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Samizadeh, S. "Bone formation on calcium phosphate bone substitute materials." Thesis, University College London (University of London), 2010. http://discovery.ucl.ac.uk/19891/.
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A large number of bone substitute materials are available; for which some authors claim osteoconductivity and some osteoinductivity. In order to rank these materials an in vivo analysis was carried out. These materials were chosen based on their availability and claimed mode of action. Silicon substituted Hydroxyapatite (SiHA), Hydroxyapatite (HA), Resorbable Calcium Phosphate Silicon, Skelite [siliconstabilized tricalcium phosphate-based bone substitute], Pro Osteon 500R [coralline HA], BiIonic [Yttrium stabilized SiHA] and two non-calcium phosphate, Dimeneralised Bone Matrix (DBM) based biomaterials: Accell Connexus DBM putty and Grafton crunch DBM were implanted in sheep femoral condyle defects for 6 weeks. Implanted calcium phosphate (CaP) based biomaterials demonstrated superior bone formation in comparison with the DBM samples. Silicon within CaPs increased the rate of bone formation in vivo. Silicon substituted HA showed increased proliferation rate (P<0.05) of human marrow stromal cells compared to pure HA in vitro. Expression of osteoblastic marker genes RUNX2, Osterix and Osteopontin within the hMSCs indicated the differentiation of preosteoblasts into osteoblasts, and osteogenic development on both HA and SiHA. Expression of osteocalcin and bone sialoprotein genes on HA and SiHA samples indicated the activation of mineralisation process. Differentiation of hMSCs into osteoblasts in vitro suggested a role in promotion of osteoinduction by both HA and SiHA. Implantation of porous SiHA and HA in paraspinous muscle of sheep, exhibited new bone formation through osteoinduction. SiHA indicated significantly higher new bone formation (P<0.01) compared to HA. SiHA and HA biomaterials with higher strut porosity (30%) indicated greater bone formation (P<0.05). In conclusion, CaP based biomaterials demonstrate superior bone formation in comparison with DBM biomaterials. Silicon substitution within HA enhances the cellular activity of hMSCs. Osteoinduction was greatest on SiHA with higher strut porosity. This result is believed to be due to a combination of the effect of interconnected porosity and chemical composition of the bone substitute.
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Chen, Jinbiao Prince of Wales Clinical School UNSW. "In vitro and in vivo bone formation - assessment and application." Awarded by:University of New South Wales. Prince of Wales Clinical School, 2006. http://handle.unsw.edu.au/1959.4/24922.
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Background: Bone-grafting materials are required in orthopaedic surgery to treat bone defects. Bone formation assessment is required for the development of new strategies and approaches and for quality assurance and quality control of currently available materials. Approaches to the assessment of bone formation are yet to be systematically established, quantified and standardized. Aims: the overall aim of this study was to establish a set of comprehensive quantitative approaches for the assessment of bone formation and to evaluate the role of osteoblastic cells, growth factors, and scaffolds on this process. Materials & methods: both in vitro and in vivo parameters for osteoblast phenotype and bone formation were tested in osteosarcoma cell lines, Saos-2 and U2OS cells, mesenchymal cell line, C2C12 cells, primary adipose derived stromal cells (ADSCs), platelet rich plasma (PRP), and morselized bone grafts. The in vitro parameters used were measurement of alkaline phosphatase (ALP) activity, detection of bone nodules and biomineralization, and quantification of immunocytochemistry and conventional RT-PCR of osteoblast genotyping. In vivo parameters involved ectopic bone formation in nude mice and nude rats and a tibial defect model in nude rats. Histomorphometric and quantitative immunohistochemical analyses were also performed. Results: The in vitro characterization and ectopic bone formation capabiltity of Saos-2 and U2OS cells have been established. Saos-2 cell line, which presents many osteoblast genotype and phenotype, is a stable positive control for both in vitro and in vivo bone formation assessments. The measurement of ALP activity in both solid and liquid phases has been standardized. Both the genotype and phenotype of osteoblast lineage cells has been quantitatively assessed during the capability testing of ADSCs and PRP. Quantitative assessment of new bone formation and related protein markers in vivo has been successfully established through the testing of the biological properties of gamma irradiated morselized bone grafts. Conclusion: A comprehensive knowledge of the assessment of bone regeneration and formation in vitro and in vivo has been integrated and developed through years of study. A whole set of in vitro and in vivo approaches for the assessment of bone formation has been modified and standardized to best suit the different clinical applications. This thesis provides an outline of both in vitro and in vivo bone formation assessment and their clinical applications.
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Hrit, Manuela. "Acceleration of bone formation in distraction osteogenesis by bone morphogenetic protein-7." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101142.
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The manipulation of the molecular mechanisms that govern distraction osteogenesis (DO) in order to increase the biomechanical strength of new bone and to accelerate its synthesis has been the topic of intense research during the past decades.Bone morphogenetic proteins (BMPs) play an important role in bone formation. In this study, using a rabbit model of DO, the expressions of BMP's major intracellular signalling molecules, Smad proteins, was analyzed and correlated with the expression of BMP ligands and receptors. Based on these results, which confirmed post-receptor activity for the BMP signalling pathway during DO, we hypothesized that exogenous BMPs injected early in the distraction phase will accelerate bone formation in cases of DO. The cellular changes induced by local application of rhBMP-7 (OP-1) on bone formation were therefore investigated, as well as the possible pathways through which OP-1 was responsible for these effects.
The present study reveals that acceleration of bone formation can be attained after injection of OP-1 early during the distraction protocol. The enhanced bone formation, which occurs through the activation of numerous pathways, most likely depends on a non-vascular mechanism.
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Hu, Kai. "VEGF-Dependent Mechanisms Controlling Osteoblast Differentiation and Bone Formation During Bone Repair." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467316.
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Osteoblast-derived vascular endothelial growth factor (VEGF) is important for bone development and postnatal bone homeostasis. Several studies have demonstrated that VEGF affects bone repair and regeneration; however, the cellular mechanisms by which it works are not fully understood. In this study, we investigated the functions of osteoblast-derived VEGF in healing of a cortical bone defect. In addition, how VEGF signaling modulates BMP2 functions during bone healing was also examined.
To define the roles of osteoblast-derived VEGF in bone repair, a mouse tibial monocortical defect model was used. The effects of deleting Vegfa or Vefgr2 in osteoblast precursors and their descendants on the bone repair process were analyzed at various time points after surgery. To study how VEGF modulates the osteogenic activity of BMP2, BMP2, with or without the soluble VEGFR (sFlt1, VEGF decoy receptor), was delivered to the cortical defects in VE-cadherin-cre;tdTomato mice.
The results indicate that osteoblast-derived VEGF is important at various stages during healing of the cortical defect. In the inflammation phase, osteoblast-derived VEGF controls neutrophil release into the circulation and macrophage-related angiogenic responses. VEGF is required, at optimal levels, for angiogenesis-osteogenesis coupling in areas where repair occurs by intramembranous ossification (IO). In this role, VEGF likely functions as a paracrine factor since deletion of Vegfr2 in osteoblast precursors and their progeny enhances osteoblastic maturation and mineralization. Furthermore, osteoblast- and hypertrophic chondrocyte-derived VEGF stimulates recruitment of blood vessels and osteoclasts, and promotes cartilage resorption at the repair site during the periosteal endochondral ossification stage. Finally, osteoblast-derived VEGF stimulates osteoclast formation in the final remodeling phase of the repair process. Our data also indicate that skeletal stem cells at different locations respond differently to BMP2, and that the osteogenic activity of BMP2 is modulated by extracellular VEGF. In the cortical defect, delivery of recombinant BMP2 inhibits intramembranous bone formation in the intramedullary space while it enhances endochondral bone formation in the injured periosteum. Inhibition of extracellular VEGF by sFlt1 reverses the inhibitory effects of BMP2 on intramembranous ossification-mediated bone repair.
These findings add to the understanding of VEGF functions and provide a basis for clinical strategies to improve bone regeneration and treat cases of compromised bone healing.Biological Sciences in Dental Medicine
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Williams, Bristol Marie. "Effects of tricalcium phosphate coated titanium on adjacent early bone formation." View the abstract Download the full-text PDF version, 2007. http://etd.utmem.edu/ABSTRACTS/2007-005-Williams-index.html.
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Thesis (M.S. )--University of Tennessee Health Science Center, 2007Title from title page screen (viewed on July 28, 2008). Research advisor: Joo L. Ong, Ph.D. Document formatted into pages (iv, 36 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 33-36).
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Lean, Jennifer Maree. "Mechanical stimulation of bone formation in the rat." Thesis, St George's, University of London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263682.
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Moroz, Adam. "Reduced order modelling of bone resorption and formation." Thesis, De Montfort University, 2011. http://hdl.handle.net/2086/5409.
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The bone remodelling process, performed by the Bone Multicellular Unit (BMU) is a key multi-hierarchically regulated process, which provides and supports various functionality of bone tissue. It is also plays a critical role in bone disorders, as well as bone tissue healing following damage. Improved modelling of bone turnover processes could play a significant role in helping to understand the underlying cause of bone disorders and thus develop more effective treatment methods. Moreover, despite extensive research in the field of bone tissue engineering, bonescaffold development is still very empirical. The development of improved methods of modelling the bone remodelling process should help to develop new implant designs which encourage rapid osteointegration. There are a number of limitations with respect to previous research in the field of mathematical modelling of the bone remodelling process, including the absence of an osteocyte loop of regulation. It is within this context that this research presented in this thesis utilises a range of modelling methods to develop a framework for bone remodelling which can be used to improve treatment methods for bone disorders. The study concentrated on dynamic and steady state variables that in perspective can be used as constraints for optimisation problem considering bone remodelling or tissue remodelling with the help of the grafts/scaffolds.The cellular and combined allosteric-regulation approaches to modelling of bone turnover, based on the osteocyte loop of regulation, have been studied. Both approaches have been studied different within wide range of rate parameters. The approach to the model validation has been considered, including a statistical approach and parameter reduction approach. From a validation perspective the cellular class of modes is preferable since it has fewer parameters to validate. The optimal control framework for regulation of remodelling has been studied. Future work in to improve the models and their application to bone scaffold design applications have been considered. The study illustrates the complexity of formalisation of the metabolic processes and the relations between hierarchical subsystems in hard tissue where a relatively small number of cells are active. Different types/modes of behaviour have been found in the study: relaxational, periodical and chaotic modes. All of these types of behaviour can be found, in bone tissue. However, a chaotic or periodic modes are ones of the hardest to verify although a number of periodical phenomena have been observed empirically in bone and skeletal development. Implementation of the allosteric loop into cellular model damps other types of behaviour/modes. In this sense it improves the robustness, predictability and control of the system. The developed models represent a first step in a hierarchical model of bone tissue (system versus local effects). The limited autonomy of any organ or tissue implies differentiation on a regulatory level as well as physiological functions and metabolic differences. Implementation into the cellular phenomenological model of allosteric-like loop of regulation has been performed. The results show that the robustness of regulation can be inherited from the phenomenological model. An attempt to correlate the main bone disorders with different modes of behaviour has been undertaken using Paget’s disorder in bone, osteoporosis and some more general skeleton disorders which lead to periodical changes in bone mass, reported by some authors. However, additional studies are needed to make this hypothesis significant. The study has revealed a few interesting techniques. When studying a multidimensional phenomenon, as a bone tissue is, the visualisation and data reduction is important for analysis and interpretation of results. In the study two novel technical methods have been proposed. The first is the graphical matrix method to visualise/project the multidimensional phase space of variables into diagonal matrix of regular combination of two-dimensional graphs. This significantly simplifies the analysis and, in principle, makes it possible to visualise the phase space higher than three-dimensional. The second important technical development is the application of the Monte-Carlo method in combination with the regression method to study the character and stability of the equilibrium points of a dynamic system. The advantage of this method is that it enables the most influential parameters that affect the character and stability of the equilibrium point to be identified from a large number of the rate parameters/constants of the dynamic system. This makes the interpretation of parameters and conceptual verification of the model much easier.
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Gundle, Roger. "Microscopical and biochemical studies of mineralised matrix production by bone-derived cells." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.282203.
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Wang, Jason Lee. "Effects of aging and remodeling on bone microdamage formation." Thesis, Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/37114.
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Skeletal fragility is characterized by low bone mass, negative changes in bone microarchitecture, and compromised tissue matrix properties, including accumulation of microdamage. Microdamage accumulates in vivo from daily physiological loading and is targeted for repair through a normal remodeling process, thus preventing microcrack growth and potential fracture. However, impaired remodeling is associated with aging and osteoporosis, resulting in an increased accumulation of microdamage which contributes to reduced bone mechanical properties. The current clinical method for assessing increased risk of fracture involves measuring bone mineral density (BMD) of the hip and spine, locations of trabecular bone where high rates of remodeling occur. The bisphosphonate alendronate (ALN) reduces clinical risk for fracture by significantly increasing BMD, but studies have shown a concomitant reduction in intrinsic properties that may be the underlying cause for recent reports of spontaneous fractures with long-term alendronate use. Another anti-resorptive agent called raloxifene (RAL) is a selective estrogen receptor modulator (SERM) and has been shown to modestly improve BMD while decreasing fracture risk to a similar degree as alendronate. The combination of RAL and ALN as a treatment for osteoporosis may provide the benefits of each drug without the negative effects of ALN.
Therefore, the overall goal of this thesis was to address the effects of aging and anti-resorptive agents on the properties of bone through the formation of microdamage. Assessment of age-related effects on bone was conducted through quantification of microdamage progression. It was found that old bone results in greater incidences of microdamage progression, reflecting a compromised tissue matrix with reduced resistance to crack growth. Effects of combination treatment with RAL and ALN were evaluated through biomechanical testing, micro-CT imaging, and microdamage quantification. Results showed improved trabecular bone volume and ultimate load with positive effects on trabecular architecture. Combination treatment reduced the proportion of microdamage that may lead to catastrophic fracture, indicating an improvement in the local tissue matrix properties.
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Lozano-Carrascal, Naroa. "Topical Application of Bisphosphonates to Enhance Alveolar New Bone Formation." Doctoral thesis, Universitat Internacional de Catalunya, 2017. http://hdl.handle.net/10803/456485.
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This PhD thesis is a compendium of three publications, which sets out to broaden our knowledge and understanding of the topical application of bisphosphonates alone or mixed with a bone graft in alveolar bone defects, to evaluate the potential capacity of them to preserve/enhance alveolar new bone formation.
In recent years, research has focused on improving bone substitutes to achieve faster and better regeneration by morphologic and biochemical modification. Bisphosphonates are a group of drugs that reduce bone resorption by inhibiting the formation, recruitment activity of mature osteoclasts; and promoting their apoptosis. In addition, some bisphosphonates enhance osteoblast differentiation and activity. Thence, it has been demonstrated that topical application of a bisphosphonates can minimize the bone resorption following muco-periostial flap surgery or in peri-
implantitis; improve the osteoconductive and regenerative capacity of a biomaterial; prevent the surface resorption of onlay bone grafts; or reduce post-extraction dimensional changes.
Mandibular second premolars (P2) and first molars (M1) were extracted from six Fox-Hound dogs. P2 were categorized as small defects (SD) and M1 as large defects (LD). Four random groups were created: SC (small control defects with MP3®), ST (small test defects MP3® + pamidronate), LC (large control defects with MP3®), and LT (large test defects MP3® + pamidronate). At four and eight weeks of healing the percentages of new bone formation (NB), residual grafts (RG) and connective tissue (CT) were analysed by histology and histomorphometric analysis. To complement the information already obtained from histological analysis, the samples were evaluated through scanning electron microscopy (SEM), and Energy dispersive X-ray spectroscopy (EDX), to identify the chemical elements present into the biomaterial and surrounding tissues, for understanding the biomaterial’s degradation process. The study was complemented with a systemic literature review of the articles published between January 2000 and December 2016, that evaluated in vivo the effects of the topical application of bisphosphonates on bone regeneration/preservation in alveolar defects. A total of 154 abstracts were identified, of which 18 potentially relevant articles were selected; a final total of nine papers were included for analysis.
Histomorphometric and histologic analysis of the present pilot study demonstrated that after 4 and 8 weeks of healing, higher new bone formation for test groups (ST and LT) treated topically with pamidronate, compared with SC and LC respectively; residual graft was significantly higher in both control groups (SC and LC) compared to test (ST and LT) groups; and connective tissue percentage was higher in large defects (LC and LT) compared to small defects (SC and ST). SEM analysis revealed more mineralized bone in test groups (ST and LT) compared with control groups, demonstrated by higher percentages of Ca obtained from EDX spectroscopy.
Within the limitations of this experimental study, the findings suggest that porcine xenografts (MP3®) modified with pamidronate favours the new bone formation and increased the porcine xenograft substitution/replacement after 4 and 8 weeks of healing. These results are in accordance with the conclusions obtained from the systematic review. Despite the comparison of the findings of the selected studies was made difficult by the heterogeneity of the articles, the topical application of bisphosphonate solution would appear to favour new bone formation in alveolar defects, and boosts the regenerative capacities of biomaterials resulting in increased bone density.
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Rivera, Jaime Rodrigo. "Bone formation around implants in adult transgenic mice with selective Runx2-II deficiency." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2008m/rivera.pdf.
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Yoshida, Keiji. "Stimulation of bone formation and prevention of bone loss by prostaglandin E EP4 receptor activation." Kyoto University, 2002. http://hdl.handle.net/2433/149332.
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Alison, Susan Jean School of Medicine UNSW. "The control of bone formation by neuropeptide Y receptors." Awarded by:University of New South Wales. School of Medicine, 2006. http://handle.unsw.edu.au/1959.4/26188.
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Osteoporosis is a growing health concern, characterised by deterioration of bone and increased fracture incidence. Anabolic treatments for reversing bone loss are presently limited. A bone anabolic response was recently reported following deletion of hypothalamic neuropeptide Y2 receptors in mice. In contrast, no discernable bone phenotype was observed in Y4 receptor knockout (Y4-/-) mice, revealing specificity between the Y receptors in their control of bone formation. Studies in this thesis revealed a second anabolic response in the absence of another Y receptor subtype; the Y1 receptor. The potential interaction between the Y1 and Y2- anabolic pathways with each other and with Y4 was investigated through the generation of mouse models lacking multiple Y receptor subtypes. Interestingly, no synergistic elevation in bone volume was observed in Y1-/-Y2-/- double knockout mice, indicative of shared mechanisms of action. In contrast, the synergistic elevation in bone volume of male Y2-/- Y4-/- mice was likely due to additive effects of leptin signalling. Consequentially, potential interaction between Y receptors and leptin was investigated by crossing the Y receptor knockouts onto the leptin deficient ob/ob background, revealing differential responses of the Y receptor pathways to leptin deficiency, with the anabolic response of the Y2-/- model retained in Y2-/-/ob mice but abolished in Y1-/-/ob mice compared to Y1-/-. Differential responses of these two pathways were also revealed following gonadectomy of Y1-/- and Y2-/- mice. Importantly, these studies also demonstrated the ability of the central Y2- anabolic pathway to halt gonadectomy-induced bone loss. Interestingly, cultured stromal cells from germline Y2-/- mice exhibited an enhanced ability to undergo mineralisation and adipocyte differentiation, associated with a greater number of mesenchymal progenitor cells present within the bone of Y2-/- mice, suggesting a potential mechanism for the greater mineralisation of the Y2-/- model in vitro and in vivo. Y1 receptor expression was also detected in stromal cells from wild type mice, but was nearly abolished in Y2-/- mice. Together these findings demonstrate an important therapeutic potential for these pathways in the treatment of osteoporosis and indicate that modulation of Y receptor signalling within the bone microenvironment may alter proportions of mesenchymal progenitor populations with effects on bone formation.
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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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Pungchanchaikul, Patimaporn. "Palatal bone formation is regulated by palatal shelf fusion." Thesis, University College London (University of London), 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.500037.
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Li, Jun. "Indian hedgehog stimulates chondrocyte hypertrophic differentiation inendochondral bone formation." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39558009.
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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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Taylor, Amanda Faith. "The role of glutamate in bone formation in vitro." Thesis, University of York, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341824.
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Baba, Ismail Yanny Marliana. "Three-dimensional structured hybrid scaffolds for enhanced bone formation." Thesis, Keele University, 2016. http://eprints.keele.ac.uk/3215/.
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The most common clinical treatments for large bone deficiencies resulting from trauma, disease or infection are autograft, allograft or bone graft substitutes (BGS). However, these treatments still have limitations for clinical applications. Thus, this project aims to fabricate an optimal scaffold design for enhanced bone formation. Human bone is not solely hydroxyapatite (HA) but consists of multi-ionic substitutions in the HA lattice. Here, we have developed multi-substituted HA (SiCHA) nanopowders as bone substitute materials. SiCHA-2 was found to closely mirror the composition of the bone mineral content associated with the most enhanced proliferation and osteogenic activity. An innovative coating materials assembly was then established using SiCHA-2 nanopowders in combination with hyaluronan and collagen type I by the Polyelectrolyte Multilayers (PEMs) technique. Increasing the number of deposition cycles resulted in linear increases of surface properties and cell activities up to 5-bilayers. One common problem in scaffold-based tissue engineering (TE) is the rapid formation of tissue on the outer edge of the scaffolds whereas inner regions of the scaffold undergo necrosis. In this study, we incorporated aligned channels on the structure of three-dimensional (3D) scaffolds by Rapid Prototyping (RP) technique using Poly (lactic acid) (PLA) followed by PEMs. We investigated the fate of human mesenchymal stem cells (hMSCs) on these scaffolds in a rotary bioreactor compared to static conditions using osteogenic and proliferation media. We demonstrate that the combination of appropriate substrates with aligned channels, biochemical cues from the osteogenic media and better mass transport provided by rotary bioreactor enhances bone formation. In order to create pre-vascularized 3DP hybrid scaffolds, proof of concept work introduces the co-culture model of human umbilical vein endothelial cells (HUVECs) and hMSCs into the best scaffold design. Co-culture shows enhanced expression of both proangiogenic markers, which is an early indication of an ability supporting vessel formation in vitro.
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Deegan, Anthony John. "Novel tissue engineering approaches to enhance natural bone formation." Thesis, Keele University, 2016. http://eprints.keele.ac.uk/3224/.
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The bone tissue engineering community has been striving to develop novel approaches that mimic natural bone formation. The rapid generation of mineralised bone tissue with a capacity for vascularisation and the selection of highly osteogenic cell sources are still the focus of research today. This study addresses three novel approaches in these key areas. Mineralisation in bone tissue involves stepwise cell – cell and cell – extracellular matrix (ECM) interactions. Regulation of the osteoblast culture microenvironment can manipulate osteoblast proliferation and mineralisation rates and consequently the quality and/or quantity of the final calcified tissue. Therefore, an in vitro model to investigate possible influential factors would be highly sought after. We developed a facile in vitro model through the modification of culture surfaces in which an osteoblast cell line and aggregate culture was used to mimic intramembranous ossification. Conventional monolayer culturing was used as a comparative control. The effects of multiple culture parameters, including culture duration and aggregate size, on mineralisation rates and subsequent mineral quantities and distributions have been examined by numerous well established methods alongside certain innovative techniques. Ultimately, spatial and temporal production of minerals differed depending upon aggregate size with larger aggregates mineralising faster with a distinct gene expression pattern compared to the smaller aggregates. We also demonstrated that mineralisation in the larger aggregates initiated from the periphery, whilst mineralisation in the smaller aggregates initiated from the centre. This implies that aggregate size influences mineral distribution and development over time. An in vivo study using a cell line and primary cell population was conducted to investigate how the observations noted during the short term in vitro studies would affect long term in vivo aggregate survival and bone formation. Both cell types saw similar results. The large aggregates appeared to disintegrate over the course of the experiment, whilst the small aggregates remained intact and produced an abundant volume of extracellular material. A monolayer cell sample was again used as a comparative control and generated a lower material volume over the same period. The data obtained from this element of the project produced some invaluable insights into how the specific variables of cellular aggregation might affect possible bone formation in vivo. In addition, a novel substrate, substrate X, was used to identify and investigate the possibility of mesenchymal stem cell (MSC) subpopulations within mixed MSC populations and their donor-dependent variations alongside their subsequent influences upon an individual’s osteogenic capacity. Substrate X successfully identified what are thought to be three subpopulations within individual MSC populations from multiple donors through distinct cellular attachments. Each of the subpopulations was shown to hold differing osteogenic capacities and their proportions were also shown to be donor-dependent. Subpopulation proportions were shown to correlate with specific cadherin levels and cellular aggregation potential was also shown to be donor-dependent. Furthermore, the novel aggregation technique developed by this study was pitted against a conventional aggregation technique to assess aggregate vascularisation and mineralisation simultaneously using cellular co-culturing. This study also investigated how mechanical stimulation would affect aggregate vascularisation and mineralisation. The method of aggregation developed earlier in this project was shown to create an inner-aggregate architecture that aided in specific cellular organisation and possible vascularisation more than the conventional aggregation technique. The mechanical stimulation reduced cellular migration from the aggregate body compared to a static culture equivalent but nodule mineralisation within the co-cultured aggregates was inconclusive due to the short culture period. To conclude, simple yet effective substrate chemistry modifications enabled us to evaluate a variety of parameters for refined bone tissue engineering. These included the development of an aggregate model for the study of developing mineralisation, possible MSC subpopulation identification, measurement and assessment and the evaluation of aggregate vascularisation.
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Kimura, Hiroaki. "Cthrc1 is a positive regulator of osteoblastic bone formation." Kyoto University, 2009. http://hdl.handle.net/2433/124307.
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Retting, Kelsey Nicole. "Smad proteins and the regulation of endochondral bone formation." Diss., Restricted to subscribing institutions, 2008. http://proquest.umi.com/pqdweb?did=1666396551&sid=5&Fmt=2&clientId=1564&RQT=309&VName=PQD.
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Minaur, Nicola Jane. "Methotrexate and bone formation and turnover in rheumatoid arthritis." Thesis, University of Bath, 1998. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.285341.
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Manitzky, Louise J. "Mathematical modelling of intramembranous bone formation during fracture healing." Thesis, Queensland University of Technology, 2014. https://eprints.qut.edu.au/78983/1/Louise_Manitzky_Thesis.pdf.
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During fracture healing, many complex and cryptic interactions occur between cells and bio-chemical molecules to bring about repair of damaged bone. In this thesis two mathematical models were developed, concerning the cellular differentiation of osteoblasts (bone forming cells) and the mineralisation of new bone tissue, allowing new insights into these processes. These models were mathematically analysed and simulated numerically, yielding results consistent with experimental data and highlighting the underlying pattern formation structure in these aspects of fracture healing.
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Liu, Jin. "Increased CKIP-1 suppresses Smad-dependent BMP signaling to inhibit bone formation during aging." HKBU Institutional Repository, 2016. https://repository.hkbu.edu.hk/etd_oa/327.
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Emerging evidence indicates that the dysregulation of protein ubiquitination plays a crucial role in aging-associated diseases. Smad-dependent canonical BMP signaling pathway is indispensable for osteoblastic bone formation, which could be disrupted by the ubiquitination and subsequent proteasomal degradation of Smad1/5, the key molecules for BMP signaling transduction. However, whether the dysregulation of Smad1/5 ubiquitination and disrupted BMP signaling pathway are responsible for the age-related bone formation reduction is still underexplored. Casein kinase-2 interacting protein-1 (CKIP-1), also known as Pleckstrin homology domain-containing family O member 1 (PLEKHO1), is a previously identified ubiquitination-related molecule that could specifically target the linker region between the WW domains of Smurf1 to promote the ubiquitination of Smad1/5. Here, we found an age-related increase in the expression of CKIP-1 in bone specimens from either fractured patients or aging rodents, which was associated with the age-related reduction in Smad-dependent BMP signaling and bone formation. By genetic approach, we demonstrated that loss of Ckip-1 in osteoblasts could promote the Smad-dependent BMP signaling and alleviated the age-related bone formation reduction. In addition, osteoblast-specific Smad1 overexpression had beneficial effect on bone formation during aging, which could be counteracted after overexpressing Ckip-1 within osteoblasts. By pharmacological approach, we showed that osteoblast-targeted CKIP-1 siRNA treatment could enhance Smad-dependent BMP signaling and promote bone formation in aging rodents. Taken together, it suggests that the increased CKIP-1 could suppress Smad-dependent BMP signaling to inhibit bone formation during aging, indicating the translational potential of targeting CKIP-1 in osteoblast as a novel bone anabolic strategy for reversing established osteoporosis during aging.
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O'Connor, Rose Deeter. "MeCP2 deficiency decreases bone formation and reduces bone volume in a rodent model of Rett syndrome." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 161 p, 2009. http://proquest.umi.com/pqdweb?did=1891570941&sid=6&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Wei, Fei. "The osteoimmune effect of bone morphogenetic protein-2 in bone regeneration and biomaterial modification." Thesis, Queensland University of Technology, 2020. https://eprints.qut.edu.au/198148/1/Fei_Wei_Thesis.pdf.
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Bone morphogenetic protein-2 (BMP2), one of most well-known osteoinductive molecules, has been extensively used in the orthopedics and dentistry. However, inflammatory reactions are regularly reported for its side effect. This project investigated the immune environment induced by BMP2 and unveiled the regulation of BMP2 in the cross talk between immune cells and bone forming cells. This project provides better understanding of BMP2 application in the treatment of fracture healing and bone-related diseases.
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Li, Jun. "Indian hedgehog stimulates chondrocyte hypertrophic differentiation in endochondral bone formation." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/HKUTO/record/B39558009.
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Hamade, Fares. "Enhanced bone formation during distraction osteogenesis in FGFR3 deficient mice." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112630.
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Distraction Osteogenesis (DO) is a technique for bone lengthening and filling of bone defects following trauma, infection or resection of tumors. DO consists of an osteotomy of the bone to be lengthened, followed by controlled distraction of the bone segments with an external fixator until the desired lengthening is obtained (distraction phase). This is followed by the consolidation phase, during which the external fixator is kept in place until the newly formed bone in the distracted zone consolidates. This phase is long and may cause numerous problems. Ongoing research aims at finding a method to accelerate the consolidation of the newly formed bone.Fibroblast Growth Factors (FGF) play a significant role in bone development and repair. FGF 18 has been shown to be the only FGF member to be expressed throughout both the distraction and the consolidation phases of DO. It was also reported that FGF18 is the physiological ligand of FGFR3. Therefore, we hypothesized that FGF18 and FGFR3 may have an important role in DO.
To test this hypothesis, we investigated DO in FGFR3 deficient mice (FGFR3-/-). (FGF18 deficient mice are not viable). A miniaturized DO apparatus was applied to the tibia followed by an osteotomy. Distraction began after a 5-day latency period at a rate of 0.2 mm/12 hours for 12 days.
Samples were collected at 3 time points comparing the mutants (FGFR3-/-) to their wild type litter' sates: end of distraction (17 days post-surgery), mid-consolidation (34 days post-surgery), and end of consolidation (51 days post surgery). The samples were analyzed using X-ray, DEXA, microCT, histology, biomechanical testing and Real-Time PCR.
Our results revealed that FGFR3 deficient mice showed accelerated bone formation compared to the W.T. littermates at mid-consolidation where the parameters measured revealed increased bone mineral density, bone mineral content and trabecular number in the mutant tibial samples. The newly regenerated bone consolidated faster in the FGFR3 knock-out mice and the bone was of better quality as revealed by biomechanical tests in which more force was needed to break the mutant bone because it exhibited higher resistance than the age matched wild-type sample. The marker gene expression patterns revealed an up-regulation of chondrogenic markers that suggest that the knock-out mice follow the endochondral ossification pathway during DO. All results were statistically significant.
These results show that signaling through FGFR3 acts to decrease bone formation during DO. Consequently, blocking FGFR3 may lead to accelerated bone formation in DO. This may have important clinical implications in attempts to improve the functional outcome of DO by decreasing the long duration that the external fixator has to be kept on.
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Gartland, Alison. "The role of the P2X7 receptor in bone cell formation." Thesis, University of Liverpool, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343968.
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García, Gareta E. "Development of a bone tissue-engineered construct to enhance new bone formation in revision total hip replacement." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1338147/.
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The main issue associated with revision total hip replacements (rTHRs) is how to generate new bone and restore bone stock for fixation of the revision stem. Bone tissue engineering (BTE) seeks the generation of constructs ex vivo in order to replace damaged or lost bone. The aim of this thesis was to develop a bone tissue-engineered construct with a calcium-phosphate (CaP) coated porous metal scaffold seeded throughout its structure with mesenchymal stem cells (MSCs) in order to enhance new bone formation at rTHRs. The study had in vitro and in vivo phases. For the in vitro phase, CaP coatings by biomimetic and electrochemical methods on the surface of titanium and tantalum discs were investigated and seeded with MSCs under static culture conditions. Different coating methods produced different morphologies and compositions with biomimetic coatings enhancing MSCs growth while the electrochemical ones enhanced their osteogenic potential. An electrochemically CaP coated porous titanium cylinder was seeded with MSCs and dynamically cultured in a perfusion bioreactor, showing an increased MSCs proliferation and osteogenic differentiation and an even distribution of cells throughout the scaffolds compared to statically cultured constructs. Tissue-engineered constructs in the perfusion bioreactor were evaluated in vivo by implantation in the medial femoral condyle of sheep with and without gap. Their osseointegration and implant-bone fixation strength were compared to non tissue-engineered constructs. The results showed that the addition of MSCs to the scaffolds did not significantly increase osseointegration or implant-bone fixation strength. However, in the defects with gap the tissue-engineered constructs showed a higher implant-bone contact area and therefore higher forces were necessary to push the tissue-engineered implants out of the bone in the defects with gap than for the non tissue-engineered ones. In conclusion, BTE can be applied in order to develop constructs with a clinical application in rTHRs where a lack of bone stock is problematic.
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Kawai, Mariko. "Ectopic bone formation by human bone morphogenetic protein-2 gene transfer to skeletal muscle using transcutaneous electroporation." Kyoto University, 2004. http://hdl.handle.net/2433/147446.
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Shekaran, Asha. "Beta 1 integrins in bone formation during development and engineering integrin-specific hydrogels for enhanced bone healing." Diss., Georgia Institute of Technology, 2013. http://hdl.handle.net/1853/51720.
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Healing large bone defects remains a clinical challenge. While autografts are the gold standard treatment for large bone defects, they are limited by availability and donor site pain. Growth factor treatments such as BMP therapy provide a promising alternative but are expensive and present clinical safety concerns, primarily due to delivery of BMPs at supraphysiological doses. Integrins are ECM receptors which mediate crucial cell functions such as adhesion and differentiation. Therefore, understanding the role of integrins in bone formation and directing desired interactions may enable modulation of host cell functions for therapeutic applications. In this work, beta 1 integrins were deleted in osteolineage cells of transgenic mice at three different stages of differentiation to elucidate their role in bone development. We also engineered bioartificial PEG-based matrices which target the pro-osteogenic alpha 2 beta 1 integrin to promote bone healing. Conditional deletion of beta 1 integrins in osteochondroprogenitor cells under the Twist 2 promoter resulted in severe pre-natal skeletal mineralization defects and embryonic lethality. Targeted deletion of beta 1 integrins in osterix-expressing osteoprogenitors resulted in growth abnormalities, reduced calvarial mineralization, impaired femur development, and tooth defects. However, mice lacking beta 1 integrins in osteocalcin-expressing osteoblasts and osteocytes displayed only a mild skeletal phenotype, indicating that beta 1 integrins play an important role in early skeletal development, but are not required for mature osteoblast function. PEG hydrogels functionalized with the integrin-specific GFOGER ligand enhanced bone regeneration, induced defect bridging in combination with low doses of rhBMP-2 and stimulated improved bone healing compared collagen sponges, which are the clinical standard delivery vector for BMP-2 therapy. These results suggest that treatment with bioartificial integrin-specific PEG hydrogels may be a promising clinical strategy for bone regeneration in large bone defects.
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Miao, Dengshun. "Studies on the actions of bone anabolic drugs in vivo and in vitro." Thesis, University of Sheffield, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300362.
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Weston, Darlene Adele. "Approaches to the investigation of periosteal new bone formation in palaeopathology." Thesis, University College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405263.
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Sanghani-Kerai, Anita. "Do stem cells transfected with CXCR4 enhance bone formation in osteoporosis?" Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10045319/.
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Osteoporosis affects bone mass and bone micro-architecture, reducing mechanical strength. SDF-1 and its ligand CXCR4 play significant roles in the migration and engraftment of mesenchymal stem cells (MSCs). The aim of this study was to investigate the effects of CXCR4 transfected MSCs on bone formation in osteopenic rats. The hypothesis was that MSCs genetically modified to over-express CXCR4, would enhance migration of stem cells from osteopenic rats and when injected intravenously in ovariectomised (OVX) rats, would improve bone formation. MSCs were harvested from femora of young, OVX and adult control rats. The differentiation, CXCR4 expression, in vitro migration and phenotypic characteristics of the cells were compared. Although the phenotypic characteristics of cells from all groups of rats were the same, their differentiation capability, CXCR4 expression and migration was significantly different. MSCs were genetically modified to over-express CXCR4 and in vitro migration investigated. It was found that although young MSCs had the highest migration capability (2x more than their uninfected counterparts, p=0.006), the OVX MSCs when transfected with CXCR4 had the most significant migration from their un-transfected counterpart cells(5x more, p=0.025). Additionally, differentiating MSCs to osteoblasts reduced their CXCR4 expression as well as their migration towards SDF1. The CXCR4 transfected MSCs were administered intravenously in OVX rats. Fluorescent labelled cells were tracked after 1 week and were located in the blood vessels of the femur. 11-weeks post-injection, OVX rats injected with young-CXCR4 MSCs had significantly higher BMD(694.0±80.1mg/cm3) (p < 0.05) in comparison to rats injected with saline. Rats injected with OVX-CXCR4 MSCs(645.4±79.3mg/ccm) had a higher BMD in comparison to those injected with OVX MSCs(631.4±69.5mg/ccm) and saline(563.4±82.9mg/ccm). The L4 vertebral stiffness was also higher in rats treated with young-CXCR4 MSCs in comparison to those treated with saline. CXCR4 genetically modified MSCs from young and OVX patients may help in boosting bone formation in osteoporosis.
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Ferguson, James. "THE SPATIAL AND TEMPORAL ROLE OF EZH2 IN SKULL BONE FORMATION." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1530898825341447.
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Horne, Jacqueline Avril. "Mathematical modelling of soft callus formation in early murine bone repair." Thesis, Queensland University of Technology, 2013. https://eprints.qut.edu.au/63823/1/Jacqueline_Avril_Horne_Thesis.pdf.
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Fracture healing is a complicated coupling of many processes. Yet despite the apparent complexity, fracture repair is usually effective. There is, however, no comprehensive mathematical model addressing the multiple interactions of cells, cytokines and oxygen that includes extra-cellular matrix production and that results in the formation of the early stage soft callus.
This thesis develops a one dimensional continuum transport model in the context of early fracture healing. Although fracture healing is a complex interplay of many local factors, critical components are identified and used to construct an hypothesis about regulation of the evolution of early callus formation. Multiple cell lines, cellular differentiation, oxygen levels and cytokine concentrations are examined as factors affecting this model of early bone repair. The model presumes diffusive and chemotactic cell migration mechanisms.
It is proposed that the initial signalling regime and oxygen availability arising as consequences of bone fracture, are sufficient to determine the quantity and quality of early soft callus formation.
Readily available software and purpose written algorithms have been used to obtain numerical solutions representative of various initial conditions. These numerical distributions of cellular populations reflect available histology obtained from murine osteotomies.
The behaviour of the numerical system in response to differing initial conditions can be described by alternative in vivo healing pathways. An experimental basis, as illustrated in murine fracture histology, has been utilised to validate the mathematical model outcomes.
The model developed in this thesis has potential for future extension, to incorporate processes leading to woven bone deposition, while maintaining the characteristics that regulate early callus formation.
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Lu, Luhui, and 陆璐慧. "Molecular control of osteo-chondroprogenitors formation." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B44673966.
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Clayton, Angela Ann. "Analysis of an Eocene Bone-bed, Contained within the Lower Lisbon Formation, Covington County, Alabama." Wright State University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=wright1310391028.
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Kim, Michael S. "Gene Expression in Bone Cells." Thesis, Griffith University, 2006. http://hdl.handle.net/10072/366180.
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Osteoclast formation is a complex process that is yet to be clearly defined. Osteoclasts differentiate from monocytic precursors to large multinuclear cells via the actions of two crucial cytokines: macrophage colony stimulating factor (M-CSF) and receptor activator of NFKB ligand (RANKL). These two cytokines bind to the osteoclast precursor cells, activating various down stream signalling pathways, inducing genes required for differentiation and for activation of osteoclasts. Exposure of monocytic precursors to M-CSF alone leads to differentiation into macrophages. Osteoclast differentiation was suppressed by granulocyte macrophage colony-stimulating factor (GM-CSF), resulting in mononuclear cells, lacking tartrate-resistant acid phosphatase (TRAP) and a bone resorptive phenotype. Further analysis determined GM-CSF dosage and temporal effects on osteoclast formation, where higher doses and earlier treatments of GM-CSF result in greater suppression of osteoclast formation. To understand the TRAP negative mononuclear cell phenotype, various osteoclast related markers and nuclear factors were tested using quantitative real-time PCR. GM-CSF suppressed the mRNA expression of osteoclast markers, including TRAP and cathepsin K (CTSK). CTSK is a cysteine protease, involved in osteoclast activity of bone resorption. Furthermore, GM-CSF down regulated the expression of critical osteoclast-related nuclear factors, including nuclear factor of activated T-cells, cytoplasmic (NFATcI), which has been identified as playing a critical role in osteoclast differentiation and ftinction in mice and to some extent in humans. The suppression of crucial osteoclast markers and transcription factors by GM-CSF indicated an overriding of the RANKL signal and possible switching of the cellular phenotype away from osteoclasts.
To determine the cellular phenotype of GM-CSF driven cell differentiation, flow cytometry analysis was employed. As the cells visualised as dendritic cell like, CDIa, a dendritic cell surface marker, was selected for investigation. CDIa was highly expressed in GM-CSF, M-CSF and RANKL (GMR) treated cells and was absent in osteoclasts (M-CSF and RANKL treatment). The CDI a observations were indicative of GM-CSF overcoming the RANKL signal for osteoclastogenesis and directing differentiation to dendritic-like cells. To ftirther understand the osteoclastogenesis suppressive effect of GM-CSF, a 19,000 gene cDNA microarray assay was examined. The microarray experiment showed that the CC chemokine, monocyte chemotactic protein I (MCP-l), was profoundly repressed by GM-CSF. CC chemokines are chemoattractants that are induced during inflammation and recruit monocytes to the site of inflammation. MCP-l and other CC chemokines, RANTES (regulated on activation normal T cell expressed and secreted) and macrophage inflammatory protein I alpha (MIP I a) permitted formation of TRAP positive multinuclear cells in the absence of RANKL. However, these cells were negative for bone resorption. In the presence of RANKL, MCP-1 significantly increased the number of TRAP positive multinuclear bone resorbing osteoclasts (p= 5.7x 105, while RANTES and MIPI a mildly increased the number of bone resorbing TRAP positive multinuclear cells. Furthermore, CC chemokines, MCP-1, RANTES and MIP I a are all induced when authentic bone resorbing human osteoclasts differentiate from monocyte precursors in vitro following M-CSF-RANKL treatment. The addition of MCP- 1, RANTES or MIP I a appeared to reverse GM-CSF suppression of osteoclast formation, resulting in TRAP positive multinuclear cells. However, only MCP- I recovered the bone resorption phenotype, while other
chemokines, RANTES or MTPIa did not. The cognate receptors for MCP-1, in particular, CCR2b and CCR4, were potently induced by RANKL (12.6 and 49-fold, p= 4.0x107 and 4.0x108, respectively), whereas the chemokine receptors for RANTES and MTP I a (CCR I and CCR5) were not regulated by RANKL. Chemokine treatment in the absence of RANKL also induced MCP- 1, RANTES and MIP I a. Unexpectedly, treatment with MCP-I in the absence of RANKL resulted in 458-fold induction of CCR4 (p I.0xI010), while RANTES treatment resulted in two fold repression (p= I .Ox ioj. Since CCR2b and CCR4 are cognate MCP-I receptors, these data support the existence of an MCP-I autocrine loop in human osteoclasts differentiated using RANKL. All three chemokines in the absence of RANKL can induce TRAP positive multinuclear cells that are negative for bone resorption. However, as MCP-I can significantly increase the number of osteoclast formation and recover the bone resorbing osteoclast phenotype from GM-CSF suppression, MCP-1 is the most potent chemokine involved in osteoclast formation. MCP-1 induced TRAP positive multinuclear cells were characterised and found to be positive for calcitonin receptor (CTR) and a number of other osteoclast markers, including NFATcI. As NFATcI is associated with osteoclast maturity in mice and has even been referred to as a master regulator of osteoclast differentiation and ftinction, a strong induction of NFATcI should theoretically allow bone resorption of MCP-l mediated TRAP positive multinuclear cells. Although great NFATcI mRNA induction and activated nuclear NFAT were observed, MCP-1 did not result in the formation of bone resorbing osteoclasts in the absence of RANKL. Despite the similar visual phenotype and expression of mature osteoclast markers TRAP and CTR when compared to osteoclasts, RANKL treatment was required for the MCP- I induced TRAP positive, CTR positive, multinuclear cells to possess bone resorption activity. This suggested that MCP-1 mediated TRAP positive multinuclear cells were primed for RANKL signal, to ftirther differentiate into authentic osteoclasts. The lack of bone resorption was ftirther correlated with a deficiency in expression of certain genes related to bone resorption, such as CTSK and matrix metalloproteinase 9 (MMP9) and integrin aV. Another observation with implications for absence of the bone resorptive activity in MCP- I cell was the absence or disruption of the F-actin ring structure, correlating with the lack of integrin aV mRNA expression. It was hypothesised that as MCP-1 mediated TRAP positive multinuclear cells possessed a high induction of CTR, the addition of calcitonin would block multinucleation. Indeed, the exogenous calcitonin blocked the MCP-I induced formation of TRAP positive, CTR positive, multinuclear cells as well as bone resorption activity in the osteoclast controls, indicating that calcitonin acts at two stages of osteoclast differentiation in the human PBMC model.
These data suggest that RANKL-induced chemokines are involved in osteoclast differentiation at the stage of multinucleation of osteoclast precursors and provides a rationale for increased osteoclast activity in inflammatory conditions where chemokines are abundant. Furthermore, MCP-I induced TRAP positive, CTR positive multinuclear cells appear to represent an arrested stage in osteoclast differentiation, afler NFATcI induction and cellular ftision, but prior to the development of bone resorption activity and therefore, could be termed 'preosteoclasts'.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
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Walker, Katherine Elizabeth. "Studies on the effects of estrogen in human osteogenic cells." Thesis, University of Sheffield, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245692.
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Morrison, Matthew Sam. "Osteoclast function : role of extracellular pH and ATP." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369218.
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Roberts, Ellen. "Investigations into a novel osteoclastic antigen." Thesis, University of Liverpool, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263794.
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Simmons, Craig Alexander. "Modelling and characterization of mechanically regulated tissue formation around bone-interfacing implants." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape3/PQDD_0022/NQ49943.pdf.
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Eijken, Hermanus Johannes Marco. "Human osteoblast differentiation and bone formation: growth factors, hormones & regulatory networks." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2007. http://hdl.handle.net/1765/10597.
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Husseini, Abdallah. "Bone formation during fracture repair in mice deficient for the cyp24a1 gene." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106532.
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Vitamin D is a key regulator of mineral and bone homeostasis. The enzyme CYP24A1 is responsible for transforming vitamin D into 24,25(OH)2D. The putative biological activity of 24,25(OH)2D remains unclear. Previous studies showed an increase in the circulating levels of this metabolite following a fracture in chicks. Our laboratory has engineered a mouse model deficient for the Cyp24a1 gene for studying the role of 24,25(OH)2D. We set out to study the role of 24,25(OH)2D in endochondral and intramembranous bone formation in mammalian fracture repair in this mouse model. Methods: Wild-type and Cyp24a1-deficient mice were subjected to two surgical procedures to simulate bone development and fracture repair. To mimic endochondral ossification, we devised a modified technique to perform intramedullary nailing of a tibia followed by an osteotomy. To evaluate intramembranous ossification, we applied distraction osteogenesis to tibiae using a mini Ilizarov external fixator. Histomorphometric parameters and gene expression differences in fracture repair between the mutant mice and the wild-type controls were measured using micro computed tomography, histology and reverse-transcription quantitative PCR. Results: Quantitative histomorphometric results showed a delay in endochondral fracture repair in the mutant as compared to wild-type mice. In the same model, gene expression of collagen type X in the callus was lower in the mutant mice. These significant differences were fully rescued by injecting the mutant mice with exogenous 24,25(OH)2D. In the intramembranous bone formation model, we found a trend towards reduced bone formation in the gap created by the distraction process in the mutant mice as compared to the wild-type mice. Conclusions: Our results support a role for CYP24A1 and its product 24,25(OH)2D in fracture repair which is more dominant in a chondrocyte-mediated bone formation pathway like endochondral ossification. Further study of the role of 24,25(OH)2D in bone healing has the potential to support novel approaches in accelerating bone formation and fracture repair.La vitamine D est un régulateur important de l'homéostasie minérale et osseuse. L'enzyme CYP24A1 métabolise la vitamine D en 24,25(OH)2D. L'activité biologique de la 24,25(OH)2D demeure imprécise. Des études ont démontré que la 24,25(OH)2D est un métabolite important pour la réparation des fractures chez le poulet. Notre laboratoire a conçu un modèle de souris déficientes pour le gène Cyp24a1 afin d'étudier le rôle de la 24,25(OH)2D. Nous avons entrepris d'étudier le rôle de ce métabolite dans l'ossification endochondrale et intramembranaire pendant la réparation des fractures dans ce modèle de souris. Méthodes: les souris sauvages et Cyp24a1-mutantes ont été soumises à deux différentes procédures chirurgicales pour simuler la formation d'os pendant la réparation des fractures. Pour imiter l'ossification endochondrale, nous avons utilisé un clou intramédullaire afin de stabiliser le tibia après la fracture. Pour évaluer l'ossification intramembranaire, nous avons appliqué l'ostéogénèse par distraction sur le tibia à l'aide d'un appareil de fixation externe. Les paramètres histomorphométriques et l'expression génique au cours de la réparation de la fracture chez les souris mutantes et sauvages ont été mesurés par microtomographie, histologie et PCR quantitative (qRT-PCR), respectivement. Résultats: l'analyse histomorphométrique démontre un retard dans la réparation des fractures stabilisée par clou intramédullaire chez les souris mutantes par rapport au type sauvage. Dans le même modèle, l'expression du collagène de type X était plus élevée chez les souris de type sauvage. Ces différences significatives ont été entièrement corrigées par l'injection de 24,25(OH)2D exogène chez les souris mutantes. Dans le modèle d'ostéogénèse par distraction, nous avons trouvé une tendance vers la formation osseuse réduite chez les souris mutantes comparativement aux souris de type sauvage. Cependant, les différences observées n'étaient pas statistiquement significatives. Conclusion: Nos résultats suggèrent un rôle pour CYP24A1 et la 24,25(OH)2D dans la réparation des fractures par ossification endochondrale. Une étude plus approfondie du rôle de la 24,25(OH)2D pourrait conduire à l'utilisation de ce métabolite afin d'accélérer la formation osseuse et la réparation des fractures.
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Rapp, Anna Elise [Verfasser]. "Effect of MSC-administration on bone formation and repair / Anna Elise Rapp." Ulm : Universität Ulm. Medizinische Fakultät, 2015. http://d-nb.info/1067924396/34.
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Malik, Ghada. "The role of Heparin in BMP2-induced osteoblast differentiation and bone formation." Thesis, University of Newcastle Upon Tyne, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.446237.
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Althnaian, Thnaian Ali. "Factors that regulate osteoclast formation and bone resorption in regenerating deer antlers." Thesis, Royal Veterinary College (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.439832.
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