca ossicles are regarded as variants of the normal. The reporting of such occurrences is inadequate from Central India. To find the incidence of Inca variants in Central India. In the present study, 380 dried adult human skulls were examined. All specimen samples were procured from various Medical colleges of Central India. They were analyzed for gross incidence, sexual dimorphism and number of fragments of Inca bones. Gross incidence of Inca bones was found to be 1.315 %. Incidence rate was higher in male skulls than female skulls (male: 1.428%; female: 1.176%). The Inca bones frequently occurred signally. Out of the five observed Inca ossicles, two were fragmented. This data gives idea regarding gross incidence, sexual dimorphism and number of fragments of Inca bones in neurocranium of human skulls from Central India. The knowledge of this variable is useful for neurosurgeons, anthropologists and radiologists.

  1. The effects of different maceration techniques on nuclear DNA amplification using human bone.

    Science.gov (United States)

    Lee, Esther J; Luedtke, Jennifer G; Allison, Jamie L; Arber, Carolyn E; Merriwether, D Andrew; Steadman, Dawnie Wolfe

    2010-07-01

    Forensic anthropologists routinely macerate human bone for the purposes of identity and trauma analysis, but the heat and chemical treatments used can destroy genetic evidence. As a follow-up to a previous study on nuclear DNA recovery that used pig ribs, this study utilizes human skeletal remains treated with various bone maceration techniques for nuclear DNA amplification using the standard Combined DNA Index System (CODIS) markers. DNA was extracted from 18 samples of human lower leg bones subjected to nine chemical and heat maceration techniques. Genotyping was carried out using the AmpFlSTR COfiler and AmpFlSTR Profiler Plus ID kits. Results showed that heat treatments via microwave or Biz/Na(2)CO(3) in sub-boiling water efficiently macerate bone and produce amplifiable nuclear DNA for genetic analysis. Long-term use of chemicals such as hydrogen peroxide is discouraged as it results in poor bone quality and has deleterious effects on DNA amplification.

  2. [A general review on the procedures in a human temporal bone laboratory].

    Science.gov (United States)

    Oktay, Mehmet Faruk; Cüreoğlu, Sebahattin; Schachern, Patricia A; Paparella, Micheal M

    2006-01-01

    Structures of the human ear are usually inaccessible during life for examination of pathologic changes of the underlying disease, which is only possible with postmortem studies of the human temporal bone. Human temporal bone laboratories serve as a unique source of material for research in this respect. They enable comparison between histologic findings of temporal bone sections and the ear pathologies documented prior to death, as well as comparison of diseased ears with any selected temporal bone specimens, both of which provide invaluable knowledge to be shared among researchers and other laboratories. This article aims to provide insight into the functions of temporal bone laboratories and to familiarize the reader with histopathologic studies conducted therein.

  3. Molecular and cellular characteristics of human and non-human primate multipotent stromal cells from the amnion and bone marrow during long term culture.

    Science.gov (United States)

    Pogozhykh, Olena; Pogozhykh, Denys; Neehus, Anna-Lena; Hoffmann, Andrea; Blasczyk, Rainer; Müller, Thomas

    2015-08-22

    Multipotent stromal cells (MSCs) are among the key candidates in regenerative medicine. However variety of MSC sources and general heterogeneity lead to controversial data in functional characterization. Furthermore, despite intensive usage as preclinical animal model, little is known about MSCs of the common marmoset monkey. MSCs derived from placental amnion and bone marrow samples from human and common marmoset were characterized in parallel over 12 passages to monitor similarities and significant differences (p ≤ 0.05, Student's t-test) in MSC markers and major histocompatibility complex (MHC) class I expression by immunohistochemistry, flow cytometry, real-time PCR, metabolic activity test, with special focus on pluripotency associated genes. Human and non-human primate MSCs were characterized for expression of MSC markers and capability of differentiation into mesenchymal lineages. MSCs could be cultured more than 100 days (26 passages), but metabolic activity was significantly enhanced in amnion vs. bone marrow MSCs. Interestingly, MHC class I expression is significantly reduced in amnion MSCs until passage 6 in human and marmoset, but not in bone marrow cells. For MSC markers, CD73 and CD105 levels remain unchanged in amnion MSCs and slightly decline in bone marrow at late passages; CD166 is significantly higher expressed in human MSCs, CD106 significantly lower vs. marmoset. All cultured MSCs showed pluripotency marker expression like Oct-4A at passage 3 significantly decreasing over time (passages 6-12) while Nanog expression was highest in human bone marrow MSCs. Furthermore, human MSCs demonstrated the highest Sox2 levels vs. marmoset, whereas the marmoset exhibited significantly higher Lin28A values. Bisulfite sequencing of the Oct-4 promoter region displayed fewer methylations of CpG islands in the marmoset vs. human. Little is known about MSC characteristics from the preclinical animal model common marmoset vs. human during long term culture

  4. MicroRNA profiling in human neutrophils during bone marrow granulopoiesis and in vivo exudation

    DEFF Research Database (Denmark)

    Larsen, Maria T; Hother, Christoffer; Häger, Mattias

    2013-01-01

    The purpose of this study was to describe the microRNA (miRNA) expression profiles of neutrophils and their precursors from the initiation of granulopoiesis in the bone marrow to extravasation and accumulation in skin windows. We analyzed three different cell populations from human bone marrow, p...

  5. Relation between in vitro and in vivo osteogenic potential of cultured human bone marrow stromal cells

    NARCIS (Netherlands)

    Mendes, SC; Tibbe, JM; Veenhof, M; Both, S; Oner, FC; van Blitterswijk, CA; de Bruijn, Joost D.

    2004-01-01

    The use of cell therapies in bone reconstruction has been the subject of extensive research. It is known that human bone marrow stromal cell (HBMSC) cultures contain a population of progenitor cells capable of differentiation towards the osteogenic lineage. In the present study, the correlation betw

  6. Multiparameter Analysis of Human Bone Marrow Stromal Cells Identifies Distinct Immunomodulatory and Differentiation-Competent Subtypes

    NARCIS (Netherlands)

    S. James (Sally); J. Fox (James); F. Afsari (Farinaz); J. Lee (Jennifer); S. Clough (Sally); C. Knight (Charlotte); J. Ashmore (James); P. Ashton (Peter); O. Preham (Olivier); M.J. Hoogduijn (Martin); R.D.A.R. Ponzoni (Raquel De Almeida Rocha); Y. Hancock; M. Coles (Mark); P.G. Genever (Paul)

    2015-01-01

    textabstractBone marrow stromal cells (BMSCs, also called bone-marrow-derived mesenchymal stromal cells) provide hematopoietic support and immunoregulation and contain a stem cell fraction capable of skeletogenic differentiation. We used immortalized human BMSC clonal lines for multi-level analysis

  7. Morphological study of bone marrow to assess the effects of lead acetate on haemopoiesis and aplasia and the ameliorating role of Carica papaya extract.

    Science.gov (United States)

    Tham, Ching S; Chakravarthi, Srikumar; Haleagrahara, Nagaraja; DE Alwis, Ranjit

    2013-02-01

    Lead causes damage to the body by inducing oxidative stress. The sites of damage include the bone marrow, where marrow hypoplasia and osteosclerosis may be observed. Leaves of Carica papaya, which have antioxidant and haemopoietic properties, were tested against the effect of lead acetate in experimental rats. The rats were divided into 8 groups; control, lead acetate only, Carica papaya (50 mg and 200 mg), post-treatment with Carica papaya (50 mg and 200 mg) following lead acetate administration and pre-treatment with Carica papaya (50 mg and 200 mg) followed by lead acetate administration. The substances were administered for 14 days. The effects were evaluated by measuring protein carbonyl content (PCC) and glutathione content (GC) in the bone marrow. Histological changes in the bone marrow were also observed. The results showed that Carica papaya induced a significant reduction in the PCC activity and significantly increased the GC in the bone marrow. Carica papaya also improved the histology of the bone marrow compared with that of the lead acetate-treated group. In summary, Carica papaya was effective against the oxidative damage caused by lead acetate in the bone marrow and had a stimulatory effect on haemopoiesis.

  8. Human bone marrow harbors cells with neural crest-associated characteristics like human adipose and dermis tissues.

    Science.gov (United States)

    Coste, Cécile; Neirinckx, Virginie; Sharma, Anil; Agirman, Gulistan; Rogister, Bernard; Foguenne, Jacques; Lallemend, François; Gothot, André; Wislet, Sabine

    2017-01-01

    Adult neural crest stem-derived cells (NCSC) are of extraordinary high plasticity and promising candidates for use in regenerative medicine. Several locations such as skin, adipose tissue, dental pulp or bone marrow have been described in rodent, as sources of NCSC. However, very little information is available concerning their correspondence in human tissues, and more precisely for human bone marrow. The main objective of this study was therefore to characterize NCSC from adult human bone marrow. In this purpose, we compared human bone marrow stromal cells to human adipose tissue and dermis, already described for containing NCSC. We performed comparative analyses in terms of gene and protein expression as well as functional characterizations. It appeared that human bone marrow, similarly to adipose tissue and dermis, contains NESTIN+ / SOX9+ / TWIST+ / SLUG+ / P75NTR+ / BRN3A+/ MSI1+/ SNAIL1+ cells and were able to differentiate into melanocytes, Schwann cells and neurons. Moreover, when injected into chicken embryos, all those cells were able to migrate and follow endogenous neural crest migration pathways. Altogether, the phenotypic characterization and migration abilities strongly suggest the presence of neural crest-derived cells in human adult bone marrow.

  9. Three-dimensional microarchitecture of human osteoporotic, osteoarthrotic and rheumatoid arthritic cancellous bones

    DEFF Research Database (Denmark)

    Ding, Ming; Overgaard, Søren

    Introduction: Osteoporosis (OP), osteoarthrosis (OA), and rheumatoid arthritis (RA) are the most common age-related degenerative bone diseases, and major public health problems in terms of enormous amount of economic cost. RA is considered as a major cause of secondary osteoporosis. At late stage......, OP often leads to skeletal fractures, and OA and RA result in severe joint disability. Over the last a few decades, much significant research on the properties has been carried out on these diseases, however, a detailed comparison of the microarchitecture of cancellous bones of these diseases...... is not available. In this study, we investigated three-dimensional (3-D) microarchitectural properties of OP, OA and RA cancellous bone. We hypothesized that there were significant differences in microarchitecture among OP, OA and RA bone tissues that might lead to different bone quality. Materials and Method...

  10. [Maxillary sinus malformations (double wall bone) lead to chronic sinusitis in a case].

    Science.gov (United States)

    Pang, Chaofu; Gu, Feng; Fang, Yingqi

    2014-09-01

    Chronic rhinosinusitis is a common otorhinolaryngological disease, although the incidence of chronic sinusitis is the result of many factors, the local anatomic abnormalities is one of the most important reasons. When maxillary sinus dysplasia that sinus cavity becomes small. These was some sinus cavity partial or complete bony septum malformation used to be reported occasionally, according to reports in the literature of this malformation rate is below 2%, bony divides sinus cavity is divided into 2 to 3 independent lacunar deformity are very rare, next we will introduce a case of sinus cavity that been divided into double deck by bone wall.

  11. Recombinant human bone morphogenetic protein-2 suspended in fibrin glue enhances bone formation during distraction osteogenesis in rabbits

    Science.gov (United States)

    Li, Yunfeng; Li, Rui; Hu, Jing; Song, Donghui; Jiang, Xiaowen

    2016-01-01

    Introduction Bone morphogenetic protein-2 (BMP-2) has high potential for bone formation, but its in vivo effects are unpredictable due to the short life time. This study was designed to evaluate the effects of recombinant human (rh) BMP-2 suspended in fibrin on bone formation during distraction osteogenesis (DO) in rabbits. Material and methods The in vitro release kinetics of rhBMP-2 suspended in fibrin was tested using an enzyme-linked immunosorbent assay. Unilateral tibial lengthening for 10 mm was achieved in 48 rabbits. At the completion of osteodistraction, vehicle, fibrin, rhBMP-2 or rhBMP-2 suspended in fibrin (rhBMP-2 + fibrin) was injected into the center of the lengthened gap, with 12 animals in each group. Eight weeks later, the distracted callus was examined by histology, micro-CT and biomechanical testing. Radiographs of the distracted tibiae were taken at both 4 and 8 weeks after drug treatment. Results It was found that fibrin prolonged the life span of rhBMP-2 in vitro with sustained release during 17 days. The rhBMP-2 + fibrin treated animals showed the best results in bone mineral density, bone volume fraction, cortical bone thickness by micro-CT evaluation and mechanical properties by the three-point bending test when compared to the other groups (p < 0.05). In histological images, rhBMP-2 + fibrin treatment showed increased callus formation and better gap bridging compared to the other groups. Conclusions The results of this study suggest that fibrin holds promise to be a good carrier of rhBMP-2, and rhBMP-2 suspended in fibrin showed a stronger promoting effect on bone formation during DO in rabbits. PMID:27279839

  12. Analysis of bone mineral density of human bones for strength evaluation

    Indian Academy of Sciences (India)

    S N Khan; R M Warkhedkar; A K Shyam

    2015-08-01

    The bone density (BMD) is a medical term normally referring to the amount of mineral matter per square centimetre of bones. Twenty-five patients (18 female and 7 male patients with a mean age of 71.3 years) undergoing both lumbar spine DXA scans and computed tomography imaging were evaluated to determine if HU correlates with BMD and T-scores. BMD is used in clinical medicine as an indirect indicator of osteoporosis and fracture risk. This medical bone density is not the true physical ``density'' of the bone, which would be computed as mass per volume. Dual-energy X-ray absorptiometry (DXA, previously DEXA), a means of measuring BMD, is the most widely used and most thoroughly studied bone density measurement technologies. Different types of bone strength are required for various applications, but this strength calculation requires different machines for each strength property or it is done by different software like X-ray, CT scan, DEXA and BIA. The paper includes the design of an experimental setup which performs different types of test like tension, compression, three point bending, four point bending and torsion. The modified correlation between BMD and HU for various strength calculations is found out and validated with the experimental results.

  13. Micro-computed tomography and histomorphometric analysis of human alveolar bone repair induced by laser phototherapy: a pilot study.

    Science.gov (United States)

    Romão, M M A; Marques, M M; Cortes, A R G; Horliana, A C R T; Moreira, M S; Lascala, C A

    2015-12-01

    Immediate dental implant placement in the molar region is critical, because of the high amount of bone loss and the discrepancy between alveolar crest thickness and the implant platform. Laser phototherapy (LPT) improves bone repair. The aim of this study was to evaluate the human alveolar bone repair 40 days after molar extraction in patients submitted to LPT. Twenty patients were selected for this randomized controlled clinical trial; 10 underwent LPT (laser group) with a GaAlAs diode laser (808 nm, 100 mW, 0.04 cm(2), 75 J/cm(2), 30s per point, 3 J per point, at five points). The control group patients (n=10) were not irradiated. Forty days later, the tissue formed inside the sockets was analyzed by micro-computed tomography and histomorphometry. Data from the two groups were compared with Student's t-test and Pearson's correlation test. The relative bone volume was significantly higher in the laser group (Palveolar bone repair after molar extraction, leading to a more homogeneous trabecular configuration represented by thin and close trabeculae.

  14. Micro-CT characterization of human trabecular bone in osteogenesis imperfecta

    Science.gov (United States)

    Jameson, John; Albert, Carolyne; Smith, Peter; Molthen, Robert; Harris, Gerald

    2011-03-01

    Osteogenesis imperfecta (OI) is a genetic syndrome affecting collagen synthesis and assembly. Its symptoms vary widely but commonly include bone fragility, reduced stature, and bone deformity. Because of the small size and paucity of human specimens, there is a lack of biomechanical data for OI bone. Most literature has focused on histomorphometric analyses, which rely on assumptions to extrapolate 3-D properties. In this study, a micro-computed tomography (μCT) system was used to directly measure structural and mineral properties in pediatric OI bone collected during routine surgical procedures. Surface renderings suggested a poorly organized, plate-like orientation. Patients with a history of bone-augmenting drugs exhibited increased bone volume fraction (BV/TV), trabecular number (Tb.N), and connectivity density (Eu.Conn.D). The latter two parameters appeared to be related to OI severity. Structural results were consistently higher than those reported in a previous histomorphometric study, but these differences can be attributed to factors such as specimen collection site, drug therapy, and assumptions associated with histomorphometry. Mineral testing revealed strong correlations with several structural parameters, highlighting the importance of a dual approach in trabecular bone testing. This study reports some of the first quantitative μCT data of human OI bone, and it suggests compelling possibilities for the future of OI bone assessment.

  15. Mechanical properties of the normal human cartilage-bone complex in relation to age

    DEFF Research Database (Denmark)

    Ding, Ming; Dalstra, M; Linde, F

    1998-01-01

    OBJECTIVE: This study investigates the age-related variations in the mechanical properties of the normal human tibial cartilage-bone complex and the relationships between cartilage and bone. DESIGN: A novel technique was applied to assess the mechanical properties of the cartilage and bone by means...... normal donors aged 16-83 years were tested in compression. The deformation was measured simultaneously in bone and cartilage to obtain the mechanical properties of both tissues. RESULTS: The stiffnesses and elastic energies of both cartilage and bone showed an initial increase, with maxima at 40 years......, followed by a steady decline. The viscoelastic energy was maximal at younger ages (16-29 years), followed by a steady decline. The energy absorption capacity did not vary with age. Stiffnesses and elastic energies were correlated significantly between cartilage and bone. CONCLUSIONS: The present study...

  16. Study on the Microstructure of Human Articular Cartilage/Bone Interface

    Institute of Scientific and Technical Information of China (English)

    Yaxiong Liu; Qin Lian; Jiankang He; Jinna Zhao; Zhongmin Jin; Dichen Li

    2011-01-01

    For improving the theory of gradient microstructure of cartilage/bone interface, human distal femurs were studied. Scanning Electron Microscope (SEM), histological sections and MicroCT were used to observe, measure and model the microstructure of cartilage/bone interface. The results showed that the cartilage/bone interface is in a hierarchical structure which is composed of four different tissue layers. The interlocking of hyaline cartilage and calcified cartilage and that of calcified cartilage and subchondral bone are in the manner of"protrusion-pore" with average diameter of 17.0 μm and 34.1 μm respectively. In addition, the cancellous bone under the cartilage is also formed by four layer hierarchical structure, and the adjacent layers are connected by bone trabecula in the shape of H, I and Y, forming a complex interwoven network structure. Finally, the simplified structure model of the cartilage/bone interface was proposed according to the natural articular cartilage/bone interface. The simplified model is a 4-layer gradient biomimetic structure, which corresponds to four different tissues of natural cartilage/bone interface. The results of this work would be beneficial to the design of bionic scaffold for the tissue engineering of articular cartilage/bone.

  17. The biomechanical effect of artificial and human bone density on stopping and stripping torque during screw insertion.

    Science.gov (United States)

    Tsuji, Matthew; Crookshank, Meghan; Olsen, Michael; Schemitsch, Emil H; Zdero, Rad

    2013-06-01

    Orthopedic surgeons apply torque to metal screws manually by "subjective feel" to obtain adequate fracture fixation, i.e. stopping torque, and attempt to avoid accidental over-tightening that leads to screw-bone interface failure, i.e. stripping torque. Few studies have quantified stripping torque in human bone, and only one older study from 1980 reported stopping/ stripping torque ratio. The present aim was to measure stopping and stripping torque of cortical and cancellous screws in artificial and human bone over a wide range of densities. Sawbone blocks were obtained having densities from 0.08 to 0.80g/cm(3). Sixteen fresh-frozen human femurs of known standardized bone mineral density (sBMD) were also used. Using a torque screwdriver, 3.5-mm diameter cortical screws and 6.5-mm diameter cancellous screws were inserted for adequate tightening as determined subjectively by an orthopedic surgeon, i.e. stopping torque, and then further tightened until failure of the screw-bone interface, i.e. stripping torque. There were weak (R=0.25) to strong (R=0.99) linear correlations of absolute and normalized torque vs. density or sBMD. Maximum stopping torques normalized by screw thread area engaged by the host material were 15.2N/mm (cortical screws) and 13.4N/mm (cancellous screws) in sawbone blocks and 20.9N/mm (cortical screws) and 6.1N/mm (cancellous screws) in human femurs. Maximum stripping torques normalized by screw thread area engaged by the host material were 23.4N/mm (cortical screws) and 16.8N/mm (cancellous screws) in sawbone blocks and 29.3N/mm (cortical screws) and 8.3N/mm (cancellous screws) in human femurs. Combined average stopping/ stripping torque ratios were 80.8% (cortical screws) and 76.8% (cancellous screws) in sawbone blocks, as well as 66.6% (cortical screws) and 84.5% (cancellous screws) in human femurs. Surgeons should be aware of stripping torque limits for human femurs and monitor stopping torque during surgery. This is the first study of the

  18. Lead concentration in meat from lead-killed moose and predicted human exposure using Monte Carlo simulation.

    Science.gov (United States)

    Lindboe, M; Henrichsen, E N; Høgåsen, H R; Bernhoft, A

    2012-01-01

    Lead-based hunting ammunitions are still common in most countries. On impact such ammunition releases fragments which are widely distributed within the carcass. In Norway, wild game is an important meat source for segments of the population and 95% of hunters use lead-based bullets. In this paper, we have investigated the lead content of ground meat from moose (Alces alces) intended for human consumption in Norway, and have predicted human exposure through this source. Fifty-two samples from different batches of ground meat from moose killed with lead-based bullets were randomly collected. The lead content was measured by atomic absorption spectroscopy. The lead intake from exposure to moose meat over time, depending on the frequency of intake and portion size, was predicted using Monte Carlo simulation. In 81% of the batches, lead levels were above the limit of quantification of 0.03 mg kg(-1), ranging up to 110 mg kg(-1). The mean lead concentration was 5.6 mg kg(-1), i.e. 56 times the European Commission limit for lead in meat. For consumers eating a moderate meat serving (2 g kg(-1) bw), a single serving would give a lead intake of 11 µg kg(-1) bw on average, with maximum of 220 µg kg(-1) bw. Using Monte Carlo simulation, the median (and 97.5th percentile) predicted weekly intake of lead from moose meat was 12 µg kg(-1) bw (27 µg kg(-1) bw) for one serving per week and 25 µg kg(-1) bw (45 µg kg(-1) bw) for two servings per week. The results indicate that the intake of meat from big game shot with lead-based bullets imposes a significant contribution to the total human lead exposure. The provisional tolerable weekly intake set by the World Health Organization (WHO) of 25 µg kg(-1) bw is likely to be exceeded in people eating moose meat on a regular basis. The European Food Safety Authority (EFSA) has recently concluded that adverse effects may be present at even lower exposure doses. Hence, even occasional consumption of big game meat with lead levels as

  19. Radiation response of mesenchymal stem cells derived from bone marrow and human pluripotent stem cells

    OpenAIRE

    Islam, Mohammad S; Stemig, Melissa E.; Takahashi, Yutaka; Hui, Susanta K.

    2014-01-01

    Mesenchymal stem cells (MSCs) isolated from human pluripotent stem cells are comparable with bone marrow-derived MSCs in their function and immunophenotype. The purpose of this exploratory study was comparative evaluation of the radiation responses of mesenchymal stem cells derived from bone marrow- (BMMSCs) and from human embryonic stem cells (hESMSCs). BMMSCs and hESMSCs were irradiated at 0 Gy (control) to 16 Gy using a linear accelerator commonly used for cancer treatment. Cells were harv...

  20. Development of a realistic in vivo bone metastasis model of human renal cell carcinoma.

    Science.gov (United States)

    Valta, Maija P; Zhao, Hongjuan; Ingels, Alexandre; Thong, Alan E; Nolley, Rosalie; Saar, Matthias; Peehl, Donna M

    2014-06-01

    About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastases. The incidence of RCC is increasing and bone metastatic RCC merits greater focus. Realistic preclinical bone metastasis models of RCC are lacking, hampering the development of effective therapies. We developed a realistic in vivo bone metastasis model of human RCC by implanting precision-cut tissue slices under the renal capsule of immunodeficient mice. The presence of disseminated cells in bone marrow of tissue slice graft (TSG)-bearing mice was screened by human-specific polymerase chain reaction and confirmed by immunohistology using human-specific antibody. Disseminated tumor cells in bone marrow of TSG-bearing mice derived from three of seven RCC patients were detected as early as 1 month after tissue implantation at a high frequency with close resemblance to parent tumors (e.g., CAIX expression and high vascularity). The metastatic patterns of TSGs correlated with disease progression in patients. In addition, TSGs retained capacity to metastasize to bone at high frequency after serial passaging and cryopreservation. Moreover, bone metastases in mice responded to Temsirolimus treatment. Intratibial injections of single cells generated from TSGs showed 100 % engraftment and produced X-ray-visible tumors as early as 3 weeks after cancer cell inoculation. Micro-computed tomography (μCT) and histological analysis revealed osteolytic characteristics of these lesions. Our results demonstrated that orthotopic RCC TSGs have potential to develop bone metastases that respond to standard therapy. This first reported primary RCC bone metastasis model provides a realistic setting to test therapeutics to prevent or treat bone metastases in RCC.

  1. Human mandible bone defect repair by the grafting of dental pulp stem/progenitor cells and collagen sponge biocomplexes

    Directory of Open Access Journals (Sweden)

    R d’Aquino

    2009-11-01

    Full Text Available In this study we used a biocomplex constructed from dental pulp stem/progenitor cells (DPCs and a collagen sponge scaffold for oro-maxillo-facial (OMF bone tissue repair in patients requiring extraction of their third molars. The experiments were carried out according to our Internal Ethical Committee Guidelines and written informed consent was obtained from the patients. The patients presented with bilateral bone reabsorption of the alveolar ridge distal to the second molar secondary to impaction of the third molar on the cortical alveolar lamina, producing a defect without walls, of at least 1.5 cm in height. This clinical condition does not permit spontaneous bone repair after extraction of the third molar, and eventually leads to loss also of the adjacent second molar. Maxillary third molars were extracted first for DPC isolation and expansion. The cells were then seeded onto a collagen sponge scaffold and the obtained biocomplex was used to fill in the injury site left by extraction of the mandibular third molars. Three months after autologous DPC grafting, alveolar bone of patients had optimal vertical repair and complete restoration of periodontal tissue back to the second molars, as assessed by clinical probing and X-rays. Histological observations clearly demonstrated the complete regeneration of bone at the injury site. Optimal bone regeneration was evident one year after grafting. This clinical study demonstrates that a DPC/collagen sponge biocomplex can completely restore human mandible bone defects and indicates that this cell population could be used for the repair and/or regeneration of tissues and organs.

  2. Concave Pit-Containing Scaffold Surfaces Improve Stem Cell-Derived Osteoblast Performance and Lead to Significant Bone Tissue Formation

    Science.gov (United States)

    Cusella-De Angelis, Maria Gabriella; Laino, Gregorio; Piattelli, Adriano; Pacifici, Maurizio; De Rosa, Alfredo; Papaccio, Gianpaolo

    2007-01-01

    Background Scaffold surface features are thought to be important regulators of stem cell performance and endurance in tissue engineering applications, but details about these fundamental aspects of stem cell biology remain largely unclear. Methodology and Findings In the present study, smooth clinical-grade lactide-coglyolic acid 85:15 (PLGA) scaffolds were carved as membranes and treated with NMP (N-metil-pyrrolidone) to create controlled subtractive pits or microcavities. Scanning electron and confocal microscopy revealed that the NMP-treated membranes contained: (i) large microcavities of 80–120 µm in diameter and 40–100 µm in depth, which we termed primary; and (ii) smaller microcavities of 10–20 µm in diameter and 3–10 µm in depth located within the primary cavities, which we termed secondary. We asked whether a microcavity-rich scaffold had distinct bone-forming capabilities compared to a smooth one. To do so, mesenchymal stem cells derived from human dental pulp were seeded onto the two types of scaffold and monitored over time for cytoarchitectural characteristics, differentiation status and production of important factors, including bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF). We found that the microcavity-rich scaffold enhanced cell adhesion: the cells created intimate contact with secondary microcavities and were polarized. These cytological responses were not seen with the smooth-surface scaffold. Moreover, cells on the microcavity-rich scaffold released larger amounts of BMP-2 and VEGF into the culture medium and expressed higher alkaline phosphatase activity. When this type of scaffold was transplanted into rats, superior bone formation was elicited compared to cells seeded on the smooth scaffold. Conclusion In conclusion, surface microcavities appear to support a more vigorous osteogenic response of stem cells and should be used in the design of therapeutic substrates to improve bone repair and

  3. Mechanisms of cancer metastasis to the bone

    Institute of Scientific and Technical Information of China (English)

    Juan Juan YIN; Claire B. POLLOCK; Kathleen KELLY

    2005-01-01

    Some of the most common human cancers, including breast cancer, prostate cancer, and lung cancer, metastasize with avidity to bone. What is the basis for their preferential growth within the bone microenvironment? Bidirectional interactions between tumor cells and cells that make up bone result in a selective advantage for tumor growth and can lead to bone destruction or new bone matrix deposition. This review discusses our current understanding of the molecular components and mechanisms that are responsible for those interactions.

  4. Analysis of fatty acid composition in human bone marrow aspirates.

    Science.gov (United States)

    Deshimaru, Ryota; Ishitani, Ken; Makita, Kazuya; Horiguchi, Fumi; Nozawa, Shiro

    2005-09-01

    In the present study, the fatty acid composition of bone marrow aspirates and serum phospholipids in nine patients with hematologic diseases was investigated, and the effect of fatty acids on osteoblast differentiation in ST2 cells was examined. The concentrations of oleic acid and palmitic acid were significantly higher in bone marrow aspirates than in serum phospholipids, but the concentrations of other fatty acids did not differ. The rate of alkaline phosphatase positive ST2 cells induced by BMP2 was significantly increased by oleic acid, but was unaffected by the presence or absence of palmitic acid. We conclude that the fatty acid composition of bone marrow aspirates differs from that of serum phospholipids. This difference may affect osteoblast differentiation in the bone marrow microenvironment.

  5. Engineering bone tissue substitutes from human induced pluripotent stem cells

    National Research Council Canada - National Science Library

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

    2013-01-01

    ...) for bone tissue engineering. We first induced three hiPSC lines with different tissue and reprogramming backgrounds into the mesenchymal lineages and used a combination of differentiation assays, surface antigen profiling...

  6. INCIDENCE OF WORMIAN BONE IN HUMAN SKULLS IN RAJAST HAN

    Directory of Open Access Journals (Sweden)

    William F.

    2013-02-01

    Full Text Available ABSTRACT: Wormian bones are formations associated with insuff icient growth at suture closure and are regarded as epigenetic and hypostatic traits. There exists racial variation in its incidence. AIM : To find the incidence of wormian bone and compare with other study. MATERIAL AND METHOD : This was autopsy study on 150 dead bodies of both sexes of all age groups. RESULT - Incidence of wormian bone in Rajasthan was 4.7 % (4.1% in males & 3.6 % in females. This is comparable with study in other par t of India & abroad and it is in accordance with racial variation. CONCLUSION - knowledge of wormian bone is important to neuroanatomist, neurosurgeon, radiologist, anthropol ogist and morphologist

  7. First forensic records of termite activity on non-fossilized human bones in Brazil.

    Science.gov (United States)

    Queiroz, R A; Soriano, E P; Carvalho, M V D; Caldas-Junior, A F; Souza, E H A; Coelho-Junior, L G T M; Campello, R I C; Almeida, A C; Farias, R C A P; Vasconcellos, A

    2016-07-25

    The aim of this study was to describe the first records of termite activity on non-fossilized human bones in Brazil. The cases reported in this study resulted from forensic analysis of six human skeletons found in northeastern Brazil between 2012 and 2014. Traces of tunnels and nests commonly produced by termites were found on several human bone surfaces as well as the specimens and characteristic signs of osteophagic activity. In four cases, the species were identified: Amitermes amifer Silvestri, 1901, Nasutitermes corniger (Motschulsky, 1855) (on two skeletons), and Microcerotermes indistinctus Mathews, 1977. In two other cases, the activity of termites on bone surfaces was evidenced by remains of nests and tunnels produced by these insects. At least in the samples of human remains available for this report, the number of termites collected was greater on bones found during autumn, the rainy season in the Northeast of Brazil. The human bones examined showed termites like insects with lots of strength at bone degradation, capable of continuing the process of decomposition of human remains even in completely skeletonized bodies.

  8. First forensic records of termite activity on non-fossilized human bones in Brazil

    Directory of Open Access Journals (Sweden)

    R. A. Queiroz

    Full Text Available Abstract The aim of this study was to describe the first records of termite activity on non-fossilized human bones in Brazil. The cases reported in this study resulted from forensic analysis of six human skeletons found in northeastern Brazil between 2012 and 2014. Traces of tunnels and nests commonly produced by termites were found on several human bone surfaces as well as the specimens and characteristic signs of osteophagic activity. In four cases, the species were identified: Amitermes amifer Silvestri, 1901, Nasutitermes corniger (Motschulsky, 1855 (on two skeletons, and Microcerotermes indistinctus Mathews, 1977. In two other cases, the activity of termites on bone surfaces was evidenced by remains of nests and tunnels produced by these insects. At least in the samples of human remains available for this report, the number of termites collected was greater on bones found during autumn, the rainy season in the Northeast of Brazil. The human bones examined showed termites like insects with lots of strength at bone degradation, capable of continuing the process of decomposition of human remains even in completely skeletonized bodies.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

    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/μCT imaging. GSK-3 inhibitors caused β-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/μCT. 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

  10. Human Bone Matrix Changes During Deep Saturation Dives

    Science.gov (United States)

    2008-08-08

    agreement notwithstanding, much remains unknown about its pathogenesis, prevention, and treatment . DON is currently disqualifying for U.S. Navy divers...recourse for symptomatic treatment is surgical joint replacement.7 The principal mechanism of bone injury is generally accepted to be bubble formation...urine concentrations of Ntx have been demonstrated in bone diseases such as osteoporosis, primary hyperthyroidism , and Paget’s disease. Also

  11. Effect of bone block removal and patellar prosthesis on stresses in the human patella.

    Science.gov (United States)

    Friis, E A; Cooke, F W; McQueen, D A; Henning, C E

    1994-01-01

    Thermoelastic stress analysis was used to examine stresses on the anterior surface of patellae after patellar bone block excision for autogenous graft anterior cruciate ligament reconstruction. Complications of anterior cruciate ligament injury often lead to degenerative changes in the knee that can require total knee joint replacement. It was hypothesized that stresses in a bone block-compromised patella may be increased even further by insertion of a patellar prosthesis. All patellae were first tested intact and then were retested after a sequence of surgical modifications including patellar prosthesis implantation, tapered bone block excision, square bone block excision, and both shapes of excised bone blocks with a patellar prosthesis in place. Stresses in patellae with bone blocks excised were significantly greater than stresses in intact patellae. The anterior surface stress pattern in the loaded patella was significantly altered by excision of a bone block. There were no significant differences between maximum stress in patellae with tapered and square bone blocks excised. A finite element analysis showed that excision of a larger trapezoid-shaped bone block greatly increased maximum stress levels. Insertion of a patellar prosthesis did not significantly alter stress patterns or maximum stress levels in the patella.

  12. Lifestyle-determined gender and hierarchical differences in the lead contamination of bones from a feudal town of the Edo period.

    Science.gov (United States)

    Nakashima, Tamiji; Matsuno, Kohji; Matsushita, Takayuki

    2007-03-01

    We analyzed lead concentrations in bones from both genders of Japanese merchants (including rohnin; masterless samurai) and farmer classes, and compared the findings with those of the samurai class in the Edo period (1603-1867) to clarify gender and hierarchical (or occupational) differences in lead exposure during the Japanese feudal age. Merchant class females had significantly higher lead exposure (90.8 microg Pb/g dry bone; n=20) than males of the same class (39.9 microg Pb/g dry bone; n=31) (p<0.01), indicating a remarkable gender difference in the urban population. In contrast to these high concentrations, males and females of the farmer class living in agricultural (or semi-rural) areas had significantly lower exposure (total mean value; 9.2 mug Pb/g dry bone; n=4) than both genders of the merchant class (p<0.001), and the gender difference was not significant in this class.

  13. Influence of bone volume fraction and architecture on computed large-deformation failure mechanisms in human trabecular bone.

    Science.gov (United States)

    Bevill, Grant; Eswaran, Senthil K; Gupta, Atul; Papadopoulos, Panayiotis; Keaveny, Tony M

    2006-12-01

    Large-deformation bending and buckling have long been proposed as failure mechanisms by which the strength of trabecular bone can be affected disproportionately to changes in bone density, and thus may represent an important aspect of bone quality. We sought here to quantify the contribution of large-deformation failure mechanisms on strength, to determine the dependence of these effects on bone volume fraction and architecture, and to confirm that the inclusion of large-deformation effects in high-resolution finite element models improves predictions of strength versus experiment. Micro-CT-based finite element models having uniform hard tissue material properties were created from 54 cores of human trabecular bone taken from four anatomic sites (age = 70+/-11; 24 male, 27 female donors), which were subsequently biomechanically tested to failure. Strength predictions were made from the models first including, then excluding, large-deformation failure mechanisms, both for compressive and tensile load cases. As expected, strength predictions versus experimental data for the large-deformation finite element models were significantly improved (p deformation models in both tension and compression. Below a volume fraction of about 0.20, large-deformation failure mechanisms decreased trabecular strength from 5-80% for compressive loading, while effects were negligible above this volume fraction. Step-wise nonlinear multiple regression revealed that structure model index (SMI) and volume fraction (BV/TV) were significant predictors of these reductions in strength (R2 = 0.83, p deformation failure mechanisms on trabecular bone strength is highly heterogeneous and is not well explained by standard architectural metrics.

  14. Lead Exposure Induces Telomere Instability in Human Cells.

    Directory of Open Access Journals (Sweden)

    Géraldine Pottier

    Full Text Available Lead (Pb is an important environmental contaminant due to its widespread use over many centuries. While it affects primarily every organ system of the body, the most pernicious effects of Pb are on the central nervous system leading to cognitive and behavioral modification. Despite decades of research, the mechanisms responsible for Pb toxicity remain poorly understood. Recent work has suggested that Pb exposure may have consequences on chromosomal integrity as it was shown that Pb exposure leads to the generation of γH2Ax foci, a well-established biomarker for DNA double stranded break (DSB formation. As the chromosomal localization of γH2Ax foci plays an important role in determining the molecular mechanism responsible for their formation, we examined the localization of Pb-induced foci with respect to telomeres. Indeed, short or dysfunctional telomeres (uncapped or damaged telomeres may be recognized as DSB by the DNA repair machinery, leading to "telomere-Induced Foci" (TIFs. In the current study, we show that while Pb exposure did not increase intra-chromosomal foci, it significantly induced TIFs, leading in some cases, to chromosomal abnormalities including telomere loss. The evidence suggests that these chromosomal abnormalities are likely due to perturbation of telomere replication, in particular on the lagging DNA strand. We propose a mechanism by which Pb exposure leads to the loss of telomere maintenance. As numerous studies have demonstrated a role for telomere maintenance in brain development and tissue homeostasis, our results suggest a possible mechanism for lead-induced neurotoxicity.

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

    Science.gov (United States)

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

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P 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 bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

  16. Early reversal cells in adult human bone remodeling: osteoblastic nature, catabolic functions and interactions with osteoclasts.

    Science.gov (United States)

    Abdelgawad, Mohamed Essameldin; Delaisse, Jean-Marie; Hinge, Maja; Jensen, Pia Rosgaard; Alnaimi, Ragad Walid; Rolighed, Lars; Engelholm, Lars H; Marcussen, Niels; Andersen, Thomas Levin

    2016-06-01

    The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter of debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts. Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone through electron microscopy and analysis of molecular markers. Periosteoclastic reversal cells show direct contacts with the osteoclasts and with the demineralized resorption debris. These early reversal cells show (1) ¾-collagen fragments typically generated by extracellular collagenases of the MMP family, (2) MMP-13 (collagenase-3) and (3) the endocytic collagen receptor uPARAP/Endo180. The prevalence of these markers was lower in the later reversal cells, which are located near the osteoid surfaces and morphologically resemble mature bone-forming osteoblasts. In conclusion, this study demonstrates that reversal cells colonizing bone surfaces right after resorption are osteoblast-lineage cells, and extends to adult human bone remodeling their role in rendering eroded surfaces osteogenic.

  17. Lead poisoning in China: a health and human rights crisis.

    Science.gov (United States)

    Cohen, Jane E; Amon, Joseph J

    2012-12-15

    Acute and chronic lead poisoning is occurring throughout China and is a major cause of childhood morbidity. The Chinese government's emphasis on industrial development and poverty reduction has, over the past three decades, decreased by 500 million the number of people surviving on less than one dollar per day, but has caused significant environmental degradation that threatens public health. Drawing upon in-depth interviews conducted in 2009 and 2010 with families affected by lead poisoning, environmental activists, journalists, government and civil society organization officials in Shaanxi, Henan, Hunan, and Yunnan provinces, as well as a review of scientific and Chinese media, and health and environmental legal and policy analysis, we examine the intersection of civil, political, economic, and social rights related to access to information, screening, treatment, and remediation related to lead poisoning. In-depth interviews in each province uncovered: censorship and intimidation of journalists, environmental activists, and parents seeking information about sources and prevention of lead poisoning; denial of screening for lead poisoning, often based upon arbitrary eligibility criteria; and inadequate and inappropriate treatment being promoted and provided by health facilities. Over the past decade, the Chinese government has prioritized health care and invested billions of dollars towards universal health coverage, and strengthened environmental to address industrial pollution and guarantee access to information on the environment. Yet, despite these reforms, information remains constrained and citizens seeking information and redress are sometimes arrested, in violation of Chinese and international law. Local government officials and national environmental policies continue to prioritize economic development over environmental protection. To effectively address lead poisoning requires an emphasis on prevention, and to combat industrial pollution requires

  18. Living with cracks: Damage and repair in human bone

    Science.gov (United States)

    Taylor, David; Hazenberg, Jan G.; Lee, T. Clive

    2007-04-01

    Our bones are full of cracks, which form and grow as a result of daily loading activities. Bone is the major structural material in our bodies. Although weaker than many engineering materials, it has one trick that keeps it ahead - it can repair itself. Small cracks, which grow under cyclic stresses by the mechanism of fatigue, can be detected and removed before they become long enough to be dangerous. This article reviews the work that has been done to understand how cracks form and grow in bone, and how they can be detected and repaired in a timely manner. This is truly an interdisciplinary research field, requiring the close cooperation of materials scientists, biologists and engineers.

  19. Use of recombinant human bone morphogenetic protein-2 with local bone graft instead of iliac crest bone graft in posterolateral lumbar spine arthrodesis.

    Science.gov (United States)

    Park, Daniel K; Kim, Sung S; Thakur, Nikhil; Boden, Scott D

    2013-05-20

    Prospective clinical study. Compare fusion rates between recombinant human bone morphogenetic protein-2 (rhBMP-2) and iliac crest bone graft (ICBG) with rhBMP-2 and local bone graft (LBG) (±bone graft extenders) in posterolateral fusion. Previous reports have shown higher fusion rates when adding rhBMP-2 to ICBG in lumbar posterolateral fusion, compared with ICBG alone. We compared the fusion success rates between rhBMP-2 delivered with ICBG versus that with LBG. Fusion rates were compared in patients with degenerative spondylolisthesis (1-2 levels) with accompanying lumbar stenosis. RhBMP-2 (INFUSE, Medtronic) was delivered on an absorbable collagen sponge (6 mg/side at 1.5 mg/mL) with ICBG alone or with LBG wrapped inside the sponge. Thin slice computed tomographic scans were assessed at 6, 12, and 24 months. In a consecutive series, 16 patients (30 levels) received ICBG with rhBMP-2 and 35 patients (49 levels) received LBG with rhBMP-2. For the ICBG cohort, 80.0%, 93.4%, 96.7% of levels were fused at 6, 12, and 24 months. In contrast, for the local bone with rhBMP-2 cohort, 87.7%, 98.0%, and 98.0% were fused at 6, 12, and 24 months. There was no statistically significant difference in fusion success rates between the 2 groups at any time point. As for fusion quality, the fusion mass showed superior quality in ICBG group than in the local bone group at each time point. This study validates the high fusion success rates previously reported by adding rhBMP-2 to ICBG and shows that local bone may be safely substituted for ICBG in 1- to 2-level posterolateral fusion. The fusion rates were comparable. The avoidance of ICBG harvest has implications for operative time, blood loss, and morbidity. Lastly, this is the first study that directly compares the fusion success rate and quality using local bone with rhBMP-2 versus ICBG with rhBMP-2 at various times. 4.

  20. Beyond the functional matrix hypothesis: a network null model of human skull growth for the formation of bone articulations.

    Science.gov (United States)

    Esteve-Altava, Borja; Rasskin-Gutman, Diego

    2014-09-01

    Craniofacial sutures and synchondroses form the boundaries among bones in the human skull, providing functional, developmental and evolutionary information. Bone articulations in the skull arise due to interactions between genetic regulatory mechanisms and epigenetic factors such as functional matrices (soft tissues and cranial cavities), which mediate bone growth. These matrices are largely acknowledged for their influence on shaping the bones of the skull; however, it is not fully understood to what extent functional matrices mediate the formation of bone articulations. Aiming to identify whether or not functional matrices are key developmental factors guiding the formation of bone articulations, we have built a network null model of the skull that simulates unconstrained bone growth. This null model predicts bone articulations that arise due to a process of bone growth that is uniform in rate, direction and timing. By comparing predicted articulations with the actual bone articulations of the human skull, we have identified which boundaries specifically need the presence of functional matrices for their formation. We show that functional matrices are necessary to connect facial bones, whereas an unconstrained bone growth is sufficient to connect non-facial bones. This finding challenges the role of the brain in the formation of boundaries between bones in the braincase without neglecting its effect on skull shape. Ultimately, our null model suggests where to look for modified developmental mechanisms promoting changes in bone growth patterns that could affect the development and evolution of the head skeleton. © 2014 Anatomical Society.

  1. Assessment of lead ecotoxicity in water using the amphibian larvae (Xenopus laevis) and preliminary study of its immobilization in meat and bone meal combustion residues.

    Science.gov (United States)

    Mouchet, F; Cren, S; Cunienq, C; Deydier, E; Guilet, R; Gauthier, L

    2007-04-01

    Lead (Pb) is a major chemical pollutant of the environment. It has been associated with human activities for the last 6000 years. Quite rightly, it remains a public health concern today. The present investigation evaluates the toxic potential of Pb in larvae of the toad Xenopus laevis after 12 days exposure in lab conditions. Acute toxicity, genotoxicity and Pb bioaccumulation were analyzed. The genotoxic effects were analyzed in the circulating blood from the levels of micronucleus induction according to the French standard micronucleus assay (AFNOR 2000 Association française de normalization. Norme NFT 90-325. Qualité de l'Eau. Evaluation de la génotoxicité au moyen de larves d'amphibien (Xenopus laevis, Pleurodeles waltl)). Lead bioaccumulation was analyzed in the liver of larvae at the end of exposure. Moreover, the toxic potential of lead, in aquatic media, was investigated in the presence of meat and bone meal combustion residues (MBMCR) known to be rich in phosphates and a potential immobiliser of lead. Previously, acute toxicity and genotoxicity of MBMCR alone were evaluated using Xenopus larvae. The results obtained in the present study demonstrated: (i) that lead is acutely toxic and genotoxic to amphibian larvae from 1 mg Pb/l and its bioaccumulation is significant in the liver of larvae from the lowest concentration of exposure (1 microg Pb/l), (ii) MBMCR were not acutely toxic nor genotoxic in Xenopus larvae, (iii) lead in presence of MBMCR induced inhibition or reduction of the toxic and genotoxic potential of lead in water at concentrations that do not exceed the capacity of MBMCR of Pb-binding (iv) Pb accumulation in larvae exposed to lead with MBMCR in water was lower than Pb-accumulation in larvae exposed to lead alone except at the concentration of 0.01 mg Pb/l suggesting complex mechanisms of MBMCR interaction in organisms. The results confirm the high toxicity and genotoxicity of lead in the aquatic compartment and suggest the potential

  2. Delayed loss of hearing after hearing preservation cochlear implantation: Human temporal bone pathology and implications for etiology.

    Science.gov (United States)

    Quesnel, Alicia M; Nakajima, Hideko Heidi; Rosowski, John J; Hansen, Marlan R; Gantz, Bruce J; Nadol, Joseph B

    2016-03-01

    After initially successful preservation of residual hearing with cochlear implantation, some patients experience subsequent delayed hearing loss. The etiology of such delayed hearing loss is unknown. Human temporal bone pathology is critically important in investigating the etiology, and directing future efforts to maximize long term hearing preservation in cochlear implant patients. Here we present the temporal bone pathology from a patient implanted during life with an Iowa/Nucleus Hybrid S8 implant, with initially preserved residual hearing and subsequent hearing loss. Both temporal bones were removed for histologic processing and evaluated. Complete clinical and audiologic records were available. He had bilateral symmetric high frequency severe to profound hearing loss prior to implantation. Since he was implanted unilaterally, the unimplanted ear was presumed to be representative of the pre-implantation pathology related to his hearing loss. The implanted and contralateral unimplanted temporal bones both showed complete degeneration of inner hair cells and outer hair cells in the basal half of the cochleae, and only mild patchy loss of inner hair cells and outer hair cells in the apical half. The total spiral ganglion neuron counts were similar in both ears: 15,138 (56% of normal for age) in the unimplanted right ear and 13,722 (51% of normal for age) in the implanted left ear. In the basal turn of the implanted left cochlea, loose fibrous tissue and new bone formation filled the scala tympani, and part of the scala vestibuli. Delayed loss of initially preserved hearing after cochlear implantation was not explained by additional post-implantation degeneration of hair cells or spiral ganglion neurons in this patient. Decreased compliance at the round window and increased damping in the scala tympani due to intracochlear fibrosis and new bone formation might explain part of the post-implantation hearing loss. Reduction of the inflammatory and immune response to

  3. Touch five factors to growing and leading a human organization

    CERN Document Server

    Maffin, Tod

    2014-01-01

    For better or worse, digital business has fundamentally changed how organizations hire, market their services, and connect with stakeholders. The problem is, in an effort to use technology to connect more effectively, we have lost the humanity - that critical person-to-person connection. This book will show you how to restore that connection.

  4. Assessment of chemical species of lead accumulated in tidemarks of human articular cartilage by X-ray absorption near-edge structure analysis

    Energy Technology Data Exchange (ETDEWEB)

    Meirer, Florian [Atominstitut, Vienna University of Technology, 1020 Wien (Austria); MiNALab, CMM-Irst, Fondazione Bruno Kessler, Via Sommarive 18, 38123 Trento (Italy); Pemmer, Bernhard, E-mail: bpemmer@ati.ac.at [Atominstitut, Vienna University of Technology, 1020 Wien (Austria); Pepponi, Giancarlo [MiNALab, CMM-Irst, Fondazione Bruno Kessler, Via Sommarive 18, 38123 Trento (Italy); Zoeger, Norbert; Wobrauschek, Peter [Atominstitut, Vienna University of Technology, 1020 Wien (Austria); Sprio, Simone; Tampieri, Anna [Istituto di Scienza e Tecnologia dei Materiali Ceramici CNR, Faenca (Italy); Goettlicher, Joerg; Steininger, Ralph; Mangold, Stefan [Institute for Synchrotron Radiation, Karlsruhe Institute of Technology, Campus South, 76344 Eggenstein-Leopoldshafen (Germany); Roschger, Paul [Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 4th Medical Department, Hanusch Hospital, Vienna (Austria); Berzlanovich, Andrea [Department of Forensic Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Hofstaetter, Jochen G. [Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 4th Medical Department, Hanusch Hospital, Vienna (Austria); Department of Orthopaedics, Vienna General Hospital, Medical University of Vienna, A-1090 Vienna (Austria); Streli, Christina [Atominstitut, Vienna University of Technology, 1020 Wien (Austria)

    2011-03-01

    Lead is a toxic trace element that shows a highly specific accumulation in the transition zone between calcified and non-calcified articular cartilage, the so-called ‘tidemark’. Excellent agreement has been found between XANES spectra of synthetic Pb-doped carbonated hydroxyapatite and spectra obtained in the tidemark region and trabecular bone of normal human samples, confirming that in both tissues Pb is incorporated into the hydroxyapatite crystal structure of bone. During this study the µ-XANES set-up at the SUL-X beamline at ANKA was tested and has proven to be well suited for speciation of lead in human mineralized tissue samples. A highly specific accumulation of the toxic element lead was recently measured in the transition zone between non-calcified and calcified normal human articular cartilage. This transition zone, the so-called ‘tidemark’, is considered to be an active calcification front of great clinical importance. However, little is known about the mechanisms of accumulation and the chemical form of Pb in calcified cartilage and bone. Using spatially resolved X-ray absorption near-edge structure analysis (µ-XANES) at the Pb L{sub 3}-edge, the chemical state of Pb in the osteochondral region was investigated. The feasibility of the µ-XANES set-up at the SUL-X beamline (ANKA synchrotron light source) was tested and confirmed by comparing XANES spectra of bulk Pb-reference compounds recorded at both the XAS and the SUL-X beamline at ANKA. The µ-XANES set-up was then used to investigate the tidemark region of human bone (two patella samples and one femoral head sample). The spectra recorded at the tidemark and at the trabecular bone were found to be highly correlated with the spectra of synthetic Pb-doped carbonated hydroxyapatite, suggesting that in both of these very different tissues Pb is incorporated into the hydroxyapatite structure.

  5. Glucose-dependent insulinotropic polypeptide inhibits bone resorption in humans

    DEFF Research Database (Denmark)

    Nissen, Anne; Christensen, Mikkel; Knop, Filip K

    2014-01-01

    -minute glucose clamps with co-infusion of GIP (4 pmol/kg/min for 15 min, followed by 2 pmol/kg/min for 45 min) or placebo. The samples were analyzed for concentrations of degradation products of C-terminal telopeptide of type I collagen (CTX), a bone resorption marker. RESULTS regarding effects...

  6. Human bone-marrow-derived mesenchymal stem cells

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Abdallah, Basem M

    2008-01-01

    Mesenchymal stem cells (MSC) are a group of cells present in bone-marrow stroma and the stroma of various organs with the capacity for mesoderm-like cell differentiation into, for example, osteoblasts, adipocytes, and chondrocytes. MSC are being introduced in the clinic for the treatment...

  7. Trabecular bone histomorphometry in humans with Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Armas, Laura A G; Akhter, Mohammed P; Drincic, Andjela; Recker, Robert R

    2012-01-01

    Patients with Type 1 Diabetes Mellitus (DM) have markedly increased risk of fracture, but little is known about abnormalities in bone microarchitecture or remodeling properties that might give insight into the pathogenesis of skeletal fragility in these patients. We report here a case-control study comparing bone histomorphometric and micro-CT results from iliac biopsies in 18 otherwise healthy subjects with Type 1 Diabetes Mellitus with those from healthy age- and sex-matched non-diabetic control subjects. Five of the diabetics had histories of low-trauma fracture. Transilial bone biopsies were obtained after tetracycline labeling. The biopsy specimens were fixed, embedded, and scanned using a desktop μCT at 16 μm resolution. They were then sectioned and quantitative histomorphometry was performed as previously described by Recker et al. [1]. Two sections, >250 μm apart, were read from the central part of each biopsy. Overall there were no significant differences between diabetics and controls in histomorphometric or micro-CT measurements. However, fracturing diabetics had structural and dynamic trends different from nonfracturing diabetics by both methods of analysis. In conclusion, Type 1 Diabetes Mellitus does not result in abnormalities in bone histomorphometric or micro-CT variables in the absence of manifest complications from the diabetes. However, diabetics suffering fractures may have defects in their skeletal microarchitecture that may underlie the presence of excess skeletal fragility.

  8. Bone mineral measurement, experiment M078. [space flight effects on human bone composition

    Science.gov (United States)

    Rambaut, P. C.; Vogel, J. M.; Ullmann, J.; Brown, S.; Kolb, F., III

    1973-01-01

    Measurement tests revealed few deviations from baseline bone mineral measurements after 56 days in a Skylab-type environment. No mineral change was observed in the right radius. One individual, however, showed a possible mineral loss in the left os calcis and another gained mineral in the right ulna. The cause of the gain is unclear but may be attributable to the heavy exercise routines engaged in by the crewmember in question. Equipment problems were identified during the experiment and rectified.

  9. Late Adherent Human Bone Marrow Stromal Cells Form Bone and Restore the Hematopoietic Microenvironment In Vivo

    Directory of Open Access Journals (Sweden)

    Verônica Fernandes Vianna

    2013-01-01

    Full Text Available Bone marrow stromal cells (BMSCs are a valuable resource for skeletal regenerative medicine because of their osteogenic potential. In spite of the very general term “stem cell,” this population of cells is far from homogeneous, and different BMSCs clones have greatly different phenotypic properties and, therefore, potentially different therapeutic potential. Adherence to a culture flask surface is a primary defining characteristic of BMSCs. We hypothesized that based on the adherence time we could obtain an enriched population of cells with a greater therapeutic potential. We characterized two populations of bone marrow-derived cells, those that adhered by three days (R-cells and those that did not adhere by three days but did by six days (L-cells. Clones derived from L-cells could be induced into adipogenic, chondrogenic, and osteogenic differentiation in vitro. L-cells appeared to have greater proliferative capacity, as manifested by larger colony diameter and clones with higher CD146 expression. Only clones from L-cells developed bone marrow stroma in vivo. We conclude that the use of late adherence of BMSCs is one parameter that can be used to enrich for cells that will constitute a superior final product for cell therapy in orthopedics.

  10. Identification of molecular markers related to human alveolar bone cells and pathway analysis in diabetic patients.

    Science.gov (United States)

    Sun, X; Ren, Q H; Bai, L; Feng, Q

    2015-10-28

    Alveolar bone osteoblasts are widely used in dental and related research. They are easily affected by systemic diseases such as diabetes. However, the mechanism of diabetes-induced alveolar bone absorption remains unclear. This study systematically explored the changes in human alveolar bone cell-related gene expression and biological pathways, which may facilitate the investigation of its mechanism. Alveolar bone osteoblasts isolated from 5 male diabetics and 5 male healthy adults were cultured. Total RNA was extracted from these cells and subjected to gene microarray analysis. Differentially expressed genes were screened, and a gene interaction network was constructed. An enrichment pathway analysis was simultaneously performed on differentially expressed genes to identify the biological pathways associated with changes in the alveolar bone cells of diabetic humans. In total, we identified 147 mRNAs that were differentially expressed in diabetic alveolar bone cells (than in the normal cells; 91 upregulated and 36 downregulated mRNAs). The constructed co-expression network showed 3 pairs of significantly-expressed genes. High-enrichment pathway analysis identified 8 pathways that were affected by changes in gene expression; three of the significant pathways were related to metabolism (inositol phosphate metabolism, propanoate metabolism, and pyruvate metabolism). Here, we identified a few potential genes and biological pathways for the diagnosis and treatment of alveolar bone cells in diabetic patients.

  11. Clinical Application of Human Mesenchymal Stromal Cells for Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Anindita Chatterjea

    2010-01-01

    Full Text Available The gold standard in the repair of bony defects is autologous bone grafting, even though it has drawbacks in terms of availability and morbidity at the harvesting site. Bone-tissue engineering, in which osteogenic cells and scaffolds are combined, is considered as a potential bone graft substitute strategy. Proof-of-principle for bone tissue engineering using mesenchymal stromal cells (MSCs has been demonstrated in various animal models. In addition, 7 human clinical studies have so far been conducted. Because the experimental design and evaluation parameters of the studies are rather heterogeneous, it is difficult to draw conclusive evidence on the performance of one approach over the other. However, it seems that bone apposition by the grafted MSCs in these studies is observed but not sufficient to bridge large bone defects. In this paper, we discuss the published human clinical studies performed so far for bone-tissue regeneration, using culture-expanded, nongenetically modified MSCs from various sources and extract from it points of consideration for future clinical studies.

  12. Local origins impart conserved bone type-related differences in human osteoblast behaviour.

    Science.gov (United States)

    Shah, M; Gburcik, V; Reilly, P; Sankey, R A; Emery, R J; Clarkin, C E; Pitsillides, A A

    2015-03-04

    Osteogenic behaviour of osteoblasts from trabecular, cortical and subchondral bone were examined to determine any bone type-selective differences in samples from both osteoarthritic (OA) and osteoporotic (OP) patients. Cell growth, differentiation; alkaline phosphatase (TNAP) mRNA and activity, Runt-related transcription factor-2 (RUNX2), SP7-transcription factor (SP7), bone sialoprotein-II (BSP-II), osteocalcin/bone gamma-carboxyglutamate (BGLAP), osteoprotegerin (OPG, TNFRSF11B), receptor activator of nuclear factor-κβ ligand (RANKL, TNFSF11) mRNA levels and proangiogenic vascular endothelial growth factor-A (VEGF-A) mRNA and protein release were assessed in osteoblasts from paired humeral head samples from age-matched, human OA/OP (n = 5/4) patients. Initial outgrowth and increase in cell number were significantly faster (p origins in OA and trabecular origins in OP. We found virtually identical bone type-related differences, however, in TNFRSF11B:TNFSF11 in OA and OP, consistent with greater potential for paracrine effects on osteoclasts in trabecular osteoblasts. Subchondral osteoblasts (OA) exhibited highest VEGF-A mRNA levels and release. Our data indicate that human osteoblasts in trabecular, subchondral and cortical bone have inherent, programmed diversity, with specific bone type-related differences in growth, differentiation and pro-angiogenic potential in vitro.

  13. Gene Expression Changes in Femoral Head Necrosis of Human Bone Tissue

    Directory of Open Access Journals (Sweden)

    Bernadett Balla

    2011-01-01

    Full Text Available Osteonecrosis of the femoral head (ONFH is the result of an interruption of the local circulation and the injury of vascular supply of bone. Multiple factors have been implicated in the development of the disease. However the mechanism of ischemia and necrosis in non-traumatic ONFH is not clear. The aim of our investigation was to identify genes that are differently expressed in ONFH vs. non-ONFH human bone and to describe the relationships between these genes using multivariate data analysis. Six bone tissue samples from ONFH male patients and 8 bone tissue samples from non-ONFH men were examined. The expression differences of selected 117 genes were analyzed by TaqMan probe-based quantitative real-time RT-PCR system. The significance test indicated marked differences in the expression of nine genes between ONFH and non-ONFH individuals. These altered genes code for collagen molecules, an extracellular matrix digesting metalloproteinase, a transcription factor, an adhesion molecule, and a growth factor. Canonical variates analysis demonstrated that ONFH and non-ONFH bone tissues can be distinguished by the multiple expression profile analysis of numerous genes controlled via canonical TGFB pathway as well as genes coding for extracellular matrix composing collagen type molecules. The markedly altered gene expression profile observed in the ONFH of human bone tissue may provide further insight into the pathogenetic process of osteonecrotic degeneration of bone.

  14. Fusion events lead to truncation of FOS in epithelioid hemangioma of bone

    DEFF Research Database (Denmark)

    van IJzendoorn, David G P; de Jong, Danielle; Romagosa, Cleofe;

    2015-01-01

    . COBRA-FISH karyotyping identified a balanced t(3;14) translocation. Transcriptome sequencing of the index case and two other epithelioid hemangiomas revealed a recurrent translocation breakpoint involving the FOS gene, which was fused to different partners in all three cases. The break was observed...... in exon 4 of the FOS gene and the fusion event led to the introduction of a stop codon. In all instances, the truncation of the FOS gene would result in the loss of the transactivation domain (TAD). Using FISH probes we found a break in the FOS gene in two additional cases, in none of these cases...... a recurrent fusion partner could be identified. In total, FOS was split in 5/7 evaluable samples. We did not observe point mutations leading to early stop codons in any of the 10 cases where RNA was available. Detection of FOS rearrangement may be a useful diagnostic tool to assist in the often difficult...

  15. Morphological Characterization of the Frontal and Parietal Bones of the Human Skull

    Science.gov (United States)

    2017-03-01

    frozen, male postmortem human subject (PMHS) donors aged 76–86 yrs. The skulls did not have a history of musculoskeletal diseases nor did they...to 17 as assessed by computed tomography. European J of Plastic Surgery. 2015;38(3):193–198. Hubbard RP. Flexure of layered cranial bone. J of...changes with age and sex from computed tomography scans. J of Bone and Mineral Research. 2016;31(2):299–307. Approved for public release

  16. Unique micro- and nano-scale mineralization pattern of human osteogenesis imperfecta type VI bone.

    Science.gov (United States)

    Fratzl-Zelman, Nadja; Schmidt, Ingo; Roschger, Paul; Roschger, Andreas; Glorieux, Francis H; Klaushofer, Klaus; Wagermaier, Wolfgang; Rauch, Frank; Fratzl, Peter

    2015-04-01

    Osteogenesis imperfecta (OI) is a heterogeneous group of inheritable connective tissue disorders characterized by mutation in genes involved in collagen synthesis and leading to increased bone fragility, low bone mass, impaired bone material properties and abnormally high bone matrix mineralization. Recessive OI type VI is caused by mutation in SERPINF1 leading to a loss-of-function of pigment epithelium-derived factor (PEDF) a collagen-binding protein with potent antiangiogenic activity. Affected patients develop a severe OI phenotype with a striking histological characteristic, rare in other OI types, of an excess of osteoid tissue and prolonged mineralization lag time. To get insights into matrix mineralization, we evaluated biopsies from 9 affected children by quantitative and by high-resolution backscattered electron imaging and assessed bone mineralization density distribution. Thickness, shape and arrangement of mineral particles were measured in a subset of 4 patients by synchrotron small angle X-ray scattering. Typical calcium content in the bone matrix was found to be increased compared to controls, even exceeding values found previously in OI patients with collagen-gene mutations. A main characteristic however, is the coexistence of this highly mineralized bone matrix with seams showing abnormally low mineral content. Atypical collagen fibril organization was found in the perilacunar region of young osteocytes, suggesting a disturbance in the early steps of mineralization. These observations are consistent with the presence of a heterogeneous population of mineral particles with unusual size, shape and arrangement, especially in the region with lower mineral content. The majority of the particles in the highly mineralized bone areas were less disorganized, but smaller and more densely packed than in controls and in previously measured OI patients. These data suggest that the lack of PEDF impairs a proper osteoblast-osteocyte transition and consequently

  17. IFITM1 increases osteogenesis through Runx2 in human alveolar-derived bone marrow stromal cells.

    Science.gov (United States)

    Kim, Beom-Su; Kim, Hyung-Jin; Kim, Jin Seong; You, Yong-Ouk; Zadeh, Homa; Shin, Hong-In; Lee, Seung-Jin; Park, Yoon-Jeong; Takata, Takashi; Pi, Sung-Hee; Lee, Jun; You, Hyung-Keun

    2012-09-01

    The exact molecular mechanisms governing the differentiation of bone marrow stromal stem/progenitor cells (BMSCs) into osteoblasts remain largely unknown. In this study, a highly expressed protein that had a high degree of homology with interferon-induced transmembrane protein 1 (IFITM1) was identified using differentially expressed gene (DEG) screening. We sought to determine whether IFITM1 influenced osteoblast differentiation. During differentiation, IFITM1 expression gradually increased from 5 to 10days and subsequently decreased at 15 days in culture. Analysis of IFITM1 protein expression in several cell lines as well as in situ studies on human tissues revealed its selective expression in bone cells and human bone. Proliferation of human alveolar-derived bone marrow stromal cells (hAD-BMSCs) was significantly inhibited by IFITM1 knockdown by using short hairpin RNA, as were bone specific markers such as alkaline phosphatase, collagen type I α 1, bone sialoprotein, osteocalcin, and osterix were decreased. Calcium accumulation also decreased following IFITM1 knockdown. Moreover, IFITM1 knockdown in hAD-BMSCs was associated with inhibition of Runx2 mRNA and protein expression. Collectively, the present data provide evidence for the role of IFITM1 in osteoblast differentiation. The exact mechanisms of IFITM1's involvement in osteoblast differentiation are still under investigation.

  18. Human maxillary sinus floor elevation as a model for bone regeneration enabling the application of one-step surgical procedures

    NARCIS (Netherlands)

    Farre-Guasch, E.; Prins, H.J.; Overman, J.R.; ten Bruggenkate, C.M.; Schulten, E.A.J.M.; Helder, M.N.; Klein-Nulend, J.

    2013-01-01

    Bone loss in the oral and maxillofacial region caused by trauma, tumors, congenital disorders, or degenerative diseases is a health care problem worldwide. To restore (reconstruct) these bone defects, human or animal bone grafts or alloplastic (synthetic) materials have been used. However, several d

  19. Total lymphatic irradiation and bone marrow in human heart transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

    1984-08-01

    Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem.

  20. Thermal Conductivity of Human Bone in Cryoprobe Freezing as Related to Density.

    Science.gov (United States)

    Walker, Kyle E; Baldini, Todd; Lindeque, Bennie G

    2016-12-09

    Cryoprobes create localized cell destruction through freezing. Bone is resistant to temperature flow but is susceptible to freezing necrosis at warmer temperatures than tumor cells. Few studies have determined the thermal conductivity of human bone. No studies have examined conductivity as related to density. The study goal was to examine thermal conductivity in human bone while comparing differences between cancellous and cortical bone. An additional goal was to establish a relationship between bone density and thermal conductivity. Six knee joints from 5 cadavers were obtained. The epiphyseal region was sliced in half coronally prior to inserting an argon-circulating cryoprobe directed away from the joint line. Thermistor thermometers were placed perpendicularly at measured increments, and the freezing cycle was recorded until steady-state conditions were achieved. For 2 cortical samples, the probe was placed intramedullary in metaphyseal samples and measurements were performed radially from the central axis of each sample. Conductivity was calculated using Fournier's Law and then plotted against measured density of each sample. Across samples, density of cancellous bone ranged from 0.86 to 1.38 g/mL and average thermal conductivity ranged between 0.404 and 0.55 W/mK. Comparatively, cortical bone had a density of 1.70 to 1.86 g/mL and thermal conductivity of 0.0742 to 0.109 W/mK. A strong 2-degree polynomial correlation was seen (R(2)=0.8226, P<.001). Bone is highly resistant to temperature flow. This resistance varies and inversely correlates strongly with density. This information is clinically relevant to maximize tumor ablation while minimizing morbidity through unnecessary bone loss and damage to surrounding structures. [Orthopedics. 201x; xx(x):xx-xx.].

  1. The relationship between the mechanical anisotropy of human cortical bone tissue and its microstructure

    Science.gov (United States)

    Espinoza Orias, Alejandro A.

    Orthopedics research has made significant advances in the areas of biomechanics, bone implants and bone substitute materials. However, to date there is no definitive model to explain the structure-property relationships in bone as a material to enable better implant designs or to develop a true biomechanical analog of bone. The objective of this investigation was to establish a relationship between the elastic anisotropy of cortical bone tissue and its microstructure. Ultrasonic wave propagation was used to measure stiffness coefficients for specimens sectioned along the length of a human femur. The elastic constants were orthotropic and varied with anatomical location. Stiffness coefficients were generally largest at the midshaft and stiffness anisotropy ratios were largest at the distal and proximal ends. These tests were run on four additional human femurs to assess the influence of phenotypic variation, and in most cases, it was found that phenotypes do not exert a significant effect. Stiffness coefficients were shown to be correlated as a power law relation to apparent density, but anisotropy ratios were not. Texture analysis was performed on selected samples to measure the orientation distribution of the bone mineral crystals. Inverse pole figures showed that bone mineral crystals had a preferred crystallographic orientation, coincident with the long axis of the femur, which is its principal loading direction. The degree of preferred orientation was represented in Multiples of a Random Distribution (MRD), and correlated to the anisotropy ratios. Variation in elastic anisotropy was shown to be primarily due to the bone mineral orientation. The results found in this work can be used to incorporate anisotropy into structural analysis for bone as a material.

  2. Targeted regeneration of bone in the osteoporotic human femur.

    Directory of Open Access Journals (Sweden)

    Kenneth E S Poole

    Full Text Available We have recently developed image processing techniques for measuring the cortical thicknesses of skeletal structures in vivo, with resolution surpassing that of the underlying computed tomography system. The resulting thickness maps can be analysed across cohorts by statistical parametric mapping. Applying these methods to the proximal femurs of osteoporotic women, we discover targeted and apparently synergistic effects of pharmaceutical osteoporosis therapy and habitual mechanical load in enhancing bone thickness.

  3. Characterization of a Composite Material to Mimic Human Cranial Bone

    Science.gov (United States)

    2015-09-01

    a general population. These file formats can be sent directly to additive manufacturing machines , generically referred to as 3-D printers, to...Illustration of the SLA additive manufacturing process. The SLA machine used in this study to manufacture specimens was a Viper Si (3D Systems, Rock...architectures while possessing physical and mechanical characteristics similar to that of bone. We are utilizing additive manufacturing , more generally

  4. Late effects on human bone marrow after extended field radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Parmentier, C.; Morardet, N.; Tubiana, M.

    1983-09-01

    Thirty-two patients with lymphoma were treated by extended radiotherapy (RT) at a dose of 40 Gy and were studied by ferrokinetic studies and surface counting at various times following irradiation. Loss of hematopoietic activity in the irradiated areas is compensated by increased activity in the non-irradiated areas. Despite the return of peripheral blood counts to normal, the hyperactivity of the non-irradiated bone marrow persists over up to 13 years after RT, while the hematopoietic activity of the irradiated areas remains depressed and is only slightly higher than immediately after RT. The hypoactivity persisted even when the hemopoietic tissues had been subjected to the intense stimulation provoked by an aplasia caused by chemotherapy. However, a recovery was observed for dose of 20 Gy or lower. The hemopoietic activity of the irradiated bone marrow appears to be related to the volume of the marrow irradiated and is higher after a mantle + inverted Y field than after a mantle field. Bone marrow scintigraphies with /sup 59/Fe in 7 out of 9 patients studied revealed an extension of hematopoiesis into a normally dormant area of the marrow, such as the femora. In 2 patients an erythropoietic activity was observed in spleens which had received a dose of 40 Gy, and extra medullary erythropoiesis was found in approximately two-thirds of the patients.

  5. Up-regulation of expression of selected genes in human bone cells with specific capacitively coupled electric fields.

    Science.gov (United States)

    Clark, Charles C; Wang, Wei; Brighton, Carl T

    2014-07-01

    The objective of the described experiments was to determine the electrical parameters that lead to optimal expression of a number of bone-related genes in cultured human bone cells exposed to a capacitively coupled electric field. Human calvarial osteoblasts were grown in modified plastic Cooper dishes in which the cells could be exposed to various capacitively coupled electric fields. The optimal duration of stimulation and optimal duration of response to the electrical field, and the optimal amplitude, frequency and duty cycle were all determined for each of the genes analyzed. Results indicated that a capacitively coupled electric field of 60 kHz, 20 mV/cm, 50% duty cycle for 2 h duration per day significantly up-regulated mRNA expression of a number of transforming growth factor (TGF)-β family genes (bone morphogenetic proteins (BMP)-2 and -4, TGF-β1, - β2 and -β3) as well as fibroblast growth factor (FGF)-2, osteocalcin (BGP) and alkaline phosphatase (ALP). Protein levels of BMP-2 and -4, and TGF-β1 and - β2 were also elevated. The clinical relevance of these findings in the context of a noninvasive treatment modality for delayed union and nonunion fracture healing is discussed.

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

    Science.gov (United States)

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

    2015-02-01

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

  7. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche

    Directory of Open Access Journals (Sweden)

    Zach S. Templeton

    2015-12-01

    Full Text Available BACKGROUND/OBJECTIVES: Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. METHODS: Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. RESULTS: Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014 and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006 and IL-1β (P = .001 in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. CONCLUSIONS: Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche.

  8. Restoration of a Critical Mandibular Bone Defect Using Human Alveolar Bone-Derived Stem Cells and Porous Nano-HA/Collagen/PLA Scaffold.

    Science.gov (United States)

    Wang, Xing; Xing, Helin; Zhang, Guilan; Wu, Xia; Zou, Xuan; Feng, Lin; Wang, Dongsheng; Li, Meng; Zhao, Jing; Du, Jianwei; Lv, Yan; E, Lingling; Liu, Hongchen

    2016-01-01

    Periodontal bone defects occur in a wide variety of clinical situations. Adult stem cell- and biomaterial-based bone tissue regeneration are a promising alternative to natural bone grafts. Recent evidence has demonstrated that two populations of adult bone marrow mesenchymal stromal cells (BMSCs) can be distinguished based on their embryonic origins. These BMSCs are not interchangeable, as bones preferentially heal using cells that share the same embryonic origin. However, the feasibility of tissue engineering using human craniofacial BMSCs was unclear. The goal of this study was to explore human craniofacial BMSC-based therapy for the treatment of localized mandibular defects using a standardized, minimally invasive procedure. The BMSCs' identity was confirmed. Scanning electron microscopy, a cell proliferation assay, and supernatant detection indicated that the nHAC/PLA provided a suitable environment for aBMSCs. Real-time PCR and electrochemiluminescence immunoassays demonstrated that osteogenic markers were upregulated by osteogenic preinduction. Moreover, in a rabbit critical-size mandibular bone defect model, total bone formation in the nHAC/PLA + aBMSCs group was significantly higher than in the nHAC/PLA group but significantly lower than in the nHAC/PLA + preinduced aBMSCs. These findings demonstrate that this engineered bone is a valid alternative for the correction of mandibular bone defects.

  9. Induction of micronuclei and sister chromatid exchange in bone-marrow cells and abnormalities in sperm of Algerian mice (Mus spretus) exposed to cadmium, lead and zinc.

    Science.gov (United States)

    Tapisso, Joaquim Torres; Marques, Carla Cristina; Mathias, Maria da Luz; Ramalhinho, Maria da Graça

    2009-08-01

    As a consequence of human activities, large amounts of cadmium, lead and zinc are released in the environment, often simultaneously. The aim of this study was to investigate under experimental conditions the DNA damage induced in Algerian mice (Mus spretus) exposed to cadmium (Cd), lead (Pb) and zinc (Zn) separately, or in selected combinations. Three cytogenetic end points were considered: the frequencies of micronucleated cells (MN) and sister chromatid exchange (SCE) in the bone marrow and the frequency of sperm abnormalities. Mice were treated by intraperitoneal (i.p.) injections with 5 or 10 doses of aqueous solutions of cadmium acetate, lead acetate and zinc acetate in concentrations corresponding to 1/10 of the LD50, respectively, 21.5, 0.46 and 1.5 mg/kg bw. The control groups were injected in the same way with distilled water. With only one exception (Cd + Zn group treated with 5 doses), the results show a significant increase of MN in all groups for both treatments (5 and 10 doses). Similarly, the results concerning the SCE revealed a statistically significant increase in all treated animals, with the exception of the Zn group treated with 5 doses. The number of sperm abnormalities was significantly higher in animals treated with 5 doses, except in the group Pb + Zn. In animals treated with 10 doses the number of sperm abnormalities was always statistically higher compared with controls. This study indicates that cadmium, lead and zinc can induce MN, SCEs and sperm abnormalities in Algerian mice and that the clastogenic potential is dependent on the time of exposure and the interaction between the three elements, confirming the environmental damage that may result from the simultaneous action of several metals. Most relevant is the toxic potential for Zn, related with the dose, which may compromise its protective effect against other metal contaminations, such as cadmium.

  10. Optical detection of carotenoid antioxidants in human bone and surrounding tissue.

    Science.gov (United States)

    Ermakov, Igor V; Ermakova, Maia R; Rosenberg, Thomas D; Gellermann, Werner

    2013-11-01

    Carotenoids are known to play an important role in health and disease state of living human tissue based on their antioxidant and optical filtering functions. In this study, we show that carotenoids exist in human bone and surrounding fatty tissue both in significant and individually variable concentrations. Measurements of biopsied tissue samples with molecule-specific Raman spectroscopy and high-performance liquid chromatography reveal that all carotenoids that are known to exist in human skin are also present in human bone. This includes all carotenes, lycopene, β-cryptoxanthin, lutein, and zeaxanthin. We propose quantitative reflection imaging as a noncontact optical method suitable for the measurement of composite carotenoid levels in bone and surrounding tissue exposed during open surgeries such as total knee arthroplasty, and as a proof of concept, demonstrate carotenoid measurements in biopsied bone samples. This will allow one to establish potential correlations between internal tissue carotenoid levels and levels in skin and to potentially use already existing optical skin carotenoid tests as surrogate marker for bone carotenoid status.

  11. T3 Regulates a Human Macrophage-Derived TSH-β Splice Variant: Implications for Human Bone Biology.

    Science.gov (United States)

    Baliram, R; Latif, R; Morshed, S A; Zaidi, M; Davies, T F

    2016-09-01

    TSH and thyroid hormones (T3 and T4) are intimately involved in bone biology. We have previously reported the presence of a murine TSH-β splice variant (TSH-βv) expressed specifically in bone marrow-derived macrophages and that exerted an osteoprotective effect by inducing osteoblastogenesis. To extend this observation and its relevance to human bone biology, we set out to identify and characterize a TSH-β variant in human macrophages. Real-time PCR analyses using human TSH-β-specific primers identified a 364-bp product in macrophages, bone marrow, and peripheral blood mononuclear cells that was sequence verified and was homologous to a human TSH-βv previously reported. We then examined TSH-βv regulation using the THP-1 human monocyte cell line matured into macrophages. After 4 days, 46.1% of the THP-1 cells expressed the macrophage markers CD-14 and macrophage colony-stimulating factor and exhibited typical morphological characteristics of macrophages. Real-time PCR analyses of these cells treated in a dose-dependent manner with T3 showed a 14-fold induction of human TSH-βv mRNA and variant protein. Furthermore, these human TSH-βv-positive cells, induced by T3 exposure, had categorized into both M1 and M2 macrophage phenotypes as evidenced by the expression of macrophage colony-stimulating factor for M1 and CCL-22 for M2. These data indicate that in hyperthyroidism, bone marrow resident macrophages have the potential to exert enhanced osteoprotective effects by oversecreting human TSH-βv, which may exert its local osteoprotective role via osteoblast and osteoclast TSH receptors.

  12. Human lead exposure in a late 19th century mental asylum population

    Energy Technology Data Exchange (ETDEWEB)

    Bower, Nathan W. [Department of Chemistry, Colorado College, Colorado Springs, CO 80903-3294 (United States)]. E-mail: nbower@coloradocollege.edu; McCants, Sarah A. [Department of Chemistry, Colorado College, Colorado Springs, CO 80903-3294 (United States); Custodio, Joseph M. [Department of Chemistry, Colorado College, Colorado Springs, CO 80903-3294 (United States); Ketterer, Michael E. [Departments of Chemistry and Biochemistry, Northern Arizona University, Flagstaff, AZ 86011-5698 (United States); Getty, Stephen R. [Biological Sciences Curriculum Study, Colorado Springs, CO 80918 (United States); Hoffman, J. Michael [Department of Anthropology, Colorado College, Colorado Springs, CO 8090-3294 (United States)

    2007-01-01

    Lead isotope ratios and lead (Pb) levels were analyzed in 33 individuals from a forgotten cemetery at the Colorado Mental Health Institute at Pueblo, Colorado dating to 1879-1899. Isotopic ratios from healing bone fractures, cortical bone, and tooth dentine provide information about sources of Pb exposures over a range of time that illuminates individual's life histories and migration patterns. Historical records and Pb production data from the 19th century were used to create a database for interpreting Pb exposures for these African, Hispanic and European Americans. The analysis of these individuals suggests that Pb exposure noticeably impacted the mental health of 5-10% of the asylum patients in this frontier population, a high number by standards today, and that differences exist in the three ancestral groups' exposure histories.

  13. Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

    Science.gov (United States)

    Meier, Raphael P H; Seebach, Jörg D; Morel, Philippe; Mahou, Redouan; Borot, Sophie; Giovannoni, Laurianne; Parnaud, Geraldine; Montanari, Elisa; Bosco, Domenico; Wandrey, Christine; Berney, Thierry; Bühler, Leo H; Muller, Yannick D

    2014-01-01

    Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow) and 10 days (kidney capsule). Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation.

  14. Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

    Directory of Open Access Journals (Sweden)

    Raphael P H Meier

    Full Text Available Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow and 10 days (kidney capsule. Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation.

  15. Noninvasive optical measurement of bone marrow lesions: a Monte Carlo study on visible human dataset

    Science.gov (United States)

    Su, Yu; Li, Ting

    2016-03-01

    Bone marrow is both the main hematopoietic and important immune organ. Bone marrow lesions (BMLs) may cause a series of severe complications and even myeloma. The traditional diagnosis of BMLs rely on mostly bone marrow biopsy/ puncture, and sometimes MRI, X-ray, and etc., which are either invasive and dangerous, or ionizing and costly. A diagnosis technology with advantages in noninvasive, safe, real-time continuous detection, and low cost is requested. Here we reported our preliminary exploration of feasibility verification of using near-infrared spectroscopy (NIRS) in clinical diagnosis of BMLs by Monte Carlo simulation study. We simulated and visualized the light propagation in the bone marrow quantitatively with a Monte Carlo simulation software for 3D voxelized media and Visible Chinese Human data set, which faithfully represents human anatomy. The results indicate that bone marrow actually has significant effects on light propagation. According to a sequence of simulation and data analysis, the optimal source-detector separation was suggested to be narrowed down to 2.8-3.2cm, at which separation the spatial sensitivity distribution of NIRS cover the most region of bone marrow with high signal-to-noise ratio. The display of the sources and detectors were optimized as well. This study investigated the light transport in spine addressing to the BMLs detection issue and reported the feasibility of NIRS detection of BMLs noninvasively in theory. The optimized probe design of the coming NIRS-based BMLs detector is also provided.

  16. Tumour necrosis factor-alpha (TNFα stimulates the growth of human bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    F. Rougier

    1997-01-01

    Full Text Available This study reports that TNF-α is a potent mitogen for human bone marrow sternal cells in vitro (assessed by [3H]-thymidine incorporation into DNA and cell counts. In contrast, cytokines such as IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, LIF, SCF, M-CSF, G-CSF and GM-CSF had no effect. The effect of TNF-α on the growth of human bone marrow stromal cells could be of importance during inflammatory processes which take place in the marrow, for example marrow fibrosis.

  17. Antinociceptive Effect of Intrathecal Injection of Genetically Engineered Human Bone Marrow Stem Cells Expressing the Human Proenkephalin Gene in a Rat Model of Bone Cancer Pain

    Directory of Open Access Journals (Sweden)

    Yi Sun

    2017-01-01

    Full Text Available Background. This study aimed to investigate the use of human bone marrow mesenchymal stem cells (hBMSCs genetically engineered with the human proenkephalin (hPPE gene to treat bone cancer pain (BCP in a rat model. Methods. Primary cultured hBMSCs were passaged and modified with hPPE, and the cell suspensions (6 × 106 were then intrathecally injected into a rat model of BCP. Paw mechanical withdrawal threshold (PMWT was measured before and after BCP. The effects of hPPE gene transfer on hBMSC bioactivity were analyzed in vitro and in vivo. Results. No changes were observed in the surface phenotypes and differentiation of hBMSCs after gene transfer. The hPPE-hBMSC group showed improved PMWT values on the ipsilateral side of rats with BCP from day 12 postoperatively, and the analgesic effect was reversed by naloxone. The levels of proinflammatory cytokines such as IL-1β and IL-6 were ameliorated, and leucine-enkephalin (L-EK secretion was augmented, in the hPPE-engineered hBMSC group. Conclusion. The intrathecal administration of BMSCs modified with the hPPE gene can effectively relieve pain caused by bone cancer in rats and might be a potentially therapeutic tool for cancer-related pain in humans.

  18. Antinociceptive Effect of Intrathecal Injection of Genetically Engineered Human Bone Marrow Stem Cells Expressing the Human Proenkephalin Gene in a Rat Model of Bone Cancer Pain

    Science.gov (United States)

    Tian, Yuke; Li, Haifeng; Zhang, Dengwen; Sun, Qiang

    2017-01-01

    Background. This study aimed to investigate the use of human bone marrow mesenchymal stem cells (hBMSCs) genetically engineered with the human proenkephalin (hPPE) gene to treat bone cancer pain (BCP) in a rat model. Methods. Primary cultured hBMSCs were passaged and modified with hPPE, and the cell suspensions (6 × 106) were then intrathecally injected into a rat model of BCP. Paw mechanical withdrawal threshold (PMWT) was measured before and after BCP. The effects of hPPE gene transfer on hBMSC bioactivity were analyzed in vitro and in vivo. Results. No changes were observed in the surface phenotypes and differentiation of hBMSCs after gene transfer. The hPPE-hBMSC group showed improved PMWT values on the ipsilateral side of rats with BCP from day 12 postoperatively, and the analgesic effect was reversed by naloxone. The levels of proinflammatory cytokines such as IL-1β and IL-6 were ameliorated, and leucine-enkephalin (L-EK) secretion was augmented, in the hPPE-engineered hBMSC group. Conclusion. The intrathecal administration of BMSCs modified with the hPPE gene can effectively relieve pain caused by bone cancer in rats and might be a potentially therapeutic tool for cancer-related pain in humans. PMID:28286408

  19. On the multiscale origins of fracture resistance in human bone and its biological degradation

    Energy Technology Data Exchange (ETDEWEB)

    Zimmermann, Elizabeth A.; Barth, Holly D.; Ritchie, Robert O.

    2012-03-09

    Akin to other mineralized tissues, human cortical bone can resist deformation and fracture due to the nature of its hierarchical structure, which spans the molecular to macroscopic length-scales. Deformation at the smallest scales, mainly through the composite action of the mineral and collagen, contributes to bone?s strength or intrinsic fracture resistance, while crack-tip shielding mechanisms active on the microstructural scale contribute to the extrinsic fracture resistance once cracking begins. The efficiency with which these structural features can resist fracture at both small and large length-scales becomes severely degraded with such factors as aging, irradiation and disease. Indeed aging and irradiation can cause changes to the cross-link profile at fibrillar length-scales as well as changes at the three orders of magnitude larger scale of the osteonal structures, both of which combine to inhibit the bone's overall resistance to the initiation and growth of cracks.

  20. In vivo measurement of mechanical properties of human long bone by using sonic sound

    Science.gov (United States)

    Hossain, M. Jayed; Rahman, M. Moshiur; Alam, Morshed

    2016-07-01

    Vibration analysis has evaluated as non-invasive techniques for the in vivo assessment of bone mechanical properties. The relation between the resonant frequencies, long bone geometry and mechanical properties can be obtained by vibration analysis. In vivo measurements were performed on human ulna as a simple beam model with an experimental technique and associated apparatus. The resonant frequency of the ulna was obtained by Fast Fourier Transformation (FFT) analysis of the vibration response of piezoelectric accelerometer. Both elastic modulus and speed of the sound were inferred from the resonant frequency. Measurement error in the improved experimental setup was comparable with the previous work. The in vivo determination of bone elastic response has potential value in screening programs for metabolic bone disease, early detection of osteoporosis and evaluation of skeletal effects of various therapeutic modalities.

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

    Science.gov (United States)

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

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P growth.

  2. Selective deletion of the membrane-bound colony stimulating factor 1 isoform leads to high bone mass but does not protect against estrogen-deficiency bone loss.

    Science.gov (United States)

    Yao, Gang-Qing; Wu, Jian-Jun; Troiano, Nancy; Zhu, Mei-Ling; Xiao, Xiao-Yan; Insogna, Karl

    2012-07-01

    To better define the biologic function of membrane-bound CSF1 (mCSF1) in vivo, we have generated mCSF1 knockout (k/o) mice. Spinal bone density (BMD) was 15.9% higher in k/o mice compared to wild-type (wt) controls (P bone marrow isolated from mCSF1 k/o mice was reduced compared to wt marrow. There were no defects in osteoblast number or function suggesting that the basis for the high bone mass phenotype was reduced resorption. In addition to a skeletal phenotype, k/o mice had significantly elevated serum triglyceride levels (123 ± 7 vs. 88 ± 3.2 mg/dl; k/o vs. wt, P bone loss following ovariectomy (OVX). OVX induced a significant fourfold increase in the expression of the soluble CSF1 isoform (sCSF1) in the bones of wt mice while expression of mCSF1 was unchanged. These findings indicate that mCSF1 is essential for normal bone remodeling since, in its absence, BMD is increased. Membrane-bound CSF1 does not appear to be required for estrogen-deficiency bone loss while in contrast; our data suggest that sCSF1 could play a key role in this pathologic process. The reasons why mCSF1 k/o mice have hypertriglyceridemia are currently under study.

  3. Age-related changes in the plasticity and toughness of human cortical bone at multiple length-scales

    Energy Technology Data Exchange (ETDEWEB)

    Zimmermann, Elizabeth A.; Schaible, Eric; Bale, Hrishikesh; Barth, Holly D.; Tang, Simon Y.; Reichert, Peter; Busse, Bjoern; Alliston, Tamara; Ager III, Joel W.; Ritchie, Robert O.

    2011-08-10

    The structure of human cortical bone evolves over multiple length-scales from its basic constituents of collagen and hydroxyapatite at the nanoscale to osteonal structures at nearmillimeter dimensions, which all provide the basis for its mechanical properties. To resist fracture, bone’s toughness is derived intrinsically through plasticity (e.g., fibrillar sliding) at structural-scales typically below a micron and extrinsically (i.e., during crack growth) through mechanisms (e.g., crack deflection/bridging) generated at larger structural-scales. Biological factors such as aging lead to a markedly increased fracture risk, which is often associated with an age-related loss in bone mass (bone quantity). However, we find that age-related structural changes can significantly degrade the fracture resistance (bone quality) over multiple lengthscales. Using in situ small-/wide-angle x-ray scattering/diffraction to characterize sub-micron structural changes and synchrotron x-ray computed tomography and in situ fracture-toughness measurements in the scanning electron microscope to characterize effects at micron-scales, we show how these age-related structural changes at differing size-scales degrade both the intrinsic and extrinsic toughness of bone. Specifically, we attribute the loss in toughness to increased non-enzymatic collagen cross-linking which suppresses plasticity at nanoscale dimensions and to an increased osteonal density which limits the potency of crack-bridging mechanisms at micron-scales. The link between these processes is that the increased stiffness of the cross-linked collagen requires energy to be absorbed by “plastic” deformation at higher structural levels, which occurs by the process of microcracking.

  4. Osteogenic potential of the human bone morphogenetic protein 2 gene activated nanobone putty

    Institute of Scientific and Technical Information of China (English)

    TIAN Xiao-bin; SUN Li; YANG Shu-hua; ZHANG Yu-kun; HU Ru-yin; FU De-hao

    2008-01-01

    Background Nanobone putty is an injectable and bioresorbable bone substitute. The neutral-pH putty resembles hard bone tissue, does not contain polymers or plasticizers, and is self-setting and nearly isothermic, properties which are helpful for the adhesion, proliferation, and function of bone cells. The aim of this study was to investigate the osteogenic potential of human bone morphogenetic protein 2(hBMP2)gene activated nanobone putty in inducing ectopic bone formation, and the effects of the hBMP2 gene activated nanobone putry on repairing bone defects. Methods Twenty four Kunming mice were randomly divided into two groups. The nanobone putty+hBMP2 plasmid was injected into the right thigh muscle pouches of the mice(experiment side). The nanobone putty+blank plasmid or nanobone putty was injected into the left thigh muscle pouches of the group 1(control side 1)or group 2(control side 2), respectively. The effects of ectopic bone formation were evaluated by radiography, histology, and molecular biology analysis at 2 and 4 weeks after operation. Bilateral 15 mm radial defects were made in forty-eight rabbits. These rabbits were randomly divided into three groups: Group A, nanobone putty+hBMP2 plasmid;Group B, putty+blank plasmid; Group C, nanobone putty only. Six rabbits with left radial defects served as blank controls. The effect of bone repairing was evaluated by radiography, histology, molecular biology, and biomechanical analysis at 4, 8, and 12 weeks after operation. Results The tissue from the experimental side of the mice expressed hBMP2. Obvious cartilage and island-distributed immature bone formation in implants of the experiment side were observed at 2 weeks after operation, and massive mature bone observed at 4 weeks. No bone formation was observed in the control side of the mice. The ALP activity in the experiment side of the mice was higher than that in the control side. The tissue of Group A rabbits expressed hBMP2 protein and higher ALP level

  5. Factors influencing uncertainties of in vivo bone lead measurement using a (109)Cd K X-ray fluorescence clover leaf geometry detector system.

    Science.gov (United States)

    Behinaein, Sepideh; Chettle, David R; Marro, Leonora; Malowany, Morie; Fisher, Mandy; Fleming, David E B; Healey, Norm; Inskip, Mike; Arbuckle, Tye E; McNeill, Fiona E

    2014-12-01

    A (109)Cd K X-ray fluorescence (KXRF) measurement system consisting of four detectors in clover-leaf geometry is a non-invasive, low-radiation-dose method of measuring bone lead concentration. Its high precision in estimating the bone lead content makes it a promising tool for the determination of the low levels of lead currently found in the general population. After developing the clover-leaf geometry system, the system was used for the first time in a major survey in 2008 to measure the lead levels of 497 smelter employees (an occupationally exposed group with high lead levels). Since the delivered effective dose of the bone lead system in clover-leaf geometry is small (on the order of nSv), the technique can be used to measure the bone lead of sensitive populations such as the elderly and children. This detector system was used from 2009 to 2011, in a pilot study that measured the bone lead concentration of 263 environmentally exposed individuals (termed the EG group) residing in Toronto, Ontario, Canada. In this paper, the factors that influence uncertainties in lead content in tibia (cortical bone) and calcaneus (trabecular bone) are discussed based on gender, age, and body mass index (BMI) by using analysis of variance (ANOVA) and multiple linear regression models. Results from the two study groups (the EG group versus the occupationally exposed smelter employees) are compared where appropriate (i.e. for males older than 20). Results from univariate analyses showed that females have higher tibia uncertainty compared to males. We observed significant differences for both calcaneus and tibia uncertainty measures (p < 0.0005) among different age groups, where the uncertainties were highest in the lowest age group (<11 years). Lastly, and perhaps most significantly, we found that the product of source activity and measurement time influenced the precision of measurements greatly, and that this factor alone could account for the higher uncertainties observed for

  6. Strontium-90 concentration measurements in human bones and teeth in Greece.

    Science.gov (United States)

    Stamoulis, K C; Assimakopoulos, P A; Ioannides, K G; Johnson, E; Soucacos, P N

    1999-05-19

    Strontium-90 concentration was measured in human bones and teeth collected in Greece during the period 1992-1996. One hundred and five bone samples, mainly cancellous bone, and 108 samples, taken from a total of 896 individual teeth were processed. Samples were classified according to the age and sex of the donors. Samples were chemically pre-treated according to a specially devised method to enable extraction of 90Y, at equilibrium with 90Sr in the original sample. Subsequently, 90Y beta activity was measured with a gas proportional counter. Radiostrontium concentration in bone samples showed small variations with respect to age or sex, with an average value of 30 mBq 90Sr/g Ca. However, 90Sr concentration measurements in teeth demonstrated a pronounced structure, which clearly reflects contamination from the 1960s atmospheric nuclear weapons tests and the more recent Chernobyl accident. This difference is attributed to the different histological structure of skeletal bones and teeth, the later consisting mainly of compact bone. An age-dependent model for radiostrontium concentration in human bones and teeth is developed which is able to successfully reproduce the experimental data. Through a fitting process, the model also yielded calcium turnover rates for compact bone, as a function of age, as well as an estimate of radiostrontium contamination of foodstuffs in Greece for the past four decades. The results obtained in this study indicate that radiostrontium environmental contamination which resulted from the atmospheric nuclear weapons tests in the 1960s, exceed by far that caused by the Chernobyl accident.

  7. Human dental pulp stem cell is a promising autologous seed cell for bone tissue engineering

    Institute of Scientific and Technical Information of China (English)

    LI Jing-hui; LIU Da-yong; ZHANG Fang-ming; WANG Fan; ZHANG Wen-kui; ZHANG Zhen-ting

    2011-01-01

    Background The seed cell is a core problem in bone tissue engineering research.Recent research indicates that human dental pulp stem cells (hDPSCs) can differentiate into osteoblasts in vitro,which suggests that they may become a new kind of seed cells for bone tissue engineering.The aim of this study was to evaluate the osteogenic differentiation of hDPSCs in vitro and bone-like tissue formation when transplanted with three-dimensional gelatin scaffolds in vivo,and hDPSCs may become appropriate seed cells for bone tissue engineering.Methods We have utilized enzymatic digestion to obtain hDPSCs from dental pulp tissue extracted during orthodontic treatment.After culturing and expansion to three passages,the cells were seeded in 6-well plates or on three-dimensional gelatin scaffolds and cultured in osteogenic medium.After 14 days in culture,the three-dimensional gelatin scaffolds were implanted subcutaneously in nude mice for 4 weeks.In 6-well plate culture,osteogenesis was assessed by alkaline phosphatase staining,Von Kossa staining,and reverse transcription-polymerase chain reaction (RT-PCR) analysis of the osteogenesis-specific genes type I collagen (COL l),bone sialoprotein (BSP),osteocalcin (OCN),RUNX2,and osterix (OSX).In three-dimensional gelatin scaffold culture,X-rays,hematoxylin/eosin staining,and immunohistochemical staining were used to examine bone formation.Results In vitro studies revealed that hDPSCs do possess osteogenic differentiation potential.In vivo studies revealed that hDPSCs seeded on gelatin scaffolds can form bone structures in heterotopic sites of nude mice.Conclusions These findings suggested that hDPSCs may be valuable as seed cells for bone tissue engineering.As a special stem cell source,hDPSCs may blaze a new path for bone tissue engineering.

  8. Inducible models of bone loss.

    Science.gov (United States)

    Doucette, Casey R; Rosen, Clifford J

    2014-12-11

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

  9. Characteristics of porous zirconia coated with hydroxyapatite as human bones

    Indian Academy of Sciences (India)

    V V Narulkar; S Prakash; K Chandra

    2007-08-01

    Since hydroxyapatite has excellent biocompatibility and bone bonding ability, porous hydroxyapatite ceramics have been intensively studied. However, porous hydroxyapatite bodies are mechanically weak and brittle, which makes shaping and implantation difficult. One way to solve this problem is to introduce a strong porous network onto which hydroxyapatite coating is applied. In this study, porous zirconia and alumina-added zirconia ceramics were prepared by ceramic slurry infiltration of expanded polystyrene bead compacts, followed by firing at 1500°C. Then slurry of hydroxyapatite–borosilicate glass mixed powder was used to coat the porous ceramics, followed by firing at 1200°C. The porous structures without the coating had high porosities of 51–69%, high pore interconnectivity, and sufficiently large pore window sizes (300–500 m). The porous ceramics had compressive strengths of 5.3∼36.8 MPa, favourably comparable to the mechanical properties of cancellous bones. In addition, porous hydroxyapatite surface was formed on the top of the composite coating, whereas a borosilicate glass layer was found on the interface. Thus, porous zirconia-based ceramics were modified with a bioactive composite coating for biomedical applications.

  10. Relationships of human plasma fluoride and bone fluoride to age

    Energy Technology Data Exchange (ETDEWEB)

    Parkins, F.M.; Tinanoff, N.; Moutinho, M.; Anstey, M.B.; Waziri, M.H.

    1976-04-01

    There is evidence that fluoride levels in plasma correlate with the fluoride content in bones. The authors determined whether or not fluoride in plasma and bones might correlate with age. In 41 in-patients at the University Hospital, Iowa City, 36 of whom had been residing in fluoridated communities plasma fluoride was determined in the fasting stage by the fluoride ion selective electrode. The teeth of these children were compared with those of a neighboring city where the natural fluoride content in drinking water was 0.1 ppm. For the second sampling 42 months following the beginning of the program only 10 and 11 year old children - who had been 6 and 7 years old at the beginning of the experiment - were selected. Twenty-five boys and girls in each group were compared with a similar group of children as controls. After 28 months (approximately 33 rinsing with sodium fluoride solution) the DMF index in the fluoride-treated children was 18.4% less than in the controls. In the second group among 10 and 11 year old children after 42 months with 55 rinsings the difference was 35.0%. The author acknowledged that factors other than applications of sodium fluoride may have contributed to the prevention of caries in the fluoride-treated groups.

  11. Organotypic culture of human bone marrow adipose tissue.

    Science.gov (United States)

    Uchihashi, Kazuyoshi; Aoki, Shigehisa; Shigematsu, Masamori; Kamochi, Noriyuki; Sonoda, Emiko; Soejima, Hidenobu; Fukudome, Kenji; Sugihara, Hajime; Hotokebuchi, Takao; Toda, Shuji

    2010-04-01

    The precise role of bone marrow adipose tissue (BMAT) in the marrow remains unknown. The purpose of the present study was therefore to describe a novel method for studying BMAT using 3-D collagen gel culture of BMAT fragments, immunohistochemistry, ELISA and real-time reverse transcription-polymerase chain reaction. Mature adipocytes and CD45+ leukocytes were retained for >3 weeks. Bone marrow stromal cells (BMSC) including a small number of lipid-laden preadipocytes and CD44+/CD105+ mesenchymal stem cell (MSC)-like cells, developed from BMAT. Dexamethasone (10 micromol/L), but not insulin (20 mU/mL), significantly increased the number of preadipocytes. Dexamethasone and insulin also promoted leptin production and gene expression in BMAT. Adiponectin production by BMAT was BMAT, in which adiponectin protein secretion is normally very low, and that BMAT may exhibit a different phenotype from that of the visceral and subcutaneous adipose tissues. BMAT-osteoblast interactions were also examined, and it was found that osteoblasts inhibited the development of BMSC and reduced leptin production, while BMAT inhibited the growth and differentiation of osteoblasts. The present novel method proved to be useful for the study of BMAT biology.

  12. Establishment of an experimental human lung adenocarcinoma cell line SPC-A-1BM with high bone metastases potency by {sup 99m}Tc-MDP bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yang Shunfang [Department of Nuclear Medicine, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China)], E-mail: yzyg@sh163.net; Dong Qianggang [Laboratory of Mol-diagnosis, Shanghai Cancer Institute of Shanghai Jiaotong University, Shanghai 200032 (China); Yao Ming [Laboratory of Pathology, Shanghai Cancer Institute of Shanghai Jiaotong University, Shanghai 200032 (China); Shi Meiping [Department of Pathology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Ye Jianding [Department of Radiology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Zhao Langxiang [Department of Pathology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Su Jianzhong; Gu Weiyong [Shanghai Thoracic Tumor Institute, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Xie Wenhui [Department of Nuclear Medicine, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Wang Kankan; Du Yanzhi [State Key Laboratory of Medical Genomics, Ruijin Hospital of Shanghai Jiaotong University, Shanghai 200025 (China); Li Yao [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433 (China); Huang Yan [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433 (China)], E-mail: huangyan@fudan.edu.cn

    2009-04-15

    Background: Bone metastasis is one of the most common clinical phenomena of late stage lung cancer. A major impediment to understanding the pathogenesis of bone metastasis has been the lack of an appropriate animal and cell model. This study aims to establish human lung adenocarcinoma cell line with highly bone metastases potency with {sup 99m}Tc-MDP bone scintigraphy. Methods: The human lung adenocarcinoma cancer cells SPC-A-1 were injected into the left cardiac ventricle of NIH-Beige-Nude-XID (NIH-BNX) immunodeficient mice. The metastatic lesions of tumor-bearing mice were imaged with {sup 99m}Tc-MDP bone scintigraphy on a Siemens multi-single photon emission computed tomography. Pinhole images were acquired on a GZ-B conventional gamma camera with a self-designed pinhole collimator. The mice with bone metastasis were sacrificed under deep anesthesia, and the lesions were resected. Bone metastatic cancer cells in the resected lesions were subjected for culture and then reinoculated into the NIH-BNX mice through left cardiac ventricle. The process was repeated for eight cycles to obtain a novel cell subline SPC-A-1BM. Real-time polymerase chain reaction (PCR) was used to compare the gene expression differences in the parental and SPC-A-1BM cells. Results: The bone metastasis sites were successfully revealed by bone scintigraphy. The established bone metastasis cell line SPC-A-1BM had a high potential to metastasize in bone, including mandible, humerus, thoracic vertebra, lumbar, femur, patella, ilium and cartilage rib. The expression level of vascular endothelial growth factor gene family, Bcl-2 and cell adhesion-related genes ECM1, ESM1, AF1Q, SERPINE2 and FN1 were examined. Gene expression difference was found between parental and bone-seeking metastasis cell SPC-A-1BM, which indicates SPC-A-1BM has metastatic capacity vs. its parental cells. Conclusion: SPC-A-1BM is a bone-seeking metastasis human lung adenocarcinoma cell line. Bone scintigraphy may be used as

  13. Establishment of an experimental human lung adenocarcinoma cell line SPC-A-1BM with high bone metastases potency by (99m)Tc-MDP bone scintigraphy.

    Science.gov (United States)

    Yang, Shunfang; Dong, Qianggang; Yao, Ming; Shi, Meiping; Ye, Jianding; Zhao, Langxiang; Su, Jianzhong; Gu, Weiyong; Xie, Wenhui; Wang, Kankan; Du, Yanzhi; Li, Yao; Huang, Yan

    2009-04-01

    Bone metastasis is one of the most common clinical phenomena of late stage lung cancer. A major impediment to understanding the pathogenesis of bone metastasis has been the lack of an appropriate animal and cell model. This study aims to establish human lung adenocarcinoma cell line with highly bone metastases potency with (99m)Tc-MDP bone scintigraphy. The human lung adenocarcinoma cancer cells SPC-A-1 were injected into the left cardiac ventricle of NIH-Beige-Nude-XID (NIH-BNX) immunodeficient mice. The metastatic lesions of tumor-bearing mice were imaged with (99m)Tc-MDP bone scintigraphy on a Siemens multi-single photon emission computed tomography. Pinhole images were acquired on a GZ-B conventional gamma camera with a self-designed pinhole collimator. The mice with bone metastasis were sacrificed under deep anesthesia, and the lesions were resected. Bone metastatic cancer cells in the resected lesions were subjected for culture and then reinoculated into the NIH-BNX mice through left cardiac ventricle. The process was repeated for eight cycles to obtain a novel cell subline SPC-A-1BM. Real-time polymerase chain reaction (PCR) was used to compare the gene expression differences in the parental and SPC-A-1BM cells. The bone metastasis sites were successfully revealed by bone scintigraphy. The established bone metastasis cell line SPC-A-1BM had a high potential to metastasize in bone, including mandible, humerus, thoracic vertebra, lumbar, femur, patella, ilium and cartilage rib. The expression level of vascular endothelial growth factor gene family, Bcl-2 and cell adhesion-related genes ECM1, ESM1, AF1Q, SERPINE2 and FN1 were examined. Gene expression difference was found between parental and bone-seeking metastasis cell SPC-A-1BM, which indicates SPC-A-1BM has metastatic capacity vs. its parental cells. SPC-A-1BM is a bone-seeking metastasis human lung adenocarcinoma cell line. Bone scintigraphy may be used as an accurate, sensitive, noninvasive tool to detect

  14. Comparison of mesenchymal stem cells from human placenta and bone marrow

    Institute of Scientific and Technical Information of China (English)

    张毅; 李长东; 江小霞; 李荷莲; 唐佩弦; 毛宁

    2004-01-01

    Background Nowadays bone marrow represents the main source of mesenchymal stem cells (MSCs). We identified a new population of MSCs derived from human placenta and compared its biological characterization with bone marrow derived MSCs.Methods Mononucleated cells (MNC) were isolated from the human placenta tissue perfusate by density gradient fractionation. Individual colonies were selected and cultured in tissue dishes. At the same time, human bone marrow derived MSCs were identified. Culture-expanded cells were characterized by immune phenotyping and cultured under conditions promoting differetiation to osteoblasts or adipocytes. The hematopoietic cytokines were assayed using reverse transcriptase polymerase chain reaction (RT-PCR). Results Human placental MSCs exhibited fibroblastoid morphology. Flow cytometric analyses showed that the placental MSC were CD29, CD44, CD73, CD105, CD166, HLA-ABC positive; but were negative for CD34, CD45, and HLA-DR. Functionally, they could be induced into adipocytes or osteocytes. Moreover, several hematopoietic cytokine mRNA was found in placenta-derived MSCs by RT-PCR analysis, including IL-6, M-CSF, Flt3-ligand and SCF. These results were consistent with the properties of bone marrow derived MSCs.Conclusion These observations implicate the postpartum human placenta as an important and novel source of multipotent stem cells that could potentially be used for investigating mesenchymal differentiation and regulation of hematopoiesis.

  15. Fe and Cu stable isotopes in archeological human bones and their relationship to sex.

    Science.gov (United States)

    Jaouen, Klervia; Balter, Vincent; Herrscher, Estelle; Lamboux, Aline; Telouk, Philippe; Albarède, Francis

    2012-07-01

    Accurate sex assignment of ancient human remains usually relies on the availability of coxal bones or well-preserved DNA. Iron (Fe) and copper (Cu) stable isotope compositions ((56)Fe/(54)Fe and (65)Cu/(63)Cu, respectively) were recently measured in modern human blood, and an unexpected result was the discovery of a (56)Fe-depletion and a (65)Cu-enrichment in men's blood compared to women's blood. Bones, being pervasively irrigated by blood, are expected to retain the (56)Fe/(54)Fe and (65)Cu/(63)Cu signature of blood, which in turn is useful for determining the sex of ancient bones. Here, we report the (56)Fe/(54)Fe, (65)Cu/(63)Cu, and (66)Zn/(64)Zn ratios from a suite of well-preserved phalanxes (n = 43) belonging to individuals buried in the 17th and 18th centuries at the necropolis of Saint-Laurent de Grenoble, France, and for which the sex was independently estimated from pelvic bone morphology. The metals were purified from the bone matrix by liquid chromatography on ion exchange resin and the isotope compositions were measured by multiple-collector inductively coupled plasma mass spectrometry. The results show that, as expected from literature data on blood, male bone iron is depleted in (56)Fe and enriched in (65)Cu relative to female. No sex difference is found in the (66)Zn/(64)Zn ratios of bone. The concentration and isotopic data show no evidence of soil contamination. Four samples of five (77%) can be assigned their correct sex, a result comparable to sex assignment using Fe and Cu isotopes in blood (81%). Isotopic analysis of metals may therefore represent a valid method of sex assignment applicable to incomplete human remains.

  16. Immune humanization of immunodeficient mice using diagnostic bone marrow aspirates from carcinoma patients.

    Directory of Open Access Journals (Sweden)

    Melanie Werner-Klein

    Full Text Available Tumor xenografts in immunodeficient mice, while routinely used in cancer research, preclude studying interactions of immune and cancer cells or, if humanized by allogeneic immune cells, are of limited use for tumor-immunological questions. Here, we explore a novel way to generate cancer models with an autologous humanized immune system. We demonstrate that hematopoietic stem and progenitor cells (HSPCs from bone marrow aspirates of non-metastasized carcinoma patients, which are taken at specialized centers for diagnostic purposes, can be used to generate a human immune system in NOD-scid IL2rγ(null (NSG and HLA-I expressing NSG mice (NSG-HLA-A2/HHD comprising both, lymphoid and myeloid cell lineages. Using NSG-HLA-A2/HHD mice, we show that responsive and self-tolerant human T cells develop and human antigen presenting cells can activate human T cells. As critical factors we identified the low potential of bone marrow HSPCs to engraft, generally low HSPC numbers in patient-derived bone marrow samples, cryopreservation and routes of cell administration. We provide here an optimized protocol that uses a minimum number of HSPCs, preselects high-quality bone marrow samples defined by the number of initially isolated leukocytes and intra-femoral or intra-venous injection. In conclusion, the use of diagnostic bone marrow aspirates from non-metastasized carcinoma patients for the immunological humanization of immunodeficient mice is feasible and opens the chance for individualized analyses of anti-tumoral T cell responses.

  17. Diagnostic Value of Ex-Vivo Three-Dimensional Micro-Computed Tomography Imaging of Primary Nonhematopoietic Human Bone Tumors: Osteosarcoma versus Chondrosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Langheinrich, A. C.; Stolle, C.; Kampschulte, M.; Lommel, D.; Rau, W. S.; Bassaly, B. (Depts. of Radiology and Pathology, Univ. of Giessen, Giessen (Germany))

    2008-10-15

    Background: Osteosarcoma and chondrosarcoma are the most common nonhematopoietic primary malignancies of bone. However, unusual radiographic appearances can lead to delay in diagnosis and confusion with benign diseases. Purpose: To evaluate the feasibility of micro-computed tomography (CT) for the analysis of primary, nonhematopoietic human bone tumors ex vivo. Material and Methods: Samples from 12 human bone specimens (osteosarcoma, n=6; chondrosarcoma, n=6) obtained for diagnostic purposes were scanned using industrial X-ray film without amplifier foil and scanned with micro-CT (7- and 12-mum-cubic voxels). Trabecular bone CT 'density' and tumor matrix CT 'density' were determined, and results were compared with those obtained from a detailed conventional histopathologic analysis of corresponding cross-sections. The significance of differences in grayscale measurements was tested with analysis of variance. Results: Micro-CT provided quantitative information on bone morphology equivalent to histopathological analysis. We established grayscale measurements by which tumor matrices of chondrosarcoma and osteosarcoma could be radiographically categorized following histological classifications (P<0.001). Conclusion: Micro-CT is feasible for the analysis and differentiation of human osteosarcoma and chondrosarcoma

  18. Synergistic effects of dimethyloxallyl glycine and recombinant human bone morphogenetic protein-2 on repair of critical-sized bone defects in rats

    Science.gov (United States)

    Qi, Xin; Liu, Yang; Ding, Zhen-Yu; Cao, Jia-Qing; Huang, Jing-Huan; Zhang, Jie-Yuan; Jia, Wei-Tao; Wang, Jing; Liu, Chang-Sheng; Li, Xiao-Lin

    2017-02-01

    In bone remodeling, osteogenesis is closely coupled to angiogenesis. Bone tissue engineering using multifunctional bioactive materials is a promising technique which has the ability to simultaneously stimulate osteogenesis and angiogenesis for repair of bone defects. We developed mesoporous bioactive glass (MBG)-doped poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) composite scaffolds as delivery vehicle. Two bioactive molecules, dimethyloxalylglycine (DMOG), a small-molecule angiogenic drug, and recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive growth factor, were co-incorporated into the scaffold. The synergistic effects of DMOG and rhBMP-2 released in the composite scaffolds on osteogenic and angiogenic differentiation of hBMSCs were investigated using real-time quantitative polymerase chain reaction and western blotting. Moreover, in vivo studies were conducted to observe bone regeneration and vascular formation of critical-sized bone defects in rats using micro-computed tomography, histological analyses, Microfil® perfusion, fluorescence labeling, and immunohistochemical analysis. The results showed that DMOG and rhBMP-2 released in the MBG-PHBHHx scaffolds did exert synergistic effects on the osteogenic and angiogenic differentiation of hBMSCs. Moreover, DMOG and rhBMP-2 produced significant increases in newly-formed bone and neovascularization of calvarial bone defects in rats. It is concluded that the co-delivery strategy of both rhBMP-2 and DMOG can significantly improve the critical-sized bone regeneration.

  19. The water jet as a new tool for endoprosthesis revision surgery--an in vitro study on human bone and bone cement.

    Science.gov (United States)

    Honl, Matthias; Rentzsch, Reemt; Schwieger, Karsten; Carrero, Volker; Dierk, Oliver; Dries, Sebastian; Louis, Hartmut; Pude, Frank; Bishop, Nick; Hille, Ekkehard; Morlock, Michael

    2003-01-01

    In revision surgeries of endoprostheses, the interface between implant and bone cement or bone must be loosened. Conventional tools have many disadvantages because of their size and limited range. Taking advantage of the selective and athermic cutting process, a plain water jet is already used in order to cut soft tissues. This study investigates the possibilities of both a plain and an abrasive water jet as cutting tools for revision surgery. Samples of the mid-diaphysis of human femora and bone cement (CMW3) were cut with a plain water jet (PWJ) and an abrasive water jet (AWJ) at two different jet-to-surface angles (30 degrees,90 degrees ) and at five different pressure levels (30, 40, 50, 60, 70 MPa). For a PWJ a selective pressure range was identified, where only bone cement was cut. Injecting a bio-compatible abrasive (lactose) to the jet stream resulted in significantly higher cut depths in both materials. Material removal in bone was significantly less at the smaller jet-to-surface angle for both techniques. No clear selectivity between bone and bone cement was observed for application of the AWJ. However, the material removal rate was significantly higher for bone cement than for bone at all pressure levels. The results indicate that an AWJ might be an alternative tool for cement removal. The possibility for localised cutting at interfaces could be an advantage for revision of a non-cemented prosthesis.

  20. Synergistic effects of dimethyloxallyl glycine and recombinant human bone morphogenetic protein-2 on repair of critical-sized bone defects in rats

    Science.gov (United States)

    Qi, Xin; Liu, Yang; Ding, Zhen-yu; Cao, Jia-qing; Huang, Jing-huan; Zhang, Jie-yuan; Jia, Wei-tao; Wang, Jing; Liu, Chang-sheng; Li, Xiao-lin

    2017-01-01

    In bone remodeling, osteogenesis is closely coupled to angiogenesis. Bone tissue engineering using multifunctional bioactive materials is a promising technique which has the ability to simultaneously stimulate osteogenesis and angiogenesis for repair of bone defects. We developed mesoporous bioactive glass (MBG)-doped poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) composite scaffolds as delivery vehicle. Two bioactive molecules, dimethyloxalylglycine (DMOG), a small-molecule angiogenic drug, and recombinant human bone morphogenetic protein-2 (rhBMP-2), an osteoinductive growth factor, were co-incorporated into the scaffold. The synergistic effects of DMOG and rhBMP-2 released in the composite scaffolds on osteogenic and angiogenic differentiation of hBMSCs were investigated using real-time quantitative polymerase chain reaction and western blotting. Moreover, in vivo studies were conducted to observe bone regeneration and vascular formation of critical-sized bone defects in rats using micro-computed tomography, histological analyses, Microfil® perfusion, fluorescence labeling, and immunohistochemical analysis. The results showed that DMOG and rhBMP-2 released in the MBG-PHBHHx scaffolds did exert synergistic effects on the osteogenic and angiogenic differentiation of hBMSCs. Moreover, DMOG and rhBMP-2 produced significant increases in newly-formed bone and neovascularization of calvarial bone defects in rats. It is concluded that the co-delivery strategy of both rhBMP-2 and DMOG can significantly improve the critical-sized bone regeneration. PMID:28230059

  1. Biological Characteristics of Human Bone Marrow Mesenchymal Stem Cell Cultured in Vitro

    Institute of Scientific and Technical Information of China (English)

    FA Xian'en; WANG Lixia; HOU Jianfeng; ZHANG Ruicheng; WANG Haiyong; YANG Chenyuan

    2005-01-01

    Summary: Some biological characteristics of human bone marrow mesenchymal stem cells (MSCs) cultured in vitro were observed. hMSCs were isolated from bone marrow and purified by density gradient centrifugation method, and then cultured in vitro. The proliferation and growth characteristics of hMSCs were observed in primary and passage culture. MSCs of passage 3 were examined for the purify by positive rate of CD29 and CD44 through flow cytometry. Human bone marrow MSCs showed active proliferation capacity in vitro. The purify of MSCs separated by our method was higher than 90 %. It was concluded that hMSCs have been successfully cultured and expanded effectively. It provided a foundation for further investigation and application of MSCs.

  2. The use of total human bone marrow fraction in a direct three-dimensional expansion approach for bone tissue engineering applications: focus on angiogenesis and osteogenesis.

    Science.gov (United States)

    Guerrero, Julien; Oliveira, Hugo; Catros, Sylvain; Siadous, Robin; Derkaoui, Sidi-Mohammed; Bareille, Reine; Letourneur, Didier; Amédée, Joëlle

    2015-03-01

    Current approaches in bone tissue engineering have shown limited success, mostly owing to insufficient vascularization of the construct. A common approach consists of co-culture of endothelial cells and osteoblastic cells. This strategy uses cells from different sources and differentiation states, thus increasing the complexity upstream of a clinical application. The source of reparative cells is paramount for the success of bone tissue engineering applications. In this context, stem cells obtained from human bone marrow hold much promise. Here, we analyzed the potential of human whole bone marrow cells directly expanded in a three-dimensional (3D) polymer matrix and focused on the further characterization of this heterogeneous population and on their ability to promote angiogenesis and osteogenesis, both in vitro and in vivo, in a subcutaneous model. Cellular aggregates were formed within 24 h and over the 12-day culture period expressed endothelial and bone-specific markers and a specific junctional protein. Ectopic implantation of the tissue-engineered constructs revealed osteoid tissue and vessel formation both at the periphery and within the implant. This work sheds light on the potential clinical use of human whole bone marrow for bone regeneration strategies, focusing on a simplified approach to develop a direct 3D culture without two-dimensional isolation or expansion.

  3. Engineering and commercialization of human-device interfaces, from bone to brain.

    Science.gov (United States)

    Knothe Tate, Melissa L; Detamore, Michael; Capadona, Jeffrey R; Woolley, Andrew; Knothe, Ulf

    2016-07-01

    Cutting edge developments in engineering of tissues, implants and devices allow for guidance and control of specific physiological structure-function relationships. Yet the engineering of functionally appropriate human-device interfaces represents an intractable challenge in the field. This leading opinion review outlines a set of current approaches as well as hurdles to design of interfaces that modulate transfer of information, i.a. forces, electrical potentials, chemical gradients and haptotactic paths, between endogenous and engineered body parts or tissues. The compendium is designed to bridge across currently separated disciplines by highlighting specific commonalities between seemingly disparate systems, e.g. musculoskeletal and nervous systems. We focus on specific examples from our own laboratories, demonstrating that the seemingly disparate musculoskeletal and nervous systems share common paradigms which can be harnessed to inspire innovative interface design solutions. Functional barrier interfaces that control molecular and biophysical traffic between tissue compartments of joints are addressed in an example of the knee. Furthermore, we describe the engineering of gradients for interfaces between endogenous and engineered tissues as well as between electrodes that physically and electrochemically couple the nervous and musculoskeletal systems. Finally, to promote translation of newly developed technologies into products, protocols, and treatments that benefit the patients who need them most, regulatory and technical challenges and opportunities are addressed on hand from an example of an implant cum delivery device that can be used to heal soft and hard tissues, from brain to bone. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  4. Glucocorticoids affect the metabolism of bone marrow stromal cells and lead to osteonecrosis of the femoral head: a review

    Institute of Scientific and Technical Information of China (English)

    TAN Gang; KANG Peng-de; PEI Fu-xing

    2012-01-01

    Objective To review the recent developments in the mechanisms of glucocorticoids induced osteonecrosis of femoral head (ONFH) and introduce a new theory of ONFH.Data sources Both Chinese- and English-language literatures were searched using MEDLINE (1997-2011),Pubmed (1997-2011 ) and the Index of Chinese-language Literature (1997-2011 ).Study selection Data from published articles about mechanisms of glucocorticoids induced ONFH in recent domestic and foreign literature were selected.Data extraction Data were mainly extracted from 61 articles which are listed in the reference section of this review.Results Glucocorticoids are steroid hormones secreted by the adrenal cortex that play a pivotal role in the regulation of a variety of developmental,metabolic and immune functions.However,high dose of exogenous glucocorticoids usage is the most common non-traumatic cause of ON FH.Glucocorticoids can affect the metabolisms of osteoblasts,osteoclasts,bone marrow stromal cells and adipocytes which decrease osteoblasts formation but increase adipocytes formation and cause ONFH finally.Conclusions Glucocorticoids affect the differentiation of mesenchymal stem cells,through activating or inhibiting the related transcript regulators of osteogenesis and adipogenesis.At last,the size and volume of mesenchymal stem cells derived adipocytes will increase amazingly,but the osteoblasts will be decreased obviously.In the meantime,the activity of the osteoclasts will be activated.So,these mechanisms work together and lead to ONFH.

  5. In Vitro Fracture of Human Cortical Bone: Local Fracture Criteria and Toughening Mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Nalla, R; Stolken, J; Kinney, J; Ritchie, R

    2004-08-18

    A micro-mechanistic understanding of bone fracture that encompasses how cracks interact with the underlying microstructure and defines their local failure mode is lacking, despite extensive research on the response of bone to a variety of factors like aging, loading, and/or disease. Micro-mechanical models for fracture incorporating such local failure criteria have been widely developed for metallic and ceramic materials systems; however, few such deliberations have been undertaken for the fracture of bone. In fact, although the fracture event in mineralized tissues such as bone is commonly believed to be locally strain controlled, until recently there has been little experimental evidence to support this widely held belief. In the present study, a series of in vitro experiments involving a double-notch bend test geometry are performed in order to shed further light on the nature of the local cracking events that precede catastrophic fracture in bone and to define their relationship to the microstructure. Specifically, crack-microstructure interactions are examined to determine the salient toughening mechanisms in human cortical bone and to characterize how these may affect the anisotropy in fracture properties. Based on preliminary micro-mechanical models of these processes, in particular crack deflection and uncracked ligament bridging, the relative importance of these toughening mechanisms is established.

  6. [Diagnostics of the skeletal massiveness and human somatotype using hand bones].

    Science.gov (United States)

    Zviagin, V N; Zamiatina, A O; Galitskaia, O I

    2003-01-01

    The skeleton massiveness (SM) and the somatotype of human constitution were determined on the basis of osteometry of bones of carpal and metacarpal bones (MB) and of phalanxes. Seventy male and 13 female skeletons from the collection of the chair for anthropology, Moscow State University, were investigated. Described are the results of examinations of 8 carpal bones made according to 3 signs (length, width, and height), and of 5 metacarpal bones made according to 4 signs (length, base and head width, and base height); investigation findings of finger phalanxes (in full) are also presented. Methods of current multidimensional statistics were used within the case study, i.e. related with the key components--for SM specification and the discriminative analysis--for constitution specification. The SM determination accuracy according to type A was 40%, according to type B--80%, according to type C--37.5% and according to type D--52.9%. The classification accuracy of constitutions by carpal bones was 50.0%, by MB--46.4%, and by MB plus finger phalanxes--48.1%. It is pointed out that it was for the first time that the elaborated quantitative criteria of osteometry of hand bones could be used in the expertise practice for the purpose of personality identification by osseous remains.

  7. Influence of Environmental Factors and Relationships between Vanadium, Chromium, and Calcium in Human Bone.

    Science.gov (United States)

    Lanocha-Arendarczyk, Natalia; Kosik-Bogacka, Danuta I; Kalisinska, Elzbieta; Sokolowski, Sebastian; Kolodziej, Lukasz; Budis, Halina; Safranow, Krzysztof; Kot, Karolina; Ciosek, Zaneta; Tomska, Natalia; Galant, Katarzyna

    2016-01-01

    The aim of this study was to investigate the impact of environmental factors on the concentrations of vanadium (V), chromium (Cr), and calcium (Ca) and to examine the synergistic or antagonistic relationships between these metals, in cartilage (C), cortical bone (CB), and spongy bone (SB) samples obtained following hip joint surgery on patients with osteoarthritis in NW Poland. We found significantly higher concentrations of V and Cr in spongy bone in patients who consumed game meat and also those with prosthetic implants. Chromium levels were significantly lower in patients with kidney diseases. The greatest positive correlations were found between spongy bone V and (i) the amount of consumed beer and (ii) seafood diet. Correlation analysis also showed a significant correlation between Cr levels and seafood diet. To a certain extent these results indicate that the concentrations of V, Cr, and Ca in the human hip joint tissues are connected with occupational exposure, kidney diseases, diet containing game meat, sea food, beer, and the presence of implants. Furthermore, we noted new types of interactions in specific parts of the femoral head. Vanadium may contribute to the lower bone Ca levels, especially in the external parts (cartilage and cortical bone).

  8. The Pyrolytic Profile of Lyophilized and Deep-Frozen Compact Part of the Human Bone

    Directory of Open Access Journals (Sweden)

    Jolanta Lodowska

    2012-01-01

    Full Text Available Background. Bone grafts are used in the treatment of nonunion of fractures, bone tumors and in arthroplasty. Tissues preserved by lyophilization or deep freezing are used as implants nowadays. Lyophilized grafts are utilized in the therapy of birth defects and bone benign tumors, while deep-frozen ones are applied in orthopedics. The aim of the study was to compare the pyrolytic pattern, as an indirect means of the analysis of organic composition of deep-frozen and lyophilized compact part of the human bone. Methods. Samples of preserved bone tissue were subjected to thermolysis and tetrahydroammonium-hydroxide- (TMAH- associated thermochemolysis coupled with gas chromatography and mass spectrometry (Py-GC/MS. Results. Derivatives of benzene, pyridine, pyrrole, phenol, sulfur compounds, nitriles, saturated and unsaturated aliphatic hydrocarbons, and fatty acids (C12–C20 were identified in the pyrolytic pattern. The pyrolyzates were the most abundant in derivatives of pyrrole and nitriles originated from proteins. The predominant product in pyrolytic pattern of the investigated bone was pyrrolo[1,2-α]piperazine-3,6-dione derived from collagen. The content of this compound significantly differentiated the lyophilized graft from the deep-frozen one. Oleic and palmitic acid were predominant among fatty acids of the investigated samples. The deep-frozen implants were characterized by higher percentage of long-chain fatty acids than lyophilized grafts.

  9. Influence of Environmental Factors and Relationships between Vanadium, Chromium, and Calcium in Human Bone

    Directory of Open Access Journals (Sweden)

    Natalia Lanocha-Arendarczyk

    2016-01-01

    Full Text Available The aim of this study was to investigate the impact of environmental factors on the concentrations of vanadium (V, chromium (Cr, and calcium (Ca and to examine the synergistic or antagonistic relationships between these metals, in cartilage (C, cortical bone (CB, and spongy bone (SB samples obtained following hip joint surgery on patients with osteoarthritis in NW Poland. We found significantly higher concentrations of V and Cr in spongy bone in patients who consumed game meat and also those with prosthetic implants. Chromium levels were significantly lower in patients with kidney diseases. The greatest positive correlations were found between spongy bone V and (i the amount of consumed beer and (ii seafood diet. Correlation analysis also showed a significant correlation between Cr levels and seafood diet. To a certain extent these results indicate that the concentrations of V, Cr, and Ca in the human hip joint tissues are connected with occupational exposure, kidney diseases, diet containing game meat, sea food, beer, and the presence of implants. Furthermore, we noted new types of interactions in specific parts of the femoral head. Vanadium may contribute to the lower bone Ca levels, especially in the external parts (cartilage and cortical bone.

  10. Mineralization of human bone tissue under hypokinesia and physical exercise with calcium supplements

    Science.gov (United States)

    Zorbas, Yan G.; Verentsov, Grigori E.; Abratov, Nikolai I.

    It has been suggested that physical exercise and calcium supplements may be used to prevent demineralization of bone tissue under hypokinesia (diminished muscular activity). Thus, the aim of this study was to determine mineral content of bones of 12 physically healthy men aged 19-24 years under 90 days of hypokinesia and intensive physical exercise (PE) with calcium lactate (C) supplements. They were divided into experimental and control groups with 6 men in each. The experimental group of men were subjected to hypokinesia (HK) and intensive PE and took 650 mg C 6 times per day; the control group was placed under pure HK, i.e. without the use of any preventive measures. The mineral content of different bone tissues was measured with a densitometric X-ray method in milligrams of calcium per 1 mm 3 before and after exposure to HK. The level of bone density of the examined bone tissues decreased by 7-9% and 5-7% for the control and experimental groups of men, respectively. A statistical analysis revealed that the reduction of bone mineralization was significant with P human organisms, since the entire animal kingdom had been formed in an environment of high motor activity which left its imprint on the evolution, structure, function and behaviour of animals and men. The impossibility of the body tissues to retain optimum amounts of fluid and electrolytes is the dominant hypokinetic effect.

  11. Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis

    DEFF Research Database (Denmark)

    Jafari Kermani, Abbas; Qanie, Diyako; Andersen, Thomas L

    2017-01-01

    Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells...

  12. The Human Figure Drawing with Donor and Nondonor Siblings of Pediatric Bone Marrow Transplant Patients.

    Science.gov (United States)

    Packman, Wendy L.; Beck, Vanessa L.; VanZutphen, Kelly H.; Long, Janet K.; Spengler, Gisele

    2003-01-01

    There is little research on the psychological impact of bone marrow transplantation (BMT) on family members. This study uses the Human Figure Drawing (HFD) to measure siblings' emotional distress toward BMT. Among the siblings, feelings of isolation, anger, depression, anxiety, and low self-esteem emerged as major themes. Findings indicate the…

  13. Forskolin enhances in vivo bone formation by human mesenchymal stromal cells

    NARCIS (Netherlands)

    Doorn, J.; Siddappa, R.; Blitterswijk, van C.A.; Boer, de J.

    2012-01-01

    Activation of the protein kinase A (PKA) pathway with dibutyryl cyclic adenosine monophosphate (db-cAMP) was recently shown to enhance osteogenic differentiation of human mesenchymal stromal cells (hMSCs) in vitro and bone formation in vivo. The major drawback of this compound is its inhibitory effe

  14. Human bone marrow mesenchymal stem cell transplantation attenuates axonal injur y in stroke rats

    Institute of Scientific and Technical Information of China (English)

    Yi Xu; Shiwei Du; Xinguang Yu; Xiao Han; Jincai Hou; Hao Guo

    2014-01-01

    Previous studies have shown that transplantation of human bone marrow mesenchymal stem cells promotes neural functional recovery after stroke, but the neurorestorative mechanisms remain largely unknown. We hypothesized that functional recovery of myelinated axons may be one of underlying mechanisms. In this study, an ischemia/reperfusion rat model was established using the middle cerebral artery occlusion method. Rats were used to test the hypothesis that in-travenous transplantation of human bone marrow mesenchymal stem cells through the femoral vein could exert neuroprotective effects against cerebral ischemia via a mechanism associated with the ability to attenuate axonal injury. The results of behavioral tests, infarction volume analysis and immunohistochemistry showed that cerebral ischemia caused severe damage to the myelin sheath and axons. After rats were intravenously transplanted with human bone marrow mesenchymal stem cells, the levels of axon and myelin sheath-related proteins, including mi-crotubule-associated protein 2, myelin basic protein, and growth-associated protein 43, were elevated, infarct volume was decreased and neural function was improved in cerebral ischemic rats. These ifndings suggest that intravenously transplanted human bone marrow mesenchymal stem cells promote neural function. Possible mechanisms underlying these beneifcial effects in-clude resistance to demyelination after cerebral ischemia, prevention of axonal degeneration, and promotion of axonal regeneration.

  15. Increased presence of capillaries next to remodeling sites in adult human cancellous bone

    DEFF Research Database (Denmark)

    Kristensen, Helene Bjoerg; Andersen, Thomas Levin; Marcussen, Niels;

    2013-01-01

    by pericytes. Furthermore, the BRC canopy cells were found to express SMA. These ordered distributions support the existence of an osteogenic-vascular interface in adult human cancellous bone. The organization of this interface fits the current knowledge on the mode of action of vasculature on osteogenesis...

  16. Development of biomimetic nanocomposites as bone extracellular matrix for human osteoblastic cells.

    Science.gov (United States)

    Bhowmick, Arundhati; Mitra, Tapas; Gnanamani, Arumugam; Das, Manas; Kundu, Patit Paban

    2016-05-05

    Here, we have developed biomimetic nanocomposites containing chitosan, poly(vinyl alcohol) and nano-hydroxyapatite-zinc oxide as bone extracellular matrix for human osteoblastic cells and characterized by Fourier transform infrared spectroscopy, powder X-ray diffraction. Scanning electron microscopy images revealed interconnected macroporous structures. Moreover, in this study, the problem related to fabricating a porous composite with good mechanical strength has been resolved by incorporating 5wt% of nano-hydroxyapatite-zinc oxide into chitosan-poly(vinyl alcohol) matrix; the present composite showed high tensile strength (20.25MPa) while maintaining appreciable porosity (65.25%). These values are similar to human cancellous bone. These nanocomposites also showed superior water uptake, antimicrobial and biodegradable properties than the previously reported results. Compatibility with human blood and pH was observed, indicating nontoxicity of these materials to the human body. Moreover, proliferation of osteoblastic MG-63 cells onto the nanocomposites was also observed without having any negative effect.

  17. Biomechanics Analysis of Pressure Ulcer Using Damaged Interface Model between Bone and Muscle in the Human Buttock

    Science.gov (United States)

    Slamet, Samuel Susanto; Takano, Naoki; Tanabe, Yoshiyuki; Hatano, Asako; Nagasao, Tomohisa

    This paper aims at building up a computational procedure to study the bio-mechanism of pressure ulcer using the finite element method. Pressure ulcer is a disease that occurs in the human body after 2 hours of continuous external force. In the very early stage of pressure ulcer, it is found that the tissues inside the body are damaged, even though skin surface looks normal. This study assumes that tension and/or shear strain will cause damage to loose fibril tissue between the bone and muscle and that propagation of damaged area will lead to fatal stage. Analysis was performed using the finite element method by modeling the damaged fibril tissue as a cutout. By varying the loading directions and watching both tensile and shear strains, the risk of fibril tissue damage and propagation of the damaged area is discussed, which may give new insight for the careful nursing for patients, particularly after surgical treatment. It was found that the pressure ulcer could reoccur for a surgical flap treatment. The bone cut and surgical flap surgery is not perfect to prevent the bone-muscle interfacial damage.

  18. [Comparison of fluoride concentrations in human, dog, fox and raccoon dog bones from northwestern Poland].

    Science.gov (United States)

    Palczewska-Komsa, Mirona

    2015-01-01

    Since the beginning of the XXth there has been a constant increase in fluoride (F-) emissions into the environment, mainly due to the development of industry, the fluoridation of drinking water, and the widespread use of toothpaste containing fluoride. All these factors have resulted in an intensive accumulation of F- in the bodies of vertebrates, mainly in their bones. It is therefore reasonable to estimate the F- concentration in humans and other long-lived mammals. Accordingly, ecotoxicologists worldwide have looked for mammalian species that may serve as good bioindicators of environmental fluoride pollution. In contrast to ungulates, long-lived domestic mammals and wild carnivores have rarely been used for this purpose (including the dog, fox and raccoon dog). The main aims of this study were to: 1) investigate F- concentrations in bones obtained from humans, dog, fox and raccoon dog from northwestern Poland, 2) perform intra- and inter-specific comparisons of F- concentrations in the studied mammalian bones against the background of environmental and living conditions, 3) examine the relationship between concentrations of F- in bones and the age or age category of the studied mammals. The study material comprised bones of the hip joint obtained from 36 patients who underwent hip replacement in Szczecin, 43 dogs from Szczecin veterinary clinics, 32 foxes and 18 raccoon dogs provided by hunters, with the whole test material consisting of 129 samples. The indications of F- (using potentiometry with Thermo Orion ion-selective electrodes) were performed in triplicate. The F- concentration was expressed on a dry weight basis. Interspecific analysis showed that the largest number of differences in the concentrations of F- were between the fox and raccoon, and then between the dog and fox, and then between the dog and the wild canids (foxes and raccoon dogs together). Close statistically significant differences were also found between the samples from humans and the

  19. Increased extracellular and intracellular Ca{sup 2+} lead to adipocyte accumulation in bone marrow stromal cells by different mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Ryota, E-mail: hryota@juntendo.ac.jp [Department of Physiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Katoh, Youichi, E-mail: katoyo@juntendo-urayasu.jp [Juntendo University Faculty of International Liberal Arts, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Department of Cardiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Miyamoto, Yuki [Juntendo University Faculty of Health Care and Nursing, Takasu 2-5-1, Urayasu-shi, Chiba 279-0023 (Japan); Itoh, Seigo; Daida, Hiroyuki [Department of Cardiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan); Nakazato, Yuji [Center for Environmental Research, Department of Cardiology, Juntendo University Faculty of Medicine Urayasu Hospital, Tomioka 2-1-1, Urayasu-shi, Chiba 279-0022 (Japan); Okada, Takao [Department of Physiology, Juntendo University Faculty of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo 113-8421 (Japan)

    2015-02-20

    Mesenchymal stem cells found in bone marrow stromal cells (BMSCs) are the common progenitors for both adipocyte and osteoblast. An increase in marrow adipogenesis is associated with age-related osteopenia and anemia. Both extracellular and intracellular Ca{sup 2+} ([Ca{sup 2+}]{sub o} and [Ca{sup 2+}]{sub i}) are versatile signaling molecules that are involved in the regulation of cell functions, including proliferation and differentiation. We have recently reported that upon treatment of BMSCs with insulin and dexamethasone, both high [Ca{sup 2+}]{sub o} and high [Ca{sup 2+}]{sub i} enhanced adipocyte accumulation, which suggested that increases in [Ca{sup 2+}]{sub o} caused by bone resorption may accelerate adipocyte accumulation in aging and diabetic patients. In this study, we used primary mouse BMSCs to investigate the mechanisms by which high [Ca{sup 2+}]{sub o} and high [Ca{sup 2+}]{sub i} may enhance adipocyte accumulation. In the process of adipocyte accumulation, two important keys are adipocyte differentiation and the proliferation of BMSCs, which have the potential to differentiate into adipocytes. Use of MTT assay and real-time RT-PCR revealed that high [Ca{sup 2+}]{sub i} (ionomycin)-dependent adipocyte accumulation is caused by enhanced proliferation of BMSCs but not enhanced differentiation into adipocytes. Using fura-2 fluorescence-based approaches, we showed that high [Ca{sup 2+}]{sub o} (addition of CaCl{sub 2}) leads to increases in [Ca{sup 2+}]{sub i}. Flow cytometric methods revealed that high [Ca{sup 2+}]{sub o} suppressed the phosphorylation of ERK independently of intracellular Ca{sup 2+}. The inhibition of ERK by U0126 and PD0325901 enhanced the differentiation of BMSCs into adipocytes. These data suggest that increased extracellular Ca{sup 2+} provides the differentiation of BMSCs into adipocytes by the suppression of ERK activity independently of increased intracellular Ca{sup 2+}, which results in BMSC proliferation. - Highlights:

  20. Effects of ionizing radiation on proteins in demineralized, lyophilized or frozen human bone

    Energy Technology Data Exchange (ETDEWEB)

    Antebi, Uri; Mathor, Monica B., E-mail: uri@usp.br, E-mail: mathor@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Guimaraes, Rodrigo P., E-mail: clinicaguimaraes@gmail.com [Santa Casa de Sao Paulo (FCM/SCSP), Sao Paulo, SP (Brazil). Faculdade de Ciencias Medicas

    2015-07-01

    The aim is the study of the application of ionizing radiation (gamma and electron) as sterilizing agents at doses of 15 kGy, 25 kGy and 50 kGy, the demineralized bone tissue frozen and freeze-dried for use in transplants. Five human femoral diaphysis of different donors demineralized bone tissues were preserved as lyophilized or frozen at - 80 deg C. The samples were divided into non-irradiated groups (control) and irradiated by gamma rays or electron beam. The bone proteins were extracted and used to determine the concentrations of total protein, BMP 2 and 7. It was observed a decrease in total protein concentrations, and BMP 2 and 7. The decrease in total protein concentrations, as compared to respective control groups was significant in the lyophilized and frozen samples irradiated at a dose of 50 kGy gamma radiation and beam electrons with greater than 30% reduction. The significant decrease in the levels of BMP 2 and 7 were also observed in higher doses and especially by electron beam. The reductions in the concentrations of total protein and osteoinductive proteins (BMP 2 and 7), were related to the radiation dose, i.e., increase with higher doses of ionizing radiation type and the type of preservation of the bones. The largest reductions in concentrations were observed in bone irradiated by electron beam and at a dose of 50 kGy. But this type of radiation and this high dose are not usual practice for the sterilization of bone tissue. Keywords: demineralized bone tissue, ionizing radiation, Tissue Bank, BMP 2, BMP 7, bone proteins. (author)

  1. The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering.

    Science.gov (United States)

    Moreno-Jiménez, Inés; Hulsart-Billstrom, Gry; Lanham, Stuart A; Janeczek, Agnieszka A; Kontouli, Nasia; Kanczler, Janos M; Evans, Nicholas D; Oreffo, Richard Oc

    2016-08-31

    Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect, and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p < 0.01). This human-avian system offers a simple refinement model for animal research and a step towards a humanized in vivo model for tissue engineering.

  2. The chorioallantoic membrane (CAM) assay for the study of human bone regeneration: a refinement animal model for tissue engineering

    Science.gov (United States)

    Moreno-Jiménez, Inés; Hulsart-Billstrom, Gry; Lanham, Stuart A.; Janeczek, Agnieszka A.; Kontouli, Nasia; Kanczler, Janos M.; Evans, Nicholas D.; Oreffo, Richard Oc

    2016-08-01

    Biomaterial development for tissue engineering applications is rapidly increasing but necessitates efficacy and safety testing prior to clinical application. Current in vitro and in vivo models hold a number of limitations, including expense, lack of correlation between animal models and human outcomes and the need to perform invasive procedures on animals; hence requiring new predictive screening methods. In the present study we tested the hypothesis that the chick embryo chorioallantoic membrane (CAM) can be used as a bioreactor to culture and study the regeneration of human living bone. We extracted bone cylinders from human femoral heads, simulated an injury using a drill-hole defect, and implanted the bone on CAM or in vitro control-culture. Micro-computed tomography (μCT) was used to quantify the magnitude and location of bone volume changes followed by histological analyses to assess bone repair. CAM blood vessels were observed to infiltrate the human bone cylinder and maintain human cell viability. Histological evaluation revealed extensive extracellular matrix deposition in proximity to endochondral condensations (Sox9+) on the CAM-implanted bone cylinders, correlating with a significant increase in bone volume by μCT analysis (p < 0.01). This human-avian system offers a simple refinement model for animal research and a step towards a humanized in vivo model for tissue engineering.

  3. Methodologies for Development of Patient Specific Bone Models from Human Body CT Scans

    Science.gov (United States)

    Chougule, Vikas Narayan; Mulay, Arati Vinayak; Ahuja, Bharatkumar Bhagatraj

    2016-06-01

    This work deals with development of algorithm for physical replication of patient specific human bone and construction of corresponding implants/inserts RP models by using Reverse Engineering approach from non-invasive medical images for surgical purpose. In medical field, the volumetric data i.e. voxel and triangular facet based models are primarily used for bio-modelling and visualization, which requires huge memory space. On the other side, recent advances in Computer Aided Design (CAD) technology provides additional facilities/functions for design, prototyping and manufacturing of any object having freeform surfaces based on boundary representation techniques. This work presents a process to physical replication of 3D rapid prototyping (RP) physical models of human bone from various CAD modeling techniques developed by using 3D point cloud data which is obtained from non-invasive CT/MRI scans in DICOM 3.0 format. This point cloud data is used for construction of 3D CAD model by fitting B-spline curves through these points and then fitting surface between these curve networks by using swept blend techniques. This process also can be achieved by generating the triangular mesh directly from 3D point cloud data without developing any surface model using any commercial CAD software. The generated STL file from 3D point cloud data is used as a basic input for RP process. The Delaunay tetrahedralization approach is used to process the 3D point cloud data to obtain STL file. CT scan data of Metacarpus (human bone) is used as the case study for the generation of the 3D RP model. A 3D physical model of the human bone is generated on rapid prototyping machine and its virtual reality model is presented for visualization. The generated CAD model by different techniques is compared for the accuracy and reliability. The results of this research work are assessed for clinical reliability in replication of human bone in medical field.

  4. Route of delivery influences biodistribution of human bone marrow-derived mesenchymal stromal cells following experimental bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Wang FJ

    2015-12-01

    Full Text Available Mesenchymal stromal cells (MSCs have shown promise as treatment for graft-versus-host disease (GvHD following allogeneic bone marrow transplantation (alloBMT. Mechanisms mediating in vivo effects of MSCs remain largely unknown, including their biodistribution following infusion. To this end, human bone-marrow derived MSCs (hMSCs were injected via carotid artery (IA or tail vein (TV into allogeneic and syngeneic BMT recipient mice. Following xenogeneic transplantation, MSC biodistribution was measured by bioluminescence imaging (BLI using hMSCs transduced with a reporter gene system containing luciferase and by scintigraphic imaging using hMSCs labeled with [99mTc]-HMPAO. Although hMSCs initially accumulated in the lungs in both transplant groups, more cells migrated to organs in alloBMT recipient as measured by in vivo BLI and scintigraphy and confirmed by ex vivo BLI imaging, immunohistochemistry and quantitative RT-PCR. IA injection resulted in persistent whole–body hMSC distribution in alloBMT recipients, while hMSCs were rapidly cleared in the syngeneic animals within one week. In contrast, TV-injected hMSCs were mainly seen in the lungs with fewer cells traveling to other organs. Summarily, these results demonstrate the potential use of IA injection to alter hMSC biodistribution in order to more effectively deliver hMSCs to targeted tissues and microenvironments.

  5. Contour changes in human alveolar bone following tooth extraction of the maxillary central incisor.

    Science.gov (United States)

    Li, Bei; Wang, Yao

    2014-12-01

    The purpose of this study was to apply cone-beam computed tomography (CBCT) to observe contour changes in human alveolar bone after tooth extraction of the maxillary central incisor and to provide original morphological evidence for aesthetic implant treatment in the maxillary anterior area. Forty patients were recruited into the study. Each patient had two CBCT scans (CBCT I and CBCT II), one taken before and one taken three months after tooth extraction of maxillary central incisor (test tooth T). A fixed anatomic reference point was used to orient the starting axial slice of the two scans. On three CBCT I axial slices, which represented the deep, middle, and shallow layers of the socket, labial and palatal alveolar bone widths of T were measured. The number of sagittal slices from the start point to the pulp centre of T was recorded. On three CBCT II axial slices, the pulp centres of extracted T were oriented according to the number of moved sagittal slices recorded in CBCT I. Labial and palatal alveolar bone widths at the oriented sites were measured. On the CBCT I axial slice which represented the middle layer of the socket, sagittal slices were reconstructed. Relevant distances of T on the sagittal slice were measured, as were the alveolar bone width and tooth length of the opposite central incisor. On the CBCT II axial slice, which represented the middle layer of the socket, relevant distances recorded in CBCT I were transferred on the sagittal slice. The height reduction of alveolar bone on labial and palatal sides was measured, as were the alveolar bone width and tooth length of the opposite central incisor at the oriented site. Intraobserver reliability assessed by intraclass correlation coefficients (ICCs) was high. Paired sample t-tests were performed. The alveolar bone width and tooth length of the opposite central incisor showed no statistical differences (P<0.05). The labial alveolar bone widths of T at the deep, middle, and shallow layers all showed

  6. Lead levels in human teeth from the inhabitants of Mexico City from three different historical periods

    Energy Technology Data Exchange (ETDEWEB)

    Mansilla, J.; Solis, C.; Chavez, M.E. [Instituto Nacional de Antropologia e Historia, Direccion de Antropologia Fisica, Mexico D.F. (Mexico)

    1999-07-01

    Human teeth from pre-Columbian, colonial and contemporary population groups were analyzed by PIXE in order to evaluate the lead contents in the inhabitants of Mexico City through different historical periods. Lead contents showed significant differences among the three groups, in Pre-Columbian teeth no lead was found, colonial teeth showed higher lead levels than contemporary ones. This results suggest that the native americans had no exposure to this toxic metal. The lead-glaze pottery introduced by the Spaniards, utilized in pottery and lead pipes, was the main source of lead in the colonial period. In recent teeth the deposited lead is mainly due to the absorption from the contaminated atmosphere. (Author)

  7. Use of a graft of demineralized bone matrix along with TGF-β1 leads to an early bone repair in dogs.

    Science.gov (United States)

    Servin-Trujillo, Miguel Angel; Reyes-Esparza, Jorge Alberto; Garrido-Fariña, German; Flores-Gazca, Enrique; Osuna-Martinez, Ulises; Rodriguez-Fragoso, Lourdes

    2011-09-01

    Tibia fractures are common in small animal practice. Over the past decade, improvements to animal internal fracture fixation have been developed. TGF-β1 has been shown to be crucial in the development, induction and repair of bone. In present study, we investigate the effect of local application of a graft demineralized bone matrix (DBM) along with TGF-β1 in a model of open osteotomy induced experimentally in dogs. Tibia fracture was brought about by using an open osteotomy model in young male dogs. Fracture repair was evaluated by a histological and biochemical analysis. Collagen content, proteolytic activity and urokinase-type plasminogen activator (uPA) expression were analyzed at the end of the study. Radiographic analysis, alkaline phosphatase and hematological evaluation were performed weekly. At the fifth week, there was an improvement and restoration of bone architecture in animals treated with a graft containing TGF-β1 (5 ng/ml) compared with the control and graft groups, as was evidenced by the presence of an early formation of wide callus and bone regeneration. In addition, local application of TGF-β1 led to an increase in collagen and proteolytic activity. More immunopositive osteoclast and mesenchymal cells were found in bone tissue from animals treated with TGF-β1 as compared with the control group. No changes in alkaline phosphatase, hematological and clinical parameters were observed. This study shows that the combined use of DBM along with TGF-β1 is able to improve and accelerate the bone repair.

  8. Correlative Light and Scanning X-Ray Scattering Microscopy of Healthy and Pathologic Human Bone Sections

    Science.gov (United States)

    Giannini, C.; Siliqi, D.; Bunk, O.; Beraudi, A.; Ladisa, M.; Altamura, D.; Stea, S.; Baruffaldi, F.

    2012-01-01

    Scanning small and wide angle X-ray scattering (scanning SWAXS) experiments were performed on healthy and pathologic human bone sections. Via crystallographic tools the data were transformed into quantitative images and as such compared with circularly polarized light (CPL) microscopy images. SWAXS and CPL images allowed extracting information of the mineral nanocrystalline phase embedded, with and without preferred orientation, in the collagen fibrils, mapping local changes at sub-osteon resolution. This favorable combination has been applied for the first time to biopsies of dwarfism syndrome and Paget's disease to shed light onto the cortical structure of natural bone in healthy and pathologic sections. PMID:22666538

  9. Evaluation of the osteogenesis and angiogenesis effects of erythropoietin and the efficacy of deproteinized bovine bone/recombinant human erythropoietin scaffold on bone defect repair.

    Science.gov (United States)

    Li, Donghai; Deng, Liqing; Xie, Xiaowei; Yang, Zhouyuan; Kang, Pengde

    2016-06-01

    Erythropoietin (EPO) could promote the angiogenesis and may also play a role in bone regeneration. This study was conducted to evaluate the osteogenesis and angiogenesis effects of EPO and the efficacy of deproteinized bovine bone/recombinant human EPO scaffold on bone defect repair. Twenty-four healthy adult goats were chosen to build goat defects model and randomly divided into four groups. The goats were treated with DBB/rhEPO scaffolds (group A), porous DBB scaffolds (group B), autogenous cancellous bone graft (group C), and nothing (group D). Animals were evaluated with radiological and histological methods at 4, 8 and 12 weeks after surgery. The grey value of radiographs was used to evaluate the healing of the defects and the outcome revealed that the group A had a better outcome of defect healing compared with group B (P 0.05). The newly formed bone area was calculated from histological sections and the results demonstrated that the amount of new bone in group A increased significantly compared with that in group B (P 0.05) at 4, 8, 12 weeks respectively. In addition, the expression of vascular endothelial growth factor (VEGF) by immunohistochemical testing and real-time polymerase chain reaction at 12 weeks in group A was significantly higher than that in group B (P 0.05). Therefore, EPO has significant effects on bone formation and angiogenesis, and has capacity to promote the repair of bone defects. It is worthy of being recommended to further studies.

  10. Relevancy of human exposure via house dust to the contaminants lead and asbestos

    NARCIS (Netherlands)

    Oomen AG; Lijzen JPA; SIR; LER

    2004-01-01

    The present report addresses the issues whether house dust is likely to contribute substantially to the exposure of humans, in particular for the contaminants lead and asbestos. House dust consists for 30-70% of soil material, indicating that contaminated soil can lead to contaminated house dust. It

  11. Relevancy of human exposure via house dust to the contaminants lead and asbestos

    NARCIS (Netherlands)

    Oomen AG; Lijzen JPA; SIR; LER

    2004-01-01

    The present report addresses the issues whether house dust is likely to contribute substantially to the exposure of humans, in particular for the contaminants lead and asbestos. House dust consists for 30-70% of soil material, indicating that contaminated soil can lead to contaminated house dust. It

  12. Selective deletion of the membrane-bound colony stimulating factor 1 isoform leads to high bone mass but does not protect against estrogen-deficiency bone loss

    OpenAIRE

    Yao, Gang-Qing; Wu, Jian-Jun; Troiano, Nancy; Zhu, Mei-Ling; Xiao, Xiao-Yan; Insogna, Karl

    2011-01-01

    To better define the biologic function of membrane-bound CSF1 (mCSF1) in vivo, we have generated mCSF1 knockout (k/o) mice. Spinal bone density (BMD) was 15.9% higher in k/o mice compared to wild-type (wt) controls (P < 0.01) and total BMD was increased by 6.8% (P < 0.05). A higher mean femur BMD was also observed but did not reach statistical significance (6.9% P = NS). The osteoclastogenic potential of bone marrow isolated from mCSF1 k/o mice was reduced compared to wt marrow. There were no...

  13. Osteogenic Differentiation Capacity of In Vitro Cultured Human Skeletal Muscle for Expedited Bone Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Chunlei Miao

    2017-01-01

    Full Text Available Expedited bone tissue engineering employs the biological stimuli to harness the intrinsic regenerative potential of skeletal muscle to trigger the reparative process in situ to improve or replace biological functions. When genetically modified with adenovirus mediated BMP2 gene transfer, muscle biopsies from animals have demonstrated success in regenerating bone within rat bony defects. However, it is uncertain whether the human adult skeletal muscle displays an osteogenic potential in vitro when a suitable biological trigger is applied. In present study, human skeletal muscle cultured in a standard osteogenic medium supplemented with dexamethasone demonstrated significant increase in alkaline phosphatase activity approximately 24-fold over control at 2-week time point. More interestingly, measurement of mRNA levels revealed the dramatic results for osteoblast transcripts of alkaline phosphatase, bone sialoproteins, transcription factor CBFA1, collagen type I, and osteocalcin. Calcified mineral deposits were demonstrated on superficial layers of muscle discs after an extended 8-week osteogenic induction. Taken together, these are the first data supporting human skeletal muscle tissue as a promising potential target for expedited bone regeneration, which of the technologies is a valuable method for tissue repair, being not only effective but also inexpensive and clinically expeditious.

  14. Osteogenic Differentiation Capacity of In Vitro Cultured Human Skeletal Muscle for Expedited Bone Tissue Engineering

    Science.gov (United States)

    Miao, Chunlei; Zhou, Lulu; Tian, Lufeng; Zhang, Yingjie; Zhang, Wei; Yang, Fanghong; Liu, Tianyi

    2017-01-01

    Expedited bone tissue engineering employs the biological stimuli to harness the intrinsic regenerative potential of skeletal muscle to trigger the reparative process in situ to improve or replace biological functions. When genetically modified with adenovirus mediated BMP2 gene transfer, muscle biopsies from animals have demonstrated success in regenerating bone within rat bony defects. However, it is uncertain whether the human adult skeletal muscle displays an osteogenic potential in vitro when a suitable biological trigger is applied. In present study, human skeletal muscle cultured in a standard osteogenic medium supplemented with dexamethasone demonstrated significant increase in alkaline phosphatase activity approximately 24-fold over control at 2-week time point. More interestingly, measurement of mRNA levels revealed the dramatic results for osteoblast transcripts of alkaline phosphatase, bone sialoproteins, transcription factor CBFA1, collagen type I, and osteocalcin. Calcified mineral deposits were demonstrated on superficial layers of muscle discs after an extended 8-week osteogenic induction. Taken together, these are the first data supporting human skeletal muscle tissue as a promising potential target for expedited bone regeneration, which of the technologies is a valuable method for tissue repair, being not only effective but also inexpensive and clinically expeditious. PMID:28210626

  15. Resorption of monetite granules in alveolar bone defects in human patients.

    Science.gov (United States)

    Tamimi, Faleh; Torres, Jesus; Bassett, David; Barralet, Jake; Cabarcos, Enrique L

    2010-04-01

    Bone grafting is often required to restore mandibular or maxillary bone volume prior to prosthetic tooth root implantation. Preclinical animal models are often used to study the in vivo properties of new bone graft products designed for human use. Although animal studies may offer valuable data regarding bioperformance, materials do not necessarily perform the same in human patients. In this study we implanted bovine hydroxyapatite (BH), a widely used porous apatite granule, and dicalcium phosphate anhydrous (monetite) granules, bilaterally in human patients post extraction alveolar sockets. After six months, histomorphometrical analysis of the biopsies revealed that the amount of bone regenerated with monetite (59.5 +/- 13%) was significantly higher than that obtained with BH (33.1% +/- 4.9), while the amount of unresorbed graft was higher in the sockets treated with BH (37.8 +/- 6.1) than in those implanted with monetite (25.8 +/- 14.3). Resorption of calcium phosphate ceramics is discussed by applying the Hixon-Crowell dissolution model.

  16. Biochemical and physical correlates of DNA contamination in archaeological human bones and teeth excavated at Matera, Italy

    DEFF Research Database (Denmark)

    Gilbert, M. T. P.; Rudbeck, L.; Willerslev, E.

    2005-01-01

    The majority of ancient DNA studies on human specimens have utilised teeth and bone as a source of genetic material. In this study the levels of endogenous contamination (i.e. present within the sample prior to sampling for the DNA analysis) are assessed within human bone and teeth specimens...... sampled from the cemetery of Santa Lucia alle Malve, Matera, Italy. This site is of exceptional interest, because the samples have been assayed for IS measures of biochemical and physical preservation, and it is the only one identified in a study of more than 107 animal and 154 human bones from 43 sites...... across Europe, where a significant number of human bones was well preserved. The findings demonstrate several important issues: (a) although teeth are more resilient to contamination than bone, both are readily contaminated (presumably through handling or washing), and (b) once contaminated in this way...

  17. A 3D in vitro bone organ model using human progenitor cells

    Directory of Open Access Journals (Sweden)

    A Papadimitropoulos

    2011-05-01

    Full Text Available Three-dimensional (3D organotypic culture models based on human cells may reduce the use of complex and costly animal models, while gaining clinical relevance. This study aimed at developing a 3D osteoblastic-osteoclastic-endothelial cell co-culture system, as an in vitro model to mimic the process of bone turnover. Osteoprogenitor and endothelial lineage cells were isolated from the stromal vascular fraction (SVF of human adipose tissue, whereas CD14+ osteoclast progenitors were derived from human peripheral blood. Cells were co-cultured within 3D porous ceramic scaffolds using a perfusion-based bioreactor device, in the presence of typical osteoclastogenic factors. After 3 weeks, the scaffolds contained cells with endothelial (2.0 ±0.3%, pre/osteoclastic (14.0 ±1.4% and mesenchymal/osteoblastic (44.0 ±8.4% phenotypes, along with tartrate-resistant acid phosphatase-positive (TRAP+ osteoclastic cells in contact with deposited bone-like matrix. Supernatant analysis demonstrated sustained matrix deposition (by C-terminus procollagen-I propeptides, resorption (by N-terminus collagen-I telopeptides and phosphate levels and osteoclastic activity (by TRAP-5b only when SVF and CD14+ cells were co-cultured. Scanning electron microscopy and magnetic resonance imaging confirmed the pattern of matrix deposition and resorption. The effectiveness of Vitamin D in replacing osteoclastogenic factors indicated a functional osteoblast-osteoclast coupling in the system. The formation of human-origin bone-like tissue, blood vessels and osteoclasts upon ectopic implantation validated the functionality of the developed cell types. The 3D co-culture system and the associated non-invasive analytical tools can be used as an advanced model to capture some aspects of the functional coupling of bone-like matrix deposition and resorption and could be exploited toward the engineering of multi-functional bone substitute implants.

  18. Osteoblast-specific deletion of Pkd2 leads to low-turnover osteopenia and reduced bone marrow adiposity.

    Directory of Open Access Journals (Sweden)

    Zhousheng Xiao

    Full Text Available Polycystin-1 (Pkd1 interacts with polycystin-2 (Pkd2 to form an interdependent signaling complex. Selective deletion of Pkd1 in the osteoblast lineage reciprocally regulates osteoblastogenesis and adipogenesis. The role of Pkd2 in skeletal development has not been defined. To this end, we conditionally inactivated Pkd2 in mature osteoblasts by crossing Osteocalcin (Oc-Cre;Pkd2+/null mice with floxed Pkd2 (Pkd2flox/flox mice. Oc-Cre;Pkd2flox/null (Pkd2Oc-cKO mice exhibited decreased bone mineral density, trabecular bone volume, cortical thickness, mineral apposition rate and impaired biomechanical properties of bone. Pkd2 deficiency resulted in diminished Runt-related transcription factor 2 (Runx2 expressions in bone and impaired osteoblastic differentiation ex vivo. Expression of osteoblast-related genes, including, Osteocalcin, Osteopontin, Bone sialoprotein (Bsp, Phosphate-regulating gene with homologies to endopeptidases on the X chromosome (Phex, Dentin matrix protein 1 (Dmp1, Sclerostin (Sost, and Fibroblast growth factor 23 (FGF23 were reduced proportionate to the reduction of Pkd2 gene dose in bone of Oc-Cre;Pkd2flox/+ and Oc-Cre;Pkd2flox/null mice. Loss of Pkd2 also resulted in diminished peroxisome proliferator-activated receptor γ (PPARγ expression and reduced bone marrow fat in vivo and reduced adipogenesis in osteoblast culture ex vivo. Transcriptional co-activator with PDZ-binding motif (TAZ and Yes-associated protein (YAP, reciprocally acting as co-activators and co-repressors of Runx2 and PPARγ, were decreased in bone of Oc-Cre;Pkd2flox/null mice. Thus, Pkd1 and Pkd2 have coordinate effects on osteoblast differentiation and opposite effects on adipogenesis, suggesting that Pkd1 and Pkd2 signaling pathways can have independent effects on mesenchymal lineage commitment in bone.

  19. Faster increases in human life expectancy could lead to slower population aging.

    Directory of Open Access Journals (Sweden)

    Warren C Sanderson

    Full Text Available Counterintuitively, faster increases in human life expectancy could lead to slower population aging. The conventional view that faster increases in human life expectancy would lead to faster population aging is based on the assumption that people become old at a fixed chronological age. A preferable alternative is to base measures of aging on people's time left to death, because this is more closely related to the characteristics that are associated with old age. Using this alternative interpretation, we show that faster increases in life expectancy would lead to slower population aging. Among other things, this finding affects the assessment of the speed at which countries will age.

  20. Faster Increases in Human Life Expectancy Could Lead to Slower Population Aging

    Science.gov (United States)

    2015-01-01

    Counterintuitively, faster increases in human life expectancy could lead to slower population aging. The conventional view that faster increases in human life expectancy would lead to faster population aging is based on the assumption that people become old at a fixed chronological age. A preferable alternative is to base measures of aging on people’s time left to death, because this is more closely related to the characteristics that are associated with old age. Using this alternative interpretation, we show that faster increases in life expectancy would lead to slower population aging. Among other things, this finding affects the assessment of the speed at which countries will age. PMID:25876033

  1. Differentiation of adult human bone marrow mesenchymal stem cells into Schwann-like cells in vitro

    Institute of Scientific and Technical Information of China (English)

    YANG Li-ye; ZHENG Jia-kun; WANG Chao-yang; LI Wen-yu

    2005-01-01

    Objective: To investigate the differentiative capability of adult human bone marrow mesenchymal stem cells (BMSCs) into Schwann-like cells. Methods: Bone marrows were aspirated from healthy donors and mononuclear cells were separated by Percoll lymphocytes separation liquid (1.073 g/ml) with centrifugation, cells were cultured in DMEM/F12 (1:1) medium containing 10% fetal bovine serum (FBS), 20 ng/ml epidermal growth factor (EGF) and 20 ng/ml basic fibroblast growth factor (bFGF). Cells of passage 1 were identified with immunocytochemistry. Conclusions: Bone marrow contains the stem cells with the ability of differentiating into Schwann-like cells, which may represent an alternative stem cell sources for neural transplantation.

  2. Early human bone response to laser metal sintering surface topography: a histologic report.

    Science.gov (United States)

    Mangano, Carlo; Piattelli, Adriano; d'Avila, Susana; Iezzi, Giovanna; Mangano, Francesco; Onuma, Tatiana; Shibli, Jamil Awad

    2010-01-01

    This histologic report evaluated the early human bone response to a direct laser metal sintering implant surface retrieved after a short period of healing. A selective laser sintering procedure using a Ti-6Al-4V alloy powder with a particle size of 25-45 microm prepared this surface topography. One experimental microimplant was inserted into the anterior mandible of a patient during conventional implant surgery of the jaw. The microimplant and surrounding tissues were removed after 2 months of unloaded healing and were prepared for histomorphometric analysis. Histologically, the peri-implant bone appeared in close contact with the implant surface, whereas marrow spaces could be detected in other areas along with prominently stained cement lines. The mean of bone-to-implant contact was 69.51%. The results of this histologic report suggest that the laser metal sintering surface could be a promising alternative to conventional implant surface topographies.

  3. Non-invasive assessment of bone quantity and quality in human trabeculae using scanning ultrasound imaging

    Science.gov (United States)

    Xia, Yi

    Fractures and associated bone fragility induced by osteoporosis and osteopenia are widespread health threat to current society. Early detection of fracture risk associated with bone quantity and quality is important for both the prevention and treatment of osteoporosis and consequent complications. Quantitative ultrasound (QUS) is an engineering technology for monitoring bone quantity and quality of humans on earth and astronauts subjected to long duration microgravity. Factors currently limiting the acceptance of QUS technology involve precision, accuracy, single index and standardization. The objective of this study was to improve the accuracy and precision of an image-based QUS technique for non-invasive evaluation of trabecular bone quantity and quality by developing new techniques and understanding ultrasound/tissue interaction. Several new techniques have been developed in this dissertation study, including the automatic identification of irregular region of interest (iROI) in bone, surface topology mapping (STM) and mean scattering spacing (MSS) estimation for evaluating trabecular bone structure. In vitro results have shown that (1) the inter- and intra-observer errors in QUS measurement were reduced two to five fold by iROI compared to previous results; (2) the accuracy of QUS parameter, e.g., ultrasound velocity (UV) through bone, was improved 16% by STM; and (3) the averaged trabecular spacing can be estimated by MSS technique (r2=0.72, p<0.01). The measurement errors of BUA and UV introduced by the soft tissue and cortical shells in vivo can be quantified by developed foot model and simplified cortical-trabecular-cortical sandwich model, which were verified by the experimental results. The mechanisms of the errors induced by the cortical and soft tissues were revealed by the model. With developed new techniques and understanding of sound-tissue interaction, in vivo clinical trail and bed rest study were preformed to evaluate the performance of QUS in

  4. Interleukin-1β modulates endochondral ossification by human adult bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    M Mumme

    2012-09-01

    Full Text Available Inflammatory cytokines present in the milieu of the fracture site are important modulators of bone healing. Here we investigated the effects of interleukin-1β (IL-1β on the main events of endochondral bone formation by human bone marrow mesenchymal stromal cells (BM-MSC, namely cell proliferation, differentiation and maturation/remodelling of the resulting hypertrophic cartilage. Low doses of IL-1β (50 pg/mL enhanced colony-forming units-fibroblastic (CFU-f and -osteoblastic (CFU-o number (up to 1.5-fold and size (1.2-fold in the absence of further supplements and glycosaminoglycan accumulation (1.4-fold upon BM-MSC chondrogenic induction. In osteogenically cultured BM-MSC, IL-1β enhanced calcium deposition (62.2-fold and BMP-2 mRNA expression by differential activation of NF-κB and ERK signalling. IL-1β-treatment of BM-MSC generated cartilage resulted in higher production of MMP-13 (14.0-fold in vitro, mirrored by an increased accumulation of the cryptic cleaved fragment of aggrecan, and more efficient cartilage remodelling/resorption after 5 weeks in vivo (i.e., more TRAP positive cells and bone marrow, less cartilaginous areas, resulting in the formation of mature bone and bone marrow after 12 weeks. In conclusion, IL-1β finely modulates early and late events of the endochondral bone formation by BM-MSC. Controlling the inflammatory environment could enhance the success of therapeutic approaches for the treatment of fractures by resident MSC and as well as improve the engineering of implantable tissues.

  5. Identification of Rorβ targets in cultured osteoblasts and in human bone

    Energy Technology Data Exchange (ETDEWEB)

    Roforth, Matthew M., E-mail: roforth.matthew@mayo.edu; Khosla, Sundeep, E-mail: khosla.sundeep@mayo.edu; Monroe, David G., E-mail: monroe.david@mayo.edu

    2013-11-01

    Highlights: •We examine the gene expression patterns controlled by Rorβ in osteoblasts. •Genes involved in extracellular matrix regulation and proliferation are affected. •Rorβ mRNA levels increase in aged, human bone biopsies. •Rorβ may affect osteoblast activity by modulation of these pathways. -- Abstract: Control of osteoblastic bone formation involves the cumulative action of numerous transcription factors, including both activating and repressive functions that are important during specific stages of differentiation. The nuclear receptor retinoic acid receptor-related orphan receptor β (Rorβ) has been recently shown to suppress the osteogenic phenotype in cultured osteoblasts, and is highly upregulated in bone marrow-derived osteogenic precursors isolated from aged osteoporotic mice, suggesting Rorβ is an important regulator of osteoblast function. However the specific gene expression patterns elicited by Rorβ are unknown. Using microarray analysis, we identified 281 genes regulated by Rorβ in an MC3T3-E1 mouse osteoblast cell model (MC3T3-Rorβ-GFP). Pathway analysis revealed alterations in genes involved in MAPK signaling, genes involved in extracellular matrix (ECM) regulation, and cytokine-receptor interactions. Whereas the identified Rorβ-regulated ECM genes normally decline during osteoblastic differentiation, they were highly upregulated in this non-mineralizing MC3T3-Rorβ-GFP model system, suggesting that Rorβ may exert its anti-osteogenic effects through ECM disruption. Consistent with these in vitro findings, the expression of both RORβ and a subset of RORβ-regulated genes were increased in bone biopsies from postmenopausal women (73 ± 7 years old) compared to premenopausal women (30 ± 5 years old), suggesting a role for RORβ in human age-related bone loss. Collectively, these data demonstrate that Rorβ regulates known osteogenic pathways, and may represent a novel therapeutic target for age-associated bone loss.

  6. The quartic piecewise-linear criterion for the multiaxial yield behavior of human trabecular bone.

    Science.gov (United States)

    Sanyal, Arnav; Scheffelin, Joanna; Keaveny, Tony M

    2015-01-01

    Prior multiaxial strength studies on trabecular bone have either not addressed large variations in bone volume fraction and microarchitecture, or have not addressed the full range of multiaxial stress states. Addressing these limitations, we utilized micro-computed tomography (lCT) based nonlinear finite element analysis to investigate the complete 3D multiaxial failure behavior of ten specimens (5mm cube) of human trabecular bone, taken from three anatomic sites and spanning a wide range of bone volume fraction (0.09–0.36),mechanical anisotropy (range of E3/E1¼3.0–12.0), and microarchitecture. We found that most of the observed variation in multiaxial strength behavior could be accounted for by normalizing the multiaxial strength by specimen-specific values of uniaxial strength (tension,compression in the longitudinal and transverse directions). Scatter between specimens was reduced further when the normalized multiaxial strength was described in strain space.The resulting multiaxial failure envelope in this normalized-strain space had a rectangular boxlike shape for normal–normal loading and either a rhomboidal box like shape or a triangular shape for normal-shear loading, depending on the loading direction. The finite element data were well described by a single quartic yield criterion in the 6D normalized strain space combined with a piecewise linear yield criterion in two planes for normalshear loading (mean error SD: 4.660.8% for the finite element data versus the criterion).This multiaxial yield criterion in normalized-strain space can be used to describe the complete 3D multiaxial failure behavior of human trabecular bone across a wide range of bone volume fraction, mechanical anisotropy, and microarchitecture.

  7. Prostaglandin E2 regulates macrophage colony stimulating factor secretion by human bone marrow stromal cells.

    Science.gov (United States)

    Besse, A; Trimoreau, F; Faucher, J L; Praloran, V; Denizot, Y

    1999-07-08

    Bone marrow stromal cells regulate marrow haematopoiesis by secreting growth factors such as macrophage colony stimulating factor (M-CSF) that regulates the proliferation, differentiation and several functions of cells of the mononuclear-phagocytic lineage. By using a specific ELISA we found that their constitutive secretion of M-CSF is enhanced by tumour necrosis factor-alpha (TNF-alpha). The lipid mediator prostaglandin E2 (PGE2) markedly reduces in a time- and dose-dependent manner the constitutive and TNF-alpha-induced M-CSF synthesis by bone marrow stromal cells. In contrast, other lipid mediators such as 12-HETE, 15-HETE, leukotriene B4, leukotriene C4 and lipoxin A4 have no effect. EP2/EP4 selective agonists (11-deoxy PGE1 and 1-OH PGE1) and EP2 agonist (19-OH PGE2) inhibit M-CSF synthesis by bone marrow stromal cells while an EP1/EP3 agonist (sulprostone) has no effect. Stimulation with PGE2 induces an increase of intracellular cAMP levels in bone marrow stromal cells. cAMP elevating agents (forskolin and cholera toxin) mimic the PGE2-induced inhibition of M-CSF production. In conclusion, PGE2 is a potent regulator of M-CSF production by human bone marrow stromal cells, its effects being mediated via cAMP and PGE receptor EP2/EP4 subtypes.

  8. Engineering a human bone marrow model: a case study on ex vivo erythropoiesis.

    Science.gov (United States)

    Mantalaris, A; Keng, P; Bourne, P; Chang, A Y; Wu, J H

    1998-01-01

    Bone marrow, with its intricate, three-dimensional tissue structure facilitating cell-cell interactions, provides a microenvironment supporting the production of hundreds of billions of multilineal blood cells everyday. We have developed a three-dimensional bone marrow culture system in which marrow cells are cultured in a reactor packed with porous microspheres. The culture supports a three-dimensional growth configuration and multilineal hemopoiesis mimicking the bone marrow in vivo. We studied ex vivo human erythropoiesis using the three-dimensional culture system. The system sustained extensive erythropoiesis at low erythropoietin concentrations (0.2 U/mL), plus stem cell factor, interleukin-3, granulocyte-macrophage colony-stimulating factor, and insulin-like growth factor-I. Erythroid cell production lasted for more than 5 weeks, and the percentage of erythroid cells in the nonadherent cell population was approximately 60%. Flow cytometric analysis using cell surface markers specific for erythroid cells (CD71 and glycophorin-A) indicated that the culture produced early, intermediate, and late erythroid cells. As the culture progressed, the erythroid cell population shifted gradually toward mature cell types. When compared to the three-dimensional culture, the traditional flask cultures failed to support extensive erythropoiesis under the same conditions. This indicates that the three-dimensional bone marrow culture system provides a microenvironment conducive to erythropoiesis under more physiological conditions and is a better bone marrow model.

  9. Effect of Aging on the Toughness of Human Cortical Bone: Evaluation by R-Curves

    Energy Technology Data Exchange (ETDEWEB)

    Kinney, J

    2004-10-08

    Age-related deterioration of the fracture properties of bone, coupled with increased life expectancy, are responsible for increasing incidence of bone fracture in the elderly, and hence, an understanding of how its fracture properties degrade with age is essential. The present study describes ex vivo fracture experiments to quantitatively assess the effect of aging on the fracture toughness properties of human cortical bone in the longitudinal direction. Because cortical bone exhibits rising crack-growth resistance with crack extension, unlike most previous studies the toughness is evaluated in terms of resistance-curve (R-curve) behavior, measured for bone taken from wide range of age groups (34-99 years). Using this approach, both the ex vivo crack-initiation and crack-growth toughness are determined and are found to deteriorate with age; the initiation toughness decreases some 40% over six decades from 40 to 100 years, while the growth toughness is effectively eliminated over the same age range. The reduction in crack-growth toughness is considered to be associated primarily with a degradation in the degree of extrinsic toughening, in particular involving crack bridging in the wake of the crack.

  10. Radiocarbon dating and compositional analysis of pre-Columbian human bones

    Science.gov (United States)

    Andrade, E.; Solís, C.; Canto, C. E.; de Lucio, O. G.; Chavez, E.; Rocha, M. F.; Villanueva, O.; Torreblanca, C. A.

    2014-08-01

    Analysis of ancient human bones found in "El Cóporo", an archaeological site in Guanajuato, Mexico; were performed using a multi techniques scheme: 14C radiocarbon dating, IBA (Ion Beam Analysis), SEM-EDS (Scanning Electron Microscope Energy Dispersive X-ray Spectroscopy). We measured the elemental composition of the bones, especially some with a superficial black pigmentation. Soil samples collected from the burial place were also analyzed. The 14C dating was performed with a new High Voltage Europe 1 MV Tandentron Accelerator Mass Spectrometer (AMS) recently installed in the IFUNAM (Instituto de Física, Universidad Nacional Autónoma de México). The radiocarbon dating allowed us to determine the date of death of the individual in a period between the year 890 and 975 AD, which is consistent with the late period of the Cóporo civilization. The element sample analysis of bones with the surface black pigmentation show higher levels of Fe, Mn and Ba compared when bone's black surface was mechanically removed. These three elements were found in soil samples from the skeleton burial place. These results indicate more likely that the bone black coloration is due to a postmortem alteration occurring in the burial environment.

  11. [Degradation of biomolecules: a comparative study of diagenesis of DNA and proteins in human bone tissue].

    Science.gov (United States)

    Harbeck, Michaela; Ritz-Timme, Stefanie; Schröder, Inge; Oehmichen, Manfred; von Wurmb-Schwark, Nicole

    2004-12-01

    Diagenesis of macromolecules is a not yet fully understood process that can be important for anthropological and forensic research. Trying to elucidate the diagenesis of DNA and proteins we investigated the process of fragmentation of DNA and razemisation of aspartic acid in human bone material. We created an in vitro-model of accelerated aging by incubating bone samples in hot water. A comparison of diagenesis of molecules in those artificially aged samples with altogether 30 historical bones from different regions and of different ages was carried out. The in vitro-model showed the expected positive correlation between the increase of razemisation of aspartic acid and DNA fragmentation, while there was a much lesser correlation when investigating historical bones. The in vitro-model showed the expected correlation between the increase of razemisation of aspartic acid and DNA fragmentation and to a much lesser extent in historical bones. This study shows that diagenesis is probably influenced by additional forces affecting different macromolecules in different ways.

  12. The effect of enamel matrix derivative (Emdogain®) on gene expression profiles of human primary alveolar bone cells.

    Science.gov (United States)

    Yan, X Z; Rathe, F; Gilissen, C; van der Zande, M; Veltman, J; Junker, R; Yang, F; Jansen, J A; Walboomers, X F

    2014-06-01

    Emdogain® is frequently used in regenerative periodontal treatment. Understanding its effect on gene expression of bone cells would enable new products and pathways promoting bone formation to be established. The aim of the study was to analyse the effect of Emdogain® on expression profiles of human-derived bone cells with the help of the micro-array, and subsequent validation. Bone was harvested from non-smoking patients during dental implant surgery. After outgrowth, cells were cultured until subconfluence, treated for 24 h with either Emdogain® (100 µg/ml) or control medium, and subsequently RNA was isolated and micro-array was performed. The most important genes demonstrated by micro-array data were confirmed by qPCR and ELISA tests. Emdogain tipped the balance between genes expressed for bone formation and bone resorption towards a more anabolic effect, by interaction of the PGE2 pathway and inhibition of IL-7 production. In addition the results of the present study indicate that Emdogain possibly has an effect on gene expression for extracellular matrix formation of human bone cells, in particular on bone matrix formation and on proliferation and differentiation. With the micro-array and the subsequent validation, the genes possibly involved in Emdogain action on bone cells were identified. These results can contribute to establishing new products and pathways promoting bone formation.

  13. Voxel-based approach to generate entire human metacarpal bone with microscopic architecture for finite element analysis.

    Science.gov (United States)

    Tang, C Y; Tsui, C P; Tang, Y M; Wei, L; Wong, C T; Lam, K W; Ip, W Y; Lu, W W J; Pang, M Y C

    2014-01-01

    With the development of micro-computed tomography (micro-CT) technology, it is possible to construct three-dimensional (3D) models of human bone without destruction of samples and predict mechanical behavior of bone using finite element analysis (FEA). However, due to large number of elements required for constructing the FE models of entire bone, this demands a substantial computational effort and the analysis usually needs a high level of computer. In this article, a voxel-based approach for generation of FE models of entire bone with microscopic architecture from micro-CT image data is proposed. To enable the FE analyses of entire bone to be run even on a general personal computer, grayscale intensity thresholds were adopted to reduce the amount of elements. Human metacarpal bone (MCP) bone was used as an example for demonstrating the applicability of the proposed method. The micro-CT images of the MCP bone were combined and converted into 3D array of pixels. Dual grayscale intensity threshold parameters were used to distinguish the pixels of bone tissues from those of surrounding soft tissues and improve predictive accuracy for the FE analyses with different sizes of elements. The method of selecting an appropriate value of the second grayscale intensity threshold was also suggested to minimize the area error for the reconstructed cross-sections of a FE structure. Experimental results showed that the entire FE MCP bone with microscopic architecture could be modeled and analyzed on a personal computer with reasonable accuracy.

  14. Ancient Human Bone Microstructure in Medieval England: Comparisons between Two Socio-Economic Groups.

    Science.gov (United States)

    Miszkiewicz, Justyna J; Mahoney, Patrick

    2016-01-01

    Understanding the links between bone microstructure and human lifestyle is critical for clinical and anthropological research into skeletal growth and adaptation. The present study is the first to report correspondence between socio-economic status and variation in bone microstructure in ancient humans. Products of femoral cortical remodeling were assessed using histological methods in a large human medieval sample (N = 450) which represented two distinct socio-economic groups. Osteonal parameters were recorded in posterior midshaft femoral sections from adult males (N = 233) and females (N = 217). Using univariate and multivariate statistics, intact, fragmentary, and osteon population densities, Haversian canal area and diameter, and osteon area were compared between the two groups, accounting for sex, age, and estimated femoral robusticity. The size of osteons and their Haversian canals, as well as osteon density, varied significantly between the socio-economic groups, although minor inconsistencies were observed in females. Variation in microstructure was consistent with historical textual evidence that describes differences in mechanical loading and nutrition between the two groups. Results demonstrate that aspects of ancient human lifestyle can be inferred from bone microstructure.

  15. Sustained Engraftment of Cryopreserved Human Bone Marrow CD34(+) Cells in Young Adult NSG Mice.

    Science.gov (United States)

    Wiekmeijer, Anna-Sophia; Pike-Overzet, Karin; Brugman, Martijn H; Salvatori, Daniela C F; Egeler, R Maarten; Bredius, Robbert G M; Fibbe, Willem E; Staal, Frank J T

    2014-06-01

    Hematopoietic stem cells (HSCs) are defined by their ability to repopulate the bone marrow of myeloablative conditioned and/or (lethally) irradiated recipients. To study the repopulating potential of human HSCs, murine models have been developed that rely on the use of immunodeficient mice that allow engraftment of human cells. The NSG xenograft model has emerged as the current standard for this purpose allowing for engraftment and study of human T cells. Here, we describe adaptations to the original NSG xenograft model that can be readily implemented. These adaptations encompass use of adult mice instead of newborns and a short ex vivo culture. This protocol results in robust and reproducible high levels of lympho-myeloid engraftment. Immunization of recipient mice with relevant antigen resulted in specific antibody formation, showing that both T cells and B cells were functional. In addition, bone marrow cells from primary recipients exhibited repopulating ability following transplantation into secondary recipients. Similar results were obtained with cryopreserved human bone marrow samples, thus circumventing the need for fresh cells and allowing the use of patient derived bio-bank samples. Our findings have implications for use of this model in fundamental stem cell research, immunological studies in vivo and preclinical evaluations for HSC transplantation, expansion, and genetic modification.

  16. A Development of a Human Cranial Bone Surrogate for Impact Studies

    Directory of Open Access Journals (Sweden)

    Jack C Roberts

    2013-10-01

    Full Text Available In order to replicate the fracture behavior of the intact human skull under impact it becomes necessary to develop a material having the mechanical properties of cranial bone. The most important properties to replicate in a surrogate human skull were found to be the fracture toughness and tensile strength of the cranial tables as well as the bending strength of the 3-layer (inner table-diplöe-outer table architecture of the human skull. The materials selected to represent the surrogate cranial tables consisted of two different epoxy resins systems with random milled glass fiber to enhance the strength and stiffness and the materials to represent the surrogate diplöe consisted of three low density foams. Forty-one three-point bending fracture toughness tests were performed on nine material combinations. The materials that best represented the fracture toughness of cranial tables were then selected and formed into tensile samples and tested. These materials were then used with the two surrogate diplöe foam materials to create the three layer surrogate cranial bone samples for three point bending tests. Drop tower tests were performed on flat samples created from these materials and the fracture patterns were very similar to the linear fractures seen in pendulum impacts of intact human skulls. The surrogate cranial tables had the quasi-static fracture toughness and tensile strength of 2.5 MPa√m and 53 ± 4.9 MPa, respectively, while the same properties of human compact bone were 3.1 ± 1.8 MPa√m and 68 ± 18 MPa, respectively. The cranial surrogate had a quasi-static bending strength of 68 ± 5.7 MPa, while that of cranial bone was 82 ± 26 MPa. This material/design is currently being used to construct spherical shell samples for drop tower and ballistic tests.

  17. Patients With High Bone Mass Phenotype Exhibit Enhanced Osteoblast Differentiation and Inhibition of Adipogenesis of Human Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

    Qiu, Weimin; Andersen, Tom; Bollerslev, Jens

    2007-01-01

    to osteoporosis), or LRP5T253 (hMSC-LRP5T253, activation mutation leading to high bone mass). We characterized Wnt signaling activation using a dual luciferase assay, cell proliferation, lineage biomarkers using real-time PCR, and in vivo bone formation. Results: In bone biopsies, we found increased trabecular...... mineralized bone when implanted subcutaneously with hydroxyapatite/tricalcium phosphate in SCID/NOD mice. Conclusions: LRP5 mutations and the level of Wnt signaling determine differentiation fate of hMSCs into osteoblasts or adipocytes. Activation of Wnt signaling can thus provide a novel approach to increase...

  18. Individual-specific multi-scale finite element simulation of cortical bone of human proximal femur

    Energy Technology Data Exchange (ETDEWEB)

    Ascenzi, Maria-Grazia, E-mail: mgascenzi@mednet.ucla.edu [UCLA/Orthopaedic Hospital, Department of Orthopaedic Surgery, Rehabilitation Bldg, Room 22-69, 1000 Veteran Avenue, University of California, Los Angeles, CA 90095 (United States); Kawas, Neal P., E-mail: nealkawas@ucla.edu [UCLA/Orthopaedic Hospital, Department of Orthopaedic Surgery, Rehabilitation Bldg, Room 22-69, 1000 Veteran Avenue, University of California, Los Angeles, CA 90095 (United States); Lutz, Andre, E-mail: andre.lutz@hotmail.de [Institute of Biomechanics and Numerical Mechanics, Leibniz University Hannover, 30167 Hannover (Germany); Kardas, Dieter, E-mail: kardas@ibnm.uni-hannover.de [ContiTech Vibration Control, Jaedekamp 30 None, 30419 Hannover (Germany); Nackenhorst, Udo, E-mail: nackenhorst@ibnm.uni-hannover.de [Institute of Biomechanics and Numerical Mechanics, Leibniz University Hannover, 30167 Hannover (Germany); Keyak, Joyce H., E-mail: jhkeyak@uci.edu [Department of Radiological Sciences, Medical Sciences I, Bldg 811, Room B140, University of California, Irvine, CA 92697-5000 (United States)

    2013-07-01

    We present an innovative method to perform multi-scale finite element analyses of the cortical component of the femur using the individual’s (1) computed tomography scan; and (2) a bone specimen obtained in conjunction with orthopedic surgery. The method enables study of micro-structural characteristics regulating strains and stresses under physiological loading conditions. The analysis of the micro-structural scenarios that cause variation of strain and stress is the first step in understanding the elevated strains and stresses in bone tissue, which are indicative of higher likelihood of micro-crack formation in bone, implicated in consequent remodeling or macroscopic bone fracture. Evidence that micro-structure varies with clinical history and contributes in significant, but poorly understood, ways to bone function, motivates the method’s development, as does need for software tools to investigate relationships between macroscopic loading and micro-structure. Three applications – varying region of interest, bone mineral density, and orientation of collagen type I, illustrate the method. We show, in comparison between physiological loading and simple compression of a patient’s femur, that strains computed at the multi-scale model’s micro-level: (i) differ; and (ii) depend on local collagen-apatite orientation and degree of calcification. Our findings confirm the strain concentration role of osteocyte lacunae, important for mechano-transduction. We hypothesize occurrence of micro-crack formation, leading either to remodeling or macroscopic fracture, when the computed strains exceed the elastic range observed in micro-structural testing.

  19. Technical note: early post-mortem changes of human bone in taphonomy with μCT.

    Science.gov (United States)

    Le Garff, Erwan; Mesli, Vadim; Delannoy, Yann; Colard, Thomas; Demondion, Xavier; Becart, Anne; Hedouin, Valéry

    2016-12-29

    Post-mortem interval (PMI) estimation is an important issue in forensic medicine, particularly for criminal purposes and legal limitation periods. The goal of the present study is to examine the evolution of the trabecular cranial vault bone after 4 weeks of conservation in a controlled environment with micro-tomography (μCT) analyses.Four bone samples were extracted from a fresh human cranial vault (a donation to science according to the French law) and conserved in an air-controlled environment. The samples were weighed and μCT scanned at a 10-μm resolution every week after death for a month. The μCT features were identical for every sample. Each set of data from the μCTs was reconstructed, registered, and analyzed in terms of the total volume, bone volume, bone surface, number of trabeculae, trabeculae thickness, and mean distance of the trabeculae. The samples were conserved in a glass box in 20 °C air with 60% humidity in a laboratory hood between each μCT acquisition. Descriptive statistics were determined. Each sample was observed and compared to itself over time.After 1 month of conservation, the mean bone volume (-1.9%), bone surface (-5.1%), and trabecular number (-12.35%) decreased, whereas the mean trabecular separation (+5.55%) and trabecular thickness (+12.7%) increased. Many variations (i.e., increases and decreases) were observed between the extraction of the sample and the end of the 4 weeks of conservation. The present observations may be explained by bone diagenesis. Previous observations have indicated that protein and lipid losses occur with bone weight and volume losses. These diagenesis effects may explain the trabecular modifications observed in the present work. We observed many bone variations with the μCT scans between the beginning and the end of the conservation that had no explanations. Additional studies, particularly studies involving statistics, need to be performed to confirm our observations and explain these results

  20. Tensile material properties of human rib cortical bone under quasi-static and dynamic failure loading and influence of the bone microstucture on failure characteristics

    CERN Document Server

    Subit, Damien; Valazquez-Ameijide, Juan; Arregui-Dalmases, Carlos; Crandall, Jeff

    2011-01-01

    Finite element models of the thorax are under development to assist vehicle safety researchers with the design of countermeasures such as advanced restrain systems. Computational models have become more refined with increasing geometrical complexity as element size decreases. These finite element models can now capture small geometrical features with an attempt to predict fracture. However, the bone material properties currently available, and in particular the rate sensitivity, have been mainly determined from compression tests or tests on long bones. There is a need for a new set of material properties for the human rib cortical bone. With this objective, a new clamping technique was developed to test small bone coupons under tensile loading. Ten coupons were harvested from the cortical shell of the sixth and seventh left ribs from three cadavers. The coupons were tested to fracture under quasi-static (target strain rate of 0.07 %/s) and dynamic loading (target strain rate of 170 %/s). Prior to testing, eac...

  1. Ex vivo expansion of Primate CD34+ Cells isolated from Bone Marrow and Human Bone Marrow Mononuclear Cells using a Novel Scaffold

    Directory of Open Access Journals (Sweden)

    Devaprasad D

    2009-01-01

    Full Text Available Bone marrow derived CD34+ cells have been in clinical application in patients with haematological malignancies. One of the major problems with this treatment is the non-availability of matched donors or the necessity of multiple transfusions depending upon the pathology. Recently evidences have been accumulating to prove the safety and efficacy of autologous CD34+ cells in diseases such as myocardial dysfunction, peripheral vascular diseases and neurological certain conditions. However there are only a few reports in the literature on ex vivo expansion of the bone marrow derived CD34+ cells. We have in two different studies proven that isolated CD34+ cells from baboon bone marrow and non-isolated BMMNCs from human bone marrow could be expanded with increase in percentage of CD34+ cells using a novel scaffold.

  2. Effect of nitrous oxide on folate coenzyme distribution and de novo synthesis of thymidylate in human bone marrow cells

    NARCIS (Netherlands)

    A.A.M. Ermens (Anton); M. Schoester (Martijn); J. Lindemans (Jan); J. Abels

    1992-01-01

    markdownabstractAbstract The effect of nitrous oxide on intracellular folate metabolism of the human bone marrow was studied in vitro. Bone marrow cells, obtained from healthy volunteers, were incubated with 5 × 10−8m-[3H]5-formyltetrahydrofolate (5-formylTHF) for 18 hr to label intracellular fola

  3. Identification and characterization of plasma cells in normal human bone marrow by high-resolution flow cytometry

    NARCIS (Netherlands)

    Terstappen, Leon W.M.M.; Johnsen, Steen; Segers-Nolten, Ine M.J.; Loken, Michael R.

    1990-01-01

    The low frequency of plasma cells and the lack of specific cell surface markers has been a major obstacle for a detailed characterization of plasma cells in normal human bone marrow. Multiparameter flow cytometry enabled the identification of plasma cells in normal bone marrow aspirates. The plasma

  4. Potential Use of Bacterial Community Succession in Decaying Human Bone for Estimating Postmortem Interval.

    Science.gov (United States)

    Damann, Franklin E; Williams, Daniel E; Layton, Alice C

    2015-07-01

    Bacteria are taphonomic agents of human decomposition, potentially useful for estimating postmortem interval (PMI) in late-stage decomposition. Bone samples from 12 individuals and three soil samples were analyzed to assess the effects of decomposition and advancing time on bacterial communities. Results indicated that partially skeletonized remains maintained a presence of bacteria associated with the human gut, whereas bacterial composition of dry skeletal remains maintained a community profile similar to soil communities. Variation in the UniFrac distances was significantly greater between groups than within groups (p < 0.001) for the unweighted metric and not the weighted metric. The members of the bacterial communities were more similar within than between decomposition stages. The oligotrophic environment of bone relative to soft tissue and the physical protection of organic substrates may preclude bacterial blooms during the first years of skeletonization. Therefore, community membership (unweighted) may be better for estimating PMI from skeletonized remains than community structure (weighted).

  5. Gene expression profiles of human bone marrow derived mesenchymal stem cells and tendon cells

    Institute of Scientific and Technical Information of China (English)

    胡庆柳; 朴英杰; 邹飞

    2003-01-01

    Objective To study the gene expression profiles of human bone marrow derived mesenchymal stem cells and tendon cells.Methods Total RNA extracted from human bone marrow derived mesenchymal stem cells and tendon cells underwent reverse transcription, and the products were labeled with α-32P dCTP. The cDNA probes of total RNA were hybridized to cDNA microarray with 1176 genes, and then the signals were analyzed by AtlasImage analysis software Version 1.01a.Results Fifteen genes associated with cell proliferation and signal transduction were up-regulated, and one gene that takes part in cell-to-cell adhesion was down-regulated in tendon cells.Conclusion The 15 up-regulated and one down-regulated genes may be beneficial to the orientational differentiation of mesenchymal stem cells into tendon cells.

  6. CD146/MCAM defines functionality of human bone marrow stromal stem cell populations

    DEFF Research Database (Denmark)

    Harkness, Linda; Zaher, Walid; Ditzel, Nicholas

    2016-01-01

    BACKGROUND: Identification of surface markers for prospective isolation of functionally homogenous populations of human skeletal (stromal, mesenchymal) stem cells (hMSCs) is highly relevant for cell therapy protocols. Thus, we examined the possible use of CD146 to subtype a heterogeneous h......MSC population. METHODS: Using flow cytometry and cell sorting, we isolated two distinct hMSC-CD146(+) and hMSC-CD146(-) cell populations from the telomerized human bone marrow-derived stromal cell line (hMSC-TERT). Cells were examined for differences in their size, shape and texture by using high......-content analysis and additionally for their ability to differentiate toward osteogenesis in vitro and form bone in vivo, and their migrational ability in vivo and in vitro was investigated. RESULTS: In vitro, the two cell populations exhibited similar growth rate and differentiation capacity to osteoblasts...

  7. CD146/MCAM defines functionality of human bone marrow stromal stem cell populations

    DEFF Research Database (Denmark)

    Harkness, Linda; Zaher, Walid; Ditzel, Nicholas;

    2016-01-01

    BACKGROUND: Identification of surface markers for prospective isolation of functionally homogenous populations of human skeletal (stromal, mesenchymal) stem cells (hMSCs) is highly relevant for cell therapy protocols. Thus, we examined the possible use of CD146 to subtype a heterogeneous h......MSC population. METHODS: Using flow cytometry and cell sorting, we isolated two distinct hMSC-CD146(+) and hMSC-CD146(-) cell populations from the telomerized human bone marrow-derived stromal cell line (hMSC-TERT). Cells were examined for differences in their size, shape and texture by using high......-content analysis and additionally for their ability to differentiate toward osteogenesis in vitro and form bone in vivo, and their migrational ability in vivo and in vitro was investigated. RESULTS: In vitro, the two cell populations exhibited similar growth rate and differentiation capacity to osteoblasts...

  8. Bone marrow CFU-GM and human tumor xenograft efficacy of three antitumor nucleoside analogs.

    Science.gov (United States)

    Bagley, Rebecca G; Roth, Stephanie; Kurtzberg, Leslie S; Rouleau, Cecile; Yao, Min; Crawford, Jennifer; Krumbholz, Roy; Lovett, Dennis; Schmid, Steven; Teicher, Beverly A

    2009-05-01

    Nucleoside analogs are rationally designed anticancer agents that disrupt DNA and RNA synthesis. Fludarabine and cladribine have important roles in the treatment of hematologic malignancies. Clofarabine is a next generation nucleoside analog which is under clinical investigation. The bone marrow toxicity, tumor cell cytotoxicity and human tumor xenograft activity of fludarabine, cladribine and clofarabine were compared. Mouse and human bone marrow were subjected to colony forming (CFU-GM) assays over a 5-log concentration range in culture. NCI-60 cell line screening data were compared. In vivo, a range of clofarabine doses was compared with fludarabine for efficacy in several human tumor xenografts. The IC90 concentrations for fludarabine and cladribine for mouse CFU-GM were >30 and 0.93 microM, and for human CFU-GM were 8 and 0.11 microM, giving mouse to human differentials of >3.8- and 8.5-fold. Clofarabine produced IC90s of 1.7 microM in mouse and 0.51 microM in human CFU-GM, thus a 3.3-fold differential between species. In the NCI-60 cell line screen, fludarabine and cladribine showed selective cytotoxicity toward leukemia cell lines while for clofarabine there was no apparent selectivity based upon origin of the tumor cells. In vivo, clofarabine produced a dose-dependent increase in tumor growth delay in the RL lymphoma, the RPMI-8226 multiple myeloma, and HT-29 colon carcinoma models. The PC3 prostate carcinoma was equally responsive to clofarabine and fludarabine. Bringing together bone marrow toxicity data, tumor cell line cytotoxicity data, and human tumor xenograft efficacy provides valuable information for the translation of preclinical findings to the clinic.

  9. Functional assay, expression of growth factors and proteins modulating bone-arrangement in human osteoblasts seeded on an anorganic bovine bone biomaterial

    Directory of Open Access Journals (Sweden)

    O Trubiani

    2010-07-01

    Full Text Available The basic aspects of bone tissue engineering include chemical composition and geometry of the scaffold design, because it is very important to improve not only cell attachment and growth but especially osteodifferentiation, bone tissue formation, and vascularization. Geistlich Bio-Oss® (GBO is a xenograft consisting of deproteinized, sterilized bovine bone, chemically and physically identical to the mineral phase of human bone.In this study, we investigated the growth behaviour and the ability to form focal adhesions on the substrate, using vinculin, a cytoskeletal protein, as a marker. Moreover, the expression of bone specific proteins and growth factors such as type I collagen, osteopontin, bone sialoprotein, bone morphogenetic protein-2 (BMP-2, BMP-7 and de novo synthesis of osteocalcin in normal human osteoblasts (NHOst seeded on xenogenic GBO were evaluated. Our observations suggest that after four weeks of culture in differentiation medium, the NHOst showed a high affinity for the three dimensional biomaterial; in fact, cellular proliferation, migration and colonization were clearly evident. The osteogenic differentiation process, as demonstrated by morphological, histochemical, energy dispersive X-ray microanalysis and biochemical analysis was mostly obvious in the NHOst grown on three-dimensional inorganic bovine bone biomaterial. Functional studies displayed a clear and significant response to calcitonin when the cells were differentiated. In addition, the presence of the biomaterial improved the response, suggesting that it could drive the differentiation of these cells towards a more differentiated osteogenic phenotype. These results encourage us to consider GBO an adequate biocompatible three-dimensional biomaterial, indicating its potential use for the development of tissue-engineering techniques.

  10. Down-regulation of mTOR leads to up-regulation of osteoprotegerin in bone marrow cells

    Energy Technology Data Exchange (ETDEWEB)

    Mogi, Makio, E-mail: makio@dpc.aichi-gakuin.ac.jp [Department of Medicinal Biochemistry, School of Pharmacy, Aichi-Gakuin University, 1-100 Kusumoto, Chikusa, Nagoya, Aichi 464-8650 (Japan); Kondo, Ayami [Department of Medicinal Biochemistry, School of Pharmacy, Aichi-Gakuin University, 1-100 Kusumoto, Chikusa, Nagoya, Aichi 464-8650 (Japan)

    2009-06-19

    Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor regulates bone mass by inhibiting osteoclastic bone resorption. mTOR, which is the mammalian target of rapamycin, is a kinase and central regulator of cell growth, proliferation, and survival. By using Rapamycin, we studied whether mTOR pathway is associated with OPG protein production in the mouse bone marrow-derived stromal cell line ST2. Rapamycin markedly increased the level of soluble OPG in ST2 cells. This antibiotic treatment resulted in the suppression of phosphorylation of mTOR. Rapamycin had no effects on the proliferation, differentiation, or apoptosis of the cells. Treatment with bone morphogenetic protein-4, which can induce OPG protein in ST2 cells, also resulted in a decrease in the density of the phospho-mTOR-band, suggesting that the suppression of the phospho-mTOR pathway is necessary for OPG production in ST2 cells. Thus, suitable suppression of mTOR phosphorylation is a necessary requirement for OPG production in bone marrow stromal cells.

  11. Bone diseases associated with human immunodeficiency virus infection: pathogenesis, risk factors and clinical management.

    Science.gov (United States)

    Bongiovanni, Marco; Tincati, Camilla

    2006-06-01

    Bone disorders such as osteopenia and osteoporosis have been recently reported in patients infected with the human immunodeficiency virus (HIV), but their etiology remains still unknown. The prevalence estimates vary widely among the different studies and can be affected by concomitant factors such as the overlapping of other possible conditions inducing bone loss as lypodystrophy, advanced HIV-disease, advanced age, low body weight or concomitant use of other drugs. All the reports at the moment available in the literature showed a higher than expected prevalence of reduced bone mineral density (BMD) in HIV-infected subjects both naïve and receiving potent antiretroviral therapy compared to healthy controls. This controversial can suggest a double role played by both antiretroviral drugs and HIV itself due to immune activation and/or cytokines disregulation. An improved understanding of the pathogenesis of bone disorders can result in better preventative and therapeutic measures. However, the clinical relevance and the risk of fractures remains undefined in HIV-population. The clinical management of osteopenia and osteoporosis in HIV-infected subjects is still being evaluated. Addressing potential underlying bone disease risk factors (e.g., smoking and alcohol intake, use of corticosteroids, advanced age, low body weight), evaluating calcium and vitamin D intake, and performing dual x-ray absorptiometry in HIV-infected individuals who have risk factors for bone disease can be important strategies to prevent osteopenia and osteoporosis in this population. The administration of bisphosphonates (e.g., alendronate), with calcium and vitamin D supplementation, may be a reasonable and effective option to treat osteoporosis in these subjects.

  12. Effect of Loading Rate and Orientation on the Compressive Response of Human Cortical Bone

    Science.gov (United States)

    2014-05-01

    Biomechanics 1975, 8, 27–40. 11. Ntim, M. M.; Bembey, A. K.; Ferguson, V. I.; Bushby, A. J. Hydration Effects on the Viscoelastic Properties of Collagen. MRS...Determination of Mechanical Properties of Human Femoral Cortical Bone by the Hopkinson Bar Stress Technique. Journal of Biomechanics 1990, 23 (11...Science and Technology 2011, 25 (9), 2211–2215. 18. Chen, W.; Song, B. Split Hopkinson (Kolsky) Bar; Springer : New York, 2010; pp 29–77. 19. Kulin, R

  13. Construction and characterization of a recombinant human adenovirus vector expressing bone morphogenetic protein 2

    OpenAIRE

    Zhang, Zheng; WANG, GUOXIAN; Li, Chen; Liu, Danping

    2013-01-01

    The aim of this study was to construct and characterize a novel recombinant human adenovirus vector expressing bone morphogenetic protein 2 (BMP2) and green fluorescent protein (GFP). The BMP2 gene in the plasmid pcDNA3-BMP2 was sequenced and the restriction enzyme recognition sites were analyzed. Following mutagenesis using polymerase chain reaction (PCR), the gene sequence after the translation termination codon was removed and new restriction sites were added. The mutated BMP2 gene (BMP2+ ...

  14. Correlative Light and Scanning X-Ray Scattering Microscopy of Healthy and Pathologic Human Bone Sections

    OpenAIRE

    Giannini, C.; D. Siliqi; Bunk, O.; Beraudi, A.; Ladisa, M.; Altamura, D.; Stea, S.; Baruffaldi, F.

    2012-01-01

    Scanning small and wide angle X-ray scattering (scanning SWAXS) experiments were performed on healthy and pathologic human bone sections. Via crystallographic tools the data were transformed into quantitative images and as such compared with circularly polarized light (CPL) microscopy images. SWAXS and CPL images allowed extracting information of the mineral nanocrystalline phase embedded, with and without preferred orientation, in the collagen fibrils, mapping local changes at sub-osteon res...

  15. Acetylcholinesterase from Human Erythrocytes as a Surrogate Biomarker of Lead Induced Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Vivek Kumar Gupta

    2015-01-01

    Full Text Available Lead induced neurotoxicity in the people engaged in different occupations has received wide attention but very little studies have been carried out to monitor occupational neurotoxicity directly due to lead exposure using biochemical methods. In the present paper an endeavour has been made in order to assess the lead mediated neurotoxicity by in vitro assay of the activity of acetylcholinesterase (AChE from human erythrocytes in presence of different concentrations of lead. The results suggested that the activity of this enzyme was localized in membrane bound fraction and it was found to be highly stable up to 30 days when stored at −20°C in phosphate buffer (50 mM, pH 7.4 containing 0.2% Triton X-100. The erythrocyte’s AChE exhibited Km for acetylcholinesterase to be 0.1 mM. Lead caused sharp inhibition of the enzyme and its IC50 value was computed to be 1.34 mM. The inhibition of the enzyme by lead was found to be of uncompetitive type (Ki value, 3.6 mM which negatively influenced both the Vmax and the enzyme-substrate binding affinity. Taken together, these results indicate that AChE from human erythrocytes could be exploited as a surrogate biomarker of lead induced neurotoxicity particularly in the people occupationally exposed to lead.

  16. Changes in the stiffness of the human tibial cartilage-bone complex in early-stage osteoarthrosis

    DEFF Research Database (Denmark)

    Ding, Ming; Dalstra, M; Linde, F

    1998-01-01

    Cylindrical human tibial cartilage-bone unit specimens were removed from 9 early-stage medial osteoarthrotic (OA) tibiae (mean age 74 years) and 10 normal age-matched tibiae (mean age 73 years). These specimens were divided into 4 groups: OA, lateral comparison, medial age-matched, and lateral ag...... and bone remained significant in the three control groups. Our findings suggest that both cartilage and bone in early-stage OA are mechanically inferior to normal, and that OA cartilage and bone have lost their unit function to mechanical loading....

  17. The role of collagen in determining bone mechanical properties

    NARCIS (Netherlands)

    Wang, X.; Bank, R.A.; teKoppele, J.M.; Mauli Agrawal, C.

    2001-01-01

    The hypothesis of this study was that collagen denaturation would lead to a significant decrease in the toughness of bone, but has little effect on the stiffness of bone. Using a heating model, effects of collagen denaturation on the biomechanical properties of human cadaveric bone were examined.

  18. The role of collagen in determining bone mechanical properties

    NARCIS (Netherlands)

    Wang, X.; Bank, R.A.; teKoppele, J.M.; Mauli Agrawal, C.

    2001-01-01

    The hypothesis of this study was that collagen denaturation would lead to a significant decrease in the toughness of bone, but has little effect on the stiffness of bone. Using a heating model, effects of collagen denaturation on the biomechanical properties of human cadaveric bone were examined. Pr

  19. Analysis of OPLA scaffolds for bone engineering constructs using human jaw periosteal cells.

    Science.gov (United States)

    Alexander, Dorothea; Hoffmann, Jürgen; Munz, Adelheid; Friedrich, Björn; Geis-Gerstorfer, Jürgen; Reinert, Siegmar

    2008-03-01

    For bone regeneration constructs using human jaw periosteal cells (JPC) the extent of osteoinductive ability of different three-dimensional scaffolds is not yet established. We analyzed open-cell polylactic acid (OPLA) scaffolds for their suitability as bone engineering constructs using human JPC. Cell adhesion and spreading was visualized on the surface of scaffolds by scanning electron microscopy. JPC proliferation within OPLA scaffolds was compared with proliferation within collagen and calcium phosphate scaffolds. We found a significant increase of proliferation rates in OPLA scaffolds versus Coll/CaP scaffolds at three time points. Live-measurements of oxygen consumption within the cell-seeded scaffolds indicate that the in vitro culturing time should not exceed 12-15 days. OPLA scaffolds, which were turned out to be the most beneficial for JPC growth, were chosen for osteogenic differentiation experiments with or without BMP-2. Gene expression analyses demonstrated induction of several osteogenic genes (alkaline phosphatase, osterix, Runx-2 and insulin-like growth factor) within the 3D-scaffolds after 12 days of in vitro culturing. Element analysis by EDX spectrometry of arising nodules during osteogenesis demonstrated that JPC growing within OPLA scaffolds are able to form CaP particles. We conclude that OPLA scaffolds provide a promising environment for bone substitutes using human JPC.

  20. On the origin of human adipocytes and the contribution of bone marrow-derived cells.

    Science.gov (United States)

    Rydén, Mikael

    2016-01-01

    In the last decade, results in both animal models and humans have demonstrated that white adipocytes are generated over the entire life-span. This adds to the plasticity of adipose tissue and alterations in adipocyte turnover are linked to metabolic dysfunction. Adipocytes are derived from precursors present primarily in the perivascular areas of adipose tissue but their precise origin remains unclear. The multipotent differentiation capacity of bone marrow-derived cells (BMDC) has prompted the suggestion that BMDC may contribute to different cell tissue pools, including adipocytes. However, data in murine transplantation models have been conflicting and it has been a matter of debate whether BMDC actually differentiate into adipocytes or just fuse with resident fat cells. To resolve this controversy in humans, we recently performed a study in 65 subjects that had undergone bone marrow transplantation. Using a set of newly developed assays including single cell genome-wide analyses of mature adipocytes, we demonstrated that bone marrow contributes with approximately 10 % to the adipocyte pool. This proportion was more than doubled in obesity, suggesting that BMDC may constitute a reserve pool for adipogenesis, particularly upon weight gain. This commentary discusses the possible relevance of these and other recent findings for human pathophysiology.

  1. American alligator proximal pedal phalanges resemble human finger bones: Diagnostic criteria for forensic investigators.

    Science.gov (United States)

    Ferraro, Joseph V; Binetti, Katie M

    2014-07-01

    A scientific approach to bone and tooth identification requires analysts to pursue the goal of empirical falsification. That is, they may attribute a questioned specimen to element and taxon only after having ruled out all other possible attributions. This requires analysts to possess a thorough understanding of both human and non-human osteology, particularly so for remains that may be morphologically similar across taxa. To date, forensic anthropologists have identified several potential 'mimics' for human skeletal remains, including pig teeth and bear paws. Here we document another possible mimic for isolated human skeletal elements--the proximal pedal phalanges of American alligators (Alligator mississippiensis) closely resemble the proximal and intermediate hand phalanges of adult humans. We detail morphological similarities and differences between these elements, with the goal of providing sufficient information for investigators to confidently falsify the hypothesis that a questioned phalanx is derived from an American alligator.

  2. Clozapine promotes the proliferation of granulocyte progenitors in the bone marrow leading to increased granulopoiesis and neutrophilia in rats.

    Science.gov (United States)

    Lobach, Alexandra R; Uetrecht, Jack

    2014-07-21

    Clozapine is an atypical antipsychotic that is limited in its use due to the risk of idiosyncratic agranulocytosis. The bone marrow is suspected to be the site of the reaction, and indirect measurements in patients suggest that neutrophil production and maturation are altered in the marrow by clozapine. Specifically, the majority of patients have elevated neutrophil counts at the start of treatment, often paired with increased serum granulocyte-colony stimulating factor (G-CSF). Employing a rat model of clozapine treatment, we set out to determine if the neutrophilia observed at the start of treatment is characteristic of G-CSF-associated bone marrow stimulation. Female Sprague-Dawley rats were treated with 30 mg/kg/day of clozapine for 10 days, and sustained neutrophilia was evident after 1 week of treatment paired with spikes in G-CSF. Within the bone marrow, clozapine was found to induce proliferation of the granulocyte progenitor colonies as measured by a methylcellulose assay. This led to elevated granulopoiesis observed by H&E and myeloperoxidase staining of bone marrow slices. Increased release of neutrophils from the marrow to the circulation was measured through 5-bromo-2'-deoxyuridine labeling in vivo, and these neutrophils appeared to be less mature based on (a) a decrease in the nuclear lobe count and (b) increased expression of surface CD62L. Furthermore, faster transit of the neutrophils through the marrow was suggested by a shift toward elevated numbers of neutrophils in the bone marrow maturation pool and increased CD11b and CD18 staining on the less mature neutrophils residing in the marrow. Taken together, these data indicate that clozapine stimulates the bone marrow to produce more neutrophils in a manner that is characteristic of endogenous G-CSF stimulation, and it is consistent with the inflammatory response observed in patients treated with clozapine.

  3. Gender difference in bone metastasis of human small cell lung cancer, SBC-5 cells in natural killer-cell depleted severe combined immunodeficient mice.

    Science.gov (United States)

    Sakaguchi, Satoshi; Goto, Hisatsugu; Hanibuchi, Masaki; Otsuka, Shinsaku; Ogino, Hirokazu; Kakiuchi, Soji; Uehara, Hisanori; Yano, Seiji; Nishioka, Yasuhiko; Sone, Saburo

    2010-05-01

    Lung cancer frequently develops multiple organ metastases, which thus makes this disease a leading cause of malignancy-related death worldwide. A gender difference is reported to affect the incidence and mortality of lung cancer; however, whether and how the gender difference is involved in lung cancer metastasis is unclear. This study evaluated the gender difference in multiple organ metastases in human small cell lung cancer (SBC-5) cells by using natural killer cell-depleted severe combined immunodeficient mice. Among multiple organ metastases, only bone metastasis formation significantly increased in female mice in comparison to males, while no significant difference was observed in the metastases to the liver and lungs. The suppression of androgen by castration or androgen receptor antagonist treatment in male mice also induced a significant increase of bone metastases. The number of osteoclasts in the bone metastatic lesions was greater in female mice and in mice with androgen suppression than in control male. However, there was no significant difference in the serum concentration of parathyroid hormone-related protein (PTHrP) associated with gender or androgen suppression. An in vitro study also indicated that sex steroid treatment had no effect on the proliferation or PTHrP production in SBC-5 cells. These results indicate that the balance of sex steroids therefore plays an important role in the formation of bone metastasis in small cell lung cancer, and suggests diverse mechanisms of interaction between cancer cells and host cells in the bone microenvironment.

  4. Determination of cadmium and lead in human biological samples by spectrometric techniques: a review.

    Science.gov (United States)

    Lemos, Valfredo Azevedo; de Carvalho, Anaildes Lago

    2010-12-01

    The analysis of human biological samples, such as blood, urine, nails, and hair, is generally used for the verification of human exposure to toxic metals. In this review, various spectrometric methods for the determination of cadmium and lead in biological samples are discussed and compared. Several spectrometric techniques are presented and discussed with respect to various characteristics such as sensitivity, selectivity, and cost. Special attention is drawn to the procedures for digestion prior to the determination of cadmium and lead in hair, nails, blood, and urine.

  5. A calibrated human PBPK model for benzene inhalation with urinary bladder and bone marrow compartments.

    Science.gov (United States)

    Knutsen, Jeffrey S; Kerger, Brent D; Finley, Brent; Paustenbach, Dennis J

    2013-07-01

    A physiologically-based pharmacokinetic (PBPK) model of benzene inhalation based on a recent mouse model was adapted to include bone marrow (target organ) and urinary bladder compartments. Empirical data on human liver microsomal protein levels and linked CYP2E1 activities were incorporated into the model, and metabolite-specific conversion rate parameters were estimated by fitting to human biomonitoring data and adjusting for background levels of urinary metabolites. Human studies of benzene levels in blood and breath, and phenol levels in urine were used to validate the rate of human conversion of benzene to benzene oxide, and urinary benzene metabolites from Chinese benzene worker populations provided model validation for rates of human conversion of benzene to muconic acid (MA) and phenylmercapturic acid (PMA), phenol (PH), catechol (CA), hydroquinone (HQ), and benzenetriol (BT). The calibrated human model reveals that while liver microsomal protein and CYP2E1 activities are lower on average in humans compared to mice, the mouse also shows far lower rates of benzene conversion to MA and PMA, and far higher conversion of benzene to BO/PH, and of BO/PH to CA, HQ, and BT. The model also differed substantially from existing human PBPK models with respect to several metabolic rate parameters of importance to interpreting benzene metabolism and health risks in human populations associated with bone marrow doses. The model provides a new methodological paradigm focused on integrating linked human liver metabolism data and calibration using biomonitoring data, thus allowing for model uncertainty analysis and more rigorous validation. © 2012 Society for Risk Analysis.

  6. Disruption of Runx1 and Runx3 Leads to Bone Marrow Failure and Leukemia Predisposition due to Transcriptional and DNA Repair Defects

    Directory of Open Access Journals (Sweden)

    Chelsia Qiuxia Wang

    2014-08-01

    Full Text Available The RUNX genes encode transcription factors involved in development and human disease. RUNX1 and RUNX3 are frequently associated with leukemias, yet the basis for their involvement in leukemogenesis is not fully understood. Here, we show that Runx1;Runx3 double-knockout (DKO mice exhibited lethal phenotypes due to bone marrow failure and myeloproliferative disorder. These contradictory clinical manifestations are reminiscent of human inherited bone marrow failure syndromes such as Fanconi anemia (FA, caused by defective DNA repair. Indeed, Runx1;Runx3 DKO cells showed mitomycin C hypersensitivity, due to impairment of monoubiquitinated-FANCD2 recruitment to DNA damage foci, although FANCD2 monoubiquitination in the FA pathway was unaffected. RUNX1 and RUNX3 interact with FANCD2 independently of CBFβ, suggesting a nontranscriptional role for RUNX in DNA repair. These findings suggest that RUNX dysfunction causes DNA repair defect, besides transcriptional misregulation, and promotes the development of leukemias and other cancers.

  7. A novel model system for the study of experimental guided bone formation in humans.

    Science.gov (United States)

    Hämmerle, C H; Schmid, J; Olah, A J; Lang, N P

    1996-03-01

    The aim of the present experiment was to test a novel model system, designed to obtain human specimens of regenerated and also newly regenerated jaw bone, for the study of the biological events under a variety of conditions. Following information and disclosure of possible risks associated with a minor oral surgical procedure, 9 systemically healthy subjects (5 men, 4 women, mean age 31.7 years) signed consent forms and volunteered to participate in this study. Hollow test cylinders with an outer diameter of 3.5 mm, an inner diameter of 2.5 mm, and 4 mm in height were used. They were manufactured from commercially pure titanium and exhibited a highly polished inner surface and a titanium plasma sprayed outer rough surface. A mucoperiosteal flap was raised in the retromolar area of the mandible corresponding to standard retrained third molar surgery. Following flap reflection a standardized hole was drilled through the cortical bone into the bone marrow using round burs. The congruent test cylinders were firmly placed into the prepared bony bed yielding primary stability. One-and-a-half to 2 mm of the test device were submerged below the level of the surrounding bone, while the remainder surpassed the level of the bone surface. The bone-facing end of the cylinder was left open, while the coronal soft tissue facing end was closed by an ePTFE-membrane. The flap was sutured to obtain primary wound closure. In order to prevent infection, penicillin was prescribed systemically and oral rinses of chlorhexidine were administered. After 2, 7, and 12 weeks one test device including the regenerated tissue was surgically harvested, while after 16, 24 and 36 weeks respectively, 2 devices were harvested and processed for soft or hard tissue histology or histochemistry. The two surgical procedures and the presence of the test cylinders during the time of healing were well tolerated by the volunteers. In all 9 subjects generated tissue could successfully be harvested. The tissue

  8. A butchered bone from Norfolk: evidence for very early human presence in Britain

    Directory of Open Access Journals (Sweden)

    Simon Parfitt

    2004-08-01

    Full Text Available Before the Anglian glaciation some 450,000 years ago, much of England was drained by large rivers that deposited sediments - known as the Cromer Forest-bed Formation - now exposed along the coast of East Anglia. The Forest-bed has yielded a great variety of fossils but until now no definite evidence of human activity. The recent discovery of cut marks on a bison bone collected from it in the nineteenth century demonstrates conclusively that humans were present in this part of East Anglia over half a million years ago.

  9. [The quality control of preanalytical variations for the determination of lead in samples of human origin].

    Science.gov (United States)

    Zhong, Kun; Wang, Wei; He, Falin; Wang, Zhiguo

    2015-02-01

    The aims of this article was to provide the quality control requirements of preanalytical variation for the determination of lead in samples of human origin, reduce the influence of preanalytical variation on the test results. According to the Clinical and Laboratory Standards Institute documents, control of preanalytical variation in trace element determinations, analytical procedures for the determination of lead in blood and urine and other references and guidelines, the methods of quality control of lead determination had been made, including: the factors needed to be considered before collection, preservation, transportation and other preanalytical factors, the abilities and considerations of laboratory staff, etc.

  10. Mechanical and mineral properties of osteogenesis imperfecta human bones at the tissue level.

    Science.gov (United States)

    Imbert, Laurianne; Aurégan, Jean-Charles; Pernelle, Kélig; Hoc, Thierry

    2014-08-01

    Osteogenesis imperfecta (OI) is a genetic disorder characterized by an increase in bone fragility on the macroscopic scale, but few data are available to describe the mechanisms involved on the tissue scale and the possible correlations between these scales. To better understand the effects of OI on the properties of human bone, we studied the mechanical and chemical properties of eight bone samples from children suffering from OI and compared them to the properties of three controls. High-resolution computed tomography, nanoindentation and Raman microspectroscopy were used to assess those properties. A higher tissue mineral density was found for OI bone (1.131 gHA/cm3 vs. 1.032 gHA/cm3, p=0.032), along with a lower Young's modulus (17.6 GPa vs. 20.5 GPa, p=0.024). Obviously, the mutation-induced collagen defects alter the collagen matrix, thereby affecting the mineralization. Raman spectroscopy showed that the mineral-to-matrix ratio was higher in the OI samples, while the crystallinity was lower, suggesting that the mineral crystals were smaller but more abundant in the case of OI. This change in crystal size, distribution and composition contributes to the observed decrease in mechanical strength.

  11. Radiocarbon dating and compositional analysis of pre-Columbian human bones

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, E., E-mail: andrade@fisica.unam.mx [Instituto de Física, Universidad Nacional Autónoma de México, Apartado Postal 20-364, 01000 México D.F. (Mexico); Solís, C.; Canto, C.E.; Lucio, O.G. de [Instituto de Física, Universidad Nacional Autónoma de México, Apartado Postal 20-364, 01000 México D.F. (Mexico); Chavez, E. [ESIME-Z, Instituto Politécnico Nacional, ALM Zacatenco, 07738 México D.F. (Mexico); Rocha, M.F.; Villanueva, O.; Torreblanca, C.A. [Centro INAH Zacatecas, Miguel Auza No. 205, Col. Centro, Zacatecas/Zacatecas CP 98000 (Mexico)

    2014-08-01

    Analysis of ancient human bones found in “El Cóporo”, an archaeological site in Guanajuato, Mexico; were performed using a multi techniques scheme: {sup 14}C radiocarbon dating, IBA (Ion Beam Analysis), SEM-EDS (Scanning Electron Microscope Energy Dispersive X-ray Spectroscopy). We measured the elemental composition of the bones, especially some with a superficial black pigmentation. Soil samples collected from the burial place were also analyzed. The {sup 14}C dating was performed with a new High Voltage Europe 1 MV Tandentron Accelerator Mass Spectrometer (AMS) recently installed in the IFUNAM (Instituto de Física, Universidad Nacional Autónoma de México). The radiocarbon dating allowed us to determine the date of death of the individual in a period between the year 890 and 975 AD, which is consistent with the late period of the Cóporo civilization. The element sample analysis of bones with the surface black pigmentation show higher levels of Fe, Mn and Ba compared when bone’s black surface was mechanically removed. These three elements were found in soil samples from the skeleton burial place. These results indicate more likely that the bone black coloration is due to a postmortem alteration occurring in the burial environment.

  12. An analysis of factors affecting the mercury content in the human femoral bone.

    Science.gov (United States)

    Zioła-Frankowska, A; Dąbrowski, M; Kubaszewski, Ł; Rogala, P; Kowalski, A; Frankowski, M

    2017-01-01

    The study was carried out to determine the content of mercury in bone tissue of the proximal femur (head and neck bone) of 95 patients undergoing total hip replacement due to osteoarthritis, using CF-AFS analytical technique. Furthermore, the investigations were aimed at assessing the impact of selected factors, such as age, gender, tobacco smoking, alcohol consumption, exposure to chemical substance at work, type of degenerative changes, clinical evaluation and radiological parameters, type of medications, on the concentration of mercury in the head and neck of the femur, resected in situ. Mercury was obtained in all samples of the head and neck of the femur (n = 190) in patients aged 25-91 years. The mean content of mercury for the whole group of patients was as follows: 37.1 ± 35.0 ng/g for the femoral neck and 24.2 ± 19.5 ng/g for the femoral head. The highest Hg contents were found in femoral neck samples, both in women and men, and they amounted to 169.6 and 176.5 ng/g, respectively. The research showed that the mercury content of bones can be associated with body mass index, differences in body anatomy, and gender. The uses of statistical analysis gave the possibility to define the influence of factors on mercury content in human femoral bones.

  13. Effect of lead on IL-8 production and cell proliferation in human oral keratinocytes

    Institute of Scientific and Technical Information of China (English)

    Thaweboon Srosiri; Poomsawat Sopee; Thaweboon Boonyanit

    2010-01-01

    Objective:To investigate the effect of lead on the production of IL-8 and cell proliferation in normal human oral keratinocytes (NHKs). Methods: NHKs were prepared as outgrowths from normal human buccal mucosa. The cells were treated with three concentrations of lead glutamate (4.5í10-5M, 4.5í10-6M and 4.5í10-7M). NHKs grown in glutamic acid were used as control. The amounts of IL-8 secreted in the culture supernatants were evaluated at 12 and 24 h using enzyme-linked immunospecific assay (ELISA). Cell proliferation was determined by the MTT colorimetric assay. Three cultures were used for each experiment, and three independent experiments were performed. Analysis of variance and Duncan’s multiple range tests were used for statistical analysis. Results:An elevation of IL-8 in culture supernatants of NHKs treated with lead at all concentrations at 12 and 24 h after exposure in a dose-dependent manner was revealed. A significant increase in cell numbers was observed only at 24 h exposed to 4.5í10-5M lead glutamate. Conclusions: The capacity of NHKs, to secrete IL-8, enhanced by lead glutamate, is demonstrated here. Induction of cell proliferation is revealed only after exposure to high lead concentration. The elevation of secreted IL-8 is a probable initial sign for the acute inflammatory response and may be involved in the pathogenesis of lead stomatitis.

  14. [Human bone marrow cell culture--a sensitive method for the evaluation of the biocompatibility of materials used in orthopedics].

    Science.gov (United States)

    Wilke, A; von Hirschheydt, S; Orth, J; Kienapfel, H; Griss, P; Franke, R P

    1995-01-01

    The objective of the study was to develop a test system to determine the cytotoxicity and biocompatibility of different biomaterials used in orthopedic surgery. This system was based on the use of a human bone marrow cell culture and the purpose was to find a screening method as a alternative to early animal experimental methods. The established human bone marrow cell culture has certain advantages when compared with other cell culture models. The result demonstrated a high conformity with animal experimental results.

  15. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy

    Energy Technology Data Exchange (ETDEWEB)

    Tsuno, Hiroaki [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Yoshida, Toshiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nogami, Makiko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Orthopedic Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Koike, Chika; Okabe, Motonori [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Noto, Zenko [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Arai, Naoya; Noguchi, Makoto [Department of Oral and Maxillofacial Surgery, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan); Nikaido, Toshio, E-mail: tnikaido@med.u-toyama.ac.jp [Department of Regenerative Medicine, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani Toyama, Toyama 930-0194 (Japan)

    2012-12-01

    Autogenous mesenchymal stem cells (MSCs) have therapeutic applications in bone regenerative therapy due to their pluripotency. However, the ability of MSCs to proliferate and differentiate varies between donors. Furthermore, alternative sources of MSCs are required for patients with contraindications to autogenous cell therapy. The aim of this study was to evaluate the potential of mesenchymal cells from the human amniotic membrane (HAM) as a source of cells for allogeneic transplantation in bone regenerative therapy. Cells that retained a proliferative capacity of more than 50 population doubling level were distinguished from other HAM cells as HAM{alpha} cells and induced to osteogenic status-their in vivo osteogenesis was subsequently investigated in rats. It was found that HAM{alpha} cells were spindle shaped and were positive for MSC markers and negative for hematopoietic stem cell markers. Alkaline phosphatase activity and calcium deposition increased with osteogenic status of HAM{alpha} cells. The expression of osteocalcin mRNA was increased in HAM{alpha} cells cultured on calcium phosphate scaffolds. Moreover, xenografted HAM{alpha} cells remained viable and produced extracellular matrix for several weeks. Thus, this study suggests that human amniotic mesenchymal cells possess osteogenic differentiation potential and could be applied to allogeneic transplantation in bone regenerative therapy. - Highlights: Black-Right-Pointing-Pointer Human amniotic mesenchymal cells include cells (HAM{alpha} cells) that have the properties of MSCs. Black-Right-Pointing-Pointer HAM{alpha} cells have excellent osteogenic differentiation potential. Black-Right-Pointing-Pointer Osteogenic differentiation ability of HAM{alpha} was amplified by calcium phosphate scaffolds. Black-Right-Pointing-Pointer HAM{alpha} cells can be applicable to allogeneic cell transplantation in bone regenerative therapy.

  16. Establishing quiescence in human bone marrow stem cells leads to enhanced osteoblast marker expression

    DEFF Research Database (Denmark)

    Harkness, Linda; Rumman, Mohammad; Kassem, Moustapha;

    expression profiling of the cells demonstrated down-regulation of cyclin (CCNA2, CCND1, CCNE1, CCNB1) and proliferation markers (Ki67) markers during G0 and up-regulation of the osteogenic genes RUNX2 and OPN. RT-PCR analysis of osteogenic differentiation of cells post G0 demonstrated an increase...

  17. Electron absorbed fractions of energy and S-values in an adult human skeleton based on {mu}CT images of trabecular bone

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, R; Cassola, V F; Khoury, H J; De O Lira, C A B [Department of Nuclear Energy, Federal University of Pernambuco, Avenida Professor Luiz Freire, 1000, CEP 50740-540, Recife (Brazil); Richardson, R B [Radiation Protection Research and Instrumentation Branch, Atomic Energy of Canada Limited, Chalk River Laboratories, Chalk River, ON, K0J 1J0 (Canada); Vieira, J W [Federal Institute of Education, Science and Technology of Pernambuco, Recife (Brazil); Brown, K Robson, E-mail: rkramer@uol.com.br [Imaging Laboratory, Department of Archaeology and Anthropology, University of Bristol, Bristol (United Kingdom)

    2011-03-21

    When the human body is exposed to ionizing radiation, among the soft tissues at risk are the active marrow (AM) and the bone endosteum (BE) located in tiny, irregular cavities of trabecular bone. Determination of absorbed fractions (AFs) of energy or absorbed dose in the AM and the BE represent one of the major challenges of dosimetry. Recently, at the Department of Nuclear Energy at the Federal University of Pernambuco, a skeletal dosimetry method based on {mu}CT images of trabecular bone introduced into the spongiosa voxels of human phantoms has been developed and applied mainly to external exposure to photons. This study uses the same method to calculate AFs of energy and S-values (absorbed dose per unit activity) for electron-emitting radionuclides known to concentrate in skeletal tissues. The modelling of the skeletal tissue regions follows ICRP110, which defines the BE as a 50 {mu}m thick sub-region of marrow next to the bone surfaces. The paper presents mono-energetic AFs for the AM and the BE for eight different skeletal regions for electron source energies between 1 keV and 10 MeV. The S-values are given for the beta emitters {sup 14}C, {sup 59}Fe, {sup 131}I, {sup 89}Sr, {sup 32}P and {sup 90}Y. Comparisons with results from other investigations showed good agreement provided that differences between methodologies and trabecular bone volume fractions were properly taken into account. Additionally, a comparison was made between specific AFs of energy in the BE calculated for the actual 50 {mu}m endosteum and the previously recommended 10 {mu}m endosteum. The increase in endosteum thickness leads to a decrease of the endosteum absorbed dose by up to 3.7 fold when bone is the source region, while absorbed dose increases by {approx}20% when the beta emitters are in marrow.

  18. Development of glass-ceramic scaffolds for bone tissue engineering: characterisation, proliferation of human osteoblasts and nodule formation.

    Science.gov (United States)

    Vitale-Brovarone, C; Verné, E; Robiglio, L; Appendino, P; Bassi, F; Martinasso, G; Muzio, G; Canuto, R

    2007-03-01

    Glass-ceramic macroporous scaffolds for tissue engineering have been developed using a polyurethane sponge template and bioactive glass powders. The starting glass (CEL2) belongs to the system SiO(2)-P(2)O(5)-CaO-MgO-Na(2)O-K(2)O and has been synthesised by a conventional melting-quenching route. A slurry of CEL2 powder, polyvinyl alcohol and water has been prepared in order to coat, by impregnation, the polymeric template. An optimised thermal treatment was then use to remove the sponge and to sinter the glass powders, leading to a glass-ceramic replica of the template. Morphological observations, image analyses, mechanical tests and in vitro tests showed that the obtained devices are good candidates as scaffolds for bone-tissue engineering, in terms of pore-size distribution, pore interconnection, surface roughness, and both bioactivity and biocompatibility. In particular, a human osteoblast cell line (MG-63) seeded onto the scaffold after a standardised preconditioning route in simulated body fluid showed a high degree of cell proliferation and a good ability to produce calcium nodules. The obtained results were enhanced by the addition of bone morphogenetic proteins after cell seeding.

  19. Differentiation of human bone marrow stem cells into cells with a neural phenotype: diverse effects of two specific treatments

    Directory of Open Access Journals (Sweden)

    Sanna Maria

    2006-02-01

    Full Text Available Abstract Background It has recently been demonstrated that the fate of adult cells is not restricted to their tissues of origin. In particular, it has been shown that bone marrow stem cells can give rise to cells of different tissues, including neural cells, hepatocytes and myocytes, expanding their differentiation potential. Results In order to identify factors able to lead differentiation of stem cells towards cells of neural lineage, we isolated stromal cells from human adult bone marrow (BMSC. Cells were treated with: (1 TPA, forskolin, IBMX, FGF-1 or (2 retinoic acid and 2-mercaptoethanol (BME. Treatment (1 induced differentiation into neuron-like cells within 24 hours, while a longer treatment was required when using retinoic acid and BME. Morphological modifications were more dramatic after treatment (1 compared with treatment (2. In BMSC both treatments induced the expression of neural markers such as NF, GFAP, TUJ-1 and neuron-specific enolase. Moreover, the transcription factor Hes1 increased after both treatments. Conclusion Our study may contribute towards the identification of mechanisms involved in the differentiation of stem cells towards cells of neural lineage.

  20. Morphometric study of distance between posterior inferior iliac spine and ischial spine of the human hip bone for sex determination

    OpenAIRE

    2014-01-01

    Background: Objective of current study was to study the distance between Posterior Inferior Iliac Spine and Ischial Spine (PIIS-IS) of human hip bone for determination of sex. Methods: The study comprised unpaired 149 adult human hip bones of known sex. The posterior inferior iliac spine and ischial spine were identified in all the hip bones and a vernier calliper was used to measure the distance between the PIIS-IS. Results: It was observed that the mean distance of PIIS-IS in males a...

  1. Association between in vivo bone formation and ex vivo migratory capacity of human bone marrow stromal cells

    DEFF Research Database (Denmark)

    Andersen, Rikke K; Zaher, Walid; Larsen, Kenneth H

    2015-01-01

    by bioluminescence imaging (BLI). In order to identify the molecular phenotype associated with enhanced migration, we carried out comparative DNA microarray analysis of gene expression of hBMSC-derived high bone forming (HBF) clones versus low bone forming (LBF) clones. RESULTS: HBF clones were exhibited higher ex...

  2. Critical values of the external magnetic field leading biological effects in the human organism

    CERN Document Server

    Kanokov, Zakirjon

    2013-01-01

    In the framework of the simplified stochastic model the critical values of an induction of the external magnetic field leading to sharp increase of fluctuations of a casual current of biologically important ions in different blood vessels of a human body are calculated.

  3. An increase in dietary n-3 fatty acids decreases a marker of bone resorption in humans

    Directory of Open Access Journals (Sweden)

    Hilpert Kirsten F

    2007-01-01

    Full Text Available Abstract Human, animal, and in vitro research indicates a beneficial effect of appropriate amounts of omega-3 (n-3 polyunsaturated fatty acids (PUFA on bone health. This is the first controlled feeding study in humans to evaluate the effect of dietary plant-derived n-3 PUFA on bone turnover, assessed by serum concentrations of N-telopeptides (NTx and bone-specific alkaline phosphatase (BSAP. Subjects (n = 23 consumed each diet for 6 weeks in a randomized, 3-period crossover design: 1 Average American Diet (AAD; [34% total fat, 13% saturated fatty acids (SFA, 13% monounsaturated fatty acids (MUFA, 9% PUFA (7.7% LA, 0.8% ALA], 2 Linoleic Acid Diet (LA; [37% total fat, 9% SFA, 12% MUFA, 16% PUFA (12.6% LA, 3.6% ALA], and 3 α-Linolenic Acid Diet (ALA; [38% total fat, 8% SFA, 12% MUFA, 17% PUFA (10.5% LA, 6.5% ALA]. Walnuts and flaxseed oil were the predominant sources of ALA. NTx levels were significantly lower following the ALA diet (13.20 ± 1.21 nM BCE, relative to the AAD (15.59 ± 1.21 nM BCE (p

  4. Enhanced human bone marrow mesenchymal stem cell functions on cathodic arc plasma-treated titanium.

    Science.gov (United States)

    Zhu, Wei; Teel, George; O'Brien, Christopher M; Zhuang, Taisen; Keidar, Michael; Zhang, Lijie Grace

    2015-01-01

    Surface modification of titanium for use in orthopedics has been explored for years; however, an ideal method of integrating titanium with native bone is still required to this day. Since human bone cells directly interact with nanostructured extracellular matrices, one of the most promising methods of improving titanium's osseointegration involves inducing bio-mimetic nanotopography to enhance cell-implant interaction. In this regard, we explored an approach to functionalize the surface of titanium by depositing a thin film of textured titanium nanoparticles via a cathodic arc discharge plasma. The aim is to improve human bone marrow mesenchymal stem cell (MSC) attachment and differentiation and to reduce deleterious effects of more complex surface modification methods. Surface functionalization was analyzed by scanning electron microscopy, atomic force microscopy, contact angle testing, and specific protein adsorption. Scanning electron microscopy and atomic force microscopy examination demonstrate the deposition of titanium nanoparticles and the surface roughness change after coating. The specific fibronectin adsorption was enhanced on the modified titanium surface that associates with the improved hydrophilicity. MSC adhesion and proliferation were significantly promoted on the nanocoated surface. More importantly, compared to bare titanium, greater production of total protein, deposition of calcium mineral, and synthesis of alkaline phosphatase were observed from MSCs on nanocoated titanium after 21 days. The method described herein presents a promising alternative method for inducing more cell favorable nanosurface for improved orthopedic applications.

  5. Bioactive Ti metal analogous to human cancellous bone: Fabrication by selective laser melting and chemical treatments.

    Science.gov (United States)

    Pattanayak, Deepak K; Fukuda, A; Matsushita, T; Takemoto, M; Fujibayashi, S; Sasaki, K; Nishida, N; Nakamura, T; Kokubo, T

    2011-03-01

    Selective laser melting (SLM) is a useful technique for preparing three-dimensional porous bodies with complicated internal structures directly from titanium (Ti) powders without any intermediate processing steps, with the products being expected to be useful as a bone substitute. In this study the necessary SLM processing conditions to obtain a dense product, such as the laser power, scanning speed, and hatching pattern, were investigated using a Ti powder of less than 45 μm particle size. The results show that a fully dense plate thinner than 1.8 mm was obtained when the laser power to scanning speed ratio was greater than 0.5 and the hatch spacing was less than the laser diameter, with a 30 μm thick powder layer. Porous Ti metals with structures analogous to human cancellous bone were fabricated and the compressive strength measured. The compressive strength was in the range 35-120 MPa when the porosity was in the range 75-55%. Porous Ti metals fabricated by SLM were heat-treated at 1300 °C for 1h in an argon gas atmosphere to smooth the surface. Such prepared specimens were subjected to NaOH, HCl, and heat treatment to provide bioactivity. Field emission scanning electron micrographs showed that fine networks of titanium oxide were formed over the whole surface of the porous body. These treated porous bodies formed bone-like apatite on their surfaces in a simulated body fluid within 3 days. In vivo studies showed that new bone penetrated into the pores and directly bonded to the walls within 12 weeks after implantation into the femur of Japanese white rabbits. The percentage bone affinity indices of the chemical- and heat-treated porous bodies were significantly higher than that of untreated implants.

  6. Effective combination of aligned nanocomposite nanofibers and human unrestricted somatic stem cells for bone tissue engineering

    Institute of Scientific and Technical Information of China (English)

    Behnaz BAKHSHANDEH; Masoud SOLEIMANI; Nasser GHAEMI; Iman SHABANI

    2011-01-01

    Aim: Bioartificial bone tissue engineering is an increasingly popular technique to solve bone defect challenges. This study aimed to investigate the interactions between matrix composition and appropriate cell type, focusing on hydroxyapatite (HA), to achieve a more effective combination for bone regeneration.Methods: Human unrestricted somatic stem cells (USSCs) were isolated from placental cord blood. The cellular and molecular events during the osteo-induction of USSCs were evaluated for 21 d under the following conditions: (1) in basal culture, (2) supplemented with hydroxyapatite nanoparticle (nHA) suspension, and (3) seeded on electrospun aligned nanoflbrous poly-ε-caprolactone/poly-L-lactic acid/nHA (PCL/PLLA/nHA) scaffolds. The scaffolds were characterized using scanning electron microscope (SEM), fourier transform infrared spectroscopy (FTIR) and tensile test.Results: Maintenance of USSCs for 21 d in basal or osteogenic culture resulted in significant increase in osteoblast differentiation. With nHA suspension, even soluble osteo-inductive additives were ineffective, probably due to induced apoptosis of the cells. In con-trast to the hindrance of proliferation by nHA suspension, the scaffolds improved cell growth. The scaffolds mimic the nanostructure of natural bone matrix with the combination of PLLA/PCL (organic phase) and HA (inorganic phase) offering a favorable surface topogra-phy, which was demonstrated to possess suitable properties for supporting USSCs. Quantitative measurement of osteogenic markers, enzymatic activity and mineralization indicated that the scaffolds did not disturb, but enhanced the osteogenic potential of USSCs.Moreover, the alignment of the fibers led to cell orientation during cell growth.Conclusion: The results demonstrated the synergism of PCL/PLLA/nHA nanoflbrous scaffolds and USSCs in the augmentation of osteo-genic differentiation. Thus, nHA grafted into PCI./PLLA scaffolds can be a suitable choice for bone tissue

  7. Effects of ionizing radiation on proteins in lyophilized or frozen demineralized human bone

    Science.gov (United States)

    Antebi, Uri; Mathor, Monica Beatriz; da Silva, André Ferreira; Guimarães, Rodrigo Pereira; Honda, Emerson Kiyoshi

    2016-01-01

    Objective The aim was to study the effects of application of ionizing radiation (gamma and electrons) as sterilizing agents at doses of 15 kGy, 25 kGy and 50 kGy, on lyophilized or frozen demineralized bone tissue for use in transplants. Methods Five human femoral diaphyses from different donors of musculoskeletal tissue were demineralized and preserved as lyophilized or frozen at −80 °C. The samples were divided into two groups: non-irradiated (control) and irradiated by means of gamma rays or an electron beam. The bone proteins were extracted and used to determine the concentrations of total protein and BMP 2 and 7. Results Decreases in total protein and BMP 2 and 7 concentrations were observed. The decreases in total protein concentrations, in comparison with the respective control groups, were significant in the lyophilized and frozen samples that were irradiated at a dose of 50 kGy of gamma radiation and electron beam, with reductions of more than 30%. Significant decreases in the levels of BMP 2 and 7 were also observed at higher doses and especially through use of the electron beam. Conclusion The reductions in the concentrations of total proteins and osteoinductive proteins (BMP 2 and 7) were related to the radiation dose, i.e. they increased with higher doses of ionizing radiation type and the type of bone preservation. The largest reductions in concentrations were observed in the bones irradiated by means of an electron beam and at a dose of 50 kGy. However, this type of radiation and this high dose are not usual practices for sterilization of bone tissue. PMID:27069893

  8. A Western Diet Pattern Is Associated with Higher Concentrations of Blood and Bone Lead among Middle-Aged and Elderly Men.

    Science.gov (United States)

    Wang, Xin; Ding, Ning; Tucker, Katherine L; Weisskopf, Marc G; Sparrow, David; Hu, Howard; Park, Sung Kyun

    2017-07-01

    Background: Little is known about the effects of overall dietary pattern on lead concentration.Objective: We examined the association of overall dietary patterns, derived from a semiquantitative food frequency questionnaire, with bone and blood lead concentrations.Methods: These longitudinal analyses included mostly non-Hispanic white, middle-aged-to-elderly men from the Veterans Affairs Normative Aging Study. Long-term lead exposures were measured as tibia and patella lead concentrations by using K-shell-X-ray fluorescence. Short-term lead exposures were measured as blood lead concentrations by using graphite furnace atomic absorption spectroscopy. Dietary pattern scores were derived by using factor analysis. Linear mixed-effects models were utilized to predict blood lead concentrations among 983 men, aged 44-92 y at baseline, with a total of 3273 observations (during 1987-2008). We constructed linear regression models to determine the relations between dietary patterns and bone lead concentrations among 649 participants with an age range of 49-93 y.Results: Two major dietary patterns were identified: a prudent dietary pattern, characterized by high intakes of fruit, legumes, vegetables, whole grains, poultry, and seafood; and a Western dietary pattern, characterized by high intakes of processed meat, red meat, refined grains, high-fat dairy products, French fries, butter, and eggs. After adjusting for age, smoking status, body mass index, total energy intake, education, occupation, neighborhood-based education and income level, men in the highest tertile of the Western pattern score (compared with the lowest) had 0.91 μg/dL (95% CI: 0.41, 1.42 μg/dL) higher blood lead, 5.96 μg/g (95% CI: 1.76, 10.16 μg/g) higher patella lead, and 3.83 μg/g (95% CI: 0.97, 6.70 μg/g) higher tibia lead. No significant association was detected with the prudent dietary pattern in the adjusted model.Conclusions: These findings suggest that the Western diet is associated with a

  9. Paramagnetic and crystallographic effects of low temperature ashing on human bone and tooth enamel.

    Science.gov (United States)

    Tochon-Danguy, H J; Very, J M; Geoffroy, M; Baud, C A

    1978-02-28

    Low temperature ashing by excited gas (LTA) causes crystallographic and paramagnetic alterations of the human bone and tooth enamel mineral. On the one hand, LTA induces variations of the alpha lattice parameter. These variations depend upon the nature of the gas used, but are little affected by its degree of excitation. Trapping of gas molecules in the crystal structure is demonstrated. On the other hand, LTA produces two preponderant paramagnetic centers in bone and enamel samples at 20 degrees C. Their inorganic origin clearly indicated. One of the two radicals has been identified as O3- (g1 = 2.002, g2 = 2.010, g3 = 2.016) and the other as (CO3-3 (parallel = 1.996, g = perpendicular 2.003). Variations of the alpha lattice parameter and trapping of paramagnetic gas species do not seem to be directly related.

  10. Oxygen isotope analysis of human bone phosphate evidences weaning age in archaeological populations.

    Science.gov (United States)

    Britton, Kate; Fuller, Benjamin T; Tütken, Thomas; Mays, Simon; Richards, Michael P

    2015-06-01

    Here we report bone phosphate oxygen (δ(18)Op) values from perinates/neonates and infants (isotope systems likely due to breastfeeding. After the age of 2-3 years, δ(18)Op values are lower, and all children between the ages of 4 and 12, along with the vast majority of sub-adults and adults sampled (aged 16 to >50 years), have δ(18)Op values consistent with the consumption of local modern drinking water. The implications of this study for the reconstruction of weaning practices in archaeological populations are discussed, including variations observed with bone δ(15)Ncoll and δ(18)Op co-analysis and the influence of culturally-modified drinking water and seasonality. The use of this method to explore human mobility and palaeoclimatic conditions are also discussed with reference to the data presented. © 2015 Wiley Periodicals, Inc.

  11. Proteome Changes of Human Bone Marrow Mesenchymal Stem Cells Induced by 1,4-Benzoquinone

    Science.gov (United States)

    2016-01-01

    Benzene is metabolized to hydroquinone in liver and subsequently transported to bone marrow for further oxidization to 1,4-benzoquinone (1,4-BQ), which may be related to the leukemia and other blood disorders. In the present study, we investigated the proteome profiles of human primary bone marrow mesenchymal stem cells (hBM-MSCs) treated by 1,4-BQ. We identified 32 proteins that were differentially expressed. Two of them, HSP27 and Vimentin, were verified at both mRNA and protein levels and their cellular localization was examined by immunofluorescence. We also found increased mRNA level of RAP1GDS1, a critical factor of metabolism that has been identified as a fusion partner in various hematopoietic malignancies. Therefore, these differentially expressed proteins can play important roles in benzene-mediated hematoxicity. PMID:28119923

  12. Bone formation of human mesenchymal stem cells harvested from reaming debris is stimulated by low-dose bone morphogenetic protein-7 application in vivo.

    Science.gov (United States)

    Westhauser, Fabian; Höllig, Melanie; Reible, Bruno; Xiao, Kai; Schmidmaier, Gerhard; Moghaddam, Arash

    2016-12-01

    Stimulation of mesenchymal stem cells (MSC) by bone morphogenetic protein-7 (BMP-7) leads to superior bone formation in vitro. In this in vivo-study we evaluated the use of BMP-7 in combination with MSC isolated from reaming debris (RIA-MSC) and iliac crest bone marrow (BMSC) with micro-computed tomography (mCT)-analysis. β-Tricalciumphosphate scaffolds coated with BMSC and RIA-MSC were stimulated with three different BMP-7-concentrations and implanted ectopically in severe combined immunodeficiency (SCID) mice. Our results demonstrate that RIA-MSC show a higher osteogenic potential in vivo compared to BMSC. Ossification increased in direct correlation with the BMP-7-dose applied, however low-dose-stimulation by BMP-7 was more effective for RIA-MSC.

  13. Heterotopic ossification after the use of recombinant human bone morphogenetic protein-7

    Science.gov (United States)

    Papanagiotou, Marianthi; Dailiana, Zoe H; Karachalios, Theophilos; Varitimidis, Sokratis; Hantes, Michael; Dimakopoulos, Georgios; Vlychou, Marianna; Malizos, Konstantinos N

    2017-01-01

    AIM To present the incidence of heterotopic ossification after the use of recombinant human bone morphogenetic protein-7 (rhBMP-7) for the treatment of nonunions. METHODS Bone morphogenetic proteins (BMPs) promote bone formation by auto-induction. Recombinant human BMP-7 in combination with bone grafts was used in 84 patients for the treatment of long bone nonunions. All patients were evaluated radiographicaly for the development of heterotopic ossification during the standard assessment for the nonunion healing. In all patients (80.9%) with radiographic signs of heterotopic ossification, a CT scan was performed. Nonunion site palpation and ROM evaluation of the adjacent joints were also carried out. Factors related to the patient (age, gender), the nonunion (location, size, chronicity, number of previous procedures, infection, surrounding tissues condition) and the surgical procedure (graft and fixation type, amount of rhBMP-7) were correlated with the development of heterotopic ossification and statistical analysis with Pearsons χ2 test was performed. RESULTS Eighty point nine percent of the nonunions treated with rhBMP-7, healed with no need for further procedures. Heterotopic bone formation occurred in 15 of 84 patients (17.8%) and it was apparent in the routine radiological evaluation of the nonunion site, in a mean time of 5.5 mo after the rhBMP-7 application (range 3-12). The heterotopic ossification was located at the femur in 8 cases, at the tibia in 6, and at the humerus in οne patient. In 4 patients a palpable mass was present and only in one patient, with a para-articular knee nonunion treated with rhBMP-7, the size of heterotopic ossification affected the knee range of motion. All the patients with heterotopic ossification were male. Statistical analysis proved that patient’s gender was the only important factor for the development of heterotopic ossification (P = 0.007). CONCLUSION Heterotopic ossification after the use of rhBMP-7 in nonunions was

  14. Flat bones and sutures formation in the human cranial vault during prenatal development and infancy: A computational model.

    Science.gov (United States)

    Burgos-Flórez, F J; Gavilán-Alfonso, M E; Garzón-Alvarado, D A

    2016-03-21

    The processes of flat bones growth, sutures formation and interdigitation in the human calvaria are controlled by a complex interaction between genetic, biochemical and environmental factors that regulate bone formation and resorption during prenatal development and infancy. Despite previous experimental evidence accounting for the role of the main biochemical factors acting on these processes, the underlying mechanisms controlling them are still unknown. Therefore, we propose a mathematical model of the processes of flat bone and suture formation, taking into account several biological events. First, we model the growth of the flat bones and the formation of sutures and fontanels as a reaction diffusion system between two proteins: TGF-β2 and TGF-β3. The former is expressed by osteoblasts and allows adjacent mesenchymal cells differentiation on the bone fronts of each flat bone. The latter is expressed by mesenchymal cells at the sutures and inhibits their differentiation into osteoblasts at the bone fronts. Suture interdigitation is modelled using a system of reaction diffusion equations that develops spatio-temporal patterns of bone formation and resorption by means of two molecules (Wnt and Sclerostin) which control mesenchymal cells differentiation into osteoblasts at these sites. The results of the computer simulations predict flat bone growth from ossification centers, sutures and fontanels formation as well as bone formation and resorption events along the sutures, giving rise to interdigitated patterns. These stages were modelled and solved by the finite elements method. The simulation results agree with the morphological characteristics of calvarial bones and sutures throughout human prenatal development and infancy.

  15. Theobromine Upregulates Osteogenesis by Human Mesenchymal Stem Cells In Vitro and Accelerates Bone Development in Rats.

    Science.gov (United States)

    Clough, Bret H; Ylostalo, Joni; Browder, Elizabeth; McNeill, Eoin P; Bartosh, Thomas J; Rawls, H Ralph; Nakamoto, Tetsuo; Gregory, Carl A

    2017-03-01

    Theobromine (THB) is one of the major xanthine-like alkaloids found in cacao plant and a variety of other foodstuffs such as tea leaves, guarana and cola nuts. Historically, THB and its derivatives have been utilized to treat cardiac and circulatory disorders, drug-induced nephrotoxicity, proteinuria and as an immune-modulator. Our previous work demonstrated that THB has the capacity to improve the formation of hydroxyl-apatite during tooth development, suggesting that it may also enhance skeletal development. With its excellent safety profile and resistance to pharmacokinetic elimination, we reasoned that it might be an excellent natural osteoanabolic supplement during pregnancy, lactation and early postnatal growth. To determine whether THB had an effect on human osteoprogenitors, we subjected primary human bone marrow mesenchymal stem cells (hMSCs) to osteogenic assays after exposure to THB in vitro and observed that THB exposure increased the rate of osteogenesis and mineralization by hMSCs. Moreover, THB exposure resulted in a list of upregulated mRNA transcripts that best matched an osteogenic tissue expression signature as compared to other tissue expression signatures archived in several databases. To determine whether oral administration of THB resulted in improved skeletal growth, we provided pregnant rats with chow supplemented with THB during pregnancy and lactation. After weaning, offspring received THB continuously until postnatal day 50 (approximately 10 mg kg(-1) day(-1)). Administration of THB resulted in neonates with larger bones, and 50-day-old offspring accumulated greater body mass, longer and thicker femora and superior tibial trabecular parameters. The accelerated growth did not adversely affect the strength and resilience of the bones. These results indicate that THB increases the osteogenic potential of bone marrow osteoprogenitors, and dietary supplementation of a safe dose of THB to expectant mothers and during the postnatal period

  16. Matrigel Enhances in vitro Bone Differentiation of Human Marrow-derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Mohamadreza Baghaban Eslaminejad

    2010-01-01

    Full Text Available The use of co-culture cells as well as extra cellular matrix are among those strategies that have been employed to direct mesenchymal stem cell (MSC bone differentiation in culture. In this regard, there is no study considering the effects of Matrigel on mesenchymal stem cell (MSC in vitro bone differentiation. This was the subject of the present study. Materials and MethodsHuman passaged-3 MSCs isolated from the marrow aspirates were seeded on either Matrigel or conventional polystyrene plastic surfaces (as control for 10 days. To compare the cell proliferation in two cultures, the cell numbers were determined during the cultivation period. For bone differentiation, the confluent cultures from either group were provided with osteogenic medium and incubated for 21 days during which the alkaline phosphates (ALP activity, culture mineralization and the expression of some bone-related genes were quantified and statistically compared.ResultsMTT assay indicated thatMatrigel-cultivated cells underwent statistically less proliferation than polystyrene-cultivated cells (P<0.05. Regarding the osteogenic differentiation, ALP activity was significantly high in Matrigel versus plastic cultures. Calcium deposition in Matrigel cultures tended to be significantly extensive compared with that of control cultures (2.533±0.017 versus 0.607±0.09 mM. Furthermore, according to the semi-quantitative RT-PCR analysis, compared with polystyrene plastic surface, Matrigel seemed to provide a microenvironment in which human MSC expressed osteocalcin and collagen I genes in a significantly higher level. ConclusionCollectively it seems that Matrigel could be considered as an appropriate matrix for MSC osteogenic differentiation.

  17. Directed migration of human bone marrow mesenchymal stem cells in a physiological direct current electric field

    Directory of Open Access Journals (Sweden)

    Z Zhao

    2011-11-01

    Full Text Available At sites of bone fracture, naturally-occurring electric fields (EFs exist during healing and may guide cell migration. In this study, we investigated whether EFs could direct the migration of bone marrow mesenchymal stem cells (BM-MSCs, which are known to be key players in bone formation. Human BM-MSCs were cultured in direct current EFs of 10 to 600 mV/mm. Using time-lapse microscopy, we demonstrated that an EF directed migration of BM-MSCs mainly to the anode. Directional migration occurred at a low threshold and with a physiological EF of ~25 mV/mm. Increasing the EF enhanced the MSC migratory response. The migration speed peaked at 300 mV/mm, at a rate of 42 ±1 µm/h, around double the control (no EF migration rate. MSCs showed sustained response to prolonged EF application in vitro up to at least 8 h. The electrotaxis of MSCs with either early (P3-P5 or late (P7-P10 passage was also investigated. Migration was passage-dependent with higher passage number showing reduced directed migration, within the range of passages examined. An EF of 200 mV/mm for 2 h did not affect cell senescence, phenotype, or osteogenic potential of MSCs, regardless of passage number within the range tested (P3-P10. Our findings indicate that EFs are a powerful cue in directing migration of human MSCs in vitro. An applied EF may be useful to control or enhance migration of MSCs during bone healing.

  18. Optimized Cryopreservation and Banking of Human Bone-Marrow Fragments and Stem Cells.

    Science.gov (United States)

    Carnevale, Gianluca; Pisciotta, Alessandra; Riccio, Massimo; De Biasi, Sara; Gibellini, Lara; Ferrari, Adriano; La Sala, Giovanni B; Bruzzesi, Giacomo; Cossarizza, Andrea; de Pol, Anto

    2016-04-01

    Adult mesenchymal stem cells are a promising source for cell therapies and tissue engineering applications. Current procedures for banking of human bone-marrow mesenchymal stem cells (hBM-MSCs) require cell isolation and expansion, and thus the use of large amounts of animal sera. However, animal-derived culture supplements have the potential to trigger infections and severe immune reactions. The aim of this study was to investigate an optimized method for cryopreservation of human bone-marrow fragments for application in cell banking procedures where stem-cell expansion and use are not immediately needed. Whole trabecular fragments enclosing the bone marrow were stored in liquid nitrogen for 1 year in a cryoprotective solution containing a low concentration of dimethyl sulfoxide and a high concentration of human serum (HuS). After thawing, the isolation, colony-forming-unit ability, proliferation, morphology, stemness-related marker expression, cell senescence, apoptosis, and multi-lineage differentiation potential of hBM-MSCs were tested in media containing HuS compared with hBM-MSCs isolated from fresh fragments. Human BM-MSCs isolated from cryopreserved fragments expressed MSC markers until later passages, had a good proliferation rate, and exhibited the capacity to differentiate toward osteogenic, adipogenic, and myogenic lineages similar to hBM-MSCs isolated from fresh fragments. Moreover, the cryopreservation method did not induce cell senescence or cell death. These results imply that minimal processing may be adequate for the banking of tissue samples with no requirement for the immediate isolation and use of hBM-MSCs, thus limiting cost and the risk of contamination, and facilitating banking for clinical use. Furthermore, the use of HuS for cryopreservation and expansion/differentiation has the potential for clinical application in compliance with good manufacturing practice standards.

  19. Human Urine Derived Stem Cells in Combination with β-TCP Can Be Applied for Bone Regeneration.

    Directory of Open Access Journals (Sweden)

    Junjie Guan

    Full Text Available Bone tissue engineering requires highly proliferative stem cells that are easy to isolate. Human urine stem cells (USCs are abundant and can be easily harvested without using an invasive procedure. In addition, in our previous studies, USCs have been proved to be able to differentiate into osteoblasts, chondrocytes, and adipocytes. Therefore, USCs may have great potential and advantages to be applied as a cell source for tissue engineering. However, there are no published studies that describe the interactions between USCs and biomaterials and applications of USCs for bone tissue engineering. Therefore, the objective of the present study was to evaluate the interactions between USCs with a typical bone tissue engineering scaffold, beta-Tricalcium Phosphate (β-TCP, and to determine whether the USCs seeded onto β-TCP scaffold can promote bone regeneration in a segmental femoral defect of rats. Primary USCs were isolated from urine and seeded on β-TCP scaffolds. Results showed that USCs remained viable and proliferated within β-TCP. The osteogenic differentiation of USCs within the scaffolds was demonstrated by increased alkaline phosphatase activity and calcium content. Furthermore, β-TCP with adherent USCs (USCs/β-TCP were implanted in a 6-mm critical size femoral defect of rats for 12 weeks. Bone regeneration was determined using X-ray, micro-CT, and histologic analyses. Results further demonstrated that USCs in the scaffolds could enhance new bone formation, which spanned bone defects in 5 out of 11 rats while β-TCP scaffold alone induced modest bone formation. The current study indicated that the USCs can be used as a cell source for bone tissue engineering as they are compatible with bone tissue engineering scaffolds and can stimulate the regeneration of bone in a critical size bone defect.

  20. Human Urine Derived Stem Cells in Combination with β-TCP Can Be Applied for Bone Regeneration.

    Science.gov (United States)

    Guan, Junjie; Zhang, Jieyuan; Li, Haiyan; Zhu, Zhenzhong; Guo, Shangchun; Niu, Xin; Wang, Yang; Zhang, Changqing

    2015-01-01

    Bone tissue engineering requires highly proliferative stem cells that are easy to isolate. Human urine stem cells (USCs) are abundant and can be easily harvested without using an invasive procedure. In addition, in our previous studies, USCs have been proved to be able to differentiate into osteoblasts, chondrocytes, and adipocytes. Therefore, USCs may have great potential and advantages to be applied as a cell source for tissue engineering. However, there are no published studies that describe the interactions between USCs and biomaterials and applications of USCs for bone tissue engineering. Therefore, the objective of the present study was to evaluate the interactions between USCs with a typical bone tissue engineering scaffold, beta-Tricalcium Phosphate (β-TCP), and to determine whether the USCs seeded onto β-TCP scaffold can promote bone regeneration in a segmental femoral defect of rats. Primary USCs were isolated from urine and seeded on β-TCP scaffolds. Results showed that USCs remained viable and proliferated within β-TCP. The osteogenic differentiation of USCs within the scaffolds was demonstrated by increased alkaline phosphatase activity and calcium content. Furthermore, β-TCP with adherent USCs (USCs/β-TCP) were implanted in a 6-mm critical size femoral defect of rats for 12 weeks. Bone regeneration was determined using X-ray, micro-CT, and histologic analyses. Results further demonstrated that USCs in the scaffolds could enhance new bone formation, which spanned bone defects in 5 out of 11 rats while β-TCP scaffold alone induced modest bone formation. The current study indicated that the USCs can be used as a cell source for bone tissue engineering as they are compatible with bone tissue engineering scaffolds and can stimulate the regeneration of bone in a critical size bone defect.

  1. Human Dental Pulp-Derived Cells Produce Bone-Like Tissue and Exhibit Bone Cell-Like Responsiveness to Mechanical Loading

    DEFF Research Database (Denmark)

    Kraft, David Christian Evar; Melsen, Birte; Bindslev, Dorthe Arenholt

    2010-01-01

    Recent studies have shown that dental pulp cells possess stem cell like potential and thus may be potential candidates for tissue engineering purposes particularly in the oro-facial region. Successful tissue engineering ideally requires that newly formed bone adapts its mass, shape, and trabecular...... and characterize cell lines from human 3rd molar dental pulp tissue to determine whether human dental pulp-derived cells (DPCs) are osteogenic and responsive to mechanical loading by pulsating fluid flow (PFF) in vitro. Methods: Human DPCs used for this study were characterized by measuring proliferation....... We also assessed bone formation by DPCs on hydroxyapatite-tricalcium phosphate granules after subcutaneous implantation in mice. Results: We found that DPCs are intrinsically mechanosensitive and, like osteogenic cells, respond to PFF-induced fluid shear stress. Implantation of DPCs resulted...

  2. Human Osteoblast Differentiation and Bone Formation: Growth Factors, Hormones and Regulatory Networks

    NARCIS (Netherlands)

    H.J.M. Eijken (Marco)

    2007-01-01

    textabstractOsteoporosis is the most common bone disease and is characterized by low bone mass, micro architectural deterioration and decreased bone quality resulting in increased risk of fractures. Osteoblasts, the bone forming cells, play a crucial role in the regulation of bone mass and

  3. Translational Research: Palatal-derived Ecto-mesenchymal Stem Cells from Human Palate: A New Hope for Alveolar Bone and Cranio-Facial Bone Reconstruction.

    Science.gov (United States)

    Grimm, Wolf Dieter; Dannan, Aous; Giesenhagen, Bernd; Schau, Ingmar; Varga, Gabor; Vukovic, Mark Alexander; Sirak, Sergey Vladimirovich

    2014-05-01

    The management of facial defects has rapidly changed in the last decade. Functional and esthetic requirements have steadily increased along with the refinements of surgery. In the case of advanced atrophy or jaw defects, extensive horizontal and vertical bone augmentation is often unavoidable to enable patients to be fitted with implants. Loss of vertical alveolar bone height is the most common cause for a non primary stability of dental implants in adults. At present, there is no ideal therapeutic approach to cure loss of vertical alveolar bone height and achieve optimal pre-implantological bone regeneration before dental implant placement. Recently, it has been found that specific populations of stem cells and/or progenitor cells could be isolated from different dental resources, namely the dental follicle, the dental pulp and the periodontal ligament. Our research group has cultured palatal-derived stem cells (paldSCs) as dentospheres and further differentiated into various cells of the neuronal and osteogenic lineage, thereby demonstrating their stem cell state. In this publication will be shown whether paldSCs could be differentiated into the osteogenic lineage and, if so, whether these cells are able to regenerate alveolar bone tissue in vivo in an athymic rat model. Furthermore, using these data we have started a proof of principle clinical- and histological controlled study using stem cell-rich palatal tissues for improving the vertical alveolar bone augmentation in critical size defects. The initial results of the study demonstrate the feasibility of using stem cell-mediated tissue engineering to treat alveolar bone defects in humans.

  4. Responsiveness of human prostate carcinoma bone tumors to interleukin-2 therapy in a mouse xenograft tumor model.

    Science.gov (United States)

    Kocheril, S V; Grignon, D J; Wang, C Y; Maughan, R L; Montecillo, E J; Talati, B; Tekyi-Mensah, S; Pontes, J e; Hillman, G G

    1999-01-01

    We have tested an immunotherapy approach for the treatment of metastatic prostate carcinoma using a bone tumor model. Human PC-3 prostate carcinoma tumor cells were heterotransplanted into the femur cavity of athymic Balb/c nude mice. Tumor cells replaced marrow cells in the bone cavity, invaded adjacent bone and muscle tissues, and formed a palpable tumor at the hip joint. PC-3/IF cell lines, generated from bone tumors by serial in vivo passages, grew with faster kinetics in the femur and metastasized to inguinal lymph nodes. Established tumors were treated with systemic interleukin-2 (IL-2) injections. IL-2 significantly inhibited the formation of palpable tumors and prolonged mouse survival at nontoxic low doses. Histologically IL-2 caused vascular damage and infiltration of polymorphonuclear cells and lymphocytes in the tumor as well as necrotic areas with apoptotic cells. These findings suggest destruction of tumor cells by systemic IL-2 therapy and IL-2 responsiveness of prostate carcinoma bone tumors.

  5. NOTE: A preliminary study for non-invasive quantification of manganese in human hand bones

    Science.gov (United States)

    Aslam; Pejović-Milić, A.; Chettle, D. R.; McNeill, F. E.; Pysklywec, M. W.; Oudyk, J.

    2008-10-01

    Manganese (Mn) is a nutrient essential for regulating neurological and skeletal functions in the human body, but it is also toxic when humans are excessively exposed to Mn. Blood (or serum/plasma) and other body fluids reflect only the most recent exposure and rapidly return to within normal ranges, even when there has been a temporary excursion in response to exposure. In this context, we have been developing a non-invasive measurement of Mn stored in bone, using in vivo neutron activation analysis. Following feasibility studies, a first pilot study, using neutron activation analysis to measure Mn in the bones of the hand of ten healthy male human subjects, was conducted with the approval of the concerned research ethics boards. The participants of this study had no known history of exposure to Mn. Two volunteers were excluded from this study due to technical problems with their measurements. The inverse variance weighted mean value of Mn/Ca for the participants of this study is 0.12 ± 0.68 µg Mn/g Ca which is comparable within uncertainties with the estimated range of 0.16 0.78 µg Mn/g Ca and mean value of 0.63 ± 0.30 µg Mn/g Ca derived from cadaver data. It is recommended to investigate the use of the diagnostic technique for in vivo measurements of workers exposed occupationally to excessive amounts of Mn who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. The technique needs further development to improve the precision of in vivo measurements in the non-exposed population.

  6. Easily-handled method to isolate mesenchymal stem cells from coagulated human bone marrow samples

    Institute of Scientific and Technical Information of China (English)

    Heng-Xiang; Wang; Zhi-Yong; Li; Zhi-Kun; Guo; Zi-Kuan; Guo

    2015-01-01

    AIM:To establish an easily-handled method to isolate mesenchymal stem cells(MSCs) from coagulated human bone marrow samples. METHODS: Thrombin was added to aliquots of seven heparinized human bone marrow samples to mimic marrow coagulation. The clots were untreated,treated with urokinase or mechanically cut into pieces before culture for MSCs. The un-coagulated samples and the clots were also stored at 4 ℃ for 8 or 16 h before the treatment. The numbers of colony-forming unit-fibroblast(CFU-F) in the different samples were determined. The adherent cells from different groups were passaged and their surface profile was analyzed with flow cytometry. Their capacities of in vitro osteogenesis and adipogenesis were observed after the cells were exposed to specific inductive agents.RESULTS: The average CFU-F number of urokinasetreated samples(16.85 ± 11.77/106) was comparable to that of un-coagulated control samples(20.22 ± 10.65/106,P = 0.293),which was significantly higher than those of mechanically-cut clots(6.5 ± 5.32/106,P < 0.01) and untreated clots(1.95 ± 1.86/106,P < 0.01). The CFU-F numbers decreased after samples were stored,but those of control and urokinase-treated clots remained higher than the other two groups. Consistently,the numbers of the attached cells at passage 0 were higher in control and urokinase-treated clots than those of mechanically-cut clots and untreated clots.The attached cells were fibroblast-like in morphology and homogenously positive for CD44,CD73 and CD90,and negative for CD31 and CD45. Also,they could be induced to differentiate into osteoblasts and adipocytes in vitro. CONCLUSION: Urokinase pretreatment is an optimal strategy to isolate MSCs from human bone marrow samples that are poorly aspirated and clotted.

  7. Evaluation of meat and bone meal combustion residue as lead immobilizing material for in situ remediation of polluted aqueous solutions and soils: "chemical and ecotoxicological studies".

    Science.gov (United States)

    Deydier, E; Guilet, R; Cren, S; Pereas, V; Mouchet, F; Gauthier, L

    2007-07-19

    As a result of bovine spongiform encephalopathy (BSE) crisis, meat and bone meal (MBM) production can no longer be used to feed cattle and must be safely disposed of or transformed. MBM specific incineration remains an alternative that could offer the opportunity to achieve both thermal valorization and solid waste recovery as ashes are calcium phosphate-rich material. The aim of this work is to evaluate ashes efficiency for in situ remediation of lead-contaminated aqueous solutions and soils, and to assess the bioavailability of lead using two biological models, amphibian Xenopus laevis larvae and Nicotiana tabaccum tobacco plant. With the amphibian model, no toxic or genotoxic effects of ashes are observed with concentrations from 0.1 to 5 g of ashes/L. If toxic and genotoxic effects of lead appear at concentration higher than 1 mg Pb/L (1 ppm), addition of only 100 mg of ashes/L neutralizes lead toxicity even with lead concentration up to 10 ppm. Chemical investigations (kinetics and X-ray diffraction (XRD) analysis) reveals that lead is quickly immobilized as pyromorphite [Pb10(PO4)6(OH)2] and lead carbonate dihydrate [PbCO(3).2H2O]. Tobacco experiments are realized on contaminated soils with 50, 100, 2000 and 10000 ppm of lead with and without ashes amendment (35.3g ashes/kg of soil). Tobacco measurements show that plant elongation is bigger in an ashes-amended soil contaminated with 10000 ppm of lead than on the reference soil alone. Tobacco model points out that ashes present two beneficial actions as they do not only neutralize lead toxicity but also act as a fertilizer.

  8. Lysophosphatidic acid mediates myeloid differentiation within the human bone marrow microenvironment.

    Directory of Open Access Journals (Sweden)

    Denis Evseenko

    Full Text Available Lysophosphatidic acid (LPA is a pleiotropic phospholipid present in the blood and certain tissues at high concentrations; its diverse effects are mediated through differential, tissue specific expression of LPA receptors. Our goal was to determine if LPA exerts lineage-specific effects during normal human hematopoiesis. In vitro stimulation of CD34+ human hematopoietic progenitors by LPA induced myeloid differentiation but had no effect on lymphoid differentiation. LPA receptors were expressed at significantly higher levels on Common Myeloid Progenitors (CMP than either multipotent Hematopoietic Stem/Progenitor Cells (HSPC or Common Lymphoid Progenitors (CLP suggesting that LPA acts on committed myeloid progenitors. Functional studies demonstrated that LPA enhanced migration, induced cell proliferation and reduced apoptosis of isolated CMP, but had no effect on either HSPC or CLP. Analysis of adult and fetal human bone marrow sections showed that PPAP2A, (the enzyme which degrades LPA was highly expressed in the osteoblastic niche but not in the perivascular regions, whereas Autotaxin (the enzyme that synthesizes LPA was expressed in perivascular regions of the marrow. We propose that a gradient of LPA with the highest levels in peri-sinusoidal regions and lowest near the endosteal zone, regulates the localization, proliferation and differentiation of myeloid progenitors within the bone marrow marrow.

  9. Lead (Pb) Isotope Baselines for Studies of Ancient Human Migration and Trade in the Maya Region.

    Science.gov (United States)

    Sharpe, Ashley E; Kamenov, George D; Gilli, Adrian; Hodell, David A; Emery, Kitty F; Brenner, Mark; Krigbaum, John

    2016-01-01

    We examined the potential use of lead (Pb) isotopes to source archaeological materials from the Maya region of Mesoamerica. The main objectives were to determine if: 1) geologic terrains throughout the Maya area exhibit distinct lead isotope ratios (206Pb/204Pb, 207Pb/204Pb, and 208Pb/204Pb), and 2) a combination of lead and strontium ratios can enhance sourcing procedures in the Mesoamerica region. We analyzed 60 rock samples for lead isotope ratios and a representative subset of samples for lead, uranium, and thorium concentrations across the Maya region, including the Northern Lowlands of the Mexican Yucatan Peninsula, the Southern Lowlands of Guatemala and Belize, the Volcanic Highlands, the Belizean Maya Mountains, and the Metamorphic Province/Motagua Valley. Although there is some overlap within certain sub-regions, particularly the geologically diverse Metamorphic Province, lead isotopes can be used to distinguish between the Northern Lowlands, the Southern Lowlands, and the Volcanic Highlands. The distinct lead isotope ratios in the sub-regions are related to the geology of the Maya area, exhibiting a general trend in the lowlands of geologically younger rocks in the north to older rocks in the south, and Cenozoic volcanic rocks in the southern highlands. Combined with other sourcing techniques such as strontium (87Sr/86Sr) and oxygen (δ18O), a regional baseline for lead isotope ratios can contribute to the development of lead isoscapes in the Maya area, and may help to distinguish among geographic sub-regions at a finer scale than has been previously possible. These isotope baselines will provide archaeologists with an additional tool to track the origin and movement of ancient humans and artifacts across this important region.

  10. [Consensus statement: recommendations for the management of metabolic bone disease in human immunodeficiency virus patients].

    Science.gov (United States)

    Martínez, Esteban; Jódar Gimeno, Esteban; Reyes García, Rebeca; Carpintero, Pedro; Casado, José Luis; Del Pino Montes, Javier; Domingo Pedrol, Pere; Estrada, Vicente; Maalouf, Jorge; Negredo, Eugenia; Ocampo, Antonio; Muñoz-Torres, Manuel

    2014-04-01

    To provide practical recommendations for the evaluation and treatment of metabolic bone disease in human immunodeficiency virus (HIV) patients. Members of scientific societies related to bone metabolism and HIV: Grupo de Estudio de Sida (GeSIDA), Sociedad Española de Endocrinología y Nutrición (SEEN), Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM), and Sociedad Española de Fractura Osteoporótica (SEFRAOS). A systematic search was carried out in PubMed, and papers in English and Spanish with a publication date before 28 May 2013 were included. Recommendations were formulated according to GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) setting both their strength and the quality of supporting evidence. Working groups were established for each major part, and the final resulting document was later discussed in a face-to-face meeting. All the authors reviewed the final written document and agreed with its content. The document provides evidence-based practical recommendations on the detection and treatment of bone disease in HIV-infected patients. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  11. A high volume extraction and purification method for recovering DNA from human bone.

    Science.gov (United States)

    Marshall, Pamela L; Stoljarova, Monika; Schmedes, Sarah E; King, Jonathan L; Budowle, Bruce

    2014-09-01

    DNA recovery, purity and overall extraction efficiency of a protocol employing a novel silica-based column, Hi-Flow(®) (Generon Ltd., Maidenhead, UK), were compared with that of a standard organic DNA extraction methodology. The quantities of DNA recovered by each method were compared by real-time PCR and quality of DNA by STR typing using the PowerPlex(®) ESI 17 Pro System (Promega Corporation, Madison, WI) on DNA from 10 human bone samples. Overall, the Hi-Flow method recovered comparable quantities of DNA ranging from 0.8ng±1 to 900ng±159 of DNA compared with the organic method ranging from 0.5ng±0.9 to 855ng±156 of DNA. Complete profiles (17/17 loci tested) were obtained for at least one of three replicates for 3/10 samples using the Hi-Flow method and from 2/10 samples with the organic method. All remaining bone samples yielded partial profiles for all replicates with both methods. Compared with a standard organic DNA isolation method, the results indicated that the Hi-Flow method provided equal or improved recovery and quality of DNA without the harmful effects of organic extraction. Moreover, larger extraction volumes (up to 20mL) can be employed with the Hi-Flow method which enabled more bone sample to be extracted at one time. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Mechanical strength of ceramic scaffolds reinforced with biopolymers is comparable to that of human bone.

    Science.gov (United States)

    Henriksen, S S; Ding, M; Juhl, M Vinther; Theilgaard, N; Overgaard, S

    2011-05-01

    Eight groups of calcium-phosphate scaffolds for bone implantation were prepared of which seven were reinforced with biopolymers, poly lactic acid (PLA) or hyaluronic acid in different concentrations in order to increase the mechanical strength, without significantly impairing the microarchitecture. Controls were un-reinforced calcium-phosphate scaffolds. Microarchitectural properties were quantified using micro-CT scanning. Mechanical properties were evaluated by destructive compression testing. Results showed that adding 10 or 15% PLA to the scaffold significantly increased the mechanical strength. The increase in mechanical strength was seen as a result of increased scaffold thickness and changes to plate-like structure. However, the porosity was significantly lowered as a consequence of adding 15% PLA, whereas adding 10% PLA had no significant effect on porosity. Hyaluronic acid had no significant effect on mechanical strength. The novel composite scaffold is comparable to that of human bone which may be suitable for transplantation in specific weight-bearing situations, such as long bone repair.

  13. Human Dental Pulp-Derived Cells Produce Bone-Like Tissue and Exhibit Bone Cell-Like Responsiveness to Mechanical Loading

    DEFF Research Database (Denmark)

    Kraft, David Christian Evar; Melsen, Birte; Bindslev, Dorthe Arenholt

    2010-01-01

    Recent studies have shown that dental pulp cells possess stem cell like potential and thus may be potential candidates for tissue engineering purposes particularly in the oro-facial region. Successful tissue engineering ideally requires that newly formed bone adapts its mass, shape, and trabecular...... and characterize cell lines from human 3rd molar dental pulp tissue to determine whether human dental pulp-derived cells (DPCs) are osteogenic and responsive to mechanical loading by pulsating fluid flow (PFF) in vitro. Methods: Human DPCs used for this study were characterized by measuring proliferation...

  14. The proteomic dataset for bone marrow derived human mesenchymal stromal cells: Effect of in vitro passaging

    Directory of Open Access Journals (Sweden)

    Samuel T. Mindaye

    2015-12-01

    Full Text Available Bone-marrow derived mesenchymal stromal cells (BMSCs have been in clinical trials for therapy. One major bottleneck in the advancement of BMSC-based products is the challenge associated with cell isolation, characterization, and ensuring cell fitness over the course of in vitro cell propagation steps. The data in this report is part of publications that explored the proteomic changes following in vitro passaging of BMSCs [4] and the molecular heterogeneity in cultures obtained from different human donors [5,6].The methodological details involving cell manufacturing, proteome harvesting, protein identification and quantification as well as the bioinformatic analyses were described to ensure reproducibility of the results.

  15. Human calcium metabolism including bone resorption measured with {sup 41}Ca tracer

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, S.P.H.T. [Lawrence Livermore National Lab., CA (United States); King, J.C. [California Univ., Berkeley, CA (United States). Dept. of Nutritional Science; Vieira, N.E. [National Inst. of Child Health and Human Development, Bethesda, MD (United States); Woodhouse, L.R. [California Univ., Berkeley, CA (United States). Dept. of Nutritional Science; Yergey, A.L. [National Inst. of Child Health and Human Development, Bethesda, MD (United States)

    1996-08-01

    Accelerator mass spectrometry is so sensitive to small quantities of {sup 41}Ca that it might be used as a tracer in the study of human calcium kinetics to generate unique kinds of data. In contrast with the use of other Ca isotopic tracers, {sup 41}Ca tracer can be so administered that the tracer movements between the various body pools achieve a quasi steady state. Resorbing bone may thus be directly measured. We have tested such a protocol against a conventional stable isotope experiment with good agreement.

  16. Molecular cloning of complementary DNA for human medullasin: an inflammatory serine protease in bone marrow cells.

    Science.gov (United States)

    Okano, K; Aoki, Y; Sakurai, T; Kajitani, M; Kanai, S; Shimazu, T; Shimizu, H; Naruto, M

    1987-07-01

    Medullasin, an inflammatory serine protease in bone marrow cells, modifies the functions of natural killer cells, monocytes, and granulocytes. We have cloned a medullasin cDNA from a human acute promyelocytic cell (ML3) cDNA library using oligonucleotide probes synthesized from the information of N-terminal amino acid sequence of natural medullasin. The cDNA contained a long open reading frame encoding 237 amino acid residues beginning from the second amino acid of natural meduallasin. The deduced amino acid sequence of medullasin shows a typical serine protease structure, with 41% homology with pig elastase 1.

  17. Rietveld Refinement on X-Ray Diffraction Patterns of Bioapatite in Human Fetal Bones

    Science.gov (United States)

    Meneghini, Carlo; Dalconi, Maria Chiara; Nuzzo, Stefania; Mobilio, Settimio; Wenk, Rudy H.

    2003-01-01

    Bioapatite, the main constituent of mineralized tissue in mammalian bones, is a calcium-phosphate-based mineral that is similar in structure and composition to hydroxyapatite. In this work, the crystallographic structure of bioapatite in human fetuses was investigated by synchrotron radiation x-ray diffraction (XRD) and microdiffraction (μ-XRD) techniques. Rietveld refinement analyses of XRD and μ-XRD data allow for quantitative probing of the structural modifications of bioapatite as functions of the mineralization process and gestational age. PMID:12609904

  18. Ablation of the PTHrP gene or the PTH/PTHrP receptor gene leads to distinct abnormalities in bone development

    OpenAIRE

    Lanske, Beate; Amling, Michael; Neff, Lynn; Guiducci, Jennifer; Baron, Roland; Kronenberg, Henry M.

    1999-01-01

    Parathyroid hormone (PTH) and parathyroid hormone–related peptide (PTHrP) bind to and activate the same PTH/PTHrP receptor. Deletion of either the PTHrP gene or the PTH/PTHrP receptor gene leads to acceleration of differentiation of growth plate chondrocytes. To explore further the functional relationships of PTHrP and the PTH/PTHrP receptor, bones of knockout mice were analyzed early in development, and the phenotypes of double-knockout mice were characterized.

  19. A novel mouse model of human breast cancer stem-like cells with high CD44+CD24-/lower phenotype metastasis to human bone

    Institute of Scientific and Technical Information of China (English)

    LING Li-jun; WANG Feng; WANG Shui; LIU Xiao-an; SHEN En-chao; DING Qiang; LU Chao; XU Jian; CAO Qin-hong; ZHU Hai-qing

    2008-01-01

    Background A satisfactory animal model of breast cancer metastasizing to bone is unavailable. In this study, we used human breast cancer stem-like cells and human bone to build a novel "human-source" model of human breast cancer skeletal metastasis.Methods Human breast cancer stem-like cells, the CD44+/CD24-/lower subpopulation, was separated and cultured. Before injection with the stem-like cells, mice were implanted with human bone in the right or left dorsal flanks. Animals in Groups A, B, and C were injected with 1x105, 1x106 human breast cancer stem-like cells, and 1x106 parental MDA-MB-231 cells, respectively. A positive control group (D) without implantation of human bone was also injected with 1x106 MDA-MB-231 cells. Immunohistochemistry was performed for determination of CD34, CD105, smooth muscle antibody, CD44, CD24, cytokine, CXC chemokine receptor-4 (CXCR4), and osteopontin (OPN). mRNA levels of CD44, CD24, CXCR4, and OPN in bone metastasis tissues were analyzed by real-time quantitative polymerase chain reaction (PCR). Results Our results demonstrated that cells in implanted human bones of group B, which received 1x106 cancer stem-like cells, stained strongly positive for CD44, CXCR4, and OPN, whereas those of other groups showed no or minimum staining. Moreover, group B had the highest incidence of human bone metastasis (77.8%, P=0.0230) and no accompaniment of other tissue metastasis. The real-time PCR showed an increase of CD44, CXCR4, and OPN mRNA in metastatic bone tissues in group B compared with those of groups C and D, however the expression of CD24 mRNA in group B were the lowest. Conclusions In the novel "human source" model of breast cancer, breast cancer stem-like cells demonstrated a higher human bone-seeking ability. Its mechanism might be related to the higher expressions of CD44, CXCR4, and OPN, and the lower expression of CD24 in breast cancer stem-like cells.

  20. In vivo measurement of lead in the bones of smelter workers using the four-element 'clover-leaf' geometry detector system

    Energy Technology Data Exchange (ETDEWEB)

    Behinaein, Sepideh; Chettle, David R; Egden, Lesley M [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, L8S 4K1 (Canada); Atanackovic, Jovica [AECL, Chalk River Laboratories, Dosimetry Services, K0J 1J0, Ontario (Canada); Fleming, David E B [Department of Physics, Mount Allison University, Sackville, New Brunswick, E4L 1E6 (Canada); Nie, Linda H [School of Health Sciences, Purdue University, West Lafayette, IN 47907 (United States); Richard, Norbert; Stever, Susan, E-mail: behinas@mcmaster.ca [Occupational Health Services, Xstrata Zinc, Brunswick Smelter, Belledune, New Brunswick, E8G 2M1 (Canada)

    2011-02-07

    A total of 497 smelter employees from New Brunswick participated in a bone lead survey conducted by McMaster University in 2008 to examine the efficiency of lead exposure control programmes and a four-element 'clover-leaf' geometry detector system. Nearly 42% of the subjects had participated in both the previous surveys performed in 1994 and 1999. After developing the clover-leaf geometry system in 2006, the reliability of the system based on examining the consistency of four detectors and improving the minimum detection limit (MDL) was tested for the first time in 2008 by measuring lead levels of a large population that was occupationally exposed to lead. The Z test was used to study the distribution of the lead concentration calculated based on K{sub {alpha}} and K{sub {beta}} lead x-rays, where the results were broadly consistent with a normal distribution criterion, with relatively small means and standard deviations of between 1 and 2. The MDL of the clover-leaf geometry system was improved on average for tibia and calcaneus by a factor of 3.1 compared to the 1999 and 1994 surveys in which a conventional system (one detector) was used. Furthermore, by comparing the results of the three mentioned surveys, the 2008 results were found to represent the highest precision.

  1. Human breast cancer cell-mediated bone collagen degradation requires plasminogen activation and matrix metalloproteinase activity

    Directory of Open Access Journals (Sweden)

    Hill Peter A

    2005-02-01

    Full Text Available Abstract Background Breast cancer cells frequently metastasize to the skeleton and induce extensive bone destruction. Cancer cells produce proteinases, including matrix metalloproteinases (MMPs and the plasminogen activator system (PAS which promote invasion of extracellular matrices, but whether these proteinases degrade bone matrix is unclear. To characterize the role that breast cancer cell proteinases play in bone degradation we compared the effects of three human breast cancer cell lines, MDA-MB-231, ZR-75-1 and MCF-7 with those of a normal breast epithelial cell line, HME. The cell lines were cultured atop radiolabelled matrices of either mineralized or non-mineralized bone or type I collagen, the principal organic constituent of bone. Results The 3 breast cancer cell lines all produced significant degradation of the 3 collagenous extracellular matrices (ECMs whilst the normal breast cell line was without effect. Breast cancer cells displayed an absolute requirement for serum to dissolve collagen. Degradation of collagen was abolished in plasminogen-depleted serum and could be restored by the addition of exogenous plasminogen. Localization of plasmin activity to the cell surface was critical for the degradation process as aprotinin, but not α2 antiplasmin, prevented collagen dissolution. During ECM degradation breast cancer cell lines expressed urokinase-type plasminogen activator (u-PA and uPA receptor, and MMPs-1, -3, -9,-13, and -14. The normal breast epithelial cell line expressed low levels of MMPs-1, and -3, uPA and uPA receptor. Inhibitors of both the PAS (aprotinin and PA inhibitor-1 and MMPs (CT1166 and tisue inhibitor of metalloproteinase blocked collagen degradation, demonstrating the requirement of both plasminogen activation and MMP activity for degradation. The activation of MMP-13 in human breast cancer cells was prevented by plasminogen activator inhibitor-1 but not by tissue inhibitor of metalloproteinase-1, suggesting

  2. Substituted 2-phenylimidazopyridines: a new class of drug leads for human African trypanosomiasis.

    Science.gov (United States)

    Tatipaka, Hari Babu; Gillespie, J Robert; Chatterjee, Arnab K; Norcross, Neil R; Hulverson, Matthew A; Ranade, Ranae M; Nagendar, Pendem; Creason, Sharon A; McQueen, Joshua; Duster, Nicole A; Nagle, Advait; Supek, Frantisek; Molteni, Valentina; Wenzler, Tanja; Brun, Reto; Glynne, Richard; Buckner, Frederick S; Gelb, Michael H

    2014-02-13

    A phenotypic screen of a compound library for antiparasitic activity on Trypanosoma brucei, the causative agent of human African trypanosomiasis, led to the identification of substituted 2-(3-aminophenyl)oxazolopyridines as a starting point for hit-to-lead medicinal chemistry. A total of 110 analogues were prepared, which led to the identification of 64, a substituted 2-(3-aminophenyl)imidazopyridine. This compound showed antiparasitic activity in vitro with an EC50 of 2 nM and displayed reasonable druglike properties when tested in a number of in vitro assays. The compound was orally bioavailable and displayed good plasma and brain exposure in mice. Compound 64 cured mice infected with Trypanosoma brucei when dosed orally down to 2.5 mg/kg. Given its potent antiparasitic properties and its ease of synthesis, compound 64 represents a new lead for the development of drugs to treat human African trypanosomiasis.

  3. Compressive properties of commercially available polyurethane foams as mechanical models for osteoporotic human cancellous bone

    Directory of Open Access Journals (Sweden)

    Shepherd Duncan ET

    2008-10-01

    Full Text Available Abstract Background Polyurethane (PU foam is widely used as a model for cancellous bone. The higher density foams are used as standard biomechanical test materials, but none of the low density PU foams are universally accepted as models for osteoporotic (OP bone. The aim of this study was to determine whether low density PU foam might be suitable for mimicking human OP cancellous bone. Methods Quasi-static compression tests were performed on PU foam cylinders of different lengths (3.9 and 7.7 mm and of different densities (0.09, 0.16 and 0.32 g.cm-3, to determine the Young's modulus, yield strength and energy absorbed to yield. Results Young's modulus values were 0.08–0.93 MPa for the 0.09 g.cm-3 foam and from 15.1–151.4 MPa for the 0.16 and 0.32 g.cm-3 foam. Yield strength values were 0.01–0.07 MPa for the 0.09 g.cm-3 foam and from 0.9–4.5 MPa for the 0.16 and 0.32 g.cm-3 foam. The energy absorbed to yield was found to be negligible for all foam cylinders. Conclusion Based on these results, it is concluded that 0.16 g.cm-3 PU foam may prove to be suitable as an OP cancellous bone model when fracture stress, but not energy dissipation, is of concern.

  4. Healing of a Large Long-Bone Defect through Serum-Free In Vitro Priming of Human Periosteum-Derived Cells

    Directory of Open Access Journals (Sweden)

    Johanna Bolander

    2017-03-01

    Full Text Available Clinical translation of cell-based strategies for regenerative medicine demands predictable in vivo performance where the use of sera during in vitro preparation inherently limits the efficacy and reproducibility. Here, we present a bioinspired approach by serum-free pre-conditioning of human periosteum-derived cells, followed by their assembly into microaggregates simultaneously primed with bone morphogenetic protein 2 (BMP-2. Pre-conditioning resulted in a more potent progenitor cell population, while aggregation induced osteochondrogenic differentiation, further enhanced by BMP-2 stimulation. Ectopic implantation displayed a cascade of events that closely resembled the natural endochondral process resulting in bone ossicle formation. Assessment in a critical size long-bone defect in immunodeficient mice demonstrated successful bridging of the defect within 4 weeks, with active contribution of the implanted cells. In short, the presented serum-free process represents a biomimetic strategy, resulting in a cartilage tissue intermediate that, upon implantation, robustly leads to the healing of a large long-bone defect.

  5. Below the Callus Surface: Applying Paleohistological Techniques to Understand the Biology of Bone Healing in Skeletonized Human Remains.

    Science.gov (United States)

    Assis, Sandra; Keenleyside, Anne

    2016-01-01

    Bone trauma is a common occurrence in human skeletal remains. Macroscopic and imaging scrutiny is the approach most currently used to analyze and describe trauma. Nevertheless, this line of inquiry may not be sufficient to accurately identify the type of traumatic lesion and the associated degree of bone healing. To test the usefulness of histology in the examination of bone healing biology, we used an integrative approach that combines gross inspection and microscopy. Six bone samples belonging to 5 adult individuals with signs of bone trauma were collected from the Human Identified Skeletal Collection from the Museu Bocage (Lisbon, Portugal). Previous to sampling, the lesions were described according to their location, morphology, and healing status. After sampling, the bone specimens were prepared for plane light and polarized light analysis. The histological analysis was pivotal: (1) to differentiate between types of traumatic lesions; (2) to ascertain the posttraumatic interval, and (3) to diagnose other associated pathological conditions. The outer surface of a bone lesion may not give a complete picture of the biology of the tissue's response. Accordingly, microscopic analysis is essential to differentiate, characterize, and classify trauma signs. © 2016 S. Karger AG, Basel.

  6. External fixation of femoral defects in athymic rats: Applications for human stem cell implantation and bone regeneration

    Directory of Open Access Journals (Sweden)

    Terasa Foo

    2013-01-01

    Full Text Available An appropriate animal model is critical for the research of stem/progenitor cell therapy and tissue engineering for bone regeneration in vivo. This study reports the design of an external fixator and its application to critical-sized femoral defects in athymic rats. The external fixator consists of clamps and screws that are readily available from hardware stores as well as Kirschner wires. A total of 35 rats underwent application of the external fixator with creation of a 6-mm bone defect in one femur of each animal. This model had been used in several separate studies, including implantation of collagen gel, umbilical cord blood mesenchymal stem cells, endothelial progenitor cells, or bone morphogenetic protein-2. One rat developed fracture at the proximal pin site and two rats developed deep tissue infection. Pin loosening was found in nine rats, but it only led to the failure of external fixation in two animals. In 8 to 10 weeks, various degrees of bone growth in the femoral defects were observed in different study groups, from full repair of the bone defect with bone morphogenetic protein-2 implantation to fibrous nonunion with collagen gel implantation. The external fixator used in these studies provided sufficient mechanical stability to the bone defects and had a comparable complication rate in athymic rats as in immunocompetent rats. The external fixator does not interfere with the natural environment of a bone defect. This model is particularly valuable for investigation of osteogenesis of human stem/progenitor cells in vivo.

  7. The response of bone to unloading

    Science.gov (United States)

    Bikle, D. D.; Halloran, B. P.

    1999-01-01

    Skeletal unloading leads to decreased bone formation and decreased bone mass. Bone resorption is uncoupled from bone formation, contributing to the bone loss. During spaceflight bone is lost principally from the bones most loaded in the 1-g environment, and some redistribution of bone from the lower extremities to the head appears to take place. Although changes in calcitropic hormones have been demonstrated during skeletal unloading (PTH and 1,25(OH)2D decrease), it remains unclear whether such changes account for or are in response to the changes in bone formation and resorption. Bed rest studies with human volunteers and hindlimb elevation studies with rats have provided useful data to help explain the changes in bone formation during spaceflight. These models of skeletal unloading reproduce a number of the conditions associated with microgravity, and the findings from such studies confirm many of the observations made during spaceflight. Determining the mechanism(s) by which loading of bone is sensed and translated into a signal(s) controlling bone formation remains the holy grail in this field. Such investigations couple biophysics to biochemistry to cell and molecular biology. Although studies with cell cultures have revealed biochemical responses to mechanical loads comparable to that seen in intact bone, it seems likely that matrix-cell interactions underlie much of the mechanocoupling. The role for systemic hormones such as PTH, GH, and 1,25(OH)2D compared to locally produced factors such as IGF-I, PTHrP, BMPs, and TGF-beta in modulating the cellular response to load remains unclear. As the mechanism(s) by which bone responds to mechanical load with increased bone formation are further elucidated, applications of this knowledge to other etiologies of osteoporosis are likely to develop. Skeletal unloading provides a perturbation in bone mineral homeostasis that can be used to understand the mechanisms by which bone mineral homeostasis is maintained, with

  8. Speckle shearing pattern interferometry to assess mechanical strain in the human mandible jaw bone under physiological stress

    Science.gov (United States)

    Moreno, V.; Vázquez-Vázquez, C.; Gallas, M.; Crespo, J.

    2011-05-01

    Electronic Speckle Pattern Interferometry (ESPI) has been used in experiments to measure displacement on the surface of bones undergoing external forces. However in order to asses directly the derivative of the displacements a related technique, Shearography, is used. This technique has been applied in biomechanical experiments although limited to small pieces of bone to determine their elastic properties. In this work we propose the use of Shearing Speckle Interferometry to evaluate the mechanical behaviour of the human mandible under compressive stress, simulating masticatory forces or impacts, in order to analyze the strain distribution on mandibular bone.

  9. Influence of object location in different FOVs on trabecular bone microstructure measurements of human mandible: a cone beam CT study

    NARCIS (Netherlands)

    Ibrahim, N.; Parsa, A.; Hassan, B.; van der Stelt, P.; Aartman, I.H.A.; Nambiar, P.

    2014-01-01

    The aim of this study was to assess the influence of different object locations in different fields of view (FOVs) of two cone beam CT (CBCT) systems on trabecular bone microstructure measurements of a human mandible. A block of dry human mandible was scanned at five different locations (centre,

  10. Influence of object location in different FOVs on trabecular bone microstructure measurements of human mandible: a cone beam CT study

    NARCIS (Netherlands)

    Ibrahim, N.; Parsa, A.; Hassan, B.; van der Stelt, P.; Aartman, I.H.A.; Nambiar, P.

    2014-01-01

    The aim of this study was to assess the influence of different object locations in different fields of view (FOVs) of two cone beam CT (CBCT) systems on trabecular bone microstructure measurements of a human mandible. A block of dry human mandible was scanned at five different locations (centre, lef

  11. [Experimental study on application recombinant human bone morphogenetic protein 2(rhBMP-2)/poly-lactide-co-glycolic acid (PLGA)/fibrin sealant(FS) on repair of rabbit radial bone defect].

    Science.gov (United States)

    Fan, Zhongkai; Cao, Yang; Zhang, Zhe; Zhang, Mingchao; Lu, Wei; Tang, Lei; Yao, Qi; Lu, Gang

    2012-10-01

    This paper is aimed to investigate the repair of rabbit radial bone defect by the recombinant human bone morphogenetic protein 2/poly-lactideco-glycolic acid microsphere with fibrin sealant (rhBMP-2/PLGA/FS). The radial bone defect models were prepared using New Zealand white rabbits, which were randomly divided into 3 groups, experiment group which were injected with eMP-2/PLGA/FS at bone defect location, control group which were injected with FS at bone defect location, and blank control group without treatment. The ability of repairing bone defect was evaluated with X-ray radiograph. Bone mineral density in the defect regions was analysed using the level of ossification. The osteogenetic ability of repairing bone defect, the degradation of the material, the morphologic change and the bone formation were assessed by HE staining and Masson staining. The result showed that rhBMP-2/PLGA/FS had overwhelming superiority in the osteogenetic ability and quality of bone defect over the control group, and it could promote the repair of bone defect and could especially repair the radial bone defect of rabbit well. It may be a promising and efficient synthetic bone graft.

  12. Graft versus host disease in the bone marrow, liver and thymus humanized mouse model.

    Directory of Open Access Journals (Sweden)

    Matthew B Greenblatt

    Full Text Available Mice bearing a "humanized" immune system are valuable tools to experimentally manipulate human cells in vivo and facilitate disease models not normally possible in laboratory animals. Here we describe a form of GVHD that develops in NOD/SCID mice reconstituted with human fetal bone marrow, liver and thymus (NS BLT mice. The skin, lungs, gastrointestinal tract and parotid glands are affected with progressive inflammation and sclerosis. Although all mice showed involvement of at least one organ site, the incidence of overt clinical disease was approximately 35% by 22 weeks after reconstitution. The use of hosts lacking the IL2 common gamma chain (NOD/SCID/γc(-/- delayed the onset of disease, but ultimately did not affect incidence. Genetic analysis revealed that particular donor HLA class I alleles influenced the risk for the development of GVHD. At a cellular level, GVHD is associated with the infiltration of human CD4+ T cells into the skin and a shift towards Th1 cytokine production. GVHD also induced a mixed M1/M2 polarization phenotype in a dermal murine CD11b+, MHC class II+ macrophage population. The presence of xenogenic GVHD in BLT mice both presents a major obstacle in the use of humanized mice and an opportunity to conduct preclinical studies on GVHD in a humanized model.

  13. Human health risk assessment of lead from mining activities at semi-arid locations in the context of total lead exposure.

    Science.gov (United States)

    Zheng, Jiajia; Huynh, Trang; Gasparon, Massimo; Ng, Jack; Noller, Barry

    2013-12-01

    Lead from historical mining and mineral processing activities may pose potential human health risks if materials with high concentrations of bioavailable lead minerals are released to the environment. Since the Joint Expert Committee on Food Additives of Food and Agriculture Organization/World Health Organization withdrew the Provisional Tolerable Weekly Intake of lead in 2011, an alternative method was required for lead exposure assessment. This study evaluated the potential lead hazard to young children (0-7 years) from a historical mining location at a semi-arid area using the U.S. EPA Integrated Exposure Uptake Biokinetic (IEUBK) Model, with selected site-specific input data. This study assessed lead exposure via the inhalation pathway for children living in a location affected by lead mining activities and with specific reference to semi-arid conditions and made comparison with the ingestion pathway by using the physiologically based extraction test for gastro-intestinal simulation. Sensitivity analysis for major IEUBK input parameters was conducted. Three groups of input parameters were classified according to the results of predicted blood concentrations. The modelled lead absorption attributed to the inhalation route was lower than 2 % (mean ± SE, 0.9 % ± 0.1 %) of all lead intake routes and was demonstrated as a less significant exposure pathway to children's blood, compared with ingestion. Whilst dermal exposure was negligible, diet and ingestion of soil and dust were the dominant parameters in terms of children's blood lead prediction. The exposure assessment identified the changing role of dietary intake when house lead loadings varied. Recommendations were also made to conduct comprehensive site-specific human health risk assessment in future studies of lead exposure under a semi-arid climate.

  14. Enhanced human bone marrow mesenchymal stem cell functions on cathodic arc plasma-treated titanium

    Directory of Open Access Journals (Sweden)

    Zhu W

    2015-12-01

    Full Text Available Wei Zhu,1 George Teel,1 Christopher M O’Brien,1 Taisen Zhuang,1 Michael Keidar,1 Lijie Grace Zhang1–3 1Department of Mechanical and Aerospace Engineering, 2Department of Biomedical Engineering, 3Department of Medicine, The George Washington University, Washington, DC, USA Abstract: Surface modification of titanium for use in orthopedics has been explored for years; however, an ideal method of integrating titanium with native bone is still required to this day. Since human bone cells directly interact with nanostructured extracellular matrices, one of the most promising methods of improving titanium’s osseointegration involves inducing biomimetic nanotopography to enhance cell–implant interaction. In this regard, we explored an approach to functionalize the surface of titanium by depositing a thin film of textured titanium nanoparticles via a cathodic arc discharge plasma. The aim is to improve human bone marrow mesenchymal stem cell (MSC attachment and differentiation and to reduce deleterious effects of more complex surface modification methods. Surface functionalization was analyzed by scanning electron microscopy, atomic force microscopy, contact angle testing, and specific protein adsorption. Scanning electron microscopy and atomic force microscopy examination demonstrate the deposition of titanium nanoparticles and the surface roughness change after coating. The specific fibronectin adsorption was enhanced on the modified titanium surface that associates with the improved hydrophilicity. MSC adhesion and proliferation were significantly promoted on the nanocoated surface. More importantly, compared to bare titanium, greater production of total protein, deposition of calcium mineral, and synthesis of alkaline phosphatase were observed from MSCs on nanocoated titanium after 21 days. The method described herein presents a promising alternative method for inducing more cell favorable nanosurface for improved orthopedic applications

  15. The effect of nicotine on osteoinduction by recombinant human bone morphogenetic protein 2.

    Science.gov (United States)

    Tamura, K; Togo, Y; Kaihara, S; Hussain, A; Takahashi, K; Bessho, K

    2014-08-01

    Nicotine, one of the constituents of tobacco, is known to have an adverse effect on human health. We sought to clarify the interaction between nicotine and recombinant human bone morphogenetic protein 2 (rhBMP-2) in terms of osteogenesis in vitro and osteoinduction in vivo. Nicotine did not inhibit or stimulate alkaline phosphatase (ALP) activity or the amount of osteocalcin in C2C12 cells in the presence of rhBMP-2 in vitro. Ectopic bone formation using a collagen sponge containing rhBMP-2 was evaluated with and without nicotine after 21 days using radiographic, histological, biochemical, and immunohistochemical analyses. ALP activity in the medium-dose group (2.2±0.9IU/mg protein; P=0.047) and the high-dose group (2.0±0.1IU/mg protein; P=0.03) was significantly lower than in the control group. The calcium content in the medium-dose group (35.4±12.9μg/mg tissue; P=0.0099) and high-dose group (34.8±10.5μg/mg tissue; P=0.006) was significantly lower than in the control group. The number of vascular endothelial growth factor-positive cells in the high-dose group (671.9±57.3cells/mm(2); P=0.03) was significantly lower than in the control group. Results showed that nicotine did not inhibit the stimulatory effect of rhBMP-2 in vitro, but a high dose of nicotine inhibited bone formation in vivo by adversely affecting vascularization.

  16. How can information on oral bioavailability improve human health risk assessment for lead-contaminated soils? Implementation and scientific basis

    NARCIS (Netherlands)

    Oomen AG; Brandon EFA; Swartjes FA; Sips AJAM; SIR; LER

    2006-01-01

    he human body, the risk assessment of soil contaminants for humans can be improved. Insight into the uptake process is obtained by simulating the human digestion process (in vitro digestion model). In this report a concrete proposal is given for using the knowledge on the uptake of lead in the human

  17. The relationship of bone and blood lead to hypertension: Further analyses of the normative aging study data

    Energy Technology Data Exchange (ETDEWEB)

    Hu, H.; Kim, Rokho; Korrick, S. [Harvard Medical School, Boston, MA (United States)]|[Harvard Health of Public Health, Boston, MA (United States); Rotnitzky, A. [Harvard School of Public Health, Boston, MA (United States)] [and others

    1996-12-31

    In an earlier report based on participants in the Veterans Administration Normative Aging Study, we found a significant association between the risk of hypertension and lead levels in tibia. To examine the possible confounding effects of education and occupation, we considered in this study five levels of education and three levels of occupation as independent variables in the statistical model. Of 1,171 active subjects seen between August 1991 and December 1994, 563 provided complete data for this analysis. In the initial logistic regression model, acre and body mass index, family history of hypertension, and dietary sodium intake, but neither cumulative smoking nor alcohol ingestion, conferred increased odds ratios for being hypertensive that were statistically significant. When the lead biomarkers were added separately to this initial logistic model, tibia lead and patella lead levels were associated with significantly elevated odds ratios for hypertension. In the final backward elimination logistic regression model that included categorical variables for education and occupation, the only variables retained were body mass index, family history of hypertension, and tibia lead level. We conclude that education and occupation variables were not confounding the association between the lead biomarkers and hypertension that we reported previously. 27 refs., 3 tabs.

  18. Multimodal imaging of the human temporal bone: A comparison of CT and optical scanning techniques

    Science.gov (United States)

    Voie, Arne H.; Whiting, Bruce; Skinner, Margaret; Neely, J. Gail; Lee, Kenneth; Holden, Tim; Brunsden, Barry

    2003-10-01

    A collaborative effort between Washington University in St. Louis and Spencer Technologies in Seattle, WA has been undertaken to create a multimodal 3D reconstruction of the human cochlea and vestibular system. The goal of this project is to improve the accuracy of in vivo CT reconstructions of implanted cochleae, and to expand the knowledge of high-resolution anatomical detail provided by orthogonal-plane optical sectioning (OPFOS). At WUSL, computed tomography (CT) images of the cochlea are used to determine the position of cochlear implant electrodes relative to target auditory neurons. The cochlear implant position is determined using pre- and post-operative CT scans. The CT volumes are cross-registered to align the semicircular canals and internal auditory canal, which have a unique configuration in 3-D space. The head of a human body donor was scanned with a clinical CT device, after which the temporal bones were removed, fixed in formalin and trimmed prior to scanning with a laboratory Micro CT scanner. Following CT, the temporal bones were sent to the OPFOS Imaging Lab at Spencer Technologies for a further analysis. 3-D reconstructions of CT and OPFOS imaging modalities were compared, and results are presented. [Work supported by NIDCD Grants R44-03623-5 and R01-00581-13.

  19. Evaluation of bioresorbable polymers of lactic acid in a culture of human bone marrow cells.

    Science.gov (United States)

    Stemberg, F; Wilke, A

    2001-01-01

    Long term cultures of human bone marrow cells on poly(L-lactide-co-D,L-lactide) 70:30 and 90:10 plates were observed by means of scanning electron microscopy (SEM), SEM-EDX (SEM combined with energy dispersive X-ray analysis), flow cytometry, histochemical stainings, and culture medium analysis. After 14 days culture, cell numbers were only slightly lower compared with our reference material, hydroxyapatite, and much higher compared with polyethylene. There was evidence of collagenous matrix production with osteoblast activity. Acridine orange stainings as well as flow cytometry after incubation with propidium iodide showed only a few non-viable cells. By means of flow cytometry, we found about 30% of cells with granulocyte-markers, some monocyte-derived cells, and only small amounts of lymphocytes. After 9 weeks culture, there was evidence of calcium-phosphate deposition with extracellular matrix. There were only slight differences between the two tested polymers. Our culture system with human bone marrow cells plated on two bioresorbable polymers suggests a biocompatibility almost as good as hydroxyapatite, which is usually well tolerated. There was even evidence of mineralized collagenous matrix after some weeks of culture, which was detected earlier than the mineralization of cell-free controls.

  20. Efficient engineering of vascularized ectopic bone from human embryonic stem cell-derived mesenchymal stem cells.

    Science.gov (United States)

    Domev, Hagit; Amit, Michal; Laevsky, Ilana; Dar, Ayelet; Itskovitz-Eldor, Joseph

    2012-11-01

    Human mesenchymal stem cells (hMSCs) can be derived from various adult and fetal tissues. However, the quality of tissues for the isolation of adult and fetal hMSCs is donor dependent with a nonreproducible yield. In addition, tissue engineering and cell therapy require large-scale production of a pure population of lineage-restricted stem cells that can be easily induced to differentiate into a specific cell type. Therefore, human embryonic stem cells (hESCs) can provide an alternative, plentiful source for generation of reproducible hMSCs. We have developed efficient differentiation protocols for derivation of hMSCs from hESCs, including coculture with murine OP9 stromal cells and feeder layer-free system. Our protocols have resulted in the generation of up to 49% of hMSCs, which expressed CD105, CD90, CD29, and CD44. The hMSCs exhibited high adipogenic, chondrocytic, and osteogenic differentiation in vitro. The latter correlated with osteocalcin secretion and vascular endothelial growth factor (VEGF) production by the differentiating hMSCs. hMSC-derived osteoblasts further differentiated and formed ectopic bone in vivo, and induced the formation of blood vessels in Matrigel implants. Our protocol enables generation of a purified population of hESC-derived MSCs, with the potential of differentiating into several mesodermal lineages, and particularly into vasculogenesis-inducing osteoblasts, which can contribute to the development of bone repair protocols.

  1. HSP10 selective preference for myeloid and megakaryocytic precursors in normal human bone marrow

    Directory of Open Access Journals (Sweden)

    F Cappello

    2009-06-01

    Full Text Available Heat shock proteins (HSPs constitute a heterogeneous family of proteins involved in cell homeostasis. During cell life they are involved in harmful insults, as well as in immune and inflammatory reactions. It is known that they regulate gene expression, and cell proliferation, differentiation and death. HSP60 is a mitochondrial chaperonin, highly preserved during evolution, responsible of protein folding. Its function is strictly dependent on HSP10 in both prokaryotic and eukaryotic elements. We investigated the presence and the expression of HSP60 and HSP10 in a series of 20 normal human bone marrow specimens (NHBM by the means of immunohistochemistry. NHBM showed no expression of HSP60, probably due to its being below the detectable threshold, as already demonstrated in other normal human tissues. By contrast, HSP10 showed a selective positivity for myeloid and megakaryocytic lineages. The positivity was restricted to precursor cells, while mature elements were constantly negative.We postulate that HSP10 plays a role in bone marrow cell differentiation other than being a mitochondrial co-chaperonin. The present data emphasize the role of HSP10 during cellular homeostasis and encourage further investigations in this field.

  2. The morphology and morphometry of the foramina of the greater wing of the human sphenoid bone.

    Science.gov (United States)

    Reymond, Jerzy; Charuta, Anna; Wysocki, Jarosław

    2005-08-01

    The greater wing of the human sphenoid bone is pierced by several foramina, which contain, as a main element, the venous anastomoses between the interior of the skull and the extracranial veins. Since data concerning these foramina are scarce in the literature, studies comprising the frequency of occurrence and morphology of the foramina of the greater wing of the human sphenoid bone were undertaken on 100 macerated skulls. We found that the foramen ovale is divided into 2 or 3 components in 4.5% of cases. Moreover, the borders of the foramen ovale in some skulls were irregular and rough. This may suggest, on radiological images, the presence of morbid changes, which might be the sole anatomical variation. Concurrent with the foramen ovale are accessory foramina. The foramen of Vesalius and the cavernous foramen were present in 17% and 33% of cases, respectively. The foramen of Vesalius was always single and the cavernous foramen also occurred in multiple form. The foramen spinosus and the foramen rotundum occurred as permanent elements of the skulls studied. The mean area of the foramina measured, excluding the foramen ovale, was not considerable, which may suggest that they play a minor role in the dynamics of blood circulation in the venous system of the head.

  3. Human bone marrow cell culture: a sensitive method for determination of the biocompatibility of implant materials.

    Science.gov (United States)

    Wilke, A; Landgraff, M; Orth, J; Poenitz, H; Kienapfel, H; Boelte, K; Griss, P; Franke, R P

    1999-01-01

    The objective of this study was to develop a test method for determining the cytotoxicity and biocompatibility of various biomaterials that are used in orthopaedic surgery. This method is based on the use of a human bone marrow cell culture and was developed as an alternative to animal experiments. Human bone marrow cell culture has certain advantages over other cell culture models, as its results show a greater conformity with animal experimental results and clinical studies. Primary cell adherence, cell number, cell proliferation, production of extracellular matrix, cell viability and cell differentiation were used as indicative parameters of biocompatibility. After 2 weeks in culture, differences could be observed between the biomaterials with respect to these parameters. Cell numbers were greatest on the hydroxyapatite ceramic specimens, but were decreased on the titanium alloy specimens. Extracellular matrix hydroxyapatite production was high for ceramics, but reduced for titanium specimens. The polymers allowed only a few cells to adhere, and there were no signs of extracellular matrix production. The influence of biomaterials on differentiation of large numbers of cells was analysed by using flow cytophotometry. There were similar populations of T cells and monocytes on all specimens. However, extended B cell and granulocyte populations were observed with titanium and polyethylene.

  4. Expression of Odontogenic Genes in Human Bone Marrow Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Seyedeh Sara Bagheri

    2013-01-01

    Full Text Available Objective: Tooth loss is a common problem and since current tooth replacement methods cannot counter balance with biological tooth structures, regenerating natural tooth structures has become an ideal goal. A challenging problem in tooth regeneration is to find a proper clinically feasible cell to seed.This study was designed to investigate the odontogenic potential of human bone marrow mesenchymal stem cells (HBMSCs for seeding in tooth regeneration.Materials and Methods: In this experimental study, three pregnant Sprague Dawley (SD rats were used at the eleventh embryonic day and rat fetuses were removed surgically using semilunar flap under general anesthesia. The primary mandible was cut using a stereomicroscope. The epithelial and mesenchymal components were separated and the dissected oral epithelium was cultured for 3 days. We used flow cytometry analysis to confirm presence of mesenchymal stem cells and not hematopoietic cells and to demonstrate the presence of oral epithelium. Bone marrow mesenchymal stem cells (BMSCs and cultured oral epithelium were then co-cultured for 14 days. BMSCs cultured alone were used as controls. Expression of two odontogenic genes Pax9 and DMP1 was assessed using quantitative reverse transcription- polymerase chain reaction (RT-PCR.Results: Expression of two odontogenic genes, Pax9 and DMP1, were detected in BMSCs co-cultured with oral epithelium but not in the control group.Conclusion: Expression of Pax9 and DMP1 by human BMSCs in the proximity of odontogenic epithelium indicates odontogenic potential of these cells.

  5. Naming the body (or the bones): Human remains, anthropological/medical collections, religious beliefs, and restitution.

    Science.gov (United States)

    Charlier, Philippe

    2014-04-01

    Human bones and biological remains conserved in anthropological, medical, and archaeological collections are foci of ethical debate, as recently illustrated by the affair of Charles Byrne's bones. In the near future, curators will have to choose between global conservation of all (or almost all) anthropological collections and systematic restitution to their original communities or families. Various proposals and examples of restitution and nonrestitution are given (with justifications) in order to support the concept that the body (especially the dead body) is not property. We propose that the only element supporting arguments in favor of restitution could be the name of the individual, highlighting the importance of all identification processes for such "artifacts." This is undoubtedly a universal value: naming the dead, identifying and then burying the person, i.e., reversing the progression along the timeline from individual to scientific specimen. Such elements could be of great interest to all universities and medical institutions that keep human remains in their collections for educational or historical purposes when they are confronted with ethical problems and/or repatriation requests.

  6. Bones and humanity. On Forensic Anthropology and its constitutive power facing forced disappearance

    Directory of Open Access Journals (Sweden)

    Anne Huffschmid

    2015-11-01

    Full Text Available Forensic anthropologists seek to decipher traces of anonymous dead, to restitute identities of human remains and to provide their families with the possibility to conclude mourning and even of justice. The article explores the contributions and meanings of forensic anthropology as state-independent practice beyond a mereley criminalistic approach, as it was conceptualized by the Argentine pioneers after the last dictatorship in this nation. I conceive this practice as a sort of arqueology of contemporary terror that seeks to confront a specific violence as the forced disappearance of persons and the deshumanization of their dead bodies. The article proposes reading forensic anthropology as a 'situated cience', with its complexities and ambigueties, that operates between nameless bones (the human remains and names without bodies (the so-called disappeared in settings of violent pasts such as Argentina or Guatemala, and especially in Mexico, where mass graves became the new symbol of a horrified present.

  7. Establishment and identification of fibroblast clones expressing human bone morphogenetic protein 2

    Institute of Scientific and Technical Information of China (English)

    Juan Wang; Weibin Sun; Chun Lu; Guixia Tang

    2005-01-01

    Objective:To establish fibroblasts stably expressing human bone morphogenetic protein 2 (hBMP2). Methods:Eukaryonic expression vector(pcDNA3.1-B2) was transduced into NIH3T3 cells using SofastTM, a new generation cationic polymer gene transfection reagent. The positive cell clones were selected with G418. The stable transfection and expression of BMP2 in the NIH3T3 cells were determined by RT-PCR and immunohistochemical stain. Results: BMP2 mRNA was transcripted and expressed in the transfected NIH3T3 cells. Conclusion: With positive compound transfection, outside human BMP2 gene can be successfully transducted into NIH3T3 cells, which is the key step to induce periodontal cells to osseous phenotypes.

  8. Spontaneous tumor development in bone marrow-rescued DNA-PKcs(3A/3A) mice due to dysfunction of telomere leading strand deprotection.

    Science.gov (United States)

    Zhang, S; Matsunaga, S; Lin, Y-F; Sishc, B; Shang, Z; Sui, J; Shih, H-Y; Zhao, Y; Foreman, O; Story, M D; Chen, D J; Chen, B P C

    2016-07-28

    Phosphorylation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) at the Thr2609 cluster is essential for its complete function in DNA repair and tissue stem cell homeostasis. This phenomenon is demonstrated by congenital bone marrow failure occurring in DNA-PKcs(3A/3A) mutant mice, which require bone marrow transplantation (BMT) to prevent early mortality. Surprisingly, an increased incidence of spontaneous tumors, especially skin cancer, was observed in adult BMT-rescued DNA-PKcs(3A/3A) mice. Upon further investigation, we found that spontaneous γH2AX foci occurred in DNA-PKcs(3A/3A) skin biopsies and primary keratinocytes and that these foci overlapped with telomeres during mitosis, indicating impairment of telomere replication and maturation. Consistently, we observed significantly elevated frequencies of telomere fusion events in DNA-PKcs(3A/3A) cells as compared with wild-type and DNA-PKcs-knockout cells. In addition, a previously identified DNA-PKcs Thr2609Pro mutation, found in breast cancer, also induces a similar impairment of telomere leading-end maturation. Taken together, our current analyses indicate that the functional DNA-PKcs T2609 cluster is required to facilitate telomere leading strand maturation and prevention of genomic instability and cancer development.

  9. First histological observations on the incorporation of a novel nanocrystalline hydroxyapatite paste OSTIM® in human cancellous bone

    Directory of Open Access Journals (Sweden)

    Huber Colette

    2006-06-01

    Full Text Available Abstract Background: A commercially available nanocrystalline hydroxyapatite paste Ostim® has been reported in few recent studies to surpass other synthetic bone substitutes with respect to the observed clinical results. However, the integration of this implantable material has been histologically evaluated only in animal experimental models up to now. This study aimed to evaluate the tissue incorporation of Ostim® in human cancellous bone after reconstructive bone surgery for trauma. Methods: Biopsy specimens from 6 adult patients with a total of 7 tibial, calcaneal or distal radial fractures were obtained at the time of osteosynthesis removal. The median interval from initial operation to tissue sampling was 13 (range 3–15 months. Samples were stained with Masson-Goldner, von Kossa, and toluidine blue. Osteoid volume, trabecular width and bone volume, and cortical porosity were analyzed. Samples were immunolabeled with antibodies against CD68, CD56 and human prolyl 4-hydroxylase to detect macrophages, osteoblasts, and fibroblasts, respectively. TRAP stainings were used to identify osteoclasts. Results: Histomorphometric data indicated good regeneration with normal bone turnover: mean osteoid volume was 1.93% of the trabecular bone mass, trabecular bone volume – 28.4%, trabecular width – 225.12 μm, and porosity index – 2.6%. Cortical and spongious bone tissue were well structured. Neither inflammatory reaction, nor osteofibrosis or osteonecrosis were observed. The implanted material was widely absorbed. Conclusion: The studied nanocrystalline hydroxyapatite paste showed good tissue incorporation. It is highly biocompatible and appears to be a suitable bone substitute for juxtaarticular comminuted fractures in combination with a stable screw-plate osteosynthesis.

  10. Bone marrow extract as a growth supplement for human iliac apophyseal chondrocyte culture

    Directory of Open Access Journals (Sweden)

    Balasubramanian Balakumar

    2016-01-01

    Full Text Available Background & objectives: Human bone marrow is rich in various growth factors which may support the chondrocyte growth. This study was conducted to compare the culture characteristics of human growth plate chondrocyte in foetal bovine serum (FBS and human autologous bone marrow extract (BME in monolayer culture. Methods: Iliac crest apophyseal cartilage was harvested from four donors, aged between two and nine years, undergoing hip surgery. Chondrocytes were propagated under two culture conditions, with 10 per cent FBS and 10 per cent autologous BME harvested from the same donors. Cells were harvested at 7, 14 and 21 days to assess viability, morphology, cell count and immunocytochemistry. Results: With an initial seeding density of 2500 cells/cm 2 , the average yield in monolayer cultured with FBS was 3.35 × 10 5 , 5.9 × 10 5 , 14.1 × 10 5 and BME was 0.66 × 10 5 , 1.57 × 10 5 and 3.48 × 10 5 at 7, 14 and 21 days, respectively. Viability was 98.21 per cent with FBS and 97.45 per cent with BME at 21 days. In BME supplemented cultures, hyaline phenotype was maintained up to 21 days. The yield was higher in the FBS supplemented group; however, the phenotype could not be maintained by the FBS group as long as BME group. Interpretation & conclusions: Autologous BME was found to be a safer alternative to FBS for human studies. BME could maintain the hyaline phenotype for a longer time. Ways to enhance the cell yield needs to be explored in future studies.

  11. Selection of apoptotic cell specific human antibodies from adult bone marrow.

    Directory of Open Access Journals (Sweden)

    Caroline Grönwall

    Full Text Available Autoreactive antibodies that recognize neo-determinants on apoptotic cells in mice have been proposed to have protective, homeostatic and immunoregulatory properties, although our knowledge about the equivalent antibodies in humans has been much more limited. In the current study, human monoclonal antibodies with binding specificity for apoptotic cells were isolated from the bone marrow of healthy adults using phage display technology. These antibodies were shown to recognize phosphorylcholine (PC-associated neo-determinants. Interestingly, three of the four identified apoptotic cell-specific antibody clones were encoded by VH3 region rearrangements with germline or nearly germline configuration without evidence of somatic hypermutation. Importantly, the different identified antibody clones had diverse heavy chain CDR3 and deduced binding surfaces as suggested by structure modeling. This may suggest a potentially great heterogeneity in human antibodies recognizing PC-related epitopes on apoptotic cells. To re-construct the postulated structural format of the parental anti-PC antibody, the dominant clone was also expressed as a recombinant human polymeric IgM, which revealed a substantially increased binding reactivity, with dose-dependent and antigen-inhibitable binding of apoptotic cells. Our findings may have implication for improved prognostic testing and therapeutic interventions in human inflammatory disease.

  12. Human dental pulp cells exhibit bone cell-like responsiveness to fluid shear stress

    NARCIS (Netherlands)

    Kraft, D.C.E.; Bindslev, D.A.; Melsen, B.; Klein-Nulend, J.

    2011-01-01

    Background aims. For engineering bone tissue to restore, for example, maxillofacial defects, mechanosensitive cells are needed that are able to conduct bone cell-specific functions, such as bone remodelling. Mechanical loading affects local bone mass and architecture in vivo by initiating a cellular

  13. Lead Poisoning

    Science.gov (United States)

    Lead is a metal that occurs naturally in the earth's crust. Lead can be found in all parts of our ... from human activities such as mining and manufacturing. Lead used to be in paint; older houses may ...

  14. Human hyoid bones from the middle Pleistocene site of the Sima de los Huesos (Sierra de Atapuerca, Spain).

    Science.gov (United States)

    Martínez, I; Arsuaga, J L; Quam, R; Carretero, J M; Gracia, A; Rodríguez, L

    2008-01-01

    This study describes and compares two hyoid bones from the middle Pleistocene site of the Sima de los Huesos in the Sierra de Atapuerca (Spain). The Atapuerca SH hyoids are humanlike in both their morphology and dimensions, and they clearly differ from the hyoid bones of chimpanzees and Australopithecus afarensis. Their comparison with the Neandertal specimens Kebara 2 and SDR-034 makes it possible to begin to approach the question of temporal variation and sexual dimorphism in this bone in fossil humans. The results presented here show that the degree of metric and anatomical variation in the fossil sample was similar in magnitude and kind to living humans. Modern hyoid morphology was present by at least 530 kya and appears to represent a shared derived feature of the modern human and Neandertal evolutionary lineages inherited from their last common ancestor.

  15. Human amnion mesenchymal stem cells promote proliferation and osteogenic differentiation in human bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Wang, Yuli; Yin, Ying; Jiang, Fei; Chen, Ning

    2015-02-01

    Human amnion mesenchymal stem cells (HAMSCs) can be obtained from human amniotic membrane, a highly abundant and readily available tissue. HAMSC sources present fewer ethical issues, have low immunogenicity, anti-inflammatory properties, considerable advantageous characteristics, and are considered an attractive potential treatment material in the field of regenerative medicine. We used a co-culture system to determine whether HAMSCs could promote osteogenesis in human bone marrow mesenchymal stem cells (HBMSCs). We isolated HAMSCs from discarded amnion samples and collected them using pancreatin/collagenase digestion. We cultured HAMSCs and HBMSCSs in basal medium. Activity of alkaline phosphatase (ALP), an early osteogenesis marker, was increased in the co-culture system compared to the control single cultures, which we also confirmed by ALP staining. We used immunofluorescence testing to investigate the effects of co-culturing with HAMSCs on HBMSC proliferation, which revealed that the co-culturing enhanced EdU expression in HBMSCs. Western blotting and quantitative real-time PCR indicated that co-culturing promoted osteogenesis in HBMSCs. Furthermore, Alizarin red S staining revealed that extracellular matrix calcium levels in mineralized nodule formation produced by the co-cultures were higher than that in the controls. Using the same co-culture system, we further observed the effects of HAMSCs on osteogenic differentiation in primary osteoblasts by Western blotting, which better addressed the mechanism for HAMSCs in bone regeneration. The results showed HAMSCs are osteogenic and not only play a role in promoting HBMSC proliferation and osteogenic differentiation but also in osteoblasts, laying the foundation for new regenerative medicine methods.

  16. Controlled Dual Growth Factor Delivery From Microparticles Incorporated Within Human Bone Marrow-Derived Mesenchymal Stem Cell Aggregates for Enhanced Bone Tissue Engineering via Endochondral Ossification.

    Science.gov (United States)

    Dang, Phuong N; Dwivedi, Neha; Phillips, Lauren M; Yu, Xiaohua; Herberg, Samuel; Bowerman, Caitlin; Solorio, Loran D; Murphy, William L; Alsberg, Eben

    2016-02-01

    Bone tissue engineering via endochondral ossification has been explored by chondrogenically priming cells using soluble mediators for at least 3 weeks to produce a hypertrophic cartilage template. Although recapitulation of endochondral ossification has been achieved, long-term in vitro culture is required for priming cells through repeated supplementation of inductive factors in the media. To address this challenge, a microparticle-based growth factor delivery system was engineered to drive endochondral ossification within human bone marrow-derived mesenchymal stem cell (hMSC) aggregates. Sequential exogenous presentation of soluble transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) at various defined time courses resulted in varying degrees of chondrogenesis and osteogenesis as demonstrated by glycosaminoglycan and calcium content. The time course that best induced endochondral ossification was used to guide the development of the microparticle-based controlled delivery system for TGF-β1 and BMP-2. Gelatin microparticles capable of relatively rapid release of TGF-β1 and mineral-coated hydroxyapatite microparticles permitting more sustained release of BMP-2 were then incorporated within hMSC aggregates and cultured for 5 weeks following the predetermined time course for sequential presentation of bioactive signals. Compared with cell-only aggregates treated with exogenous growth factors, aggregates with incorporated TGF-β1- and BMP-2-loaded microparticles exhibited enhanced chondrogenesis and alkaline phosphatase activity at week 2 and a greater degree of mineralization by week 5. Staining for types I and II collagen, osteopontin, and osteocalcin revealed the presence of cartilage and bone. This microparticle-incorporated system has potential as a readily implantable therapy for healing bone defects without the need for long-term in vitro chondrogenic priming. Significance: This study demonstrates the regulation of chondrogenesis

  17. Evaluation of complications associated with off-label use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in pediatric orthopaedics.

    Science.gov (United States)

    Stiel, Norbert; Hissnauer, Tim N; Rupprecht, Martin; Babin, Kornelia; Schlickewei, Carsten W; Rueger, Johannes M; Stuecker, Ralf; Spiro, Alexander S

    2016-12-01

    The off-label use of recombinant human bone morphogenetic protein-2 to promote bone healing in adults has significantly increased in recent years, while reports of recombinant human bone morphogenetic protein-2 application in children and adolescents are very rare. The aim of this study was to evaluate the safety of single and repetitive recombinant human bone morphogenetic protein-2 use in pediatric orthoapedics. Therefore we reviewed the medical records of 39 patients who had been treated with recombinant human bone morphogenetic protein-2 at our institution. Their mean age was 10.9 years. Recombinant human bone morphogenetic protein-2 was used in 17 patients for spine fusion, in 11