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1
Shum, Laura C. "Mitochondrial Metabolism in Bone Physiology and Pathology." Thesis, University of Rochester, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10792056.
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<p> Worldwide, 1 in 3 women and 1 in 5 men over age 50 will experience fractures due to a decline in bone quality. Elucidating the mechanisms for declining bone quality can lead to better therapeutics. A vital, yet overlooked aspect of bone health is the role of mitochondrial metabolism in both bone physiology and pathology. We have found that the ability of stem cells to differentiate into bone forming osteoblasts is sensitive to mitochondrial dysfunction, and therefore preserving mitochondrial function is essential to maintaining bone quality. In human patient samples, we found that osteogenesis following a spinal fusion is correlated with mitochondrial function of bone marrow stem cells. While the decline of bone with aging has been well studied, we were the first to find a concomitant decline in mitochondrial function in bone tissue. The most common mechanism of mitochondrial dysfunction is opening of the mitochondrial permeability transition pore (MPTP), a non-selective proteinaceous pore on the inner mitochondrial membrane, positively regulated by the protein cyclophilin D (CypD). Our CypD knockout mouse model has protected mitochondrial function in bone tissue and no decline in bone quality during aging. While we did show that protecting mitochondrial function is beneficial to age-associated bone loss, our ovariectomy model in the CypD knockout mouse did not show any protection. Thus, age-related and estrogen-related bone loss are likely controlled through different mechanisms. Overall, this work has shown the importance of mitochondrial metabolism in bone health and should be further explored as a new avenue for therapeutic interventions. </p><p>
2
Shah, Mittal. "The role of 5' adenosine monophosphate-activated protein kinase (AMPK) in bone physiology." Thesis, Royal Veterinary College (University of London), 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.559073.
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Blackwell, Penelope J. "Bone turnover in hyperprolactinaemic states." Thesis, University of Nottingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.366417.
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Charras, Guillaume. "Cellular mechano-transduction in bone." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269783.
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Wakley, Glenn Keith. "Space flight and bone." Thesis, University of Bristol, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246296.
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Bannerman, Alistair L. "Imaging the development of a bone-to-bone ligament construct." Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6425/.
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Ligament injuries are commonplace, with poor native healing leaving injury sites exposed to instability and further damage. A number of surgical methods have been established for reconstruction using a range of materials, but these have a high failure rate and a number of undesirable side-effects. Much recent work has been focused on the development of tissue engineered ligament grafts. One of the major challenges for this is the formation of an effective ligament-bone interface. In native tissue a multi-phase interface enables smooth transfer of forces between the mechanically mismatched bone and ligament tissue, however this has proved hard to replicate. Previous work has developed a bone-bone ligament construct model intended to emulate the native interface through formation of a mineralised region by soluble cement anchors. Development and optimisation of the model has seen an increasing mechanical strength, but the mechanisms involved are poorly understood. This study investigates the development of the ligament construct through the use of multiple complimentary imaging techniques to provide information on the biological, chemical, and topological development of the construct as it forms from initially homogeneous and separate materials to a complex non-homogeneous system.
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New, Susan A. "An epidemiological investigation into the influence of nutritional factors on bone mineral density and bone metabolism." Thesis, University of Aberdeen, 1995. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU602275.
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A food frequency questionnaire (FFQ) was developed for a study investigating dietary influences on bone mineral density (BMD) and bone metabolism (BM). The percentage contribution of food groups to nutrients of interest were identified from 20 7d weighed records (WR) and incorporated to form a 98 food item FFQ. The FFQ was validated against a further 20 7d WR, and the short (6 weeks) and long-term (1 year) reproducibility tested. Mean nutrient intakes by 7d WR and FFQ, and initial and repeat FFQ were similar and cross-classification showed few women to be grossly misclassified. Information was also collected on past intakes of milk and fruit, weight, height, smoking, social class and physical activity. The effect of dietary intake on BMD was investigated in 994 healthy premenopausal women aged 45-49 years. BMD was measured using dual energy X-ray absorptiometry at the lumbar spine (LS) and hip (femoral neck [FN], trochanter [FT], Wards [FW]). Nutrient intakes were adjusted for energy intake by calculating the residual from regression analysis. Positive relationships were found between BMD and intakes of Mg, K, Zn and vitamin C, remaining significant after adjustment for confounding variables. LS BMD was lower in women who reported a low intake of milk and fruit in their childhood and early adulthood. The influence of dietary intake on BM was assessed in 62 healthy peri-menopausal women aged 45-55 years. Bone resorption was determined by urinary excretion of pyridinoline (Pyd) and deoxypyridinoline (Dpd) using reversed-phase HPLC, and bone formation by serum osteocalcin (OC) using an ELISA. Energy adjusted intakes of K, Mg, carotene and vitamin C were negatively associated with Pyd and Dpd concentrations, remaining significant after appropriate adjustment including menopausal status. OC was positively associated with energy intake and weight. Twenty-six women were measured after one year, but no relationships were found between changes in bone mass and baseline bone metabolism markers or dietary intake. Results suggest there is a higher bone mass and lower bone resorption in women with high intakes of K, Mg, carotene and vitamin C, independent of confounding factors. Positive effects on acid-base balance, Mg deficiency or the role of vitamin C in collagen liydroxylation may provide some explanations for these findings.
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PAOLETTI, Nicola. "Formal Computational Modelling of Bone Physiology and Disease Processes." Doctoral thesis, Università degli Studi di Camerino, 2014. http://hdl.handle.net/11581/401835.
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This thesis addresses the definition and the application of formal techniques in the field of Computational Systems Biology, with particular focus on bone remodelling (BR), the cellular process of bone renewal, and on the analysis and control of disease processes. Firstly, we study the multiscale and spatial mechanisms that connects disruptions at the molecular signalling level, to osteoporosis and other diseases characterized by low bone mass and structural weakening at the tissue level. We define a modelling framework based on a formal specification language which extends the Shape Calculus, a process algebra with spatial and geometrical primitives. The executable side is obtained by encoding the specification into an agent-based model, where agents are enriched with stochastic actions and perception. This framework is used to define a novel spatial and individual-based model of bone remodelling, parametrized in order to reproduce both healthy and osteoporotic conditions, and to analyse how the disposition of bone cells affects bone microstructure at the tissue level. Secondly, we propose a methodological study aiming at evaluating and comparing different models of bone remodelling and different techniques for the analysis of bone diseases and of stabilization and homeostasis-related properties. We consider a non-linear ODE model, over which we perform simulation and sensitivity analysis; a stochastic model on which we employ probabilistic model checking; and a hybrid piecewise-multiaffine approximation of the ODEs, supporting model checking and LTL-based parameter synthesis. We extend the model in order to describe osteoporosis and osteomyelitis (a bone infection) and we show how quantitative verification methods could provide clinically meaningful diagnostic estimators. Thirdly, we investigate the use of formal languages and hybrid techniques in the modelling of disease processes and in the synthesis of treatment strategies. In particular, hybrid models allow us to describe the disease dynamics in a continuous fashion, while the scheduling of multiple drugs discretely. We define a process-algebraic language for specifying general disease processes and treatments, called D-CGF (an extension to the CGF process algebra), from which multiple semantics can be derived: stochastic hybrid automata and hybrid dynamical systems. Then, hybrid non-linear control is employed to compute the optimal scheduling of multiple therapies. The approach is applied to an epidemic model of the H1N1 influenza, where we derive the optimal combination of vaccination and antiviral treatments.
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Breckon, Anke. "An investigation of the morphological and mechanical properties of cancellous bone in rheumatoid arthritis and osteoarthritis of the hip." Master's thesis, University of Cape Town, 1993. http://hdl.handle.net/11427/26328.
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Oreffo, R. O. C. "Vitamin A and bone." Thesis, University of Oxford, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376950.
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Yu, Vionnie Wing Chi. "Factor inhibiting ATF4-mediated transcription is a novel leucine zipper transcriptional repressor that regulates bone mass." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103311.
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Skeletal development is a complex event that requires a delicate balance between bone formation and bone resorption. Multiple transcription factors expressed in the bone-forming cells, osteoblasts, play crucial roles during the process of bone formation. Among them, ATF4 (Activating Transcription Factor 4) is a basic domain-leucine zipper transcriptional activator that is responsible for osteoblast differentiation, osteoblast-specific genes expression, synthesis of type I collagen, and osteoclast differentiation. Mice deficient for ATF4 are runted and exhibit severe skeletal dysplasia. Our laboratory has discovered Factor Inhibiting ATF4-mediated Transcription (FIAT), whose name was coined for its interaction with ATF4 and subsequent repression of ATF4-mediated osteocalcin gene transcription. FIAT is a leucine zipper nuclear molecule lacking a basic domain for DNA binding. We hypothesize that FIAT suppresses the bone-forming activities of osteoblasts by interacting with ATF4 and thereby blocking ATF4 attachment to the DNA to mediate downstream signalling pathways. To prove this hypothesis, we monitored the expression profiles of FIAT in parallel with ATF4 during osteoblastogenesis. Mechanism of FIAT repression of ATF4 was investigated through structure-function and mutation analysis. The physiological significance of FIAT expression in osteoblasts was studied through silencing FIAT in osteoblasts by RNA interference, as well as through characterization of two genetic mouse models: FIAT transgenic mice which overexpress FIAT in osteoblasts, and osteoblast-specific FIAT knockout mice. These studies showed that FIAT and ATF4 are co-expressed in osteoblasts, and that FIAT inhibition of matrix mineralization requires dimerization with ATF4 through the second leucine zipper. Furthermore, transgenic mice overexpressing FIAT exhibited osteopenia whereas FIAT knockout mice showed enhanced bone formation. These results support our hypothesis and demonstrate that FIAT is a key transcriptional repressor that modulates osteoblast function.
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Romero, Rodney Gray. "The histology of bone and its piezoelectric characteristics." Thesis, Kingston University, 1986. http://eprints.kingston.ac.uk/20508/.
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An investigation into the effects of micro electric currents on the material of bone is presented along with a review of the ideas and concepts associated with bone’s response to load and the alleged piezoelectric phenomena. A comparison is made between the structure of bone, its strength and stress generated potential. Evidence is forwarded to show that micro currents may influence the behaviour of bone material and it is demonstrated that these effects may be understood through reference to the limiting molar conductivities of the ions in the material and the solutions used.
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Ellis, Tiffany A. "Comparison of bone density in female vollyball players and age-matched non-athletes." Virtual Press, 2005. http://www.oregonpdf.org.
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Allsopp, Richard Patrick. "The role of the vascular endothelium in bone formation." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386827.
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Orr, J. F. "Experimental measurement of stresses in bone and joint replacements." Thesis, Queen's University Belfast, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373559.
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Dobson, Katharine Rebecca. "Studies into the effects of androgens on bone formation." Thesis, University of Sheffield, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301007.
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Avenell, Alison. "Nutritional influences on bone metabolism : three studies in postmenopausal women." Thesis, University of Aberdeen, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361777.
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Eleven postmenopausal women made weighed food intakes and urine collections for one week, to determine influences on urinary calcium and deoxypyridinoline excretion. Urinary calcium was influenced by both dietary calcium and dietary fibre. Urinary deoxypyridinoline was increased in women consuming more dietary fibre. The influence of ketosis was examined in five postmenopausal women, who increased urinary hydrogen ion excretion, but had no consistent changes in urinary calcium or deoxypyridinoline excretion. Forty-six postmenopausal women, with body mass index greater than 27kg/m<sup>2</sup>, were randomised to diet XA (5010kJ, 89g protein, 110g carbohydrate, 17g dietary fibre daily) or diet XK (5010kJ, 62g protein, 186g carbohydrate, 28g dietary fibre daily) for six months later. Calcium intakes fell significantly in both groups and fibre intakes were significantly increased in XK dieters compared to XA. Throughout the year group XA had significantly greater weight loss than XK, at one year XA-6.5kg (SE 1.1) and XK-3.0kg (0.8), p < 0.05. No significant changes in deoxypyridinoline or osteocalcin were found for XA or XK during the six months of dieting. Sex hormone binding globulin and follicle stimulating hormone rose particularly in group XA, suggesting a decline in endogenous oestrogen levels. Bone mineral density changes were compared to 46 normal weight non-dieting controls. Sixteen XK dieters lost 20% of their excess body weight, but returned to their starting weight. Annual changes in lumbar spine bone mineral density, measured by dual energy X-ray absorptiometry, for this group were -4.8% (SE 0.9), controls -2.5% (0.5), 95% confidence interval of difference between groups -0.2 to -4.3%, p = 0.03. For group XA, the annual percentage change in lumbar spine bone mineral density was -3.3% (1.0), incorporating a correction factor for truncal thickness. This was not significantly different from the control group. No significant difference in changes of annual femoral neck bone mineral density was found between XA, XK and the control group.
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Campbell, Craig. "Bone health in children with cerebral palsy." Thesis, University of Ottawa (Canada), 2006. http://hdl.handle.net/10393/27231.
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Background. Children with cerebral palsy (CP) encounter a number of orthopedic complications as a result of abnormalities in motor function. One of the most significant complications is fragility fractures, occurring in up to 23% of children in prior reports. Despite a growing literature on how to best interpret bone densitometry in children, little research has determined optimal utilization of dual x-ray absorptiometry (DXA) in children with CP in order to characterize the patients' bone health status. This study outlines the use of the mechanostat theory of bone physiology to classify osteopenia and interpret bone complications in this population. The mechanostat theory posits that muscle forces have the greatest impact on bone strength and that low bone mass will result from one of two pathologic circumstances: a primary disorder of abnormally low bone mass despite normal muscle forces, and a secondary disorder of bone mass due to abnormally low muscle forces on bone. The later category, secondary osteopenia, is hypothesized to be the bone health state of most children with CP, due to the motor dysfunction resulting from brain injury in these children. Bone morbidity is expected to be greater in those with osteopenia.
Methods. Single, community-based, rehabilitation centre, cross sectional study of 53 subjects with CP age 2-15 years of age. Subjects underwent a baseline interview, examination, x-ray, laboratory and DXA bone densitometry. Calculations of z-score values for total body bone mineral content and muscle mass were made based on published normal children. The z-scores determined the classification of osteopenia with -2 defined as abnormally low bone mineral content or muscle mass.
Results. The subjects (51% females) had a mean age of 9 years (s.d.=3.8, range=2.5-15.8). All types and severity of CP were represented in the sample. Normal DXA bone parameters were seen in 24 children, with 11 children classified as having primary osteopenia, five having secondary osteopenia and three with both primary and secondary (mixed). Three children had fragility fractures. Using the classification proposed herein, the fractures occurred only in children defined as having osteopenia. Having at least one bone complication and joint subluxation were more prevalent in the osteopenic subjects compared to non-osteopenic subjects (Chi square, p<0.05). Using z-scores for bone mineral content as an outcome variable, only one CP specific factor, the Gross Motor Function Classification System, was an important independent variable (beta=-0.48, R2=0.18, p<0.05). The final model also included age (beta=0.52, R2=0.34, p<0.05) and gender (beta=-0.36, R2=0.12, p<0.05), showing lower z-scores in males and those of younger age. Use of anti-convulsants, type of CP, family history, calcium and vitamin D intake did not contribute to the model. Measures of pain or quality of life, although worse in osteopenic subjects, were not significantly related to reductions in bone mineral content, when severity of CP was controlled.
Conclusions. Using the mechanostat theory to interpret bone density DXA measurements is a more physiologic way to interpret bone health in children and appears foundationally sound in this sample of children with CP. In the reported subjects orthopedic complications were more common in those with osteopenia, and fragility fractures were accurately classified in functional terms according to whether the osteopenia resulted from a primary or secondary bone defects.
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Gambari, Laura <1985>. "Hydrogen Sulfide (H2S) Based Therapeutics for Bone Diseases: Translating Physiology to Treatments." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7535/1/gambari_laura_tesi.pdf.
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Much progress has been made in the past decade in elucidating the physiological, pathophysiological and pharmacological role of Hydrogen Sulphide (H2S). Recently a function of H2S virtually in every tissue of the human organism has emerged. However, the H2S-mediated regulation of bone homeostasis has been scarcely investigated. Despite a recent increased interest in the field, many fundamental issues remain indeterminate. The main objective of this study was to increase the basic knowledge on the role of H2S in bone through in vitro and in vivo studies and develop novel therapeutic strategies for bone diseases. Ex vivo experiments revealed that H2S-generating enzymes (Cystathionine-β-synthase, CBS; Cystathionine-γ-lyase, CSE) are expressed in human bone tissues and human bone-derived cells. In vitro experiments evidenced that CBS and CSE expression is a distinctive feature of the transition of mesenchymal stromal cells (h-MSCs) toward mature osteoblast. Furthermore, loss of function experiments on CBS and CSE during osteogenic differentiation of h-MSCs revealed an impaired mineralization ability. In vivo experiments in mice highlighted the role of CBS, CSE and H2S in the maintenance of bone homeostasis and CBS, CSE and H2S were found to be depleted in post-menopausal osteoporosis. Furthermore, our in vitro and in vivo data validated the use of H2S-donors as novel potential candidates for the treatment of bone pathologies. In particular H2S administration prevented and reversed ovariectomy-induced bone loss in mice. Based on these evidences, we firstly developed an H2S-releasing hybrid drug (DM-22) by modifying a clinically relevant anti-resorptive drug in order to improve the therapy of bone loss. DM-22 displayed improved biological properties compared to the parent drug; in particular, it increased the osteogenic differentiation ability of h-MSCs. Secondly, we developed an H2S-releasing scaffold to improve bone regeneration which was permissive for h-MSCs colonization and supported their osteogenic differentiation.
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Gambari, Laura <1985>. "Hydrogen Sulfide (H2S) Based Therapeutics for Bone Diseases: Translating Physiology to Treatments." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7535/.
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Much progress has been made in the past decade in elucidating the physiological, pathophysiological and pharmacological role of Hydrogen Sulphide (H2S). Recently a function of H2S virtually in every tissue of the human organism has emerged. However, the H2S-mediated regulation of bone homeostasis has been scarcely investigated. Despite a recent increased interest in the field, many fundamental issues remain indeterminate. The main objective of this study was to increase the basic knowledge on the role of H2S in bone through in vitro and in vivo studies and develop novel therapeutic strategies for bone diseases. Ex vivo experiments revealed that H2S-generating enzymes (Cystathionine-β-synthase, CBS; Cystathionine-γ-lyase, CSE) are expressed in human bone tissues and human bone-derived cells. In vitro experiments evidenced that CBS and CSE expression is a distinctive feature of the transition of mesenchymal stromal cells (h-MSCs) toward mature osteoblast. Furthermore, loss of function experiments on CBS and CSE during osteogenic differentiation of h-MSCs revealed an impaired mineralization ability. In vivo experiments in mice highlighted the role of CBS, CSE and H2S in the maintenance of bone homeostasis and CBS, CSE and H2S were found to be depleted in post-menopausal osteoporosis. Furthermore, our in vitro and in vivo data validated the use of H2S-donors as novel potential candidates for the treatment of bone pathologies. In particular H2S administration prevented and reversed ovariectomy-induced bone loss in mice. Based on these evidences, we firstly developed an H2S-releasing hybrid drug (DM-22) by modifying a clinically relevant anti-resorptive drug in order to improve the therapy of bone loss. DM-22 displayed improved biological properties compared to the parent drug; in particular, it increased the osteogenic differentiation ability of h-MSCs. Secondly, we developed an H2S-releasing scaffold to improve bone regeneration which was permissive for h-MSCs colonization and supported their osteogenic differentiation.
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Westfall, Carola Hammer 1953. "Bone mineral content of femur, lumbar vertebrae, and radius in eumenorrheic female athletes." Thesis, The University of Arizona, 1988. http://hdl.handle.net/10150/276757.
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This study compared bone mineral index (BMI, gm/cm²) of the femur, spine, and radius, measured by photon absorptiometry in various groups of eumenorrheic female athletes. The sample included body builders (11), swimmers (13), runners (5 collegiate, 11 recreational), and inactive controls (18) averaging 25 years of age, ranging from 17 to 38 years. Lumbar vertebral BMI for body builders (1.40 gm/cm²) was significantly (p ≤ 0.05) greater than controls (1.25 gm/cm²). The body builders' femoral neck BMI (1.09 gm/cm²) was significantly greater than swimmers (0.97 gm/cm², recreational runners and controls (0.95 gm/cm²). Years of exercise history and calcium consumption were not significant predictors of BMI. Correlation coefficients between fat-free body and all BMI sites were significant and more closely related to bone mineral than other variables (weight, height, weight/height²). Correlation coefficients for proximal and distal radius BMI and femoral and spine BMI were significant, the distal radius having higher association.
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De, Boef Maria Elizabeth. "Effects of phylogeny, physiology, and function on bone microstructure in extant endothermic vertebrates." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86513.
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A strong relationship between bone macrostructural morphology and bone mechanical function has been well documented and is an essential component of many vertebrate biomechanical studies. However, a vastly richer data set could be had if the relationship between bone microstructure and bone function were as well understood. This thesis enumerates the bone microstructure-function relationship in a statistically consistent manor in extant endotherms.<br>Phylogeny, physiology and function have been shown to independently contribute to bone microstructure morphology. However, rarely have two or more of these factors been examined in combination. In this work the author used various statistical and experimental techniques to quantify the contribution of each of these factors to bone microstructure.<br>This work is organized into four parts: First, a review of methods used to quantify bone microstructure is given and a new method for quantifying vascular orientation proposed. This method allows the researcher to observe vascular orientation as an unbiased continuous measure and therefore complete more extensive statistical testing. Second, an analysis of the use of skeletochronology for aging three species of extant carnivores is given. This technique, although rarely used in extant endotherms, is commonly used for aging specimens from palaeontological findings. Upon discovering a significant discordance between organismal age and skeletochronology in the carnivorans studied here, I discuss the validity of its use in palaeontology. Third, using a sample of seven carnivoran species, the impact of phylogeny, function and physiology on bone microstructure was tested using a variance partitioning method. It was found that phylogeny has a large and significant impact on bone microstructural characteristics but only in conjunction with functional and physiological variables. When considering the effects of the three "pure" factors I found that physiological factors are the major drivers of bone microstructure. To further explore these findings, the final chapter presents an experimental study on the effects of biomechanical function and repeated loading on the humerus and tibiotarsus in Helmeted GuineaFowl. It was found that the type of strain and the repetition of strain from exercise both significantly impact bone microstructure but the relationship between tensile, compressive and shear strains to microstructure is complex with no obvious correlation.<br>Il existe une forte relation entre la morphologie de la structure macroscopique des os et leurs caractéristiques fonctionnelles au niveau mécanique. Cette relation est bien documentée et est un aspect essentiel de plusieurs études sur la biomécanique des vertébrés. Cependant, un ensemble de données beaucoup plus étoffé serait disponible si la relation entre la morphologie de la microstructure des os et leur fonction était mieux comprise. La présente thèse comporte une énumération des relations entre la microstructure des os et leurs caractéristiques fonctionnelles chez certaines espèces actuelles d'endothermes, en suivant une approche statistique cohérente.<br>Il a été démontré que la phylogénie, la fonction et la physiologie contribuent séparément à la morphologie de la microstructure des os. Cependant, les effets combinés de deux ou plusieurs de ces facteurs ont rarement été examinés. Dans la présente étude, l'auteur a utilisé plusieurs méthodes statistiques et expérimentales afin de quantifier l'impact respectif de chacun de ces facteurs sur la microstructure des os.<br>Cette thèse est organisée en quatre parties. D'abord, une revue des méthodes utilisées pour quantifier la microstructure des os est présentée et une nouvelle méthode pour quantifier l'orientation vasculaire est proposée. Cette nouvelle méthode permet d'observer l'orientation vasculaire d'une manière continue et non-biaisée, et permet donc une analyse statistique plus approfondie. Ensuite, l'utilisation de la squelettochronologie pour la détermination de l'âge de trois espèces de carnivores est analysée. Cette technique, bien que rarement utilisée pour déterminer l'âge chez les endothermes actuels, est communément employée pour les espèces paléontologiques. À la suite de la découverte d'une discordance significative entre l'âge des organismes et la squelettochronologie chez les carnivores étudiés ici, la validité de cette technique en paléontologie est discutée. En troisième partie, à partir d'un échantillon de sept espèces de carnivores et au moyen d'une analyse de partition de variance, l'impact de la phylogénie, de la fonction et de la physiologie sur la microstructure des os a été testé. Il a été découvert que la phylogénie avait un impact important sur la microstructure des os, mais seulement en conjonction avec les variables liées à la fonction et à la physiologie. Lorsque les effets des trois facteurs « purs » étaient considérés, la physiologie était le facteur qui contribuait le plus à la variabilité observée dans la microstructure des os. Afin d'examiner ces résultats plus en détail, le chapitre final présente une expérience investiguant les effets d'une charge répétée et de la fonction biomécanique sur l'humérus et le tibiotarse de la pintade de Numidie (Numida meleagris). Le type d'effort et la répétition de l'effort imposé par l'exercice avaient tous les deux un impact significatif sur la microstructure des os, mais les relations entre les forces de tension, de compression et de cisai
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Micklesfield, Lisa Kim. "Exercise and bone mass in mature premenopausal women." Master's thesis, University of Cape Town, 1996. http://hdl.handle.net/11427/26979.
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Akter, Rahima. "Role of lamin A/C in the cellular features of age-related bone loss." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=32525.
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Lamin A/C, an important component of the nuclear envelope, has been associated with cell differentiation and tissue development. In bone, recent studies have described that altered function of lamin A/C, due to mutations or incorrect processing, is associated with accelerated and severe bone loss. This could be due to alterations in the differentiation of mesenchymal stem cells (MSC) induced by lack of lamin A/C activity. Therefore, considering that decreased osteoblastogenesis and increased adipogenesis are the characteristic changes observed within bone marrow microenvironment that leads to age-related bone loss, we have studied the effect of inhibition of lamin A/C on MSC into either osteoblasts or adipocytes both in vitro and in vivo. For in vitro studies, we identified the effect of pharmacological inhibition of lamin A/C on adipogenesis. Subsequently, we inhibited lamin A/C by using different doses of lamin A/C siRNA in osteogenic and adipogenic differentiating MSCs as well as normal human osteoblasts. To further verify our results, we have used Zmpste24-/- null progeroid mice that lacks mature lamin A/C and studied the bone changes in absence of mature lamin A/C in in vivo. We have found that partial inhibition of lamin A/C decreased osteoblast differention and function without affecting their survival. Furthermore, our animal studies showed that absence of mature lamin A/C induced a reduction in bone mass and bone quality associated with low bone turnover. In contrast, accumulation of prelamin A induced significant levels of adipogenesis within the bone marrow cavity. In summary, our results provide evidence in support of a pivotal role of lamin A/C in the comm<br>Lamin A/C, un important composant de l'enveloppe nucléaire, a été associé avec la différentiation cellulaire et le développement tissulaire. Dans l'os, des études récentes ont demontrée que l'alteration de lamin A/C, due a des mutations du gène LMNA, est associée avec une perte accélérée et sevère de l'os. Ceci pourrait être dû à une altération de la différentiation des cellules souches mésenchymateuses (CSM) induit par une perte de l'activité de lamin A/C. Par conséquent, en considerant que la diminution de l'ostéoblastogènese et l'augmentation de l'adipogènese sont les changements caractéristiques observés à l'intérieur du micro-environnement de la moelle osseuse qui mènent à une perte osseuse relié à l'âge, nous avons étudié l'effet de l'inhibition de lamin A/C sur la différentiation des cellules souches soit en adipocyte ou en ostéoblast in vitro et in vivo. Pour les études in vitro, nous avons identifiés l'effet de l'inhibition pharmacologique de lamin A/C sur l'adipogènese. Par la suite, nous avons inhibé lamin A/C en utilisant différentes doses de lamin A/C siRNA sur les cellules souches en différentiatiation en ostéoblast et en adipocytes et aussi sur des ostéoblast humaine. Pour confirmer nos résultats précedents, nous avons utilisés un modèle progerique murin Zmste24-/-. Ces souris ne possedent pas la forme mature de lamin A/C. Nous avons etudiés les changements osseux en absence de la forme mature de lamin A/C in vivo. Nous avons trouvé qu'une inhibition partielle de lamin A/C diminue la différentiation et la fonction des ostéoblastes sans affecter leur survie. En outre, nos études sur les souris ont d
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Young, Julia, and n/a. "Bone morphogenetic proteins are involved in controlling mammalian fertility." University of Otago. Department of Biochemistry, 2008. http://adt.otago.ac.nz./public/adt-NZDU20090112.122706.
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Transforming growth factor beta (TGFβ) superfamily members are involved in controlling mammalian fertility. The largest subset of the TGFβ superfamily are the bone morphogenetic proteins (BMP). BMP ligands signal through the type I and II BMP receptors and utilise the Smads1/5/8 phosphorylation cascade to control gene expression in the cell nucleus. Although BMPs act through the same pathway, they have the ability to activate unique sets of genes dependant on the identity of the ligand. In this study, HEK293T cells were challenged with BMP ligands for four hours and gene expression profiles were compared using microarray technology. The genes upregulated in the presence of BMP2, BMP4, BMP6 and BMP7 play roles in cellular proliferation and differentiation. These functions are critical stages in the successful development of an ovarian follicle whilst undergoing folliculogenesis. All of the BMP ligands investigated in this study were also observed to upregulate the expression of a small group of common genes indicating that a shared regulatory pattern occurs within the BMP pathway. Of these genes, Smad6 and Smad7, inhibitor of DNA binding proteins 1-4 (ID 1-4), and msh homeobox homolog 2 (MSX2) were previously known BMP target genes. However, none of the remaining genes upregulated by all BMPs were previously shown to be BMP targets.
The results from the microarray experiment were used as founding data for the in silico mining of novel genes not present on the array that may be differentially expressed in response to these ligands. The expression levels of several of the novel genes identified by in silico mining were then measured in vitro, however the results showed no differential expression in the HEK293T cells.
To apply the knowledge of the microarray studies to the tissue of interest, eight genes were selected for assessment in ovine granulosa cells. Four of the genes upregulated in response to BMP6 in HEK293T cells were also differentially expressed in primary ovine granulosa cell cultures in response to BMP6 addition.
The identification of several sheep breeds with mutations in TGFβ superfamily members has enabled investigations into the roles that specific TGFβ components play in controlling fertility. The highly fertile Booroola sheep has a substitution mutation in the type IB BMP receptor that results in an additive effect on ovulation rate. The Booroola mutation causes precocious maturation of ovarian follicles with fewer granulosa cells surrounding an enlarged oocyte, and carriers of the mutation have higher levels of circulating follicle stimulating hormone (FSH). BMPs have previously been shown to influence the regulation of FSH synthesis and secretion in the pituitary gland. In this study, primary pituitary cells were harvested and cultured from homozygous Booroola ewes and from wildtype ewes to determine if the mutation caused alterations in FSH secretion in vitro. The cells were collected 24 h following induction of luteolysis and cultured for 72 h prior to being challenged for 24 h with bone morphogenetic proteins (BMP2, BMP4, BMP6), growth and differentiation factor-9 (GDF9), transforming growth factor β1 (TGFβ1), activin-A and gonadotropin releasing hormone (GnRH). The levels of FSH and luteinising hormone (LH) were measured by radioimmunoassay and compared to the untreated controls. Primary pituitary cell cultures from Booroola ewes secreted less FSH than wildtype cells in the presence of BMP2, BMP4 and BMP6. These BMPs did not affect the FSH stores within the cells, or the levels of LH released. GDF9 appeared to act in a BMP-like manner by suppressing FSH secretion. The BMPRIB receptor however, was not found to co-localise with gonadotroph cells in either Booroola or wildtype pituitary tissues. These findings imply that the increased sensitivity of Booroola cells to BMP2, BMP4, BMP6, and GDF9 cannot be due to the direct action of the BMPRIB mutant Booroola receptor in the cells that synthesize FSH. The alternative type I BMP receptor to BMPRIB that can act in BMP signal transduction is BMPRIA. This receptor was also not found in gonadotroph cells of wildtype orBooroola ewes This is in contrast to findings in other flocks which have been shown to express BMPRIA in gonadotroph cells.
This study has identified unique sets of differentially regulated genes in response to BMP-2, 4, 6, and 7 as well as TGFβ1 in a human HEK293T cell culture system. Among the differentially expressed genes, a common set of 12 genes were upregulated by all BMP ligands. None of these genes were present in the TGFβ1 set. Selected genes were validated in ovine primary granulosa cell cultures, showing that the human cell culture system functions similarly to cells of biologial relevance in fertility. Within the pituitary gland, BMPs are shown to influence FSH secretion. The presence of the Booroola mutation enhances the BMP effects on gonadotroph cells, however the lack of BMPRIB on gonadotroph cells indicates that the effects are indirect.
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Yoo, Andrew Cha. "Hierarchical modeling of the mechanical behavior of human trabecular bone." Thesis, Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/17550.
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Lau, Hoi-lun, and 劉海倫. "Genetic and environmental determinants of bone mineral density in Southern Chinese." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B31930633.
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Ward, Ryan C. "Contribution of high school sport participation to young adult bone strength." Thesis, University of Iowa, 2018. https://ir.uiowa.edu/etd/6333.
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Nearly 8 million American adolescents participate in sports. Many sports (e.g. basketball, volleyball) require powerful muscle movements. Normally, participation declines in young adulthood. The purpose of this study was to assess longitudinal effects of interscholastic high school sport participation and muscle power on young adult bone strength. 295 young adults from the Iowa Bone Development Study participated in this study. Participants were classified into sport participation groups based on an interscholastic sport participation history questionnaire. Groups included Power Sport Participant (PSP), Other Sport Participant (OSP), and Nonparticipant (NP). Current physical activity (PA) behaviors were assessed via questionnaire. Dual x-ray absorptiometry (DXA) assessed hip areal bone mineral density (aBMD) and was used with hip structure analysis (HSA) to estimate femoral neck section modulus (FN Z) and hip cross-sectional area (CSA). Peripheral quantitative computed tomography (pQCT) provided stress-strain index (SSI) and bone strength index (BSI) at 38% and 4% cross-sectional tibial sites respectively. Vertical jump estimated muscle power at age 19. Gender-specific multiple linear regression predicted young adult bone outcomes based on sport participation groups. Mediation analysis analyzed effects of muscle power on relationships between sport participation and bone outcomes. All analyses were adjusted for current PA. For both males and females, bone outcomes for PSPs were greater than bone outcomes for NPs (P < 0.025). Bone outcomes for PSPs were also greater than OSPs in females (P < 0.025). Mean differences for PSPs and NPs differed between 6.5% to 15.7%. 14.2% to 27.5% of the effect of sport participation on bone outcomes was mediated by muscle power. These results provide evidence to say that former male power sport participants and other sport participants and female power sport participants have stronger bones than peers even when adjusting for current PA. Muscle power did not fully explain differences in all bone outcomes suggesting that sport participation has additional bone health benefits.
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O'Neill, G. "Analysis of the physical and physiological events resulting from caloric irrigation of the human temporal bone." Thesis, University of South Wales, 1985. https://pure.southwales.ac.uk/en/studentthesis/analysis-of-the-physical-and-physiological-events-resulting-from-caloric-irrigation-of-the-human-temporal-bone(cfc9ee81-9359-4a9e-915f-6dcbf6263173).html.
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Analysis of results obtained from caloric tests showed that, on average, a significant sequential response decline was present for the four caloric responses. The effect of this decline was to produce an 'apparent 1 canal paresis of 4% of the second ear to be irrigated. There was no significant effect upon the calculation of directional preponderance. Also, differences in both maximum slow phase velocity and the latency of this maximum were found to exist between the warm and cold caloric responses. Although the difference of nystagmus intensities may be explained by the difference in the magnitude of the respective water temperatures, there remained a possible influence of a stimulus-related adaptation effect upon the response latencies. Regarding pathways and mechanisms of heat transfer during caloric stimulation of the labyrinth, a study of horizontal serial sections of human temporal bones showed that the most direct anatomical route from the external auditory meatus to the lateral semicircular canal is through the air of the middle ear cleft. The bony posterior-inferior extension of the external meatus, which has been generally accepted as the main route for caloric stimulation, was found to be a highly cellular structure and was not seen in serial section until a level was reached which was well below that of the lateral limb of the semicircular canal. Additionally, temperature measurement in isolated temporal bones showed that convection within the middle ear cleft was a significant heat transfer mechanism in caloric stimulation. The mathematical model incorporating temperature profiles based on those from cadaveric temporal bones and which also included a term describing adaptation gave good prediction of caloric primary nystagmus. The true mechanism of vestibular adaptation was however considered to be stimulus related and would therefore be more accurately modelled by a non linear term.
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Bauldry, Sue Ann. "Factors influencing the in vitro proliferation of rat bone marrow fibroblasts /." The Ohio State University, 1985. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487259125218486.
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Croker, Sarah L. "Comparative cortical bone thickness in human and non-human mammal long bones : biomechanical and forensic perspectives." Thesis, The University of Sydney, 2011. https://hdl.handle.net/2123/24898.
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The determination of the human or non-human origin of skeletal material can be particularly
difficult if the bone is fragmented. It has been suggested that differences in the thickness of
the cortical bone between human and non-human mammal long bones may be used to
distinguish them, though little clear data exist. The aim of this thesis was to determine the
extent of such difference, and whether it could be used to identify fragments of bone shafts.
Potential differences in cortical bone thickness were investigated by comparing adult human
limb bones (humerus, radius, femur and tibia) with those of kangaroos, sheep, pigs, large
dogs and cattle. Each bone was radiographed in two projections perpendicular to each other,
allowing measurement of the medial, lateral, anterior and posterior cortices and the shaft
diameters in each projection at five sites located down the length of the shaft. A qualitative
assessment of comparative radiographic differences was made; and corrections for
radiographic magnification and tests of observer error ensured the validity of the study data.
Cortical bone thickness, shaft diameter, and an index of relative cortical thickness to shaft
diameter were compared across all groups. Tests between humans and each non-human group
showed significant differences in several cases, though this depended on which part of the
shaft, skeletal element, particular non-human mammal, and sex of the human sample was
being compared. Previous research stating an overall difference, especially that non-human
bones were relatively thicker, was not supported.
Discriminant function analysis was used to show whether distinction between human and
non-human shaft fragments was possible using the combination of shaft diameter and cortical
bone thickness measurements from a single measurement site. One analysis compared all
skeletal elements together, yielding a cross-validated rate of correct classification of 69.5%.
Though this rate of classification is not high enough to serve as a standalone method, it does
represent a simple, useful tool to provide quantitative support to other identification methods.
Expected patterns of greater cortical bone thickness in relation to greater loading of the long
bones were not clearly apparent. It is perhaps too simplistic to expect just one factor to
influence cortical bone thickness, or that just this feature can distinguish all human from nonhuman
bone fragments. Nevertheless, the data in this thesis provide a valuable contribution to
assist in solving the difficult problem of the identification of bone fragments.
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Yellowley, Clare Elizabeth. "Electrophysiological characterisation of human osteoblast-like cells." Thesis, University of Bristol, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.240717.
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Graham, Jason Michael. "Mathematical representations in musculoskeletal physiology and cell motility." Diss., University of Iowa, 2012. https://ir.uiowa.edu/etd/3305.
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Research in the biomedical sciences is incredibly diverse and often involves the interaction of specialists in a variety of fields. In particular, quantitative, mathematical, and computational methods are increasingly playing significant roles in studying problems arising in biomedical science. This is particularly exciting for mathematical modeling as the complexity of biological systems poses new challenges to modelers and leads to interesting mathematical problems. On the other hand mathematical modeling can provide considerable insight to laboratory and clinical researchers.
In this thesis we develop mathematical representations for three biological processes that are of current interest in biomedical science. A deeper understanding of these processes is desirable not only from the standpoint of basic science, but also because of the connections these processes have with certain diseases. The processes we consider are collective cell motility, bone remodeling, and injury response in articular cartilage. Our goals are to develop mathematical representations of these processes that can provide a conceptual framework for understanding the processes at a fundamental level, that make rigorous the intuition biological researchers have developed about these processes, and that help to translate theoretical and experimental work into information that can be used in clinical settings where the primary concern is in treating diseases associated with the process.
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Warnock, Sarah M. "Cortical Bone Mechanics Technology (CBMT) and Dual X-Ray Absorptiometry (DXA) Sensitivity to Bone Collagen Degradation in Human Ulna Bone." Ohio University Honors Tutorial College / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1556305540256918.
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Zierath, Juleen R. "Bone mineral content in laboratory rats following swim and run training." Virtual Press, 1986. http://liblink.bsu.edu/uhtbin/catkey/472942.
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Increased bone density has been observed following physical training. However, it is not known whether the mechanical forces of muscular contraction, gravitational pull, or a combination of these forces are required to cause this adaptation. Therefore, the purpose of this study was to determine which mechanical force, muscular contraction or gravitational pull, offered the greatest contribution to increased bone mineral content observed following either swim or run training. METHODS: Female Wistar rats were randomly assigned to one of three groups: 1) Sedentary Control (SC; n = 12), 2) Run Trained (RT; 27.7 m/m, 8% incline, 2 hrs/day; n = 20), and 3) Swim Trained (ST; 2 hrs/day, 2Y/ body weight; n = 14). The animals were sacrificed after 9 weeks of training and the humeri and femurs were removed for analysis.RESULTS: Femur weight, length, diameter, and ponderal index (a measure of robustness), and bone mineral content (BMC) were not different between the three treatment groups. However, femur cortical thickness was significantly (p < 0.01) smaller in the RT when compared to ST and SC rats. The ST humeri were significantly (p < 0.05) heavier, wider, and had a greater BMC when compared with those of the RT and SC rats, while cross sectional area was unaffected by physical training. CONCLUSION: The results of this study indicate that the mechanical forces applied by the swim training protocol produced marked bone adaptation in the ST animals following 9 weeks of physical training. Whereas, the combined mechanical and gravitational forces applied during running by the RT rats produced minimal adaptation of bone following 9 weeks of physical training.
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Qian, Guofeng [Verfasser]. "Role of peroxisomes in physiology and pathology of ossification and bone metabolism / by Qian, Guofeng." Giessen : VVB Laufersweiler, 2011. http://d-nb.info/1010869108/34.
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Jones, Christopher David Stanford. "On the cross-sectional form of the patella in several primates." Title page, table of contents and abstract only, 2003. http://web4.library.adelaide.edu.au/theses/09PH/09phj764.pdf.
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Alfonso, Durruty Marta Pilar. "Biosignificance of Harris lines as stress markers in relation to moderate undernutrition and bone growth velocity a New Zealand white rabbit model for the study of bone growth /." Diss., Online access via UMI:, 2008.
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Milliken, Laura Ann 1970. "Bone mineral density, bone remodeling, insulin-like growth factors, hormone replacement therapy, and exercise training in postmenopausal women." Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/282746.
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Osteoporosis is a condition of reduced bone mineral density (BMD) resulting in an increased susceptibility to bone fractures. The purpose of this study was to determine the effects of 12 months of weight bearing and resistance exercise on BMD, bone formation, measured by serum osteocalcin (OC) and bone resorption, measured by urinary excretion of deoxypyridinoline crosslinks (Dpd), in 2 groups of postmenopausal women who were either taking or not taking hormone replacement therapy (HRT). Secondary aims were to characterize the changes in insulin-like growth factors-l and -2 (IGF-l and -2) and IGF binding protein 3 (IGFBP3) in response to exercise training, and to determine the contribution of these growth factors in predicting changes in bone mineral density in the 2 populations of postmenopausal women. Women who were three to ten years postmenopausal and aged 40-65 years were included in the study. Women in HRT and no HRT groups were randomized into the exercise intervention resulting in four groups: (1) women not taking HRT, not exercising; (2) women taking HRT, not exercising; (3) women exercising, not taking HRT; and (4) women exercising, taking HRT. The number of subjects per group after one year was 27, 21, 25, and 16, respectively. Exercise training and HRT increase BMD similarly at most BMD sites whereas the combination of exercise and HRT produced increases in BMD greater than either treatment alone. Bone remodeling was surpressed in the groups taking HRT regardless of exercise status. The bone remodeling response to exercise training in women not taking HRT was not significantly different from those not exercising but the direction of change suggests an elevation in bone remodeling in response to exercise training. Exercise training does not stimulate a change in IGF-1, IGF-2, IGF-1:IGF-2, and IGFBP3. Markers of bone remodeling and IGF-1 are significant predictors of BMD changes but the overall amount of variation in BMD changes accounted for is low. Exercise and HRT status were significant predictors of changes in BMD even after accounting for variation due to bone remodeling indicating that bone changes are regulated by factors not addressed in this study.
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Al, Kawas Sausan. "A comparative study of maturation processes in enamel and bone in the rat." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ36951.pdf.
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Panda, Dibyendu. "Role of Tuberoinfundibular peptide 39 (TIP 39)/ parathyroid hormone 2 receptor (PTH2R) signalling in the control of endochondral bone formation." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=104517.
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Parathyroid hormone (PTH) family members participate actively in various steps of endochondral bone development, in maintenance of bone health, and in mineral homeostasis. PTH type 2 receptor (PTH2R) and its ligand tuberoinfundibular peptide of 39 residues (TIP39) are recent additions to the PTH family of receptors and ligands. They are abundantly expressed in brain where it is proposed to possess neurotransmitter function.In this study, we demonstrate the presence of both TIP39 and PTH2R in the growth plate of murine long bones, and we show that the periarticular chondrocytes which express PTH2R are spatially separated from the hypertrophic chondrocytes expressing TIP39. Using CFK2 chondrocytic cells as an in vitro model, we demonstrate that TIP39/PTH2R signalling impairs cell proliferation through inhibition of progression at the G0/G1 phase of the cell cycle. We also show that this signalling inhibits cell differentiation through deregulated expression of the master transcription factor of chondrocyte function, Sox9.In order to investigate the in vivo functions of the TIP39/PTH2R signalling pathway, we generated transgenic mice overexpressing PTH2R in chondrocytes under the control of the Collagen type II promoter/enhancer. We observed that PTH2R overexpression reduced chondrocyte proliferation and impaired trabecular bone formation likely through alterations in Wnt signalling and β-catenin expression. In addition, PTH2R overexpression was observed to delay growth plate secondary ossification in postnatal development, thus retarding endochondral bone growth. We further observed a downregulation of GDF5, a member of the bone morphogeneticprotein family, and of WDR5, a transcriptional modulator of articular chondrocytes, two factors previously shown to influence the development of the secondary ossification centre.Taken together, our results indicate that TIP39 and PTH2R in growth plate chondrocytes exert a crucial signalling role during endochondral bone development. Further studies are needed to explore these functions in experimental pathological models such as chondrodysplasias and possibly osteoarthritis.<br>Les membres de la famille de l'hormone parathyroïdienne (PTH) participent au développement de l'os endochondral, et au maintien de la santé osseuse et de l'homéostasie minérale. Le récepteur de type 2 de la PTH (PTH2R), et son ligand le peptide tubéroinfundibulaire de 39 acides aminés (TIP39) sont des nouveaux membres de la famille des récepteurs de la PTH et ses ligands. Ils sont exprimés en abondance dans le cerveau où on leur attribue des fonctions de neurotransmetteurs.Dans la présente étude, nous démontrons chez la souris la présence du TIP39 et du PTH2R dans la plaque de croissance des os longs, et nous mettons en évidence la séparation spatiale des chondrocytes périarticulaires exprimant le PTH2R, et des chondrocytes hypertrophiques exprimant le TIP39. A l'aide du modèle in vitro de cellules chondrocytiques CFK2, nous démontrons que la signalisation du complexe TIP39/PTH2R ralentit la prolifération cellulaire en inhibant la progression au delà de la phase G0/G1 du cycle cellulaire. De plus, nous demontrons que la différenciation cellulaire est inhibée par la dérégulation de l'expression du Sox9, le principal facteur de transcription contrôlant la fonction chondrocytaire.Afin d'évaluer les fonctions in vivo de la voie de signalisation du complexe TIP39/PTH2R, nous avons géneré des souris transgéniques surexprimant le PTH2R dans les chondrocytes sous le contrôle du promoteur du gène du Collagène de type II. La surexpression du PTH2R a réduit la prolifération des chondrocytes et inhibé la formation de l'os trabéculaire, probablement par une modification de la signalisation du Wnt et de l'expression de la β-caténine. De plus, durant le développement post-natal, la surexpression du PTH2R a ralenti l'ossification de la plaque de croissancesecondaire, retardant ainsi la croissance de l'os endochondral. Nous avons de plus observé une diminution de l'activité de GDF5 et de WDR5 (respectivement membre de la famille des protéines morphogéniques de l'os, et modulateur transcriptionel des chondrocytes articulaires), deux facteurs connus pour influencer le développement du centre d'ossification secondaire.En conclusion, nos résultats indiquent que le TIP39 et le PTH2R jouent un rôle crucial de signalisation au cours du développement de l'os endochondral. Des études futures sont nécessaires afin d'explorer les fonctions du TIP39 et du PTH2R dans divers modèles expérimentaux, dont ceux de la chondrodysplasie et possiblement dans l'ostéoarthrite.
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Conradie, Maria Martha. "Abnormalities of bone and mineral metabolism in patients with eating disorders." Thesis, Stellenbosch : Stellenbosch University, 2001. http://hdl.handle.net/10019.1/52058.
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Thesis (MScMedSc) -- Stellenbosch University, 2001.<br>ENGLISH ABSTRACT: Osteopenia is a well documented complication of anorexia nervosa (AN). The
pathogenesis of this bone loss is presently poorly defined in the literature.
Pathogenetic mechanisms that have been implicated include certain nutritional
factors, exercise abuse, hypogonadism, hypercortisolism and/or vitamin 0
deficiency.
We studied, 59 Caucasian eating disorder patients aged 15-45yr. The eating
disorder was classified by a single, qualified psychiatrist according to OSM IV R
criteria as either anorexia nervosa (AN: n =25), bulimia nervosa (BN: n = 17) or
eating disorder not otherwise specified (EONOS: n = 17). All patients were
subjected to a detailed dietary and general history. We assessed the prevalence
and severity (OEXA), the nature (osteocalcin, deoxypyridinoline) and site
(vertebral versus hip) of osteopenla in these patients. he role of nutritional
factors (energy intake, weight, height, BMI, plasma albumin, lipids), physical
activity, hypercortisolemia (plasma and urinary free cortisol), vitamin 0 deficiency
(plasma 250HD) and hypogonadism (amenorrhoea, E2, LH, FSH) in the
pathogenesis of bone loss were also evaluated.
Mild osteopenia (BMO decreased by more than 1SO below age-matched
controls) was documented in 46% of the total study population, with more
marked osteopenia (Z-Score < -2 SO) present in 15%. Both vertebral and hip
osteopenia were documented. In the study population those patients with AN
(Lumbar BMO (q/cm") = 0.869 ± 0.121) were most likely to develop osteoporosis,
although a significant percentage of patients with BN (Lumbar BMO (q/crn") =
0.975 ± 0.16) and EONOS (Lumbar BMO (g/cm2) = 0.936 ± 0.10) were also
osteopenic (29% and 35% respectively). Twenty four percent (24%) of the total
patient population had a history of fragility fractures. These fractures were
reported more commonly amongst patients with AN and EONOS (28% and29.4%). Fracture prevalence was however similar in patients with normal and low
bone mass.
Conventional risk factors were similar in patients with normal and low bone
mass, except for a significantly longer duration of amenorrhoea (p = 0.009), a
lower BMI (p = 0.0001) and greater alcohol consumption (p = 0.05) in the
osteopenic patients. Nutritional parameters (S-albumin, protein, Ca, and P04
intakes), physical activity, as well as 25(OH) vitamin D levels were similar in AN
and BN subjects, as well as in patients with a low versus normal BMD. Plasma
and urine cortisol levels were also similar in these subgroups.
With the exception of two patients with borderline osteopenia, significant bone
loss was only documented in those patients with a past or current history of
amenorrhoea. In the total patient population the duration of amenorrhoea was
significantly (p<0.009) longer in patients with osteopenia versus those with a
normal bone mass. A significant negative correlation between BMD (Z-Score)
and duration of amenorrhoea was also documented in the total patient
population (r = -0.4, P = 0.001) as well as in all three eating disorder groups (AN r
- -0.4, P = 0.03; BN r = - 0.6, P = 0.008; EDNOS r = -0.6, P = 0.005).
In the total patient population, those patients with amenorrhoea, had lower BMD
and BMI values and lower estrogen levels compared to those with a normal
menstrual cycle.
We conclude that osteopenia commonly attends AN, as well as BN and EDNOS.
Nutritional (with the exception of alcohol consumption) and mechanical factors as
well as hypercortisolemia did not appear to contribute significantly to bone loss in
this study population. Hypogonadism appeared to be the main cause of the bone
loss observed in these patients.<br>AFRIKAANSE OPSOMMING: Osteopenie is In welbekende komplikasie van anorexia nervosa (AN). Die
patogenese van hierdie beenverlies is swak in die huidige literatuur omskryf en
nutrisiele faktore, 'n vita mien 0 gebrek, oormatige oefening, hiperkortisolemie en
hipogonadisme word onder andere qeimpliseer.
Vir die doel van die studie is In totaal van 59 Kaukasier eetsteurnis pasiente
patients volledig ondersoek. Die tipe eetsteurnis is deur In enkel gekwalifiseerde
psigiater volgens die DSM IV R kriteria geklassifiseer as anorexia nervosa (AN: n
=25) of bulimia nervosa (BN: n = 17) of eetsteurnis nie anders gespesifiseer
(EDNOS: n = 17). Elke pasient is ook aan In gedetailleerde dieet en algemene
risikofaktor vraelys vir osteoporose onderwerp. Die voorkoms en graad (DEXA),
die aard (osteokalsien, deoksipiridinolien) asook die tipe (werwelkolom/heup)
osteopenie is ondersoek. Die rol van nutrisiele faktore (totale kalorie-inmame,
gewig ,Iente LMI, plasma albumien, lipiede) en vitamien 0 gebrek, oefening,
hiperkortisolemie (plasma en urinere kortisol) en hipogonadisme (amenoree,
plasma E2, LH,FSH) in die patogenese van die beenverlies is ook evalueer.
Matige osteopenie (BMD meer as 1 SO onder die van ouderdomskontrole) is in
46% van die totale pasientpopulasie gedokumenteer, met erge osteopenie
(Z-Telling < -2) in 15%. Aantasting van beide werwelkolom en heup is
aangetoon. In hierdie studiepopulasie kom osteopenie meer algemeen voor in
die AN (Lumbaal BMD (g/cm2) = 0.869 ± 0.121) groep (64%) in vergelyking met
BN (Lumbaal BMD (g/cm2) = 0.975 ± 0.16) (29%) en (EDNOS) (Lumbaal BMD
(g/cm2) = 0.936 ± 0.10) (32%). Vier-en-twintig persent van die totale
pasientpopulasie het In geskiedenis van frakture gehad. Frakture het meer
algemeen in AN en EDNOS pasiente voorgekom (28% en 29%).
Pasiente met 'n lae beenmassa was gekenmerk deur In betekenisvolle laer LMI
(p = 0.0001), hoer alkolholverbruik (p = 0.05) en langer duurte van amenoree(p = 0.009). Nutrisiele parameters (s-albumien, protetene, Ca, P04 inname)
oefening, asook 25(OH) vitamien 0 vlakke was soortgelyk in AN en BN pasiente.
Hierdie parameters het ook nie verskil tussen pasiente met osteopenie en die
met In normale BMD nie. Plasma en urinere vry kortisolvlakke was ook
soortgelyk in hierdie twee groepe.
Betekenisvolle beenverlies (met die uitsondering van twee pasiente met grenslyn
osteopenie) het slegs voorgekom in pasiete met 'n huidige of In vorige
geskiedenis van amenoree. In die totale pasientpopulasie was die duurte van
amenoree (p< 0.009) betekenisvollanger in die pasiente met osteopenie. In
Betekenisvolle negatiewe korrelasie tussen BMD (Z-Telling) en die duurte van
amenoree in die toale pasient populasie (r = -0.4; P = 0.001) asook in al drie
eetsteurnis groepe (AN: r = -0.4; P = 0.03; BN: r = -0.06; P = 0.008; EDNOS: r = -
0.6, P = 0.005) is aangetoon. In die groep as 'n geheel, het die amenoree
pasiente In laer LMI, E2vlakke en BMD gehad in vergelyking met die pasiente
met normale menses.
Opsommend dus, kom osteopenie algemeen in pasiente met AN, asook BN en
EDNOS voor. In Betekenisvolle bydrae van nutrisiele (met die uitsondering van
alkoholinname) en meganiese faktore asook hiperkortisolemie tot been verlies,
kon nie in hierdie tudie populasie gedemonstreer word nie. Hipogonadisme is as
die hoofoorsaak van osteopenie in die pasiente qefdentifiseer.
43
Dreyer, Craig William. "Clast cell activity in a model of aseptic root resorption." Title page, table of contents and abstract only, 2002. http://web4.library.adelaide.edu.au/theses/09PH/09phd778.pdf.
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Shah, Karan Mehul. "The effects of clinically relevant concentrations of metal ions after hip replacement on bone cell physiology." Thesis, University of Sheffield, 2014. http://etheses.whiterose.ac.uk/6722/.
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45
Iordachescu, Alexandra. "An in-vitro model for the development of mature bone containing an osteocyte network." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8064/.
Texto completo da fonteResumo:
Bone tissue continuously adapts to changes in mechanical load. This process can also result in a maladaptive ectopic bone response to mechanical insult, known as heterotopic ossification. The pathological differences at the molecular and structural levels are poorly understood. In vivo models exist but can often be too complex to allow isolation of factors which may stimulate disease progression. This thesis presents the development of a biologically self-structuring bone culture system using a fibrin gel which self-organises between two calcium phosphate anchors when seeded with cells. These bioinspired wound analogues are seeded with primary femoral periosteal cells - key players in bone repair and a range of pathologies- and develop longitudinally over time, allowing to study the temporal evolution of bone mineral and microstructure in excess of a year. Raman spectroscopy and XRD revealed that the mineral was hydroxyapatite and associated with collagen, which was organized like the in vivo tissue. The initial stem cell population differentiated to the terminal osteocytic phase, was linked by longitudinal canalicular networks (demonstrated using nanoCT) and remained viable over the year of culture. This work also demonstrated that pharmacological compounds can prevent the progress of ossification, displaying promise for applications in drug screening.
46
容冠宇 and Koon-yu Samuel Yung. "Effects of green tea on bone loss in mature ovariectomized rat." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B31970333.
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47
Briscoe, Adam. "Characterization and computational modelling of acrylic bone cement polymerisation." Thesis, University of Southampton, 2006. https://eprints.soton.ac.uk/64795/.
Texto completo da fonteResumo:
Total joint replacement is one of the most successful surgical procedures and is a proven treatment for arthritis. Despite low failure rates, the wide application of the treatment means that large numbers of prostheses fail and must be revised. Improved pre-clinical testing methods for these orthopaedic devices may assist in developing new prostheses with improved clinical results. Computational modelling of biological systems is becoming increasingly accurate and is a much quicker and cheaper alternative to physical testing, but continued development is necessary to ensure computational models produce accurate and reliable predictions of implant behaviour. Acrylic bone cements have been used as a method of fixation for over 50 years but despite improvements in cement handling techniques and numerous attempts to improve the mechanical properties of the cement in other ways, the cement is often highlighted as the weak link in the joint replacement system. Aseptic loosening is cited as the cause for the majority of revision operations and cement degradation has been shown to be a contributor to the loosening process. In-vivo, cement is subject to cyclic loads and these are the primary cause of cement damage. Residual stresses generated during the polymerisation of the cement are now thought to play a significant role in cement failure. This thesis examines the development of residual stresses as a result of thermal and chemical changes during polymerisation of the cement. Experimental techniques for characterising the evolution of materials properties during the polymerisation reaction are discussed. Differential scanning calorimetry was used to measure the reaction variables such as the activation energy of polymerisation. The development of an ultrasonic rheometry technique for monitoring the mechanical property evolution within a bone cement specimen is discussed. Computational models were generated to predict the reaction behaviour of the cement in terms of the heat produced and the evolution of the physical properties of the curing mass. Some advantages and disadvantages of candidate mathematical models have been evaluated and are discussed, along with applications in several implant fixation scenarios. The model compared well with experimental data and was used to predict thermal necrosis in the bone surrounding both a hip resurfacing implant and a knee replacement. Using the output reaction path produced by the thermal model a mechanical model was also produced simulating the shrinkage and mechanical property evolution exhibited by the polymerising cement. Two material models were compared with and without the effects of plasticity. Residual stress magnitudes were assessed in comparison with published values and showed better agreement when plasticity was included. Peak stresses were observed to occur during polymerisation. The location of the peak stresses were compared with experimental data on pre-load crack locations in the literature and showed good agreement.
48
Kaluarachchi, Thambilipitiyage Kusumsiri Priyantha Kumara. "Impact of collagen type X deficiency on bone fracture healing." Thesis, Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk/hkuto/record.jsp?B23501807.
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Wilkins, Bridget Sally. "Cell-stroma interactions in haemopoiesis studied by immunocytochemistry and in situ hybridisation in long-term cultures and trephine biopsies of human bone marrow." Thesis, University of Southampton, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242221.
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Byrd, Alyson. "Evidence for a receptor binding 24R, 25-dihydroxyvitamin D3 in developing bone." Thesis, McGill University, 1999. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=21519.
Texto completo da fonteResumo:
Although 24R,25(OH)2D3 has been implicated in bone development, its biological role and mechanism of action remain controversial. In search for evidence of a receptor, nuclear and cytosol extracts were isolated from mandibles and calvaria of E17.5 mice. Competition and saturation analysis identified a saturable, specific and high affinity (Kd=1.1nM) 24R,25(OH) 2D3 binding-protein. The results of these and sucrose sedimentation studies indicate that this protein is not vitamin D receptor (VDR) or vitamin D binding protein (DBP). Tissue specificity experiments suggest that this putative receptor is also present in liver but not brain.<br>pBDGal4-hRXRalpha bait was used to screen neonate and embryonal mandible/calvaria cDNA libraries using the yeast two-hybrid system. PCR screening was also performed using primers from the zinc-finger region of the VDR. To date no positive clones have been identified. Isolation of this putative receptor will provide valuable insight into the mechanism of this metabolite's role in bone development.