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Sample records for bone remodeling dynamics

  1. Cellular and Molecular Mechanisms of Bone Remodeling*

    OpenAIRE

    Raggatt, Liza J; Partridge, Nicola C

    2010-01-01

    Physiological bone remodeling is a highly coordinated process responsible for bone resorption and formation and is necessary to repair damaged bone and to maintain mineral homeostasis. In addition to the traditional bone cells (osteoclasts, osteoblasts, and osteocytes) that are necessary for bone remodeling, several immune cells have also been implicated in bone disease. This minireview discusses physiological bone remodeling, outlining the traditional bone biology dogma in light of emerging ...

  2. Application of Petri Nets in Bone Remodeling

    Directory of Open Access Journals (Sweden)

    Lingxi Li

    2009-07-01

    Full Text Available Understanding a mechanism of bone remodeling is a challenging task for both life scientists and model builders, since this highly interactive and nonlinear process can seldom be grasped by simple intuition. A set of ordinary differential equations (ODEs have been built for simulating bone formation as well as bone resorption. Although solving ODEs numerically can provide useful predictions for dynamical behaviors in a continuous time frame, an actual bone remodeling process in living tissues is driven by discrete events of molecular and cellular interactions. Thus, an event-driven tool such as Petri nets (PNs, which may dynamically and graphically mimic individual molecular collisions or cellular interactions, seems to augment the existing ODE-based systems analysis. Here, we applied PNs to expand the ODE-based approach and examined discrete, dynamical behaviors of key regulatory molecules and bone cells. PNs have been used in many engineering areas, but their application to biological systems needs to be explored. Our PN model was based on 8 ODEs that described an osteoprotegerin linked molecular pathway consisting of 4 types of bone cells. The models allowed us to conduct both qualitative and quantitative evaluations and evaluate homeostatic equilibrium states. The results support that application of PN models assists understanding of an event-driven bone remodeling mechanism using PN-specific procedures such as places, transitions, and firings.

  3. Parallel mechanisms suppress cochlear bone remodeling to protect hearing.

    Science.gov (United States)

    Jáuregui, Emmanuel J; Akil, Omar; Acevedo, Claire; Hall-Glenn, Faith; Tsai, Betty S; Bale, Hrishikesh A; Liebenberg, Ellen; Humphrey, Mary Beth; Ritchie, Robert O; Lustig, Lawrence R; Alliston, Tamara

    2016-08-01

    Bone remodeling, a combination of bone resorption and formation, requires precise regulation of cellular and molecular signaling to maintain proper bone quality. Whereas osteoblasts deposit and osteoclasts resorb bone matrix, osteocytes both dynamically resorb and replace perilacunar bone matrix. Osteocytes secrete proteases like matrix metalloproteinase-13 (MMP13) to maintain the material quality of bone matrix through perilacunar remodeling (PLR). Deregulated bone remodeling impairs bone quality and can compromise hearing since the auditory transduction mechanism is within bone. Understanding the mechanisms regulating cochlear bone provides unique ways to assess bone quality independent of other aspects that contribute to bone mechanical behavior. Cochlear bone is singular in its regulation of remodeling by expressing high levels of osteoprotegerin. Since cochlear bone expresses a key PLR enzyme, MMP13, we examined whether cochlear bone relies on, or is protected from, osteocyte-mediated PLR to maintain hearing and bone quality using a mouse model lacking MMP13 (MMP13(-/-)). We investigated the canalicular network, collagen organization, lacunar volume via micro-computed tomography, and dynamic histomorphometry. Despite finding defects in these hallmarks of PLR in MMP13(-/-) long bones, cochlear bone revealed no differences in these markers, nor hearing loss as measured by auditory brainstem response (ABR) or distortion product oto-acoustic emissions (DPOAEs), between wild type and MMP13(-/-) mice. Dynamic histomorphometry revealed abundant PLR by tibial osteocytes, but near absence in cochlear bone. Cochlear suppression of PLR corresponds to repression of several key PLR genes in the cochlea relative to long bones. These data suggest that cochlear bone uniquely maintains bone quality and hearing independent of MMP13-mediated osteocytic PLR. Furthermore, the cochlea employs parallel mechanisms to inhibit remodeling by osteoclasts and osteoblasts, and by

  4. Parallel mechanisms suppress cochlear bone remodeling to protect hearing.

    Science.gov (United States)

    Jáuregui, Emmanuel J; Akil, Omar; Acevedo, Claire; Hall-Glenn, Faith; Tsai, Betty S; Bale, Hrishikesh A; Liebenberg, Ellen; Humphrey, Mary Beth; Ritchie, Robert O; Lustig, Lawrence R; Alliston, Tamara

    2016-08-01

    Bone remodeling, a combination of bone resorption and formation, requires precise regulation of cellular and molecular signaling to maintain proper bone quality. Whereas osteoblasts deposit and osteoclasts resorb bone matrix, osteocytes both dynamically resorb and replace perilacunar bone matrix. Osteocytes secrete proteases like matrix metalloproteinase-13 (MMP13) to maintain the material quality of bone matrix through perilacunar remodeling (PLR). Deregulated bone remodeling impairs bone quality and can compromise hearing since the auditory transduction mechanism is within bone. Understanding the mechanisms regulating cochlear bone provides unique ways to assess bone quality independent of other aspects that contribute to bone mechanical behavior. Cochlear bone is singular in its regulation of remodeling by expressing high levels of osteoprotegerin. Since cochlear bone expresses a key PLR enzyme, MMP13, we examined whether cochlear bone relies on, or is protected from, osteocyte-mediated PLR to maintain hearing and bone quality using a mouse model lacking MMP13 (MMP13(-/-)). We investigated the canalicular network, collagen organization, lacunar volume via micro-computed tomography, and dynamic histomorphometry. Despite finding defects in these hallmarks of PLR in MMP13(-/-) long bones, cochlear bone revealed no differences in these markers, nor hearing loss as measured by auditory brainstem response (ABR) or distortion product oto-acoustic emissions (DPOAEs), between wild type and MMP13(-/-) mice. Dynamic histomorphometry revealed abundant PLR by tibial osteocytes, but near absence in cochlear bone. Cochlear suppression of PLR corresponds to repression of several key PLR genes in the cochlea relative to long bones. These data suggest that cochlear bone uniquely maintains bone quality and hearing independent of MMP13-mediated osteocytic PLR. Furthermore, the cochlea employs parallel mechanisms to inhibit remodeling by osteoclasts and osteoblasts, and by

  5. Using PET/CT Bone Scan Dynamic Data to Evaluate Tibia Remodeling When a Taylor Spatial Frame Is Used: Short and Longer Term Differences

    Science.gov (United States)

    Lundblad, Henrik; Maguire, Gerald Q.; Karlsson-Thur, Charlotte; Jonsson, Cathrine; Noz, Marilyn E.; Zeleznik, Michael P.; Jacobsson, Hans; Weidenhielm, Lars

    2015-01-01

    Eighteen consecutive patients, treated with a Taylor Spatial Frame for complex tibia conditions, gave their informed consent to undergo Na18F− PET/CT bone scans. We present a Patlak-like analysis utilizing an approximated blood time-activity curve eliminating the need for blood aliquots. Additionally, standardized uptake values (SUV) derived from dynamic acquisitions were compared to this Patlak-like approach. Spherical volumes of interest (VOIs) were drawn to include broken bone, other (normal) bone, and muscle. The SUVm(t) (m = max, mean) and a series of slopes were computed as (SUVm(ti) − SUVm(tj))/(ti − tj), for pairs of time values ti and tj. A Patlak-like analysis was performed for the same time values by computing ((VOIp(ti)/VOIe(ti))−(VOIp(tj)/VOIe(tj)))/(ti − tj), where p = broken bone, other bone, and muscle and e = expected activity in a VOI. Paired comparisons between Patlak-like and SUVm slopes showed good agreement by both linear regression and correlation coefficient analysis (r = 84%, rs = 78%-SUVmax, r = 92%, and rs = 91%-SUVmean), suggesting static scans could substitute for dynamic studies. Patlak-like slope differences of 0.1 min−1 or greater between examinations and SUVmax differences of ~5 usually indicated good remodeling progress, while negative Patlak-like slope differences of −0.06 min−1 usually indicated poor remodeling progress in this cohort. PMID:26436093

  6. Using PET/CT Bone Scan Dynamic Data to Evaluate Tibia Remodeling When a Taylor Spatial Frame Is Used: Short and Longer Term Differences

    Directory of Open Access Journals (Sweden)

    Henrik Lundblad

    2015-01-01

    Full Text Available Eighteen consecutive patients, treated with a Taylor Spatial Frame for complex tibia conditions, gave their informed consent to undergo Na18F− PET/CT bone scans. We present a Patlak-like analysis utilizing an approximated blood time-activity curve eliminating the need for blood aliquots. Additionally, standardized uptake values (SUV derived from dynamic acquisitions were compared to this Patlak-like approach. Spherical volumes of interest (VOIs were drawn to include broken bone, other (normal bone, and muscle. The SUVm(t (m=max, mean and a series of slopes were computed as (SUVm(ti-SUVm(tj/(ti-tj, for pairs of time values ti and tj. A Patlak-like analysis was performed for the same time values by computing ((VOIp(ti/VOIe(ti-(VOIp(tj/VOIe(tj/(ti-tj, where p = broken bone, other bone, and muscle and e = expected activity in a VOI. Paired comparisons between Patlak-like and SUVm slopes showed good agreement by both linear regression and correlation coefficient analysis (r=84%,rs=78%-SUVmax,r=92%, and rs=91%-SUVmean, suggesting static scans could substitute for dynamic studies. Patlak-like slope differences of 0.1 min−1 or greater between examinations and SUVmax differences of ~5 usually indicated good remodeling progress, while negative Patlak-like slope differences of −0.06 min−1 usually indicated poor remodeling progress in this cohort.

  7. Bone Remodelling Markers in Rheumatoid Arthritis

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    Patrice Fardellone

    2014-01-01

    Full Text Available Bone loss in rheumatoid arthritis (RA patients results from chronic inflammation and can lead to osteoporosis and fractures. A few bone remodeling markers have been studied in RA witnessing bone formation (osteocalcin, serum aminoterminal propeptide of type I collagen (PINP, serum carboxyterminal propeptide of type I collagen (ICTP, bone alkaline phosphatase (BAP, osteocalcin (OC, and bone resorption: C-terminal telopeptide of type 1 collagen (I-CTX, N-terminal telopeptide of type 1 collagen (I-NTX, pyridinolines (DPD and PYD, and tartrate-resistant acid phosphatase (TRAP. Bone resorption can be seen either in periarticular bone (demineralization and erosion or in the total skeleton (osteoporosis. Whatever the location, bone resorption results from activation of osteoclasts when the ratio between osteoprotegerin and receptor activator of nuclear factor kappa-B ligand (OPG/RANKL is decreased under influence of various proinflammatory cytokines. Bone remodeling markers also allow physicians to evaluate the effect of drugs used in RA like biologic agents, which reduce inflammation and exert a protecting effect on bone. We will discuss in this review changes in bone markers remodeling in patients with RA treated with biologics.

  8. The population model of bone remodelling employed the optimal control.

    Science.gov (United States)

    Moroz, Adam

    2012-11-01

    Several models have been developed in recent years which apply population dynamics methods to describe the mechanisms of bone remodelling. This study incorporates the population kinetics model of bone turnover (including the osteocyte loop regulation) with the optimal control technique. Model simulations have been performed with a wide range of rate parameters using the Monte Carlo method. The regression method has also been used to investigate the interdependence of the location of equilibrium and the characteristics of the equilibrium/relaxation time on the rate parameters employed. The dynamic optimal control outlook for the regulation of bone remodelling processes, in the context of the osteocyte-control population model, has been discussed. Optimisation criteria have been formulated from the perspective of the energetic and metabolic losses in the tissue, with respect to the performance of the bone multicellular unit.

  9. Connecting mechanics and bone cell activities in the bone remodeling process: an integrated finite element modeling.

    Science.gov (United States)

    Hambli, Ridha

    2014-01-01

    Bone adaptation occurs as a response to external loadings and involves bone resorption by osteoclasts followed by the formation of new bone by osteoblasts. It is directly triggered by the transduction phase by osteocytes embedded within the bone matrix. The bone remodeling process is governed by the interactions between osteoblasts and osteoclasts through the expression of several autocrine and paracrine factors that control bone cell populations and their relative rate of differentiation and proliferation. A review of the literature shows that despite the progress in bone remodeling simulation using the finite element (FE) method, there is still a lack of predictive models that explicitly consider the interaction between osteoblasts and osteoclasts combined with the mechanical response of bone. The current study attempts to develop an FE model to describe the bone remodeling process, taking into consideration the activities of osteoclasts and osteoblasts. The mechanical behavior of bone is described by taking into account the bone material fatigue damage accumulation and mineralization. A coupled strain-damage stimulus function is proposed, which controls the level of autocrine and paracrine factors. The cellular behavior is based on Komarova et al.'s (2003) dynamic law, which describes the autocrine and paracrine interactions between osteoblasts and osteoclasts and computes cell population dynamics and changes in bone mass at a discrete site of bone remodeling. Therefore, when an external mechanical stress is applied, bone formation and resorption is governed by cells dynamic rather than adaptive elasticity approaches. The proposed FE model has been implemented in the FE code Abaqus (UMAT routine). An example of human proximal femur is investigated using the model developed. The model was able to predict final human proximal femur adaptation similar to the patterns observed in a human proximal femur. The results obtained reveal complex spatio-temporal bone

  10. Histamine in regulation of bone remodeling processes

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    Marek Wiercigroch

    2013-08-01

    Full Text Available Bone remodeling is under autocrine, paracrine, endocrine and central nervous system control. One of the potential endogenous factors affecting bone remodeling is histamine, an endogenous amine which acts as a mediator of allergic reactions and neuromediator, and induces production of gastric acid. Histamine H1 receptor antagonists are widely used in the treatment of allergic conditions, H2 receptor antagonists in peptic ulcer disease, and betahistine (an H3 receptor antagonist and H1 receptor agonist is used in the treatment of Ménière’s disease.Excess histamine release in mastocytosis and allergic diseases may lead to development of osteoporosis. Clinical and population-based studies on the effects of histamine receptor antagonists on the skeletal system have not delivered unequivocal results.Expression of mRNA of histamine receptors has been discovered in bone cells (osteoblasts and osteoclasts. Histamine synthesis has been demonstrated in osteoclast precursors. Histamine increases bone resorption both by direct effects on osteoclast precursors and osteoclasts, and indirectly, by increasing the expression of RANKL in osteoblasts. In in vivo studies, H1 and H2 receptor antagonists exerted protective effects on the bone tissue, although not in all experimental models. In the present article, in vitro and in vivo studies conducted so far, concerning the effects of histamine and drugs modifying its activity on the skeletal system, have been reviewed.

  11. [Histamine in regulation of bone remodeling processes].

    Science.gov (United States)

    Wiercigroch, Marek; Folwarczna, Joanna

    2013-01-01

    Bone remodeling is under autocrine, paracrine, endocrine and central nervous system control. One of the potential endogenous factors affecting bone remodeling is histamine, an endogenous amine which acts as a mediator of allergic reactions and neuromediator, and induces production of gastric acid. Histamine H₁ receptor antagonists are widely used in the treatment of allergic conditions, H₂ receptor antagonists in peptic ulcer disease, and betahistine (an H₃ receptor antagonist and H₁ receptor agonist) is used in the treatment of Ménière's disease. Excess histamine release in mastocytosis and allergic diseases may lead to development of osteoporosis. Clinical and population-based studies on the effects of histamine receptor antagonists on the skeletal system have not delivered unequivocal results. Expression of mRNA of histamine receptors has been discovered in bone cells (osteoblasts and osteoclasts). Histamine synthesis has been demonstrated in osteoclast precursors. Histamine increases bone resorption both by direct effects on osteoclast precursors and osteoclasts, and indirectly, by increasing the expression of RANKL in osteoblasts. In in vivo studies, H₁ and H₂ receptor antagonists exerted protective effects on the bone tissue, although not in all experimental models. In the present article, in vitro and in vivo studies conducted so far, concerning the effects of histamine and drugs modifying its activity on the skeletal system, have been reviewed. PMID:24018454

  12. Osteoblast recruitment routes in human cancellous bone remodeling

    DEFF Research Database (Denmark)

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

    2014-01-01

    It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling is...... lacking. We addressed this question by quantifying cell densities, cell proliferation, osteoblast differentiation markers, and capillaries in human iliac crest biopsy specimens. We found that recruitment occurs on both reversal and bone-forming surfaces, as shown by the cell density and osterix levels on...

  13. Probabilistic Study of Bone Remodeling Using Finite Element Analysis

    Science.gov (United States)

    Werner, C.; Gorla, R. S. R.

    2013-08-01

    The dynamic bone remodeling process is a computationally challenging research area that struggles to understand the actual mechanisms. It has been observed that a mechanical stimulus in the bone greatly affects the remodeling process. A 3D finite element model of a femur is created and a probabilistic analysis is performed on the model. The probabilistic analysis measures the sensitivities of various parameters related to the material properties, geometric properties, and the three load cases defined as Single Leg Stance, Abduction, and Adduction. The sensitivity of each parameter is based on the calculated maximum mechanical stimulus and analyzed at various values of probabilities ranging from 0.001 to 0.999. The analysis showed that the parameters associated with the Single Leg Stance load case had the highest sensitivity with a probability of 0.99 and the angle of the force applied to the joint of the proximal femur had the overall highest sensitivity

  14. The behavior of adaptive bone-remodeling simulation models

    NARCIS (Netherlands)

    H.H. Weinans (Harrie); R. Huiskes (Rik); H.J. Grootenboer

    1992-01-01

    textabstractThe process of adaptive bone remodeling can be described mathematically and simulated in a computer model, integrated with the finite element method. In the model discussed here, cortical and trabecular bone are described as continuous materials with variable density. The remodeling rule

  15. Multiscale Bone Remodelling with Spatial P Systems

    CERN Document Server

    Cacciagrano, Diletta; Merelli, Emanuela; Tesei, Luca; 10.4204/EPTCS.40.6

    2010-01-01

    Many biological phenomena are inherently multiscale, i.e. they are characterized by interactions involving different spatial and temporal scales simultaneously. Though several approaches have been proposed to provide "multilayer" models, only Complex Automata, derived from Cellular Automata, naturally embed spatial information and realize multiscaling with well-established inter-scale integration schemas. Spatial P systems, a variant of P systems in which a more geometric concept of space has been added, have several characteristics in common with Cellular Automata. We propose such a formalism as a basis to rephrase the Complex Automata multiscaling approach and, in this perspective, provide a 2-scale Spatial P system describing bone remodelling. The proposed model not only results to be highly faithful and expressive in a multiscale scenario, but also highlights the need of a deep and formal expressiveness study involving Complex Automata, Spatial P systems and other promising multiscale approaches, such as ...

  16. Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Gulshan B., E-mail: gbsharma@ucalgary.ca [Emory University, Department of Radiology and Imaging Sciences, Spine and Orthopaedic Center, Atlanta, Georgia 30329 (United States); University of Pittsburgh, Swanson School of Engineering, Department of Bioengineering, Pittsburgh, Pennsylvania 15213 (United States); University of Calgary, Schulich School of Engineering, Department of Mechanical and Manufacturing Engineering, Calgary, Alberta T2N 1N4 (Canada); Robertson, Douglas D., E-mail: douglas.d.robertson@emory.edu [Emory University, Department of Radiology and Imaging Sciences, Spine and Orthopaedic Center, Atlanta, Georgia 30329 (United States); University of Pittsburgh, Swanson School of Engineering, Department of Bioengineering, Pittsburgh, Pennsylvania 15213 (United States)

    2013-07-01

    Shoulder arthroplasty success has been attributed to many factors including, bone quality, soft tissue balancing, surgeon experience, and implant design. Improved long-term success is primarily limited by glenoid implant loosening. Prosthesis design examines materials and shape and determines whether the design should withstand a lifetime of use. Finite element (FE) analyses have been extensively used to study stresses and strains produced in implants and bone. However, these static analyses only measure a moment in time and not the adaptive response to the altered environment produced by the therapeutic intervention. Computational analyses that integrate remodeling rules predict how bone will respond over time. Recent work has shown that subject-specific two- and three dimensional adaptive bone remodeling models are feasible and valid. Feasibility and validation were achieved computationally, simulating bone remodeling using an intact human scapula, initially resetting the scapular bone material properties to be uniform, numerically simulating sequential loading, and comparing the bone remodeling simulation results to the actual scapula’s material properties. Three-dimensional scapula FE bone model was created using volumetric computed tomography images. Muscle and joint load and boundary conditions were applied based on values reported in the literature. Internal bone remodeling was based on element strain-energy density. Initially, all bone elements were assigned a homogeneous density. All loads were applied for 10 iterations. After every iteration, each bone element’s remodeling stimulus was compared to its corresponding reference stimulus and its material properties modified. The simulation achieved convergence. At the end of the simulation the predicted and actual specimen bone apparent density were plotted and compared. Location of high and low predicted bone density was comparable to the actual specimen. High predicted bone density was greater than

  17. Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

    International Nuclear Information System (INIS)

    Shoulder arthroplasty success has been attributed to many factors including, bone quality, soft tissue balancing, surgeon experience, and implant design. Improved long-term success is primarily limited by glenoid implant loosening. Prosthesis design examines materials and shape and determines whether the design should withstand a lifetime of use. Finite element (FE) analyses have been extensively used to study stresses and strains produced in implants and bone. However, these static analyses only measure a moment in time and not the adaptive response to the altered environment produced by the therapeutic intervention. Computational analyses that integrate remodeling rules predict how bone will respond over time. Recent work has shown that subject-specific two- and three dimensional adaptive bone remodeling models are feasible and valid. Feasibility and validation were achieved computationally, simulating bone remodeling using an intact human scapula, initially resetting the scapular bone material properties to be uniform, numerically simulating sequential loading, and comparing the bone remodeling simulation results to the actual scapula’s material properties. Three-dimensional scapula FE bone model was created using volumetric computed tomography images. Muscle and joint load and boundary conditions were applied based on values reported in the literature. Internal bone remodeling was based on element strain-energy density. Initially, all bone elements were assigned a homogeneous density. All loads were applied for 10 iterations. After every iteration, each bone element’s remodeling stimulus was compared to its corresponding reference stimulus and its material properties modified. The simulation achieved convergence. At the end of the simulation the predicted and actual specimen bone apparent density were plotted and compared. Location of high and low predicted bone density was comparable to the actual specimen. High predicted bone density was greater than

  18. Correlation between absence of bone remodeling compartment canopies, reversal phase arrest, and deficient bone formation in post-menopausal osteoporosis

    DEFF Research Database (Denmark)

    Levin Andersen, Thomas; Hauge, Ellen M; Rolighed, Lars;

    2014-01-01

    Bone remodeling compartments (BRCs) were recently recognized to be present in patients with primary hyperparathyroidism and critical for bone reconstruction in multiple myeloma and endogenous Cushing's syndrome. The BRCs are outlined by a cellular canopy separating the bone remodeling events...

  19. Early reversal cells in adult human bone remodeling

    DEFF Research Database (Denmark)

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

    2016-01-01

    . Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone...... demonstrates that reversal cells colonizing bone surfaces right after resorption are osteoblast-lineage cells, and extends to adult human bone remodeling their role in rendering eroded surfaces osteogenic....

  20. Modalities for visualization of cortical bone remodeling: the past, present and near future

    Directory of Open Access Journals (Sweden)

    Kimberly Dawn Harrison

    2015-08-01

    Full Text Available Bone’s ability to respond to load-related phenomena and repair microdamage is achieved through the remodeling process which renews bone by activating groups of cells known as Basic Multicellular Units (BMUs. The products of BMUs, secondary osteons, have been extensively studied via classic two-dimensional (2D techniques which have provided a wealth of information on how histomorphology relates to skeletal structure and function. Remodeling is critical in maintaining healthy bone tissue; however, in osteoporotic bone imbalanced resorption results in increased bone fragility and fracture. With increasing life expectancy, such degenerative bone diseases are a growing concern. The three-dimensional (3D morphology of BMUs and their correlation to function, however, are not well characterized and little is known about the specific mechanisms that initiate and regulate their activity within cortical bone. We believe a key limitation has been the lack 3D information about BMU morphology and activity. Thus, this paper reviews methodologies for 3D investigation of cortical bone remodeling and, specifically, structures associated with BMU activity (resorption spaces and the structures they create (secondary osteons, spanning from histology to modern ex vivo imaging modalities, culminating with the growing potential of in vivo imaging. This collection of papers focuses on the theme of putting the why back into bone archytecture. Remodeling is one of two mechanisms how bone structure is dynamically modified and thus an improved 3D understanding of this fundamental process is crucial to ultimately understanding the why.

  1. [Bone and Calcium Metabolisms Associated with Dental and Oral-Maxillofacial Diseases. Bone remodeling and alveolar bone homeostasis].

    Science.gov (United States)

    Nakashima, Tomoki

    2015-08-01

    Bone, which support motile organ and periodontal tissue, is renewing throughout our life. This restructuring process is called "bone remodeling" , and osteoclasts and osteoblasts play a crucial role in this process. Bone remodeling is important not only for normal bone mass and strength, but also for mineral homeostasis. Bone remodeling is stringently regulated by communication between bone component cells such as osteoclasts, osteoblasts and osteocytes. An imbalance of this process is often linked to various bone diseases. Alveolar bone remodeling is directly influenced by occlusal force from the teeth. Thus, the elucidation of the regulatory mechanisms involved in alveolar bone remodeling is critical for a deeper understanding of the maintenance of healthy tooth and dental disease.

  2. High-dose therapy improved the bone remodelling compartment canopy and bone formation in multiple myeloma

    DEFF Research Database (Denmark)

    Hinge, Maja; Delaissé, Jean-Marie; Plesner, Torben;

    2015-01-01

    . Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell...... transplantation, and from 20 control patients with monoclonal gammopathy of undetermined significance were histomorphometrically investigated. This investigation confirmed that MM patients exhibited uncoupled bone formation to resorption and reduced canopy coverage. More importantly, this study revealed......Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling...

  3. Role of Cannabinoids in the Regulation of Bone Remodelling

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    Aymen I Idris

    2012-11-01

    Full Text Available The endocannabinoid system plays a key role in regulating a variety of physiological processes such as appetite control and energy balance, pain perception, and immune responses. Recent studies have implicated the endocannabinoid system in the regulation of bone cell activity and bone remodelling. These studies showed that endogenous cannabinoid ligands, cannabinoid receptors and the enzymes responsible for ligand synthesis and breakdown all play important roles in bone mass and in the regulation of bone disease. These findings suggest that the endocannabinoid pathway could be of value as a therapeutic target for the prevention and treatment of bone diseases. Here, we review the role of the skeletal endocannabinoid system in the regulation of bone remodelling in health and disease.

  4. Dynamics of the ethanolamine glycerophospholipid remodeling network.

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    Lu Zhang

    Full Text Available Acyl chain remodeling in lipids is a critical biochemical process that plays a central role in disease. However, remodeling remains poorly understood, despite massive increases in lipidomic data. In this work, we determine the dynamic network of ethanolamine glycerophospholipid (PE remodeling, using data from pulse-chase experiments and a novel bioinformatic network inference approach. The model uses a set of ordinary differential equations based on the assumptions that (1 sn1 and sn2 acyl positions are independently remodeled; (2 remodeling reaction rates are constant over time; and (3 acyl donor concentrations are constant. We use a novel fast and accurate two-step algorithm to automatically infer model parameters and their values. This is the first such method applicable to dynamic phospholipid lipidomic data. Our inference procedure closely fits experimental measurements and shows strong cross-validation across six independent experiments with distinct deuterium-labeled PE precursors, demonstrating the validity of our assumptions. In contrast, fits of randomized data or fits using random model parameters are worse. A key outcome is that we are able to robustly distinguish deacylation and reacylation kinetics of individual acyl chain types at the sn1 and sn2 positions, explaining the established prevalence of saturated and unsaturated chains in the respective positions. The present study thus demonstrates that dynamic acyl chain remodeling processes can be reliably determined from dynamic lipidomic data.

  5. Ameloblastin is not implicated in bone remodelling and repair

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    S Kuroda

    2011-07-01

    Full Text Available Ameloblastin (AMBN is an enamel matrix protein produced by ameloblasts. It has been suggested that AMBN might also be implicated in craniofacial bone formation. Our objective was to determine whether AMBN has an effect on osteogenic mineralisation and influences bone remodelling and repair. MC3T3-E1 cells were screened for endogenous expression of enamel proteins using real time PCR. Various osteogenic cells were infected with lentivirus encoding for AMBN and protein expression was verified using immunochemistry. Cultures were stained with alizarin red and mineralisation was quantified. Healing bone was probed for expression of AMBN by DNA microarray analysis. Tooth extraction, experimental tooth movement (ETM, and creation of a non-critical size bone defect in the tibia (BDT were carried out in wild type and AMBNΔ5-6 mutant mice. Tissues were processed for immunolabelling of AMBN and Bril, an osteoblast specific protein associated with active bone formation. MC3T3-E1 cells and healing bone showed no significant expression of AMBN. Overexpression of AMBN in osteogenic cultures induced no noticeable changes in mineralisation. In wild type mice, AMBN was immunodetected in ameloblasts and enamel, but not in normal bone, and at sites where bone remodelling and repair were induced. Bone remodelling during ETM and BDT repair in AMBNΔ5-6 mice were not significantly different from that in wild type animals. Our results suggest that AMBN does not influence osteogenic activity in vitro under the conditions used, and does not participate in craniofacial bone remodelling under mechanical stress and in repair of non-critical size bone defects.

  6. The role of microRNAs in bone remodeling

    Institute of Scientific and Technical Information of China (English)

    Dian Jing; Jin Hao; Yu Shen; Ge Tang; Mei-Le Li; Shi-Hu Huang; Zhi-He Zhao

    2015-01-01

    Bone remodeling is balanced by bone formation and bone resorption as well as by alterations in the quantities and functions of seed cells, leading to either the maintenance or deterioration of bone status. The existing evidence indicates that microRNAs (miRNAs), known as a family of short non-coding RNAs, are the key post-transcriptional repressors of gene expression, and growing numbers of novel miRNAs have been verified to play vital roles in the regulation of osteogenesis, osteoclastogenesis, and adipogenesis, revealing how they interact with signaling molecules to control these processes. This review summarizes the current knowledge of the roles of miRNAs in regulating bone remodeling as well as novel applications for miRNAs in biomaterials for therapeutic purposes.

  7. Mechanical Signaling for Bone Modeling and Remodeling

    OpenAIRE

    Robling, Alexander G.; Turner, Charles H.

    2009-01-01

    Proper development of the skeleton in utero and during growth requires mechanical stimulation. Loading results in adaptive changes in bone that strengthen bone structure. Bone’s adaptive response is regulated by the ability of resident bone cells to perceive and translate mechanical energy into a cascade of structural and biochemical changes within the cells — a process known as mechanotransduction. Mechanotransduction pathways are among the most anabolic in bone, and consequently, there is g...

  8. Prediction of denosumab effects on bone remodeling: A combined pharmacokinetics and finite element modeling.

    Science.gov (United States)

    Hambli, Ridha; Boughattas, Mohamed Hafedh; Daniel, Jean-Luc; Kourta, Azeddine

    2016-07-01

    Denosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclearfactor-kappa B ligand (RANKL). This key mediator of osteoclast activities has been shown to inhibit osteoclast differentiation and hence, to increase bone mineral density (BMD) in treated patients. In the current study, we develop a computer model to simulate the effects of denosumab treatments (dose and duration) on the proximal femur bone remodeling process quantified by the variation in proximal femur BMD. The simulation model is based on a coupled pharmacokinetics model of denosumab with a pharmacodynamics model consisting of a mechanobiological finite element remodeling model which describes the activities of osteoclasts and osteoblasts. The mechanical behavior of bone is described by taking into account the bone material fatigue damage accumulation and mineralization. A coupled strain-damage stimulus function is proposed which controls the level of bone cell autocrine and paracrine factors. The cellular behavior is based on Komarova et al.׳s (2003) dynamic law which describes the autocrine and paracrine interactions between osteoblasts and osteoclasts and computes cell population dynamics and changes in bone mass at a discrete site of bone remodeling. Therefore, when an external mechanical stress is applied, bone formation and resorption is governed by cell dynamics rather than by adaptive elasticity approaches. The proposed finite element model was implemented in the finite element code Abaqus (UMAT routine). In order to perform a preliminary validation, in vivo human proximal femurs were selected and scanned at two different time intervals (at baseline and at a 36-month interval). Then, a 3D FE model was generated and the denosumab-remodeling algorithm was applied to the scans at t0 simulating daily walking activities for a duration of 36 months. The predicted results (density variation) were compared to existing published ones performed on a human cohort (FREEDOM

  9. Bone remodeling around cementless tantalum cups

    NARCIS (Netherlands)

    Grillo, J. -C.; Flecher, X.; Bouvenot, J.; Argenson, J. -N.

    2008-01-01

    Purpose of the study.-Most studies have reported a significant decrease in periacetabular bone stock one year after implantation of a cementless cup. The purpose of this work was to study the bone-implant interface of the tantalum cup using plain X-rays and dual-energy X-ray absorptiometry (DEXA). M

  10. Expression of RANKL/OPG during bone remodeling in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, H., E-mail: tnk@ymghp.jp [Department of Orthopedic Surgery, Yamaguchi Grand Medical Center, 77 Ohsaki, Hofu, Yamaguchi 747-8511 (Japan); Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 (United States); Mine, T. [Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Ogasa, H. [Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 (United States); Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Taguchi, T. [Department of Orthopedic Surgery, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505 (Japan); Liang, C.T. [Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 (United States); National Health Research Institutes, Taipei 115, Taiwan (China)

    2011-08-12

    Highlights: {yields} This is the first study to determine the relationship between osteogenic differentiation and RANKL/OPG expression during bone remodeling in vivo. {yields} The OPG expression peak occurred during the bone formation phase, whereas the marked elevation of RANKL expression was observed during the bone resorption phase. {yields} Histological analysis showed that RANKL/OPG immunoreactivity was predominantly associated with bone marrow cells in the marrow cavity. {yields} The present study confirmed that RANKL/OPG are key factors linking bone formation to resorption during the bone remodeling process. -- Abstract: The interaction between receptor activator of nuclear factor {kappa}B ligand (RANKL) and osteoprotegerin (OPG) plays a dominant role in osteoclastogenesis. As both proteins are produced by osteoblast lineage cells, they are considered to represent a key link between bone formation and resorption. In this study, we investigated the expression of RANKL and OPG during bone remodeling in vivo to determine the relationship between osteoclastogenic stimulation and osteoblastic differentiation. Total RNA was prepared from rat femurs after marrow ablation on days 0, 3, 6, and 9. The temporal activation patterns of osteoblast-related genes (procollagen {alpha}1 (I), alkaline phosphatase, osteopontin, and osteocalcin) were examined by Northern blot analysis. An appreciable increase in the expression of these osteoblast markers was observed on day 3. The peak increase in gene expression was observed on day 6 followed by a slight reduction by day 9. Real-time PCR analysis showed that the OPG mRNA expression was markedly upregulated on day 6 and slightly decreased on day 9. In contrast, RANKL mRNA expression was increased by more than 20-fold on day 9. The RANKL/OPG ratio, an index of osteoclastogenic stimulation, peaked on day 9. Histological analysis showed that RANKL and OPG immunoreactivity were predominantly associated with bone marrow cells. The

  11. Inflammatory and Bone Remodeling Responses to the Cytolethal Distending Toxins

    Directory of Open Access Journals (Sweden)

    Georgios N. Belibasakis

    2014-04-01

    Full Text Available The cytolethal distending toxins (CDTs are a family of exotoxins produced by a wide range of Gram-negative bacteria. They are known for causing genotoxic stress to the cell, resulting in growth arrest and eventually apoptotic cell death. Nevertheless, there is evidence that CDTs can also perturb the innate immune responses, by regulating inflammatory cytokine production and molecular mediators of bone remodeling in various cell types. These cellular and molecular events may in turn have an effect in enhancing local inflammation in diseases where CDT-producing bacteria are involved, such as Aggregatibacter actinomycetemcomitans, Haemophilus ducreyi, Campylobacter jejuni and Helicobacter hepaticus. One special example is the induction of pathological bone destruction in periodontitis. The opportunistic oral pathogen Aggregatibatcer actinoycemetemcomitans, which is involved in the aggressive form of the disease, can regulate the molecular mechanisms of bone remodeling in a manner that favors bone resorption, with the potential involvement of its CDT. The present review provides an overview of all known to-date inflammatory or bone remodeling responses of CDTs produced by various bacterial species, and discusses their potential contribution to the pathogenesis of the associated diseases.

  12. A mathematical model of cortical bone remodeling at cellular level under mechanical stimulus

    Institute of Scientific and Technical Information of China (English)

    Qing-Hua Qin; Ya-Nan Wang

    2012-01-01

    A bone cell population dynamics model for cortical bone remodeling under mechanical stimulus is developed in this paper.The external experiments extracted from the literature which have not been used in the creation of the model are used to test the validity of the model.Not only can the model compare reasonably well with these experimental results such as the increase percentage of final values of bone mineral content (BMC) and bone fracture energy (BFE) among different loading schemes (which proves the validity of the model),but also predict the realtime development pattern of BMC and BFE,as well as the dynamics of osteoblasts (OBA),osteoclasts (OCA),nitric oxide (NO) and prostaglandin E2 (PGE2) for each loading scheme,which can hardly be monitored through experiment.In conclusion,the model is the first of its kind that is able to provide an insight into the quantitative mechanism of bone remodeling at cellular level by which bone cells are activated by mechanical stimulus in order to start resorption/formation of bone mass.More importantly,this model has laid a solid foundation based on which future work such as systemic control theory analysis of bone remodeling under mechanical stimulus can be investigated.The to-be identified control mechanism will help to develop effective drugs and combined nonpharmacological therapies to combat bone loss pathologies.Also this deeper understanding of how mechanical forces quantitatively interact with skeletal tissue is essential for the generation of bone tissue for tissue replacement purposes in tissue engineering.

  13. Phase field approaches of bone remodeling based on TIP

    Science.gov (United States)

    Ganghoffer, Jean-François; Rahouadj, Rachid; Boisse, Julien; Forest, Samuel

    2016-01-01

    The process of bone remodeling includes a cycle of repair, renewal, and optimization. This adaptation process, in response to variations in external loads and chemical driving factors, involves three main types of bone cells: osteoclasts, which remove the old pre-existing bone; osteoblasts, which form the new bone in a second phase; osteocytes, which are sensing cells embedded into the bone matrix, trigger the aforementioned sequence of events. The remodeling process involves mineralization of the bone in the diffuse interface separating the marrow, which contains all specialized cells, from the newly formed bone. The main objective advocated in this contribution is the setting up of a modeling and simulation framework relying on the phase field method to capture the evolution of the diffuse interface between the new bone and the marrow at the scale of individual trabeculae. The phase field describes the degree of mineralization of this diffuse interface; it varies continuously between the lower value (no mineral) and unity (fully mineralized phase, e.g. new bone), allowing the consideration of a diffuse moving interface. The modeling framework is the theory of continuous media, for which field equations for the mechanical, chemical, and interfacial phenomena are written, based on the thermodynamics of irreversible processes. Additional models for the cellular activity are formulated to describe the coupling of the cell activity responsible for bone production/resorption to the kinetics of the internal variables. Kinetic equations for the internal variables are obtained from a pseudo-potential of dissipation. The combination of the balance equations for the microforce associated to the phase field and the kinetic equations lead to the Ginzburg-Landau equation satisfied by the phase field with a source term accounting for the dissipative microforce. Simulations illustrating the proposed framework are performed in a one-dimensional situation showing the evolution of

  14. Mechanobiological regulation of bone remodeling -- Theoretical development of a coupled systems biology-micromechanical approach

    OpenAIRE

    Scheiner, Stefan; Pivonka, Peter; Hellmich, Christian; Smith, David W.

    2012-01-01

    Bone remodeling involves the coordinated removal of bone by osteoclasts and addition of bone by osteoblasts, a process that is modulated by the prevailing mechanical environment. In this paper a fully coupled model of bone remodeling is developed, based on coupling a bone cell population model with a micromechanical homogenization scheme of bone stiffness. While the former model considers biochemical regulatory mechanisms between bone cells such as the RANK-RANKL-OPG pathway and action of TGF...

  15. Targeting Bone Remodeling by Isoflavone and 3,3′-Diindolylmethane in the Context of Prostate Cancer Bone Metastasis

    OpenAIRE

    Yiwei Li; Dejuan Kong; Aamir Ahmad; Bin Bao; Sarkar, Fazlul H

    2012-01-01

    Prostate cancer (PCa) bone metastases have long been believed to be osteoblastic because of bone remodeling leading to the formation of new bone. However, recent studies have shown increased osteolytic activity in the beginning stages of PCa bone metastases, suggesting that targeting both osteolytic and osteoblastic mediators would likely inhibit bone remodeling and PCa bone metastasis. In this study, we found that PCa cells could stimulate differentiation of osteoclasts and osteoblasts throu...

  16. External bone remodeling after injectable calcium-phosphate cement in benign bone tumor: two cases in the hand.

    Science.gov (United States)

    Ichihara, S; Vaiss, L; Acciaro, A L; Facca, S; Liverneaux, P

    2015-12-01

    Bone remodeling commonly occurred after fracture and curettage benign bone tumor. A lot of previous articles reported "internal" trabecular bone remodeling. There were no previous clinical reports about "external" cortical bone remodeling. We present here 2 clinical cases of "external" bone remodeling after injectable calcium-phosphate in benign bone tumor in the hand. In two cases of benign bone tumor, we performed complete removal of the tumor and immediate filling of the metacarpal bone with injectable calcium-phosphate cement Arexbone(®) from the mechanical viewpoint. With respect to the shape of the calcium-phosphate, by using an injection-type, calcium-phosphate is adhered uniformly to the bone cortex by injecting, remodeling has been promoted. After 5 and 8years, both cases were no recurrences, and the shape of the metacarpal looked close to the contralateral side. These findings supposed to be concerned with potential self-healing and self-protection mechanism in human body.

  17. Epigenetic Regulation of Bone Remodeling and Its Impacts in Osteoporosis

    Science.gov (United States)

    Ghayor, Chafik; Weber, Franz E.

    2016-01-01

    Epigenetics describes mechanisms which control gene expression and cellular processes without changing the DNA sequence. The main mechanisms in epigenetics are DNA methylation in CpG-rich promoters, histone modifications and non-coding RNAs (ncRNAs). DNA methylation modifies the function of the DNA and correlates with gene silencing. Histone modifications including acetylation/deacetylation and phosphorylation act in diverse biological processes such as transcriptional activation/inactivation and DNA repair. Non-coding RNAs play a large part in epigenetic regulation of gene expression in addition to their roles at the transcriptional and post-transcriptional level. Osteoporosis is the most common skeletal disorder, characterized by compromised bone strength and bone micro-architectural deterioration that predisposes the bones to an increased risk of fracture. It is most often caused by an increase in bone resorption that is not sufficiently compensated by a corresponding increase in bone formation. Nowadays it is well accepted that osteoporosis is a multifactorial disorder and there are genetic risk factors for osteoporosis and bone fractures. Here we review emerging evidence that epigenetics contributes to the machinery that can alter DNA structure, gene expression, and cellular differentiation during physiological and pathological bone remodeling. PMID:27598138

  18. Epigenetic Regulation of Bone Remodeling and Its Impacts in Osteoporosis.

    Science.gov (United States)

    Ghayor, Chafik; Weber, Franz E

    2016-01-01

    Epigenetics describes mechanisms which control gene expression and cellular processes without changing the DNA sequence. The main mechanisms in epigenetics are DNA methylation in CpG-rich promoters, histone modifications and non-coding RNAs (ncRNAs). DNA methylation modifies the function of the DNA and correlates with gene silencing. Histone modifications including acetylation/deacetylation and phosphorylation act in diverse biological processes such as transcriptional activation/inactivation and DNA repair. Non-coding RNAs play a large part in epigenetic regulation of gene expression in addition to their roles at the transcriptional and post-transcriptional level. Osteoporosis is the most common skeletal disorder, characterized by compromised bone strength and bone micro-architectural deterioration that predisposes the bones to an increased risk of fracture. It is most often caused by an increase in bone resorption that is not sufficiently compensated by a corresponding increase in bone formation. Nowadays it is well accepted that osteoporosis is a multifactorial disorder and there are genetic risk factors for osteoporosis and bone fractures. Here we review emerging evidence that epigenetics contributes to the machinery that can alter DNA structure, gene expression, and cellular differentiation during physiological and pathological bone remodeling. PMID:27598138

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  20. [Effect of dosed diet restriction on physiological remodeling and bioelectric properties of bone].

    Science.gov (United States)

    Levashov, M I; Ianko, R V; Chaka, E G; Safonov, S L

    2014-07-01

    The effect of dosed diet restriction on the physiological remodeling and bioelectric properties of bone tissue was studied in 48 male Wistar rats 3- and 18-months of age. The rate of bone tissue apposition was studied by the dynamic histomorphometry method (intravital tetracycline labeling). Electric potentials on the periosteal surface of the freshly isolated femurs were recorded. The magnitude of dielectric loss factor was determined to assess the quality of bone tissue. The control rats received a standard diet. The experimental rats received a limited diet (60 % of the standard mass) for 28 days. The magnitude and rate of the bone tissue apposition on the endosteal and periosteal surface of the tibia were less by 38.4% and 122.7% respectively in experimental rats after dosed diet restriction. Electric potential in the metaphyseal-epiphyseal growth zones of the femur was 29.7% lower, and the dielectric loss factor increased by 15.8%. The bone tissue apposition rate and the electric potential magnitude were increased 10 days after completion of the dosed diet restriction. The magnitude of the dielectric loss factor decreased after returning to the standard diet. Key words: dosed diet restriction, bone, remodelling, bioelectric properties. PMID:25669112

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    STUDY DESIGN: A finite element analysis-based bone remodeling study in human was conducted in the lumbar spine operated on with pedicle screws. Bone remodeling results were compared to prospective experimental bone mineral content data of patients operated on with pedicle screws. OBJECTIVE......, in the human spine, the bone remodeling algorithms have neither been evaluated experimentally nor been examined by comparing to unsystematic experimental data. METHODS: The site-specific and nonsite-specific iterative bone remodeling algorithms were applied to a finite element model of the lumbar spine...... operated on with pedicle screws between L4 and L5. The stress shielding effect was also examined. The bone remodeling results were compared with prospective bone mineral content measurements of 4 patients. They were measured after surgery, 3-, 6- and 12-months postoperatively. RESULTS: After 1 year...

  2. A mechanostatistical approach to cortical bone remodelling: an equine model.

    Science.gov (United States)

    Wang, X; Thomas, C D L; Clement, J G; Das, R; Davies, H; Fernandez, J W

    2016-02-01

    In this study, the development of a mechanostatistical model of three-dimensional cortical bone remodelling informed with in vivo equine data is presented. The equine model was chosen as it is highly translational to the human condition due to similar Haversian systems, availability of in vivo bone strain and biomarker data, and furthermore, equine models are recommended by the US Federal Drugs Administration for comparative joint research. The model was derived from micro-computed tomography imaged specimens taken from the equine third metacarpal bone, and the Frost-based 'mechanostat' was informed from both in vivo strain gauges and biomarkers to estimate bone growth rates. The model also described the well-known 'cutting cone' phenomena where Haversian canals tunnel and replace bone. In order to make this model useful in practice, a partial least squares regression (PLSR) surrogate model was derived based on training data from finite element simulations with different loads. The PLSR model was able to predict microstructure and homogenised Young's modulus with errors less than 2.2% and 0.6%, respectively. PMID:25862068

  3. Premature loss of bone remodeling compartment canopies is associated with deficient bone formation

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Søe, Kent;

    2011-01-01

    support to this hypothesis by analyzing the changes in prevalence of BRC canopies during the progress of the remodeling cycle in a cohort of healthy individuals and in patients with endogenous Cushing's syndrome (CS), and by relating these changes in prevalence with the extent of bone forming surfaces...

  4. The Effect of Inital-Phase Bone Remodeling on Implant Wound Healing.

    Science.gov (United States)

    Hsu, Yung-Ting; Oh, Tae-Ju; Rudek, Ivan; Wang, Hom-Lay

    2016-01-01

    This case series aimed to investigate the initial-phase bone remodeling during implant wound healing and to discuss the possible contributing factors. A total of 11 implants with polished collars were placed in premaxillary regions via flapless approach with the aid of computer technology. After 15 months of follow-up, the results suggested that the presence of polished collars triggered bone resorption via a bone remodeling mechanism. The overall vertical crestal resorption was 0.78 ± 0.46 mm on average. This initial-phase bone remodeling primarily occurred within the first 3 months postoperatively. The slightly exposed polished collar may not worsen crestal bone level. PMID:27560679

  5. Influence of different mechanical stimuli in a multi-scale mechanobiological isotropic model for bone remodelling.

    Science.gov (United States)

    Mercuri, E G F; Daniel, A L; Hecke, M B; Carvalho, L

    2016-09-01

    This work represents a study of a mathematical model that describes the biological response to different mechanical stimuli in a cellular dynamics model for bone remodelling. The biological system discussed herein consists of three specialised cellular types, responsive osteoblasts, active osteoblasts and osteoclasts, three types of signalling molecules, transforming growth factor beta (TGF-β), receptor activator of nuclear factor kappa-b ligand (RANKL) and osteoprotegerin (OPG) and the parathyroid hormone (PTH). Three proposals for mechanical stimuli were tested: strain energy density (SED), hydrostatic and deviatoric parts of SED. The model was tested in a two-dimensional geometry of a standard human femur. The spatial discretization was performed by the finite element method while the temporal evolution of the variables was calculated by the 4th order Runge-Kutta method. The obtained results represent the temporal evolution of the apparent density distribution and the mean apparent density and thickness for the cortical bone after 600 days of remodelling simulation. The main contributions of this paper are the coupling of mechanical and biological models and the exploration of how the different mechanical stimuli affect the cellular activity in different types of physical activities. The results revealed that hydrostatic SED stimulus was able to form more cortical bone than deviatoric SED and total SED stimuli. The computational model confirms how different mechanical stimuli can impact in the balance of bone homeostasis.

  6. Evaluating treatment of osteoporosis using particle swarm on a bone remodelling mathematical model.

    Science.gov (United States)

    Chen, Andy B; Zhang, Ping; Yokota, Hiroki

    2013-12-01

    Bone loss in osteoporosis, commonly observed in postmenopausal women and the elderly, is caused by an imbalance in activities of bone-forming osteoblasts and bone-resorbing osteoclasts. To treat osteoporosis and increase bone mineral density (BMD), physical activities and drugs are often recommended. Complex systems dynamics prevent an intuitive prediction of treatment strategies, and little is known about an optimal sequence for the combinatorial use of available treatments. In this study, the authors built a mathematical model of bone remodelling and developed a treatment strategy for mechanical loading and salubrinal, a synthetic chemical agent that enhances bone formation and prevents bone resorption. The model formulated a temporal BMD change of a mouse's whole skeleton in response to ovariectomy, mechanical loading and administration of salubrinal. Particle swarm optimisation was employed to maximise a performance index (a function of BMD and treatment cost) to find an ideal sequence of treatment. The best treatment was found to start with mechanical loading followed by salubrinal. As treatment costs increased, the sequence started with no treatment and usage of salubrinal became scarce. The treatment strategy will depend on individual needs and costs, and the proposed model is expected to contribute to the development of personalised treatment strategies. PMID:24712100

  7. Meshless methods in biomechanics bone tissue remodelling analysis

    CERN Document Server

    Belinha, Jorge

    2014-01-01

    This book presents the complete formulation of a new advanced discretization meshless technique: the Natural Neighbour Radial Point Interpolation Method (NNRPIM). In addition, two of the most popular meshless methods, the EFGM and the RPIM, are fully presented. Being a truly meshless method, the major advantages of the NNRPIM over the FEM, and other meshless methods, are the remeshing flexibility and the higher accuracy of the obtained variable field. Using the natural neighbour concept, the NNRPIM permits to determine organically the influence-domain, resembling the cellulae natural behaviour. This innovation permits the analysis of convex boundaries and extremely irregular meshes, which is an advantage in the biomechanical analysis, with no extra computational effort associated.   This volume shows how to extend the NNRPIM to the bone tissue remodelling analysis, expecting to contribute with new numerical tools and strategies in order to permit a more efficient numerical biomechanical analysis.

  8. Nucleosome dynamics during chromatin remodeling in vivo.

    Science.gov (United States)

    Ramachandran, Srinivas; Henikoff, Steven

    2016-01-01

    Precise positioning of nucleosomes around regulatory sites is achieved by the action of chromatin remodelers, which use the energy of ATP to slide, evict or change the composition of nucleosomes. Chromatin remodelers act to bind nucleosomes, disrupt histone-DNA interactions and translocate the DNA around the histone core to reposition nucleosomes. Hence, remodeling is expected to involve nucleosomal intermediates with a structural organization that is distinct from intact nucleosomes. We describe the identification of a partially unwrapped nucleosome structure using methods that map histone-DNA contacts genome-wide. This alternative nucleosome structure is likely formed as an intermediate or by-product during nucleosome remodeling by the RSC complex. Identification of the loss of histone-DNA contacts during chromatin remodeling by RSC in vivo has implications for the regulation of transcriptional initiation. PMID:26933790

  9. The influence of bone surface availability in bone remodelling - A mathematical model including coupled geometrical and biomechanical regulations of bone cells

    OpenAIRE

    Pivonka, Peter; Buenzli, Pascal R.; Scheiner, Stefan; Hellmich, Christian; Dunstan, Colin R.

    2012-01-01

    Bone is a biomaterial undergoing continuous renewal. The renewal process is known as bone remodelling and is operated by bone-resorbing cells (osteoclasts) and bone-forming cells (osteoblasts). Both biochemical and biomechanical regulatory mechanisms have been identified in the interaction between osteoclasts and osteoblasts. Here we focus on an additional and poorly understood potential regulatory mechanism of bone cells, that involves the morphology of the microstructure of bone. Bone cells...

  10. The zebrafish as a model for tissue regeneration and bone remodelling

    NARCIS (Netherlands)

    Sharif, Faiza

    2011-01-01

    The aim of this thesis was to investigate the expression, and function of genes associated with remodelling and regeneration in the zebrafish model species. Here, we studied the role of cell populations, defined by their expression of markers, in bone regeneration and remodelling in zebrafish embryo

  11. Soy Isoflavones and Osteoporotic Bone Loss: A Review with an Emphasis on Modulation of Bone Remodeling.

    Science.gov (United States)

    Zheng, Xi; Lee, Sun-Kyeong; Chun, Ock K

    2016-01-01

    Osteoporosis is an age-related disorder that affects both women and men, although estrogen deficiency induced by menopause accelerates bone loss in older women. As the demographic shifts to a more aged population, a growing number of men and women will be afflicted with osteoporosis. Since the current drug therapies available have multiple side effects, including increased risk of developing certain types of cancer or complications, a search for potential nonpharmacologic alternative therapies for osteoporosis is of prime interest. Soy isoflavones (SI) have demonstrated potential bone-specific effects in a number of studies. This article provides a systematic review of studies on osteoporotic bone loss in relation to SI intake from diet or supplements to comprehensively explain how SI affect the modulation of bone remodeling. Evidence from epidemiologic studies supports that dietary SI attenuate menopause-induced osteoporotic bone loss by decreasing bone resorption and stimulating bone formation. Other studies have also illustrated that bone site-specific trophic and synergistic effects combined with exercise intervention might contribute to improve the bioavailability of SI or strengthen the bone-specific effects. To date, however, the effects of dietary SI on osteoporotic bone loss remain inconclusive, and study results vary from study to study. The current review will discuss the potential factors that result in the conflicting outcomes of these studies, including dosages, intervention materials, study duration, race, and genetic differences. Further well-designed studies are needed to fully understand the underlying mechanism and evaluate the effects of SI on osteoporosis in humans. PMID:26670451

  12. Bone Remodeling Around Implants with External Hexagon and Morse-Taper Connections

    DEFF Research Database (Denmark)

    Pessoa, Roberto S; Sousa, Ravel M; Pereira, Leandro M;

    2016-01-01

    OBJECTIVES: To evaluate clinical, radiographic, microbiologic, and biomechanical parameters related to bone remodeling around implants with external hexagon (EH) and Morse-taper (MT) connections. MATERIALS AND METHODS: Twelve totally edentulous patients received four custom-made implants in the i......OBJECTIVES: To evaluate clinical, radiographic, microbiologic, and biomechanical parameters related to bone remodeling around implants with external hexagon (EH) and Morse-taper (MT) connections. MATERIALS AND METHODS: Twelve totally edentulous patients received four custom-made implants...

  13. Distraction Osteogenesis Enhances Remodeling of Remote Bones of the Skeleton: A Pilot Study

    OpenAIRE

    Funk, Julia F.; Krummrey, Gert; Perka, Carsten; Raschke, Michael J.; Bail, Hermann J.

    2009-01-01

    Bone injuries have a systemic influence on the remodeling of bone. This effect has not been examined concerning its extent and duration. We measured the systemic effect of distraction osteogenesis on the remodeling of bones of the axial skeleton by means of the mineral apposition rate and bone formation rate in an animal experiment. Distraction osteogenesis was performed on the tibiae of 24 mature Yucatan minipigs. After a 4-day latency period, the tibiae were distracted 2 mm/day for 10 days....

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

    Science.gov (United States)

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

    2016-05-01

    The objective of this study was to investigate the process of mandibular bone remodeling induced by implant-supported overdentures. computed tomography (CT) images were collected from edentulous patients to reconstruct the geometry of the mandibular bone and overdentures supported by implants. Based on the theory of strain energy density (SED), bone remodeling models were established using the user material subroutine (UMAT) in abaqus. The stress distribution in the mandible and bone density change was investigated to determine the effect of implant number on the remodeling of the mandibular bone. The results indicated that the areas where high Mises stress values were observed were mainly situated around the implants. The stress was concentrated in the distal neck region of the distal-most implants. With an increased number of implants, the biting force applied on the dentures was almost all taken up by implants. The stress and bone density in peri-implant bone increased. When the stress reached the threshold of remodeling, the bone density began to decrease. In the posterior mandible area, the stress was well distributed but increased with decreased implant numbers. Changes in bone density were not observed in this area. The computational results were consistent with the clinical data. The results demonstrate that the risk of bone resorption around the distal-most implants increases with increased numbers of implants and that the occlusal force applied to overdentures should be adjusted to be distributed more in the distal areas of the mandible. PMID:26963740

  15. Kinetics of gene expression and bone remodelling in the clinical phase of collagen induced arthritis

    DEFF Research Database (Denmark)

    Denninger, Katja Caroline Marie; Litman, Thomas; Marstrand, Troels;

    2015-01-01

    ), and secreted phosphoprotein 1 (Spp1). Pregnancy-associated protein A (Pappa) and periostin (Postn), differentially expressed in the early disease phase, are proposed to participate in bone formation, and we suggest that they play a role in early bone formation in the CIA model. Comparison to human genome......Introduction: Pathological bone changes differ considerably between inflammatory arthritic diseases and most studies have focused on bone erosion. Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis, which, in addition to bone erosion, demonstrates bone formation at the time...... of clinical manifestations. The objective of this study was to use this model to characterise the histological and molecular changes in bone remodelling, and relate these to the clinical disease development. Methods: A histological and gene expression profiling time-course study on bone remodelling in CIA...

  16. Instrumental and laboratory assessment of stressful remodelling processes in bone tissue at total hip replacement

    Directory of Open Access Journals (Sweden)

    E.V. Karjakina

    2010-06-01

    Full Text Available Research objective is to estimate stressful remodelling features of bone tissue according to the densitometry data and to the level of biochemical markers of bone resorption and formation in total hip replacement (THR. Bone tissue mineral density (BTMD, condition of calcium-phosphoric metabolism and biochemical markers of bone formation (osteocalcin and bone isoenzyme of alkaline phosphatase and resorption (С-terminal bodypeptide of the I type collagen have been determined in 52 patients with coxarthrosis of ll-lll stages with marked joint dysfunction before and after THR. The control group included 24 donors. The data were considered to be reliable when the probability index was р<0,05. The reliable (р<0,05 change of BTMD was determined only in 3-6 months after the operation, whereas the change of biochemical markers of remodeling had already been done after 1,5-3 months, allowing to define the group of patients with obvious negative bone balance: strong predominance of resorption processes without compensation of the subsequent adequate osteogenesis, that subsequently could lead to significant bone tissue deficiency in the area adjacent to the endoprosthesis. Changes of indices of calcium-phosphoric metabolism were not certain during the investigation term. ln conclusion it is to state that biochemical markers of remodeling in comparison with BTMD allow to estimate objectively features of adaptive bone tissue remodeling after THR in earlier periods and to define group of patients with sharp intensification of metabolism and obvious negative bone balance

  17. Numerical investigations on the strain-adaptive bone remodelling in the periprosthetic femur: Influence of the boundary conditions

    Directory of Open Access Journals (Sweden)

    Stukenborg-Colsman Christina

    2009-04-01

    Full Text Available Abstract Background There are several numerical investigations on bone remodelling after total hip arthroplasty (THA on the basis of the finite element analysis (FEA. For such computations certain boundary conditions have to be defined. The authors chose a maximum of three static load situations, usually taken from the gait cycle because this is the most frequent dynamic activity of a patient after THA. Materials and methods The numerical study presented here investigates whether it is useful to consider only one static load situation of the gait cycle in the FE calculation of the bone remodelling. For this purpose, 5 different loading cases were examined in order to determine their influence on the change in the physiological load distribution within the femur and on the resulting strain-adaptive bone remodelling. First, four different static loading cases at 25%, 45%, 65% and 85% of the gait cycle, respectively, and then the whole gait cycle in a loading regime were examined in order to regard all the different loadings of the cycle in the simulation. Results The computed evolution of the apparent bone density (ABD and the calculated mass losses in the periprosthetic femur show that the simulation results are highly dependent on the chosen boundary conditions. Conclusion These numerical investigations prove that a static load situation is insufficient for representing the whole gait cycle. This causes severe deviations in the FE calculation of the bone remodelling. However, accompanying clinical examinations are necessary to calibrate the bone adaptation law and thus to validate the FE calculations.

  18. A joined role of canopy and reversal cells in bone remodeling - Lessons from glucocorticoid-induced osteoporosis

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Hauge, Ellen-Margrethe;

    2015-01-01

    Successful bone remodeling demands that osteoblasts restitute the bone removed by osteoclasts. In human cancellous bone, a pivotal role in this restitution is played by the canopies covering the bone remodeling surfaces, since disruption of canopies in multiple myeloma, postmenopausal- and glucoc......Successful bone remodeling demands that osteoblasts restitute the bone removed by osteoclasts. In human cancellous bone, a pivotal role in this restitution is played by the canopies covering the bone remodeling surfaces, since disruption of canopies in multiple myeloma, postmenopausal....... In postmenopausal osteoporosis, this concept is supported by the coincidence between the absence of canopies and scarcity of cells on reversal surfaces together with abortion of the remodeling cycle. Here we tested whether this concept holds true in glucocorticoid-induced osteoporosis. A histomorphometric analysis...

  19. Computational biomechanics of bone's responses to dental prostheses - osseointegration, remodeling and resorption

    Science.gov (United States)

    Li, Wei; Rungsiyakull, Chaiy; Field, Clarice; Lin, Daniel; Zhang, Leo; Li, Qing; Swain, Michael

    2010-06-01

    Clinical and experimental studies showed that human bone has the ability to remodel itself to better adapt to its biomechanical environment by changing both its material properties and geometry. As a consequence of the rapid development and extensive applications of major dental restorations such as implantation and fixed partial denture (FPD), the effect of bone remodeling on the success of a dental restorative surgery is becoming critical for prosthetic design and pre-surgical assessment. This paper aims to provide a computational biomechanics framework to address dental bone's responses as a result of dental restoration. It explored three important issues of resorption, apposition and osseointegration in terms of remodeling simulation. The published remodeling data in long bones were regulated to drive the computational remodeling prediction for the dental bones by correlating the results to clinical data. It is anticipated that the study will provide a more predictive model of dental bone response and help develop a new design methodology for patient-specific dental prosthetic restoration.

  20. Osteoblastogenesis and Role of Osteoblasts in Calcıum Homeostasis and Remodeling of Bone

    Directory of Open Access Journals (Sweden)

    Neslihan Başcıl Tütüncü

    2008-05-01

    Full Text Available Bone remodeling is very important for repair of microfractures and fatigue damage and prevention of excessive aging and its consequences. Bone remodeling lasts for about 6-9 months. During this period osteoclasts resorb damaged bone and osteoblasts synthesize new bone. The lifespan of mature osteoclasts is about 15 days and for osteoblasts 3 months. Therefore, the time required for the remodeling of a given segement of bone is much longer than the lifespan of its cells which perform remodeling. A supply of new osteoblasts and osteoclasts are therefore needed for succesful remodeling by the basic multicellular unit. The major event that triggers osteogenesis is the transition of mesenchymal stem cells into bone differentiating osteoblast cells. Osteoblast commitment and differentation are controlled by complex activities. Many factors are involved in the regulation of osteoblastogenesis. Bone morphogenetic proteins and the Wnt glycoproteins play crucial roles in signaling osteoblast commitment and differentiation, and are the only known factors capable of initiating osteoblastogenesis from uncommitted progenitors. They can initiate commitment of mesenchymal cells to osteoblastic lineage. The initial cell division is asymmetric, giving rise to another stem cell and a committed osteoprogenitor. After commitment to the osteoblastic lineage, a osteoprogenitor cell gives rise to the transit-amplifying compartment. At this stage osteoprogenitor cells proliferate intensively. After this stage, the cells are more differentiated and give rise to preosteoblasts which express both STRO1, alkaline phosphatase, pyrophosphate, and type 1 collagen. Preosteoblasts are committed to the osteoblast lineage with extensive replicative capacity, but have no self-renewal capacity. Preosteoblasts form the intermediate stage of osteoblastogenesis. The mature osteoblasts express osteopontin, alkaline phosphatase, bone sialoprotein, and osteocalcin. This stage is

  1. Targeting bone remodeling by isoflavone and 3,3'-diindolylmethane in the context of prostate cancer bone metastasis.

    Directory of Open Access Journals (Sweden)

    Yiwei Li

    Full Text Available Prostate cancer (PCa bone metastases have long been believed to be osteoblastic because of bone remodeling leading to the formation of new bone. However, recent studies have shown increased osteolytic activity in the beginning stages of PCa bone metastases, suggesting that targeting both osteolytic and osteoblastic mediators would likely inhibit bone remodeling and PCa bone metastasis. In this study, we found that PCa cells could stimulate differentiation of osteoclasts and osteoblasts through the up-regulation of RANKL, RUNX2 and osteopontin, promoting bone remodeling. Interestingly, we found that formulated isoflavone and 3,3'-diindolylmethane (BR-DIM were able to inhibit the differentiation of osteoclasts and osteoblasts through the inhibition of cell signal transduction in RANKL, osteoblastic, and PCa cell signaling. Moreover, we found that isoflavone and BR-DIM down-regulated the expression of miR-92a, which is known to be associated with RANKL signaling, EMT and cancer progression. By pathway and network analysis, we also observed the regulatory effects of isoflavone and BR-DIM on multiple signaling pathways such as AR/PSA, NKX3-1/Akt/p27, MITF, etc. Therefore, isoflavone and BR-DIM with their multi-targeted effects could be useful for the prevention of PCa progression, especially by attenuating bone metastasis mechanisms.

  2. Using smooth particle hydrodynamics to investigate femoral cortical bone remodelling at the Haversian level.

    Science.gov (United States)

    Fernandez, J W; Das, R; Cleary, P W; Hunter, P J; Thomas, C D L; Clement, J G

    2013-01-01

    In the neck of the femur, about 70% of the strength is contributed by the cortical bone, which is the most highly stressed part of the structure and is the site where failure is almost certainly initiated. A better understanding of cortical bone remodelling mechanisms can help discern changes at this anatomical site, which are essential if an understanding of the mechanisms by which hips weaken and become vulnerable to fracture is to be gained. The aims of this study were to (i) examine a hypothesis that low strain fields arise because of subject-specific Haversian canal distributions causing bone resorption and reduced bone integrity and (ii) introduce the use of a meshless particle-based computational modelling approach SPH to capture bone remodelling features at the level of the Haversian canals. We show that bone remodelling initiated by strain at the Haversian level is highly influenced by the subject-specific pore distribution, bone density, loading and osteocyte density. SPH is shown to be effective at capturing the intricate bone pore shapes that evolved over time.

  3. A Femur-Implant Model for the Prediction of Bone Remodeling Behavior Induced by Cementless Stem

    Institute of Scientific and Technical Information of China (English)

    He Gong; Lingyan Kong; Rui Zhang; Juan Fang; Meisheng Zhao

    2013-01-01

    Bone remodeling simulation is an effective tool for the prediction of long-term effect of implant on the bone tissue,as well as the selection of an appropriate implant in terms of architecture and material.In this paper,a finite element model of proximal femur was develop.ed to simulate the structures of internal trabecular and cortical bones by incorporating quantitative bone functional adaptation theory with finite element analysis.Cementless stems made of titanium,two types of Functionally Graded Material (FGM) and flexible 'iso-elastic' material as comparison were implanted in the structure of proximal femur respectively to simulate the bone remodeling behaviors of host bone.The distributions of bone density,von Mises stress,and interface shear stress were obtained.All the prosthetic stems had effects on the bone remodeling behaviors of proximal femur,but the degrees of stress shielding were different.The amount of bone loss caused by titanium implant was in agreement with the clinical observation.The FGM stems caused less bone loss than that of the titanium stem,in which FGM I stem (titanium richer at the top to more HAP/Col towards the bottom) could relieve stress shielding effectively,and the interface shear stresses were more evenly distributed in the model with FGM I stem in comparison with those in the models with FGM II (titanium and bioglass) and titanium stems.The numerical simulations in the present study provided theoretical basis for FGM as an appropriate material of femoral implant from a biomechanical point of view.The next steps are to fabricate FGM stem and to conduct animal experiments to investigate the effects of FGM stem on the remodeling behaviors using animal model.

  4. Numerical simulation of strain-adaptive bone remodelling in the ankle joint

    Directory of Open Access Journals (Sweden)

    Stukenborg-Colsman Christina

    2011-07-01

    Full Text Available Abstract Background The use of artificial endoprostheses has become a routine procedure for knee and hip joints while ankle arthritis has traditionally been treated by means of arthrodesis. Due to its advantages, the implantation of endoprostheses is constantly increasing. While finite element analyses (FEA of strain-adaptive bone remodelling have been carried out for the hip joint in previous studies, to our knowledge there are no investigations that have considered remodelling processes of the ankle joint. In order to evaluate and optimise new generation implants of the ankle joint, as well as to gain additional knowledge regarding the biomechanics, strain-adaptive bone remodelling has been calculated separately for the tibia and the talus after providing them with an implant. Methods FE models of the bone-implant assembly for both the tibia and the talus have been developed. Bone characteristics such as the density distribution have been applied corresponding to CT scans. A force of 5,200 N, which corresponds to the compression force during normal walking of a person with a weight of 100 kg according to Stauffer et al., has been used in the simulation. The bone adaptation law, previously developed by our research team, has been used for the calculation of the remodelling processes. Results A total bone mass loss of 2% in the tibia and 13% in the talus was calculated. The greater decline of density in the talus is due to its smaller size compared to the relatively large implant dimensions causing remodelling processes in the whole bone tissue. In the tibia, bone remodelling processes are only calculated in areas adjacent to the implant. Thus, a smaller bone mass loss than in the talus can be expected. There is a high agreement between the simulation results in the distal tibia and the literature regarding. Conclusions In this study, strain-adaptive bone remodelling processes are simulated using the FE method. The results contribute to a better

  5. Regional variability in secondary remodeling within long bone cortices of catarrhine primates: the influence of bone growth history.

    Science.gov (United States)

    McFarlin, Shannon C; Terranova, Carl J; Zihlman, Adrienne L; Enlow, Donald H; Bromage, Timothy G

    2008-09-01

    Secondary intracortical remodeling of bone varies considerably among and within vertebrate skeletons. Although prior research has shed important light on its biomechanical significance, factors accounting for this variability remain poorly understood. We examined regional patterning of secondary osteonal bone in an ontogenetic series of wild-collected primates, at the midshaft femur and humerus of Chlorocebus (Cercopithecus) aethiops (n = 32) and Hylobates lar (n = 28), and the midshaft femur of Pan troglodytes (n = 12). Our major objectives were: 1) to determine whether secondary osteonal bone exhibits significant regional patterning across inner, mid-cortical and outer circumferential cortical rings within cross-sections; and if so, 2) to consider the manner in which this regional patterning may reflect the influence of relative tissue age and other circumstances of bone growth. Using same field-of-view images of 100-microm-thick cross-sections acquired in brightfield and circularly polarized light microscopy, we quantified the percent area of secondary osteonal bone (%HAV) for whole cross-sections and across the three circumferential rings within cross-sections. We expected bone areas with inner and middle rings to exhibit higher %HAV than the outer cortical ring within cross-sections, the latter comprising tissues of more recent depositional history. Observations of primary bone microstructural development provided an additional context in which to evaluate regional patterning of intracortical remodeling. Results demonstrated significant regional variability in %HAV within all skeletal sites. As predicted,%HAV was usually lowest in the outer cortical ring within cross-sections. However, regional patterning across inner vs. mid-cortical rings showed a more variable pattern across taxa, age classes, and skeletal sites examined. Observations of primary bone microstructure revealed that the distribution of endosteally deposited bone had an important influence on

  6. Dynamic regulation of transcription factors by nucleosome remodeling.

    Science.gov (United States)

    Li, Ming; Hada, Arjan; Sen, Payel; Olufemi, Lola; Hall, Michael A; Smith, Benjamin Y; Forth, Scott; McKnight, Jeffrey N; Patel, Ashok; Bowman, Gregory D; Bartholomew, Blaine; Wang, Michelle D

    2015-06-05

    The chromatin landscape and promoter architecture are dominated by the interplay of nucleosome and transcription factor (TF) binding to crucial DNA sequence elements. However, it remains unclear whether nucleosomes mobilized by chromatin remodelers can influence TFs that are already present on the DNA template. In this study, we investigated the interplay between nucleosome remodeling, by either yeast ISW1a or SWI/SNF, and a bound TF. We found that a TF serves as a major barrier to ISW1a remodeling, and acts as a boundary for nucleosome repositioning. In contrast, SWI/SNF was able to slide a nucleosome past a TF, with concurrent eviction of the TF from the DNA, and the TF did not significantly impact the nucleosome positioning. Our results provide direct evidence for a novel mechanism for both nucleosome positioning regulation by bound TFs and TF regulation via dynamic repositioning of nucleosomes.

  7. The ARF tumor suppressor regulates bone remodeling and osteosarcoma development in mice.

    Directory of Open Access Journals (Sweden)

    Daniel A Rauch

    Full Text Available The ARF tumor suppressor regulates p53 as well as basic developmental processes independent of p53, including osteoclast activation, by controlling ribosomal biogenesis. Here we provide evidence that ARF is a master regulator of bone remodeling and osteosarcoma (OS development in mice. Arf(-/- mice displayed increased osteoblast (OB and osteoclast (OC activity with a significant net increase in trabecular bone volume. The long bones of Arf(-/- mice had increased expression of OB genes while Arf(-/- OB showed enhanced differentiation in vitro. Mice transgenic for the Tax oncogene develop lymphocytic tumors with associated osteolytic lesions, while Tax+Arf(-/- mice uniformly developed spontaneous OS by 7 months of age. Tax+Arf(-/- tumors were well differentiated OS characterized by an abundance of new bone with OC recruitment, expressed OB markers and displayed intact levels of p53 mRNA and reduced Rb transcript levels. Cell lines established from OS recapitulated characteristics of the primary tumor, including the expression of mature OB markers and ability to form mineralized tumors when transplanted. Loss of heterozygosity in OS tumors arising in Tax+Arf(+/- mice emphasized the necessity of ARF-loss in OS development. Hypothesizing that inhibition of ARF-regulated bone remodeling would repress development of OS, we demonstrated that treatment of Tax+Arf(-/- mice with zoledronic acid, a bisphosphonate inhibitor of OC activity and repressor of bone turnover, prevented or delayed the onset of OS. These data describe a novel role for ARF as a regulator of bone remodeling through effects on both OB and OC. Finally, these data underscore the potential of targeting bone remodeling as adjuvant therapy or in patients with genetic predispositions to prevent the development of OS.

  8. Adaptive bone-remodeling theory applied to prosthetic-design analysis

    NARCIS (Netherlands)

    R. Huiskes (Rik); H.H. Weinans (Harrie); H.J. Grootenboer; M. Dalstra; B. Fudala; T.J. Slooff

    1987-01-01

    textabstractThe subject of this article is the development and application of computer-simulation methods to predict stress-related adaptive bone remodeling, in accordance with 'Wolff's Law'. These models are based on the Finite Element Method (FEM) in combination with numerical formulations of adap

  9. Finite element simulation of bone remodelling in human mandible around osseointegrated dental implant

    International Nuclear Information System (INIS)

    Modern dental implant is a biocompatible titanium device surgically placed into a jawbone to support a prosthetic tooth crown in order to replace missing teeth. Implants are superior to conventional prostheses, in both function and long-term predictability. However, placement of an implant changes the normal mechanical environment of jawbone, which causes the bone density to redistribute and adapt to the new environment through a process of remodelling. This study aims to predict the density distribution in human jawbone around osseointegrated dental implant. Based on two popular, yet distinctive theories for bone remodelling, a new remodelling algorithm is proposed. The proposed algorithm is verified by a two-dimensional (2D) plate model. Then, a 2D finite element model of implant and jawbone is studied. The effects of two parameters, viz the reference value of strain energy density (SED) and 'lazy zone' region, on density distribution, are also examined. This study has demonstrated that consideration of the lazy zone, is less important than consideration of the stress and strain (quantified as SED) induced within the bone. Taking into account both 'lazy zone' effect and self-organisational control process, the proposed bone remodelling algorithm has overcome the shortcomings of the two existing theories.

  10. Trabecular bone structure and strength - remodelling and repair

    DEFF Research Database (Denmark)

    Mosekilde, Lis; Ebbesen, Ebbe Nils; Erikstrup, Lise Tornvig;

    2000-01-01

    The strength of the spinal trabecular bone declines by a factor of 4-5 from the age of 20 to 80 years. At the same time, the volumetric (apparent) density declines by a factor of only 2. This discrepancy can be explained by the known power relationship between density and strength; this power rel...... the hydraulic effect of the bone marrow. In order to answer these questions, more in vitro and in vivo studies on human bone in relation to aging, to immobilisation, to exercise and in relation to different treatment regimens are needed.......The strength of the spinal trabecular bone declines by a factor of 4-5 from the age of 20 to 80 years. At the same time, the volumetric (apparent) density declines by a factor of only 2. This discrepancy can be explained by the known power relationship between density and strength; this power...

  11. Bone remodeling during pregnancy and post-partum assessed by metal lead levels and isotopic concentrations.

    Science.gov (United States)

    Gulson, Brian; Taylor, Alan; Eisman, John

    2016-08-01

    Bone remodeling is normally evaluated using bone turnover markers/indices as indicators of bone resorption and formation. However, during pregnancy and post-partum, there have been inconsistent results between and within biomarkers for bone formation and resorption. These differences may relate to pregnancy-related changes in metabolism and/or hemodilution altering measured marker levels. An alternative approach to evaluating bone remodeling is to use the metal lead (Pb) concentrations and Pb isotopic compositions in blood. These measurements can also provide information on the amount of Pb that is mobilized from the maternal skeleton. Despite some similarities with accepted bone turnover markers, the Pb data demonstrate increased bone resorption throughout pregnancy that further continues post-partum independent of length of breast-feeding, dietary intake and resumption of menses. Furthermore the isotopic measurements are not affected by hemodilution. These data confirm calcium balance studies that indicate increased bone resorption throughout pregnancy and lactation. They also indicate potentially major public health implications of the transfer of maternal Pb burden to the fetus and new born. PMID:27233973

  12. Bone morphogenetic protein-2: a potential regulator in scleral remodeling

    OpenAIRE

    Hu, Jianmin; Cui, Dongmei; Yang, Xiao; Wang, Shaowei; Hu, Shoulong; Li, Chuanxu; Zeng, Junwen

    2008-01-01

    Purpose Bone morphogenetic protein 2 (BMP-2) is a member of the main subgroup of bone morphogenetic proteins within the transforming growth factor-β superfamily. BMP-2 is involved in numerous cellular functions including development, cell proliferation, apoptosis, and extracellular matrix synthesis. We examined BMP-2 expression in human scleral fibroblasts (HSF) and assessed the effects of recombinant human BMP-2 (rhBMP-2) on HSF proliferation, matrix metalloproteinase-2 (MMP-2), and tissue i...

  13. Akt1 in osteoblasts and osteoclasts controls bone remodeling.

    Directory of Open Access Journals (Sweden)

    Naohiro Kawamura

    Full Text Available Bone mass and turnover are maintained by the coordinated balance between bone formation by osteoblasts and bone resorption by osteoclasts, under regulation of many systemic and local factors. Phosphoinositide-dependent serine-threonine protein kinase Akt is one of the key players in the signaling of potent bone anabolic factors. This study initially showed that the disruption of Akt1, a major Akt in osteoblasts and osteoclasts, in mice led to low-turnover osteopenia through dysfunctions of both cells. Ex vivo cell culture analyses revealed that the osteoblast dysfunction was traced to the increased susceptibility to the mitochondria-dependent apoptosis and the decreased transcriptional activity of runt-related transcription factor 2 (Runx2, a master regulator of osteoblast differentiation. Notably, our findings revealed a novel role of Akt1/forkhead box class O (FoxO 3a/Bim axis in the apoptosis of osteoblasts: Akt1 phosphorylates the transcription factor FoxO3a to prevent its nuclear localization, leading to impaired transactivation of its target gene Bim which was also shown to be a potent proapoptotic molecule in osteoblasts. The osteoclast dysfunction was attributed to the cell autonomous defects of differentiation and survival in osteoclasts and the decreased expression of receptor activator of nuclear factor-kappaB ligand (RANKL, a major determinant of osteoclastogenesis, in osteoblasts. Akt1 was established as a crucial regulator of osteoblasts and osteoclasts by promoting their differentiation and survival to maintain bone mass and turnover. The molecular network found in this study will provide a basis for rational therapeutic targets for bone disorders.

  14. A possible etiology for the dilaceration and flexion of permanent tooth roots relative to bone remodeling gradients in alveolar bone

    Directory of Open Access Journals (Sweden)

    Richard G Standerwick

    2014-01-01

    Full Text Available Introduction: Trauma, altered tooth germ position and delayed tooth eruption have been hypothesized as possible causes of tooth root dilacerations and flexion, however these anatomical variations appear more commonly associated with posterior teeth and absence of traumatic history. The Hypothesis: Postulated is that tooth root dilaceration or flexion may be a result of tooth root sheath displacement due to gradients of bone remodeling present within alveolar bone. Evaluation of the Hypothesis: Alveolar bone displays bone remodeling gradients between coronal, apical and basal sections which affect bone plasticity. As a tooth is erupting or experiences delayed eruption, there are other relative dento-skeletal alterations occurring, such as the mesial drift of the dentition and transverse growth of the maxilla. It is plausible that during the physiologic and growth related alteration of the alveolar and basal bones, portions of developing tooth could be found within one or more of the plasticity zones, contributing to alteration of the root sheath and tooth root dilaceration.

  15. 4D confocal microscopy for visualisation of bone remodelling

    NARCIS (Netherlands)

    Konijn, GA; Vardaxis, NJ; Boon, ME; Kok, LP; Rietveld, DC; SCHUT, JJ

    1996-01-01

    Until recently it was very time consuming and difficult to make three-dimensional (3D) images of newly formed bone. With the advent of confocal technologies and increased computer power 3D imaging is greatly facilitated. In this paper we demonstrate that enhanced confocal visualisation of newly form

  16. [Bone formation and corticotomy-induced accelerated bone remodeling: can alveolar corticotomy induce bone formation?].

    Science.gov (United States)

    Moreau, Nathan; Charrier, Jean-Baptiste

    2015-03-01

    Current orthodontic treatments must answer an increasing demand for faster yet as efficient treatments, especially in adult patients. These past years, the amelioration of orthodontic, anesthetic and orthognathic surgery techniques have allowed considerable improvement of orthodontico-surgical treatments and of adult orthodontic treatments. Alveolar corticotomy (an example of such techniques) accelerates orthodontic tooth movements by local modifications of bone metabolism, inducing a transient osteopenia. This osteopenia allows greater tooth movements than conventional techniques. Whereas there is a growing understanding of the underlying biological mechanisms of alveolar corticotomies, there is little data regarding the osteogenic potential of such technique. In the present article, we review the literature pertaining to alveolar corticotomies and their underlying biological mechanisms and present a clinical case underlining the osteogenic potential of the technique. PMID:25888047

  17. Multiscale approach for bone remodeling simulation based on finite element and neural network computation

    CERN Document Server

    Hambli, Ridha

    2011-01-01

    The aim of this paper is to develop a multiscale hierarchical hybrid model based on finite element analysis and neural network computation to link mesoscopic scale (trabecular network level) and macroscopic (whole bone level) to simulate bone remodelling process. Because whole bone simulation considering the 3D trabecular level is time consuming, the finite element calculation is performed at macroscopic level and a trained neural network are employed as numerical devices for substituting the finite element code needed for the mesoscale prediction. The bone mechanical properties are updated at macroscopic scale depending on the morphological organization at the mesoscopic computed by the trained neural network. The digital image-based modeling technique using m-CT and voxel finite element mesh is used to capture 2 mm3 Representative Volume Elements at mesoscale level in a femur head. The input data for the artificial neural network are a set of bone material parameters, boundary conditions and the applied str...

  18. A supra-cellular model for coupling of bone resorption to formation during remodeling: lessons from two bone resorption inhibitors affecting bone formation differently.

    Science.gov (United States)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Pennypacker, Brenda L; Duong, Le T; Engelholm, Lars H; Delaissé, Jean-Marie

    2014-01-10

    The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released by the osteoclasts. However, the osteoclasts are separated from the mature bone forming osteoblasts in time and space. Therefore the target cell of these osteoclastic factors has remained unknown. Recent explorations of the physical microenvironment of osteoclasts revealed a cell layer lining the bone marrow and forming a canopy over the whole remodeling surface, spanning from the osteoclasts to the bone forming osteoblasts. Several observations show that these canopy cells are a source of osteoblast progenitors, and we hypothesized therefore that they are the likely cells targeted by the osteogenic factors of the osteoclasts. Here we provide evidence supporting this hypothesis, by comparing the osteoclast-canopy interface in response to two types of bone resorption inhibitors in rabbit lumbar vertebrae. The bisphosphonate alendronate, an inhibitor leading to low bone formation levels, reduces the extent of canopy coverage above osteoclasts. This effect is in accordance with its toxic action on periosteoclastic cells. In contrast, odanacatib, an inhibitor preserving bone formation, increases the extent of the osteoclast-canopy interface. Interestingly, these distinct effects correlate with how fast bone formation follows resorption during these respective treatments. Furthermore, canopy cells exhibit uPARAP/Endo180, a receptor able to bind the collagen made available by osteoclasts, and reported to mediate osteoblast recruitment. Overall these observations support a mechanism where the recruitment of bone forming osteoblasts from the canopy is induced by osteoclastic factors, thereby favoring initiation of bone formation. They lead to a model where the osteoclast-canopy interface is

  19. Would increased interstitial fluid flow through in situ mechanical stimulation enhance bone remodeling?

    Science.gov (United States)

    Letechipia, J E; Alessi, A; Rodriguez, G; Asbun, J

    2010-08-01

    Bone accommodates to changes in its functional environment ensuring that sufficient skeletal mass is appropriately positioned to withstand the mechanical loads that result from functional activities. Increasing physical activity will result in increased bone mass, while the removal of functional loading would result in bone loss. Bone is a composite material made up of a collagen-hydroxyapatite matrix and a complex network of lacunae-canaliculi channels occupied by osteocyte and osteoblast processes, immersed in interstitial fluid. There are strong indications that changes in interstitial fluid flow velocity or pressure are the means by which an external load signal is communicated to the cell. In vitro studies indicate that shear stress, induced by interstitial fluid flow, is a potent bone cell behavior regulator. One of the forms of altering interstitial fluid flow is through the mechanical deformation of skeletal tissue in response to applied loads. Other methods include increased intramedullary pressure, negative-pressure tissue regeneration, or external mechanical stimulation. Analysis of these methods poses the question of process effectiveness. The efficacy of each method theoretically will depend on the mechanical efficiency of transmitting an external load and converting it into changes in interstitial fluid flow. In this paper, we combine recent knowledge on the effect of the bone's interstitial fluid flow, different fluid patterns, the role of gap junctions, and the concept of mechanical effectiveness of different methods that influence interstitial fluid flow within bone, and we hypothesize that the efficiency of bone remodeling can be improved if a small mechanical percussion device could be placed directly in contact with the bone, thus inducing local interstitial fluid flow variations. Enhancement of bone repair and remodeling through controlled interstitial fluid flow possesses many clinical applications. Further investigations and in vivo

  20. Evaluation of bone remodeling around single dental implants of different lengths: a mechanobiological numerical simulation and validation using clinical data.

    Science.gov (United States)

    Sotto-Maior, Bruno Salles; Mercuri, Emílio Graciliano Ferreira; Senna, Plinio Mendes; Assis, Neuza Maria Souza Picorelli; Francischone, Carlos Eduardo; Del Bel Cury, Altair Antoninha

    2016-01-01

    Algorithmic models have been proposed to explain adaptive behavior of bone to loading; however, these models have not been applied to explain the biomechanics of short dental implants. Purpose of present study was to simulate bone remodeling around single implants of different lengths using mechanoregulatory tissue differentiation model derived from the Stanford theory, using finite elements analysis (FEA) and to validate the theoretical prediction with the clinical findings of crestal bone loss. Loading cycles were applied on 7-, 10-, or 13-mm-long dental implants to simulate daily mastication and bone remodeling was assessed by changes in the strain energy density of bone after a 3, 6, and 12 months of function. Moreover, clinical findings of marginal bone loss in 45 patients rehabilitated with same implant designs used in the simulation (n = 15) were computed to validate the theoretical results. FEA analysis showed that although the bone density values reduced over time in the cortical bone for all groups, bone remodeling was independent of implant length. Clinical data showed a similar pattern of bone resorption compared with the data generated from mathematical analyses, independent of implant length. The results of this study showed that the mechanoregulatory tissue model could be employed in monitoring the morphological changes in bone that is subjected to biomechanical loads. In addition, the implant length did not influence the bone remodeling around single dental implants during the first year of loading. PMID:26249362

  1. A prospective randomised study of periprosthetic femoral bone remodeling using four different bearings in hybrid total hip arthroplasty

    DEFF Research Database (Denmark)

    Zerahn, Bo; Borgwardt, Lotte; Ribel-Madsen, Søren;

    2011-01-01

    Abstract: We performed a study to assess whether different bearing materials have an impact on femoral bone remodeling within the first four years after a hybrid total hip arthroplasty. 205 of 300 patients were available for 4 years follow-up after being randomly allocated to four prosthetic...... 1, 6, and 7.Bone remodeling after total hip arthroplasty may depend on the composition of bearing materials, but age, height, weight, and stem size are also related to changes in BMD....

  2. Changes in the population of perivascular cells in the bone tissue remodeling zones under microgravity

    Science.gov (United States)

    Katkova, Olena; Rodionova, Natalia; Shevel, Ivan

    2016-07-01

    Microgravity and long-term hypokinesia induce reduction both in bone mass and mineral saturation, which can lead to the development of osteoporosis and osteopenia. (Oganov, 2003). Reorganizations and adaptive remodeling processes in the skeleton bones occur in the topographical interconnection with blood capillaries and perivascular cells. Radioautographic studies with 3H- thymidine (Kimmel, Fee, 1980; Rodionova, 1989, 2006) have shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic. Hence the study of populations of perivascular stromal cells in areas of destructive changes is actual. Perivascular cells from metaphysis of the rat femoral bones under conditions of modeling microgravity were studied using electron microscopy and cytochemistry (hindlimb unloading, 28 days duration) and biosatellite «Bion-M1» (duration of flight from April 19 till May 19, 2013 on C57, black mice). It was revealed that both control and test groups populations of the perivascular cells are not homogeneous in remodeling adaptive zones. These populations comprise of adjacent to endothelium poorly differentiated forms and isolated cells with signs of differentiation (specific increased volume of rough endoplasmic reticulum in cytoplasm). Majority of the perivascular cells in the control group (modeling microgravity) reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In poorly differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of experimental animals reaction to the alkaline phosphatase is registered not in all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. Under microgravity some poorly differentiated perivascular

  3. The role of muscle loading on bone (Remodeling at the developing enthesis.

    Directory of Open Access Journals (Sweden)

    Alexander M Tatara

    Full Text Available Muscle forces are necessary for the development and maintenance of a mineralized skeleton. Removal of loads leads to malformed bones and impaired musculoskeletal function due to changes in bone (remodeling. In the current study, the development of a mineralized junction at the interface between muscle and bone was examined under normal and impaired loading conditions. Unilateral mouse rotator cuff muscles were paralyzed using botulinum toxin A at birth. Control groups consisted of contralateral shoulders injected with saline and a separate group of normal mice. It was hypothesized that muscle unloading would suppress bone formation and enhance bone resorption at the enthesis, and that the unloading-induced bony defects could be rescued by suppressing osteoclast activity. In order to modulate osteoclast activity, mice were injected with the bisphosphonate alendronate. Bone formation was measured at the tendon enthesis using alizarin and calcein fluorescent labeling of bone surfaces followed by quantitative histomorphometry of histologic sections. Bone volume and architecture was measured using micro computed tomography. Osteoclast surface was determined via quantitative histomorphometry of tartrate resistant acid phosphatase stained histologic sections. Muscle unloading resulted in delayed initiation of endochondral ossification at the enthesis, but did not impair bone formation rate. Unloading led to severe defects in bone volume and trabecular bone architecture. These defects were partially rescued by suppression of osteoclast activity through alendronate treatment, and the effect of alendronate was dose dependent. Similarly, bone formation rate was increased with increasing alendronate dose across loading groups. The bony defects caused by unloading were therefore likely due to maintained high osteoclast activity, which normally decreases from neonatal through mature timepoints. These results have important implications for the treatment of

  4. Peptide YY regulates bone remodeling in mice: a link between gut and skeletal biology.

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    Iris P L Wong

    Full Text Available BACKGROUND & AIMS: Gastrointestinal peptides are increasingly being linked to processes controlling the maintenance of bone mass. Peptide YY (PYY, a gut-derived satiety peptide of the neuropeptide Y family, is upregulated in some states that also display low bone mass. Importantly, PYY has high affinity for Y-receptors, particularly Y1R and Y2R, which are known to regulate bone mass. Anorexic conditions and bariatric surgery for obesity influence circulating levels of PYY and have a negative impact on bone mass, but the precise mechanism behind this is unclear. We thus examined whether alterations in PYY expression affect bone mass. METHODS: Bone microstructure and cellular activity were analyzed in germline PYY knockout and conditional adult-onset PYY over-expressing mice at lumbar and femoral sites using histomorphometry and micro-computed tomography. RESULTS: PYY displayed a negative relationship with osteoblast activity. Male and female PYY knockout mice showed enhanced osteoblast activity, with greater cancellous bone mass. Conversely, PYY over-expression lowered osteoblast activity in vivo, via a direct Y1 receptor mediated mechanism involving MAPK stimulation evident in vitro. In contrast to PYY knockout mice, PYY over expression also altered bone resorption, as indicated by greater osteoclast surface, despite the lack of Y-receptor expression in osteoclastic cells. While evident in both sexes, cellular changes were generally more pronounced in females. CONCLUSIONS: These data demonstrate that the gut peptide PYY is critical for the control of bone remodeling. This regulatory axis from the intestine to bone has the potential to contribute to the marked bone loss observed in situations of extreme weight loss and higher circulating PYY levels, such as anorexia and bariatric obesity surgery, and may be important in the maintenance of bone mass in the general population.

  5. Bone morphogenetic protein-2: a potential regulator in scleral remodeling

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    Hu, Jianmin; Cui, Dongmei; Yang, Xiao; Wang, Shaowei; Hu, Shoulong; Li, Chuanxu

    2008-01-01

    Purpose Bone morphogenetic protein 2 (BMP-2) is a member of the main subgroup of bone morphogenetic proteins within the transforming growth factor-β superfamily. BMP-2 is involved in numerous cellular functions including development, cell proliferation, apoptosis, and extracellular matrix synthesis. We examined BMP-2 expression in human scleral fibroblasts (HSF) and assessed the effects of recombinant human BMP-2 (rhBMP-2) on HSF proliferation, matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-2 (TIMP-2). Methods We used confocal fluorescence microscopy (CFM) to study BMP-2 distribution in HSF cells and frozen human scleral sections. The influence of rhBMP-2 on cell proliferation at different concentrations (0 ng/ml, 1 ng/ml, 10 ng/ml, and 100 ng/ml) was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The effects of rhBMP-2 on the cell cycle were investigated with flow cytometric analysis. Reverse transcription polymerase chain reaction (RT–PCR) and enzyme-linked immunosorbent assay (ELISA) were used to examine MMP-2 and TIMP-2 mRNAs and secreted proteins in HSF that were incubated with rhBMP-2. Results BMP-2 protein expression from human sclera was confirmed by CFM. Cell proliferation was significantly increased with 100 ng/ml rhBMP-2 in a time-dependent manner (p<0.05). The HSF cell cycle moved to the S and S+G2M phases after rhBMP-2 stimulation at 100 ng/ml compared to normal cells (p<0.05). TIMP-2 mRNA levels were significantly increased in HSF incubated for 24 h with 100 ng/ml rhBMP-2 (p<0.01). A 48 h incubation with 10 ng/ml or 100 ng/ml rhBMP-2 resulted in significantly increased TIMP-2 mRNA and protein expression and significantly decreased MMP-2 mRNA expression (p<0.01) while MMP-2 protein expression significantly decreased at 100 ng/ml rhBMP-2 (p<0.01). Conclusions Human sclera fibroblasts expressed BMP-2, which promoted cell proliferation, and elicited changes in MMP-2 and TIMP-2

  6. Analysis of donor sites for mandibular bone grafts by computerized cone beam tomography to evaluate bone remodeling

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    Thomaz Wassall

    2009-01-01

    Full Text Available Objective: To analyze the graft donor site (posterior region of the mandible by means of cone-beam volumetric tomographies to assess boneremodeling, verifying the degree of morbidity with regard to this parameter. Methods: The sample was composed of twenty individuals, irrespective of age, gender and ASA I and ASA II surgical risk classification. Three volume computed tomographies were performed: one before surgery, another seven days after surgery and the last 180 days after surgery. Image acquisition by volumetric cone-beam tomography and the computer program Dental Slice were used to make the measurements. Results: Statistics showed that there was significant bone remodeling. Although there are several concerns about the graft donor sites, no data were obtained in the literature, about the assessment of bone remodeling of the donor site. Conclusion: Mean remodeling in the posterior region of the mandible, assessed 180 days after graft removal is 81.3%, on an average, andmorbidity in the posterior donor site of the mandible has been small, when compared with the other donor sites, both intra-oral and extra-oral, according to the data in the specific literature.

  7. Adaptive Bone Remodeling of the Femoral Bone After Tumor Resection Arthroplasty With an Uncemented Proximally Hydroxyapatite-Coated Stem.

    Science.gov (United States)

    Andersen, Mikkel R; Petersen, Michael M

    2016-01-01

    Loss of bone stock and stress shielding is a significant challenge in limb salvage surgery. This study investigates the adaptive bone remodeling of the femoral bone after implantation of a tumor prosthesis with an uncemented press fit stem. We performed a prospective 1 yr follow-up of 6 patients (mean age: 55 (26-78) yr, female/male=3/3) who underwent bone tumor resection surgery of the proximal femur (n=3) or distal femur (n=3). Reconstruction was done using a Global Modular Replacement System (Stryker® Orthopaedics, Mahwah, NJ) tumor prosthesis, and all patients received a straight-fluted 125-mm uncemented press-fit titanium alloy stem with hydroxyapatite coating of the proximal part of the stem. Measurements of bone mineral density (BMD; g/cm2) were done postoperatively and after 3, 6, and 12 mo in the part of the femur bone containing the Global Modular Replacement System stem using dual-energy X-ray absorptiometry. BMD was measured in 3 regions of interest (ROIs) in the femur bone. Nonparametric analysis of variance (Friedman test) for evaluation of changes in BMD over time. BMD decreased in all 3 ROIs with time. In ROI 1 (p=0.01), BMD decreased by 10% after 3 mo and ended with a total decrease of 14% after 1 yr. In ROI 2 (p=0.006), BMD was decreased by 6% after 3 and 6 mo; after 1 yr of follow-up, BMD was 9% below the postoperative value. In ROI 3 (p=0.009), BMD decreased by 6% after 3 and 6 mo; after 1 yr of follow-up, BMD was 8% below the postoperative value. A bone loss of 8%-9% during the first postoperative year was seen along the femoral stem, but in the bone containing the hydroxyapatite-coated part of the stem, the decrease in BMD was 14%, thus indicating that stress shielding of this part of the bone may play a role for the adaptive bone remodeling. PMID:25843447

  8. The Regulatory Roles of MicroRNAs in Bone Remodeling and Perspectives as Biomarkers in Osteoporosis

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    Mengge Sun

    2016-01-01

    Full Text Available MicroRNAs are involved in many cellular and molecular activities and played important roles in many biological and pathological processes, such as tissue formation, cancer development, diabetes, neurodegenerative diseases, and cardiovascular diseases. Recently, it has been reported that microRNAs can modulate the differentiation and activities of osteoblasts and osteoclasts, the key cells that are involved in bone remodeling process. Meanwhile, the results from our and other research groups showed that the expression profiles of microRNAs in the serum and bone tissues are significantly different in postmenopausal women with or without fractures compared to the control. Therefore, it can be postulated that microRNAs might play important roles in bone remodeling and that they are very likely to be involved in the pathological process of postmenopausal osteoporosis. In this review, we will present the updated research on the regulatory roles of microRNAs in osteoblasts and osteoclasts and the expression profiles of microRNAs in osteoporosis and osteoporotic fracture patients. The perspective of serum microRNAs as novel biomarkers in bone loss disorders such as osteoporosis has also been discussed.

  9. The Regulatory Roles of MicroRNAs in Bone Remodeling and Perspectives as Biomarkers in Osteoporosis.

    Science.gov (United States)

    Sun, Mengge; Zhou, Xiaoya; Chen, Lili; Huang, Shishu; Leung, Victor; Wu, Nan; Pan, Haobo; Zhen, Wanxin; Lu, William; Peng, Songlin

    2016-01-01

    MicroRNAs are involved in many cellular and molecular activities and played important roles in many biological and pathological processes, such as tissue formation, cancer development, diabetes, neurodegenerative diseases, and cardiovascular diseases. Recently, it has been reported that microRNAs can modulate the differentiation and activities of osteoblasts and osteoclasts, the key cells that are involved in bone remodeling process. Meanwhile, the results from our and other research groups showed that the expression profiles of microRNAs in the serum and bone tissues are significantly different in postmenopausal women with or without fractures compared to the control. Therefore, it can be postulated that microRNAs might play important roles in bone remodeling and that they are very likely to be involved in the pathological process of postmenopausal osteoporosis. In this review, we will present the updated research on the regulatory roles of microRNAs in osteoblasts and osteoclasts and the expression profiles of microRNAs in osteoporosis and osteoporotic fracture patients. The perspective of serum microRNAs as novel biomarkers in bone loss disorders such as osteoporosis has also been discussed.

  10. Histological Comparison in Rats between Carbonate Apatite Fabricated from Gypsum and Sintered Hydroxyapatite on Bone Remodeling

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    Yasunori Ayukawa

    2015-01-01

    Full Text Available Carbonate apatite (CO3Ap, the form of apatite found in bone, has recently attracted attention. The purpose of the present study was to histologically evaluate the tissue/cellular response toward the low-crystalline CO3Ap fabricated using a dissolution-precipitation reaction with set gypsum as a precursor. When set gypsum was immersed in a 100°C 1 mol/L Na3PO4 aqueous solution for 24 h, the set gypsum transformed into CO3Ap. Both CO3Ap and sintered hydroxyapatite (s-HAp, which was used as a control, were implanted into surgically created tibial bone defects of rats for histological evaluation. Two and 4 weeks after the implantation, histological sections were created and observed using light microscopy. The CO3Ap granules revealed both direct apposition of the bone matrix by osteoblasts and osteoclastic resorption. In contrast, the s-HAp granules maintained their contour even after 4 weeks following implantation which implied that there was a lack of replacement into the bone. The s-HAp granules were sometimes encapsulated with fibrous tissue, and macrophage polykaryon was occasionally observed directly apposed to the implanted granules. From the viewpoint of bone remodeling, the CO3Ap granules mimicked the bone matrix, suggesting that CO3Ap may be an appropriate bone substitute.

  11. Differentiation potentials of perivascular cells in the bone tissue remodeling zones under microgravity

    Science.gov (United States)

    Rodionova, Natalia; Katkova, Olena

    Adaptive remodeling processes in the skeleton bones occur in the close topographical interconnection with blood capillaries followed by perivascular cells. Radioautographic studies with 3Н- thymidine (Kimmel D.B., Fee W.S., 1980; Rodionova N.V., 1989, 2006) has shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic ones. Using electron microscopy and cytochemistry we studied perivsacular cells in metaphysis of the rats femoral bones under conditions of modeling microgravity (28 days duration) and in femoral bonеs metaphyses of rats flown on board of the space laboratory (Spacelab - 2) It was revealed that population of the perivascular cells is not homogeneous in adaptive zones of the remodeling in both control and test groups (lowering support loading). This population comprises adjacent to endothelium little differentiated forms and isolated cells with differentiation features (specific volume of rough endoplasmic reticulum in cytoplasm is increased). Majority of the perivascular cells in the control group reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In little differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of animals under microgravitaty reaction to the alkaline phosphatase is registered not for all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. There is also visible trend of individual alkaline phosphatase containing perivascular cells amounts decrease (i.e. osteogenic cells-precursors). Under microgravity some little differentiated perivascular cells reveal destruction signs. Found decrease trend of the alkaline phosphatase containing cells (i.e. osteogenic cells) number in

  12. Periosteal PTHrP Regulates Cortical Bone Remodeling During Fracture Healing.

    Science.gov (United States)

    Wang, Meina; Nasiri, Ali R; Broadus, Arthur E; Tommasini, Steven M

    2015-12-01

    Parathyroid hormone-related protein (PTHrP) is widely expressed in the fibrous outer layer of the periosteum (PO), and the PTH/PTHrP type I receptor (PTHR1) is expressed in the inner PO cambial layer. The cambial layer gives rise to the PO osteoblasts (OBs) and osteoclasts (OCs) that model/remodel the cortical bone surface during development as well as during fracture healing. PTHrP has been implicated in the regulation of PO modeling during development, but nothing is known as regards a role of PTHrP in this location during fracture healing. We propose that PTHrP in the fibrous layer of the PO may be a key regulatory factor in remodeling bone formation during fracture repair. We first assessed whether PTHrP expression in the fibrous PO is associated with PO osteoblast induction in the subjacent cambial PO using a tibial fracture model in PTHrP-lacZ mice. Our results revealed that both PTHrP expression and osteoblast induction in PO were induced 3 days post-fracture. We then investigated a potential functional role of PO PTHrP during fracture repair by performing tibial fracture surgery in 10-week-old CD1 control and PTHrP conditional knockout (PTHrP cKO) mice that lack PO PTHrP. We found that callus size and formation as well as woven bone mineralization in PTHrP cKO mice were impaired compared to that in CD1 mice. Concordant with these findings, functional enzyme staining revealed impaired OB formation and OC activity in the cKO mice. We conclude that deleting PO PTHrP impairs cartilaginous callus formation, maturation and ossification as well as remodeling during fracture healing. These data are the initial genetic evidence suggesting that PO PTHrP may induce osteoblastic activity and regulate fracture healing on the cortical bone surface. PMID:26164475

  13. Low-dose hydrocortisone (HC) replacement therapy is associated with improved bone remodeling balance in hypopituitary subjects

    LENUS (Irish Health Repository)

    Behan, L A

    2011-06-01

    The effect of commonly used glucocorticoid replacement regimens on bone health in hypopituitary subjects is not well known. We aimed to assess the effect of 3 hydrocortisone (HC) replacement dose regimens on bone turnover in this group.10 hypopituitary men with severe ACTH deficiency were randomised in a crossover design to 3 HC dose regimens, Dose A (20mg mane, 10mg tarde), Dose B (10mg twice daily) and Dose C (10mg mane, 5mg tarde). Following 6 weeks of each regimen participants underwent fasting sampling of bone turnover markers.Data from matched controls were used to produce a Z score for subject bone formation and resorption markers and to calculate the bone remodeling balance (formation Z score-resorption Z score) and turnover index ((formation Z + resorption Z)\\/2). A positive bone remodeling balance with increased turnover is consistent with a favourable bone cycle. Data are expressed as median (range).The Pro Collagen Type 1 Peptide (PINP) bone formation Z-score was significantly increased in Dose C, (1.805 (-0.6-10.24)) compared to Dose A (0.035 (-1.0-8.1)) p<0.05 while there was no difference in the C-terminal crosslinking telopeptide (CTx) resorption Z score. The bone remodeling balance was significantly lower for dose A -0.02 (-1.05-4.12) compared to dose C 1.13 (0.13-6.4) (p<0.05). Although there was a trend to an increased bone turnover index with the lower dose regimen, this was not statistically significant.Low dose HC replacement (10mg mane\\/5 mg tarde) was associated with increased bone formation and improved bone remodeling balance which is associated with a more favourable bone cycle. This may have a long term beneficial effect on bone health.

  14. Impaired bone remodeling and its correction by combination therapy in a mouse model of mucopolysaccharidosis-I.

    Science.gov (United States)

    Kuehn, Sonja C; Koehne, Till; Cornils, Kerstin; Markmann, Sandra; Riedel, Christoph; Pestka, Jan M; Schweizer, Michaela; Baldauf, Christina; Yorgan, Timur A; Krause, Matthias; Keller, Johannes; Neven, Mona; Breyer, Sandra; Stuecker, Ralf; Muschol, Nicole; Busse, Bjoern; Braulke, Thomas; Fehse, Boris; Amling, Michael; Schinke, Thorsten

    2015-12-15

    Mucopolysaccharidosis-I (MPS-I) is a lysosomal storage disease (LSD) caused by inactivating mutations of IDUA, encoding the glycosaminoglycan-degrading enzyme α-l-iduronidase. Although MPS-I is associated with skeletal abnormalities, the impact of IDUA deficiency on bone remodeling is poorly defined. Here we report that Idua-deficient mice progressively develop a high bone mass phenotype with pathological lysosomal storage in cells of the osteoblast lineage. Histomorphometric quantification identified shortening of bone-forming units and reduced osteoclast numbers per bone surface. This phenotype was not transferable into wild-type mice by bone marrow transplantation (BMT). In contrast, the high bone mass phenotype of Idua-deficient mice was prevented by BMT from wild-type donors. At the cellular level, BMT did not only normalize defects of Idua-deficient osteoblasts and osteocytes but additionally caused increased osteoclastogenesis. Based on clinical observations in an individual with MPS-I, previously subjected to BMT and enzyme replacement therapy (ERT), we treated Idua-deficient mice accordingly and found that combining both treatments normalized all histomorphometric parameters of bone remodeling. Our results demonstrate that BMT and ERT profoundly affect skeletal remodeling of Idua-deficient mice, thereby suggesting that individuals with MPS-I should be monitored for their bone remodeling status, before and after treatment, to avoid long-term skeletal complications. PMID:26427607

  15. A histomorphometric study of alveolar bone modeling and remodeling in mice fed a boron-deficient diet

    Science.gov (United States)

    Background and Objective: Emerging evidence indicates that boron (B) plays a role in bone formation and maintenance. Thus, a study was performed to determine whether dietary B-deficiency affects periodontal alveolar bone modeling and remodeling. Material and Methods: Weanling Swiss mice (n=30) were ...

  16. The effect of bisphosphonate treatment on the biochemical and cellular events during bone remodelling in response to microinjury stimulation.

    Science.gov (United States)

    Mulcahy, L E; Curtin, C M; McCoy, R J; O'Brien, F J; Taylor, D; Lee, T C; Duffy, G P

    2015-01-01

    Osteoporosis is one of the most prevalent bone diseases worldwide and is characterised by high levels of bone turnover, a marked loss in bone mass and accumulation of microdamage, which leads to an increased fracture incidence that places a huge burden on global health care systems. Bisphosphonates have been used to treat osteoporosis and have shown great success in conserving bone mass and reducing fracture incidence. In spite of the existing knowledge of the in vivo responses of bone to bisphosphonates, the cellular responses to these drugs have yet to be fully elucidated. In vitro model systems that allow the decoupling of complex highly integrated events, such as bone remodelling, provide a tool whereby these biological processes may be studied in a more simplified context. This study firstly utilised an in vitro model system of bone remodelling and comprising all three major cell types of the bone (osteocytes, osteoclasts and osteoblasts), which was representative of the bone's capacity to sense microdamage and subsequently initiate a basic multicellular unit response. Secondly, this system was used to study the effect of two commonly utilised aminobisphosphonate treatments for osteoporosis, alendronate and zoledronate. We demonstrated that microinjury to osteocyte networks being treated with bisphosphonates modulates receptor activator of nuclear factor kappa-B ligand and osteoprotegerin activity, and subsequently osteoclastogenesis. Furthermore, bisphosphonates increased the osteogenic potential following microinjury. Thus, we have shown for the first time that bisphosphonates act at all three stages of bone remodelling, from microinjury to osteoclastogenesis and ultimately osteogenesis. PMID:26614482

  17. Longitudinal assessment of in vivo bone dynamics in a mouse tail model of postmenopausal osteoporosis.

    Science.gov (United States)

    Lambers, Floor M; Kuhn, Gisela; Schulte, Friederike A; Koch, Kathleen; Müller, Ralph

    2012-02-01

    Recently, it has been shown that transient bone biology can be observed in vivo using time-lapse micro-computed tomography (μCT) in the mouse tail bone. Nevertheless, in order for the mouse tail bone to be a model for human disease, the hallmarks of any disease must be mimicked. The aim of this study was to investigate whether postmenopausal osteoporosis could be modeled in caudal vertebrae of C57Bl/6 mice, considering static and dynamic bone morphometry as well as mechanical properties, and to describe temporal changes in bone remodeling rates. Twenty C57Bl/6 mice were ovariectomized (OVX, n = 11) or sham-operated (SHM, n = 9) and monitored with in vivo μCT on the day of surgery and every 2 weeks after, up to 12 weeks. There was a significant decrease in bone volume fraction for OVX (-35%) compared to SHM (+16%) in trabecular bone (P bone loss was observed, with the bone resorption rate exceeding the bone formation rate (P bone stiffness for OVX (-16%) compared to SHM (+11%, P tail vertebra mimics postmenopausal bone loss with respect to these parameters and therefore might be a suitable model for postmenopausal osteoporosis. When evaluating temporal changes in remodeling rates, we found that OVX caused an immediate increase in bone resorption rate (P bone formation rate (P bone biology is a promising method for future research.

  18. Bone effects of space flight analysis by quantum concept of bone remodelling

    Science.gov (United States)

    Parfitt, A. M.

    During the manned Skylab flights mineral losses from the calcaneum and changes in external calcium balance were in the ranges found for healthy subjects at bedrest. Calcium balance reached a nadir of -200 mg/day by two months with no change thereafter; the negative balance was due to increased urinary excretion with no change in net absorption. The total calcium loss averaged 18 g in the longest flight of 84 days; the densitiometric data suggested that about two-thirds of this came from trabecular bone and about one-third from cortical bone. These data could represent reversible bone loss due to increased birth rate of normal osteoclasts and osteoblasts and consequent increase in bone turnover and in reversible mineral deficit, or irreversible bone loss due to overactive osteoclasts and/or underactive osteoblasts. If the former explanation is correct, significant bone loss is unlikely whatever the duration of future flights, except in older persons already losing bone; if the latter explanation is correct, space flights longer than six months may lead to a significant increase in fracture risk in later life. Neither terrestrial immobilization nor unwilling animals in orbit are ideal models for the effects of space flight on human bone. To choose between reversible and irreversible mechanisms of bone loss, and to determine the effects of space flight on lifelong fracture risk, future astronauts and cosmonauts must undergo adequate histologic study of bone after in vivo tetracycline labeling.

  19. Involvement of the Nonneuronal Cholinergic System in Bone Remodeling in Rat Midpalatal Suture after Rapid Maxillary Expansion

    Science.gov (United States)

    Guo, Jie; Wang, Lue; Miao, Cong; Ge, Lihua; Tian, Zhenchuan; Wang, Jianhong

    2016-01-01

    Few studies sought to analyze the expression and function of the nonneuronal acetylcholine system in bone remodeling in vivo due to the lack of suitable models. We established a rat maxilla expansion model in which the midline palatine suture of the rat was rapidly expanded under mechanical force application, inducing tissue remodeling and new bone formation, which could be a suitable model to investigate the role of the nonneuronal acetylcholine system in bone remodeling in vivo. During the expansion, the expression pattern changes of the nonneuronal cholinergic system components and the mRNA levels of OPG/RANKL were detected by immunohistochemistry or real-time PCR. The value of the RANKL/OPG ratio significantly increased after 1 day of expansion, indicating dominant bone resorption induced by the mechanical stimulation; however after 3 days of expansion, the value of the RANKL/OPG ratio significantly decreased, suggesting a dominant role of the subsequent bone formation process. Increasing expression of Ach was detected after 3 days of expansion which indicated that ACh might play a role in bone formation. The mRNA expression levels of other components also showed observable changes during the expansion which confirmed the involvement of the nonneuronal cholinergic system in the process of bone remodeling in vivo. Further researches are still needed to figure out the detailed functions of the nonneuronal cholinergic system and its components. PMID:27478838

  20. Remodelling of bone and bones. Effects of altered mechanical stress on anlages.

    Science.gov (United States)

    Storey, E; Feik, S A

    1982-04-01

    Tails from 4-day-old Sprague-Dawley rats were bent in situ or skinned bent tail segments were transplanted s.c. into 50 g hosts. Tissue changes were studied for up to 24 weeks by radiographic and histological techniques. The early changes in situ resulted largely from limited translation of bones within their encasing tissues with resorption on the leading (pressure) side inducing thinning, and on the trailing (tension) side thickening of bone. The changes in transplanted anlages occurred in 3 stages: initially, bending of the anlages, with tension between the stretched periosteum and the outer bone surface inducing formation, and compression of cartilage and bone on the inner aspect leading to resorption; then resumption of longitudinal growth and expansion of the bent loop leading to translation of bones within the encasing soft tissues with resorption and thinning of bone on the leading pressure side and formation, with thickening of the inner shaft, on the trailing tension side; and finally with cessation of growth and translation, a reversal to the previous phase. The results support the hypothesis that 2 processes are involved: first, internal stress, and second, translation of bones with, in all instances, pressure inducing resorption and tension inducing formation of bone.

  1. Nicotine effect on bone remodeling during orthodontic tooth movement: Histological study in rats

    Directory of Open Access Journals (Sweden)

    Ricardo Lima Shintcovsk

    2014-04-01

    Full Text Available Introduction: Nicotine is harmful to angiogenesis, osteogenesis and synthesis of collagen. Objective: The aim of this study was to investigate the effect of nicotine on bone remodeling during orthodontic movement in rats. Methods: Eighty male Wistar rats were randomly divided into three groups: Group C (control, group CM (with orthodontic movement and group NM (nicotine with orthodontic movement groups. The animals comprising groups C and CM received 0.9% saline solution while group NM received nicotine solution (2 mg/kg. A nickel-titanium closed-coil spring was used to induce tooth movement. The animals were euthanized and tissue specimens were processed histologically. We quantified blood vessels, Howship's lacunae and osteoclast-like cells present in the tension and compression areas of periodontal ligaments. The extent of bone formation was evaluated under polarized light to determine the percentage of immature/mature collagen. Results: We observed lower blood vessel densities in the NM group in comparison to the CM group, three (p < 0.001 and seven (p < 0.05 days after force application. Osteoclast-like cells and Howship's lacunae in the NM group presented lower levels of expression in comparison to the CM group, with significant differences on day 7 (p < 0.05 for both variables and day 14 (p < 0.05 for osteoclast-like cells and p < 0.01 for Howship's lacunae. The percentage of immature collagen increased in the NM group in comparison to the CM group with a statistically significant difference on day 3 (p < 0.05, day 7 (p < 0.001, day 14 (p < 0.001 and day 21 (p < 0.001. Conclusions: Nicotine affects bone remodeling during orthodontic movement, reducing angiogenesis, osteoclast-like cells and Howship's lacunae, thereby delaying the collagen maturation process in developed bone matrix.

  2. Growth and the modeling/remodeling of the alveolar bone of the rat incisor.

    Science.gov (United States)

    Merzel, José; Salmon, Cristiane R

    2008-07-01

    The modeling and remodeling of the rat incisor alveolar bone was followed as the animals grew. The weight of the hemimandible, the length of the socket, and the width of the lower incisor were measured. Osteoclasts and resorption areas were identified by tartrate-resistant acid phosphatase staining. Fluorochrome markers were used to detect and measure osteogenic activities. In the socket related to the periodontal ligament, osteoclasts appeared in scattered sites as well as isolated sites of osteogenic activity, apparently without any variation related to the age of the animals. At the socket facing the dental follicle of young rats, the inner surface was lined with osteoclasts. The number of osteoclasts decreased steadily as the rats grew. In 1-year-old rats, in addition to a few scattered osteoclasts, the internal aspect of the labial wall showed some sites lined with osteoblasts and cement lines indicative of prior bone formation. In young rats, there was a continuous osteogenic activity at the external surface of this wall. The thickness of the labial wall of the socket remained apparently constant; therefore, bone resorption must have occurred at the internal side of the wall. Such osteogenic activity was not observed in old rats. The main forces acting on rat incisors, biting and eruption, are continuous through the life of the animals. Thus, these results indicate that the modeling of the alveolar bone related to the dental follicle, in young rats, can only be associated with another force, specifically, the growth of the incisor. PMID:18461598

  3. Functions and mechanisms of green tea catechins in regulating bone remodeling.

    Science.gov (United States)

    Shen, Chwan-Li; Kwun, In-Sook; Wang, Shu; Mo, Huanbiao; Chen, Lixia; Jenkins, Marjorie; Brackee, Gordon; Chen, Chung-Hwan; Chyu, Ming-Chien

    2013-12-01

    Osteoporosis is caused by an imbalance in bone remodeling, a process involving bone-building osteoblasts and bone-resorptive osteoclasts. Excessive reactive oxygen species and inflammatory responses have been shown to stimulate differentiation and function of osteoclasts while inducing osteoblast apoptosis and suppressing osteoblastic proliferation and differentiation via extracellular signal-regulated kinases (ERK), ERK-dependent nuclear factor-κB and Wnt/β-catenin signaling pathways. The anti-oxidant and anti-inflammatory green tea catechins (GTC) have been shown to promote osteoblastogenesis, suppress osteoclastogenesis and stimulate the differentiation of mesenchymal stem cells into osteoblasts rather than adipocytes by modulating the signaling pathways. This paper reviews the pharmacokinetics and metabolism of GTC, their bone-protective activities evidenced in in vitro and in vivo studies, and the limited clinical studies supporting these preclinical findings. In light of the physical, economical, and social burdens due to osteoporosis, easily accessible and affordable preventive measures such as GTC deserves further clinical studies prior to its clinical application.

  4. Numerical model of bone remodeling sensitive to loading frequency through a poroelastic behavior and internal fluid movements.

    Science.gov (United States)

    Malachanne, Etienne; Dureisseix, David; Jourdan, Franck

    2011-08-01

    In this article, a phenomenological numerical model of bone remodeling is proposed. This model is based on the poroelasticity theory in order to take into account the effects of fluid movements in bone adaptation. Moreover, the proposed remodeling law is based on the classical 'Stanford' law, enriched in order to take into account the loading frequency, through fluid movements. This coupling is materialized by a quadratic function of Darcy velocity. The numerical model is carried out, using a finite element method, and calibrated using experimental results at macroscopic level, from the literature. First results concern cyclic loadings on a mouse ulna, at different frequencies between 1 Hz and 30 Hz, for a force amplitude of 1.5 N and 2 N. Experimental results exhibit a sensitivity to the loading frequency, with privileged frequency for bone remodeling between 5 Hz and 10 Hz, for the force amplitude of 2 N. For the force amplitude of 1.5 N, no privileged frequencies for bone remodeling are highlighted. This tendency is reproduced by the proposed numerical computations. The model is identified on a single case (one frequency and one force amplitude) and validated on the other ones. The second experimental validation deals with a different loading regime, an internal fluid pressure at 20 Hz on a turkey ulna. The same framework is applied, and the numerical and experimental data are still matching in terms of gain in bone mass density. PMID:21616466

  5. Development of the lateral line canal system through a bone remodeling process in zebrafish.

    Science.gov (United States)

    Wada, Hironori; Iwasaki, Miki; Kawakami, Koichi

    2014-08-01

    The lateral line system of teleost fish is composed of mechanosensory receptors (neuromasts), comprising superficial receptors and others embedded in canals running under the skin. Canal diameter and size of the canal neuromasts are correlated with increasing body size, thus providing a very simple system to investigate mechanisms underlying the coordination between organ growth and body size. Here, we examine the development of the trunk lateral line canal system in zebrafish. We demonstrated that trunk canals originate from scales through a bone remodeling process, which we suggest is essential for the normal growth of canals and canal neuromasts. Moreover, we found that lateral line cells are required for the formation of canals, suggesting the existence of mutual interactions between the sensory system and surrounding connective tissues.

  6. Remodeling of heat-treated cortical bone allografts for posterior lumbar interbody fusion: serial 10-year follow-up.

    Science.gov (United States)

    Muramatsu, Koichi; Hachiya, Yudo; Izawa, Hiroyuki; Yamada, Harumoto

    2012-12-01

    We have selected heat-treated bone allografts as the graft material since the Tokai Bone Bank, the first regional bone bank in Japan, was established in 1992. In this study, we examined changes in bone mineral density (BMD), and morphology observed by magnetic resonance imaging (MRI), and histological findings of bone grafts in cases followed up for 7-10 years after bone grafting to grasp the remodeling of heat-treated cortical bone allografts for posterior lumber interbody fusion (PLIF). BMD of bone grafts was reduced by half at 10 years after grafting. MRI revealed that bone grafts were indistinguishable initially in only 22.2% of cases, whereas after a lengthy period of 10 years distinguishable in many cases. Histologically, new bone formation at the graft-host interface was observed earlier, at 1 year after grafting, than that at the periphery of canals in the specimens. The laminated structure of the cortical bone eroded over time, and fragmented bone trabeculae were observed in the specimens at 8 years or longer after grafting, though necrotic bone still remained in some sites.

  7. Does collagen trigger the recruitment of osteoblasts into vacated bone resorption lacunae during bone remodeling?

    DEFF Research Database (Denmark)

    Abdelgawad, Mohamed Essameldin; Søe, Kent; Andersen, Thomas Levin;

    2014-01-01

    and cell migration in various cell types, and whose inactivation is reported to lead to lack of bone formation and skeletal deformities. In the present study, an antibody directed against this receptor inhibits collagen internalization in osteoblast lineage cells and decreases to some extent...... recruitment potential are already known. Here we draw the attention on the osteoblast recruitment potential of the collagen that is freshly demineralized by the osteoclast. Our evidence is based on observations on adult human cancellous bone, combined with in vitro assays. First, freshly eroded surfaces where...... osteoblasts have to be recruited show the presence of non-degraded demineralized collagen and close cell-collagen interactions, as revealed by electron microscopy, while surface-bound collagen strongly attracts osteoblast lineage cells in a transmembrane migration assay. Compared with other extracellular...

  8. Bone-Remodeling Transcript Levels Are Independent of Perching in End-of-Lay White Leghorn Chickens

    Directory of Open Access Journals (Sweden)

    Maurice D. Dale

    2015-01-01

    Full Text Available Osteoporosis is a bone disease that commonly results in a 30% incidence of fracture in hens used to produce eggs for human consumption. One of the causes of osteoporosis is the lack of mechanical strain placed on weight-bearing bones. In conventionally-caged hens, there is inadequate space for chickens to exercise and induce mechanical strain on their bones. One approach is to encourage mechanical stress on bones by the addition of perches to conventional cages. Our study focuses on the molecular mechanism of bone remodeling in end-of-lay hens (71 weeks with access to perches. We examined bone-specific transcripts that are actively involved during development and remodeling. Using real-time quantitative PCR, we examined seven transcripts (COL2A1 (collagen, type II, alpha 1, RANKL (receptor activator of nuclear factor kappa-B ligand, OPG (osteoprotegerin, PTHLH (PTH-like hormone, PTH1R (PTH/PTHLH type-1 receptor, PTH3R (PTH/PTHLH type-3 receptor, and SOX9 (Sry-related high mobility group box in phalange, tibia and femur. Our results indicate that the only significant effect was a difference among bones for COL2A1 (femur > phalange. Therefore, we conclude that access to a perch did not alter transcript expression. Furthermore, because hens have been used as a model for human bone metabolism and osteoporosis, the results indicate that bone remodeling due to mechanical loading in chickens may be a product of different pathways than those involved in the mammalian model.

  9. Dynamic scintigraphy of bone and bone marrow in multiple myeloma patients with bone-marrow transplants

    International Nuclear Information System (INIS)

    Purpose: To determine whether dynamic registration at bone and bone-marrow scintigraphy produces additional information compared to subsequent static registrations of bone-marrow transplants in multiple myeloma patients. Material and Methods: In a prospective study, 8 dynamic bone and 6 dynamic bone-marrow scintigraphies were performed in 10 patients. The dynamic scintigraphies were compared with conventional radiography, MR images, and static scintigraphies of bone and bone marrow. Results: No additional information was revealed by the dynamic registration method; on the contrary, 4 of the 8 known lesions were not discerned at dynamic registration. An incidental observation was that the time-activity curves of both radiopharmaceuticals had a specific pattern. (orig.)

  10. Numerical evaluation of bone remodelling associated with trans-femoral osseointegration implant--A 68 month follow-up study.

    Science.gov (United States)

    Xu, D H; Crocombe, A D; Xu, W

    2016-02-01

    Osseointegrated trans-femoral implant is a relatively new orthopaedic anchoring method for connecting a stump with a prosthesis. Through a follow-up study of a patient over six years, significant bone remodelling has been observed. Finite element (FE) simulations were carried out to investigate the relationship between the bone remodelling and the strain re-distribution around the trans-femoral osseointegrated implant system. An initial FE model representing the original status of the femur-implant assembly was created from CT scans of the subject prior to osseointegration. Follow-up X-ray images were acquired at various stages post-surgery, which allowed the changes in bone wall thickness to be measured. By updating the bone thickness in the initial model, a series of follow-up FE models were created. Representative load associated with the subject's body weight was applied to the models, and the strain re-distributions were calculated. The results showed that in order to minimise the adverse effect of bone remodelling, an osseointegration implant made by functionally gradient materials are preferred over homogeneous materials. PMID:26776932

  11. Mid-term study of bone remodeling after femoral cemented stem implantation: comparison between DXA and finite element simulation.

    Science.gov (United States)

    Herrera, Antonio; Rebollo, Sarai; Ibarz, Elena; Mateo, Jesús; Gabarre, Sergio; Gracia, Luis

    2014-01-01

    This five-year prospective study was designed to investigate periprosthetic bone remodeling associated with two cemented stem models, ABG-II (Stryker) and VerSys (Zimmer), randomly implanted in patients older than 75 years. The sample consisted of 64 cases (32, ABG-II; 32, VerSys). Inclusion criterion was diagnosis of osteoarthritis recommended for cemented total hip arthroplasty. Besides clinical study, Finite Element (FE) simulation was used to analyze biomechanical changes caused by hip arthroplasty. Bone Mineral Density (BMD) measurements showed a progressive increase in bone mass throughout the entire follow-up period for both stems, well correlated with FE results except in Gruen zones 4, 5, 6 for ABG-II and in zones 4, 5 for VerSys, denoting that remodeling in those zones does not depend on mechanical factors but rather on biological or physiological ones. PMID:23725926

  12. Effects of Resveratrol Supplementation on Bone Growth in Young Rats and Microarchitecture and Remodeling in Ageing Rats

    Directory of Open Access Journals (Sweden)

    Alice M. C. Lee

    2014-12-01

    Full Text Available Osteoporosis is a highly prevalent skeletal disorder in the elderly that causes serious bone fractures. Peak bone mass achieved at adolescence has been shown to predict bone mass and osteoporosis related risk fracture later in life. Resveratrol, a natural polyphenol compound, may have the potential to promote bone formation and reduce bone resorption. However, it is unclear whether it can aid bone growth and bone mass accumulation during rapid growth and modulate bone metabolism during ageing. Using rat models, the current study investigated the potential effects of resveratrol supplementation during the rapid postnatal growth period and in late adulthood (early ageing on bone microarchitecture and metabolism. In the growth trial, 4-week-old male hooded Wistar rats on a normal chow diet were given resveratrol (2.5 mg/kg/day or vehicle control for 5 weeks. In the ageing trial, 6-month-old male hooded Wistar rats were treated with resveratrol (20 mg/kg/day or vehicle for 3 months. Treatment effects in the tibia were examined by μ-computer tomography (μ-CT analysis, bone histomorphometric measurements and reverse transcription-polymerase chain reaction (RT-PCR gene expression analysis. Resveratrol treatment did not affect trabecular bone volume and bone remodeling indices in the youth animal model. Resveratrol supplementation in the early ageing rats tended to decrease trabecular bone volume, Sirt1 gene expression and increased expression of adipogenesis-related genes in bone, all of which were statistically insignificant. However, it decreased osteocalcin expression (p = 0.03. Furthermore, serum levels of bone resorption marker C-terminal telopeptides type I collagen (CTX-1 were significantly elevated in the resveratrol supplementation group (p = 0.02 with no changes observed in serum levels of bone formation marker alkaline phosphatase (ALP. These results in rat models suggest that resveratrol supplementation does not significantly affect bone

  13. Effects of particle size and porosity on in vivo remodeling of settable allograft bone/polymer composites.

    Science.gov (United States)

    Prieto, Edna M; Talley, Anne D; Gould, Nicholas R; Zienkiewicz, Katarzyna J; Drapeau, Susan J; Kalpakci, Kerem N; Guelcher, Scott A

    2015-11-01

    Established clinical approaches to treat bone voids include the implantation of autograft or allograft bone, ceramics, and other bone void fillers (BVFs). Composites prepared from lysine-derived polyurethanes and allograft bone can be injected as a reactive liquid and set to yield BVFs with mechanical strength comparable to trabecular bone. In this study, we investigated the effects of porosity, allograft particle size, and matrix mineralization on remodeling of injectable and settable allograft/polymer composites in a rabbit femoral condyle plug defect model. Both low viscosity and high viscosity grafts incorporating small (<105 μm) particles only partially healed at 12 weeks, and the addition of 10% demineralized bone matrix did not enhance healing. In contrast, composite grafts with large (105-500 μm) allograft particles healed at 12 weeks postimplantation, as evidenced by radial μCT and histomorphometric analysis. This study highlights particle size and surface connectivity as influential parameters regulating the remodeling of composite bone scaffolds. PMID:25581686

  14. Characterization of a new fish-derived bioactive neuropeptide involved in bone remodelling. Its physiological function and therapeutic potential.

    Directory of Open Access Journals (Sweden)

    Paula Suarez-Bregua

    2014-04-01

    Full Text Available A complex network of autocrine and paracrine signals, hormones and neuronal factors preserve the structural integrity of the skeleton and regulate mineral metabolism in vertebrates. We have characterized a new neuropeptide belonging to parathyroid hormone (PTH family. PTH family members are known to play a key role in maintaining mineral homeostasis, bone remodeling and in regulating embryonic development of skeleton and other tissues. This new neuropeptide is synthesized by two clusters of neurons located in lateral hypothalamus as showed in whole mount in situ hybridization. The functional characterization of the gene using a stable transgenic line revealed its key role in the regulation of bone mineral density. Moreover, phylogenetic analyses and comparative genomics results of conserved synteny reveal that this new neuropeptide is a new ohnolog of the PTH family present in teleosts and some tetrapods like chicken, but absent in mammals . Our findings suggest a new brain to bone pathway, where neuronal factors from hypothalamus signal to receptors on bone cells promoting bone remodeling. Further investigations about this new neuropeptide system would be relevant for developing therapies for bone mineral disorders in humans, since this neuropeptide has a conserved domain similar to other PTH-related peptides which have anabolic effects on bone.

  15. Histone deacetylase 3 supports endochondral bone formation by controlling cytokine signaling and matrix remodeling.

    Science.gov (United States)

    Carpio, Lomeli R; Bradley, Elizabeth W; McGee-Lawrence, Meghan E; Weivoda, Megan M; Poston, Daniel D; Dudakovic, Amel; Xu, Ming; Tchkonia, Tamar; Kirkland, James L; van Wijnen, Andre J; Oursler, Merry Jo; Westendorf, Jennifer J

    2016-01-01

    Histone deacetylase (HDAC) inhibitors are efficacious epigenetic-based therapies for some cancers and neurological disorders; however, each of these drugs inhibits multiple HDACs and has detrimental effects on the skeleton. To better understand how HDAC inhibitors affect endochondral bone formation, we conditionally deleted one of their targets, Hdac3, pre- and postnatally in type II collagen α1 (Col2α1)-expressing chondrocytes. Embryonic deletion was lethal, but postnatal deletion of Hdac3 delayed secondary ossification center formation, altered maturation of growth plate chondrocytes, and increased osteoclast activity in the primary spongiosa. HDAC3-deficient chondrocytes exhibited increased expression of cytokine and matrix-degrading genes (Il-6, Mmp3, Mmp13, and Saa3) and a reduced abundance of genes related to extracellular matrix production, bone development, and ossification (Acan, Col2a1, Ihh, and Col10a1). Histone acetylation increased at and near genes that had increased expression. The acetylation and activation of nuclear factor κB (NF-κB) were also increased in HDAC3-deficient chondrocytes. Increased cytokine signaling promoted autocrine activation of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and NF-κB pathways to suppress chondrocyte maturation, as well as paracrine activation of osteoclasts and bone resorption. Blockade of interleukin-6 (IL-6)-JAK-STAT signaling, NF-κB signaling, and bromodomain extraterminal proteins, which recognize acetylated lysines and promote transcriptional elongation, significantly reduced Il-6 and Mmp13 expression in HDAC3-deficient chondrocytes and secondary activation in osteoclasts. The JAK inhibitor ruxolitinib also reduced osteoclast activity in Hdac3 conditional knockout mice. Thus, HDAC3 controls the temporal and spatial expression of tissue-remodeling genes and inflammatory responses in chondrocytes to ensure proper endochondral ossification during development. PMID:27507649

  16. Disrupted bone remodeling leads to cochlear overgrowth and hearing loss in a mouse model of fibrous dysplasia.

    Directory of Open Access Journals (Sweden)

    Omar Akil

    Full Text Available Normal hearing requires exquisite cooperation between bony and sensorineural structures within the cochlea. For example, the inner ear secretes proteins such as osteoprotegrin (OPG that can prevent cochlear bone remodeling. Accordingly, diseases that affect bone regulation can also result in hearing loss. Patients with fibrous dysplasia develop trabecular bone overgrowth resulting in hearing loss if the lesions affect the temporal bones. Unfortunately, the mechanisms responsible for this hearing loss, which could be sensorineural and/or conductive, remain unclear. In this study, we used a unique transgenic mouse model of increased Gs G-protein coupled receptor (GPCR signaling induced by expression of an engineered receptor, Rs1, in osteoblastic cells. These ColI(2.3+/Rs1+ mice showed dramatic bone lesions that histologically and radiologically resembled fibrous dysplasia. We found that ColI(2.3+/Rs1+ mice showed progressive and severe conductive hearing loss. Ossicular chain impingement increased with the size and number of dysplastic lesions. While sensorineural structures were unaffected, ColI(2.3+/Rs1+ cochleae had abnormally high osteoclast activity, together with elevated tartrate resistant acid phosphatase (TRAP activity and receptor activator of nuclear factor kappa-B ligand (Rankl mRNA expression. ColI(2.3+/Rs1+ cochleae also showed decreased expression of Sclerostin (Sost, an antagonist of the Wnt signaling pathway that normally increases bone formation. The osteocyte canalicular networks of ColI(2.3+/Rs1+ cochleae were disrupted and showed abnormal osteocyte morphology. The osteocytes in the ColI(2.3+/Rs1+ cochleae showed increased expression of matrix metalloproteinase 13 (MMP-13 and TRAP, both of which can support osteocyte-mediated peri-lacunar remodeling. Thus, while the ossicular chain impingement is sufficient to account for the progressive hearing loss in fibrous dysplasia, the deregulation of bone remodeling extends to the

  17. Extracellular Matrix Remodeling by Dynamic Strain in a Three-Dimensional Tissue-Engineered Human Airway Wall Model

    OpenAIRE

    Choe, Melanie M.; Sporn, Peter H. S.; Swartz, Melody A.

    2006-01-01

    Airway wall remodeling is a hallmark of asthma, characterized by subepithelial thickening and extracellular matrix (ECM) remodeling. Mechanical stress due to hyperresponsive smooth muscle cells may contribute to this remodeling, but its relevance in a three-dimensional environment (where the ECM plays an important role in modulating stresses felt by cells) is unclear. To characterize the effects of dynamic compression in ECM remodeling in a physiologically relevant three-dimensional environme...

  18. Mechanism of Action of Bortezomib and the New Proteasome Inhibitors on Myeloma Cells and the Bone Microenvironment: Impact on Myeloma-Induced Alterations of Bone Remodeling

    Directory of Open Access Journals (Sweden)

    Fabrizio Accardi

    2015-01-01

    Full Text Available Multiple myeloma (MM is characterized by a high capacity to induce alterations in the bone remodeling process. The increase in osteoclastogenesis and the suppression of osteoblast formation are both involved in the pathophysiology of the bone lesions in MM. The proteasome inhibitor (PI bortezomib is the first drug designed and approved for the treatment of MM patients by targeting the proteasome. However, recently novel PIs have been developed to overcome bortezomib resistance. Interestingly, several preclinical data indicate that the proteasome complex is involved in both osteoclast and osteoblast formation. It is also evident that bortezomib either inhibits osteoclast differentiation induced by the receptor activator of nuclear factor kappa B (NF-κB ligand (RANKL or stimulates the osteoblast differentiation. Similarly, the new PIs including carfilzomib and ixazomib can inhibit bone resorption and stimulate the osteoblast differentiation. In a clinical setting, PIs restore the abnormal bone remodeling by normalizing the levels of bone turnover markers. In addition, a bone anabolic effect was described in responding MM patients treated with PIs, as demonstrated by the increase in the osteoblast number. This review summarizes the preclinical and clinical evidence on the effects of bortezomib and other new PIs on myeloma bone disease.

  19. Skeletal remodeling dynamics: New approaches with imaging instrumentation

    International Nuclear Information System (INIS)

    This report of progress and future objectives timetable is based on an included schematic of goals and objectives and the project abstract which is included as Appendix 1. Five matters are summarized in the order of (1) novel methods of calcified bone confocal microscopy and reconstruction image analysis of decalcified beagle and human cortical bone serial sections, (2) macroscopic cross-correlation of beagle and human cortical and cancellous bone fractions with CT analysis, (3) guidance to the most radiobiologically important skeletal regions of interest with the just completed 90Sr bone tumor map from life time beagle studies, (4) deposition patterns of radioactive agents that participate in apatite crystal nucleation processes in bone and leave radiation-excited electrons trapped in bone mineral, and (5) the budget period timetable. The discovery that beta particles from 166Ho (T1/2 =26 hr, βmax = 1.8 MeV) phosphonic acid bone agents leave detectable, long-lived, electron paramagnetic resonance signals in bone is included in Appendix 2 as a joint report

  20. Bioprinting Organotypic Hydrogels with Improved Mesenchymal Stem Cell Remodeling and Mineralization Properties for Bone Tissue Engineering.

    Science.gov (United States)

    Duarte Campos, Daniela Filipa; Blaeser, Andreas; Buellesbach, Kate; Sen, Kshama Shree; Xun, Weiwei; Tillmann, Walter; Fischer, Horst

    2016-06-01

    3D-manufactured hydrogels with precise contours and biological adhesion motifs are interesting candidates in the regenerative medicine field for the culture and differentiation of human bone-marrow-derived mesenchymal stem cells (MSCs). 3D-bioprinting is a powerful technique to approach one step closer the native organization of cells. This study investigates the effect of the incorporation of collagen type I in 3D-bioprinted polysaccharide-based hydrogels to the modulation of cell morphology, osteogenic remodeling potential, and mineralization. By combining thermo-responsive agarose hydrogels with collagen type I, the mechanical stiffness and printing contours of printed constructs can be improved compared to pure collagen hydrogels which are typically used as standard materials for MSC osteogenic differentiation. The results presented here show that MSC not only survive the 3D-bioprinting process but also maintain the mesenchymal phenotype, as proved by live/dead staining and immunocytochemistry (vimentin positive, CD34 negative). Increased solids concentrations of collagen in the hydrogel blend induce changes in cell morphology, namely, by enhancing cell spreading, that ultimately contribute to enhanced and directed MSC osteogenic differentiation. 3D-bioprinted agarose-collagen hydrogels with high-collagen ratio are therefore feasible for MSC osteogenic differentiation, contrarily to low-collagen blends, as proved by two-photon microscopy, Alizarin Red staining, and real-time polymerase chain reaction. PMID:27072652

  1. The influence of different loads on the remodeling process of a bone and bioresorbable material mixture with voids

    Science.gov (United States)

    Giorgio, Ivan; Andreaus, Ugo; Madeo, Angela

    2016-03-01

    A model of a mixture of bone tissue and bioresorbable material with voids was used to numerically analyze the physiological balance between the processes of bone growth and resorption and artificial material resorption in a plate-like sample. The adopted model was derived from a theory for the behavior of porous solids in which the matrix material is linearly elastic and the interstices are void of material. The specimen—constituted by a region of bone living tissue and one of bioresorbable material—was acted by different in-plane loading conditions, namely pure bending and shear. Ranges of load magnitudes were identified within which physiological states become possible. Furthermore, the consequences of applying different loading conditions are examined at the end of the remodeling process. In particular, maximum value of bone and material mass densities, and extensions of the zones where bone is reconstructed were identified and compared in the two different load conditions. From the practical view point, during surgery planning and later rehabilitation, some choice of the following parameters is given: porosity of the graft, material characteristics of the graft, and adjustment of initial mixture tissue/bioresorbable material and later, during healing and remodeling, optimal loading conditions.

  2. Uncemented Total Hip Replacement Stem Loosening after Long Term Compressive Stress Application: A Simulated FEA Study of Cortical Bone Remodeling

    Science.gov (United States)

    Jung, Duk-Young; Tsutsumi, Sadami; Nakai, Ryusuke; Ikeuchi, Ken; Sekel, Ron

    The purpose of this study is to predict with the use of FEA, the differing predisposition to cortical bone resorption and subsequent distal migration of an un-cemented femoral hip replacement stem subjected to long term biomechanical high compressive stresses, while varying the load angles, the material properties of the stem, and the stem length. A two-dimensional hip model was constructed to estimate the minimum principle stresses (P3) and migration magnitudes. Bone remodeling at the interface between the bone and the prosthesis was performed by comparison of the local compressive stress to physiological stress values governing bone resorption. With respect to load angles, migrations of the hip prosthesis did not occur with load angles between 63° and 74° load angle in relation to the longitudinal axis of the bony femur, as the compressive stress generated on the cortical bone was under the criteria threshold for bone resorption (-50MPa). In addition, the magnitude of migration (17%decrease) was relatively more sensitive to changes in stem length than those (92%decrease) of changes of material properties. In conclusion, using an FEA model for bone remodeling, based on the high compressive stresses exerted on distal cortical bone, it is possible to estimate migration magnitudes of cementless hip prostheses in the long term. The load angles have been shown to be an important parameter affecting the migration magnitudes and furthermore, it can be demonstrated that the stiffer materials and reduction of stem length can decrease the migration of cementless hip prosthesis in the long term.

  3. Wnt Signalling Promotes Actin Dynamics during Axon Remodelling through the Actin-Binding Protein Eps8.

    Directory of Open Access Journals (Sweden)

    Eleanna Stamatakou

    Full Text Available Upon arrival at their synaptic targets, axons slow down their growth and extensively remodel before the assembly of presynaptic boutons. Wnt proteins are target-derived secreted factors that promote axonal remodelling and synaptic assembly. In the developing spinal cord, Wnts secreted by motor neurons promote axonal remodelling of NT-3 responsive dorsal root ganglia neurons. Axon remodelling induced by Wnts is characterised by growth cone pausing and enlargement, processes that depend on the re-organisation of microtubules. However, the contribution of the actin cytoskeleton has remained unexplored. Here, we demonstrate that Wnt3a regulates the actin cytoskeleton by rapidly inducing F-actin accumulation in growth cones from rodent DRG neurons through the scaffold protein Dishevelled-1 (Dvl1 and the serine-threonine kinase Gsk3β. Importantly, these changes in actin cytoskeleton occurs before enlargement of the growth cones is evident. Time-lapse imaging shows that Wnt3a increases lamellar protrusion and filopodia velocity. In addition, pharmacological inhibition of actin assembly demonstrates that Wnt3a increases actin dynamics. Through a yeast-two hybrid screen, we identified the actin-binding protein Eps8 as a direct interactor of Dvl1, a scaffold protein crucial for the Wnt signalling pathway. Gain of function of Eps8 mimics Wnt-mediated axon remodelling, whereas Eps8 silencing blocks the axon remodelling activity of Wnt3a. Importantly, blockade of the Dvl1-Eps8 interaction completely abolishes Wnt3a-mediated axonal remodelling. These findings demonstrate a novel role for Wnt-Dvl1 signalling through Eps8 in the regulation of axonal remodeling.

  4. Osteocytes, not Osteoblasts or Lining Cells, are the Main Source of the RANKL Required for Osteoclast Formation in Remodeling Bone.

    Directory of Open Access Journals (Sweden)

    Jinhu Xiong

    Full Text Available The cytokine receptor activator of nuclear factor kappa B ligand (RANKL, encoded by the Tnfsf11 gene, is essential for osteoclastogenesis and previous studies have shown that deletion of the Tnfsf11 gene using a Dmp1-Cre transgene reduces osteoclast formation in cancellous bone by more than 70%. However, the Dmp1-Cre transgene used in those studies leads to recombination in osteocytes, osteoblasts, and lining cells making it unclear whether one or more of these cell types produce the RANKL required for osteoclast formation in cancellous bone. Because osteoblasts, osteocytes, and lining cells have distinct locations and functions, distinguishing which of these cell types are sources of RANKL is essential for understanding the orchestration of bone remodeling. To distinguish between these possibilities, we have now created transgenic mice expressing the Cre recombinase under the control of regulatory elements of the Sost gene, which is expressed in osteocytes but not osteoblasts or lining cells in murine bone. Activity of the Sost-Cre transgene in osteocytes, but not osteoblast or lining cells, was confirmed by crossing Sost-Cre transgenic mice with tdTomato and R26R Cre-reporter mice, which express tdTomato fluorescent protein or LacZ, respectively, only in cells expressing the Cre recombinase or their descendants. Deletion of the Tnfsf11 gene in Sost-Cre mice led to a threefold decrease in osteoclast number in cancellous bone and increased cancellous bone mass, mimicking the skeletal phenotype of mice in which the Tnfsf11 gene was deleted using the Dmp1-Cre transgene. These results demonstrate that osteocytes, not osteoblasts or lining cells, are the main source of the RANKL required for osteoclast formation in remodeling cancellous bone.

  5. Three-dimensional design optimisation of patient-specific femoral plates as a means of bone remodelling reduction.

    Science.gov (United States)

    Nobari, S; Katoozian, H R; Zomorodimoghadam, S

    2010-12-01

    Previous investigations into the optimisation of internal plates have mostly focused on the material properties of the implant. In this work, we optimise the shape, size and placement of the plate for successfully minimising bone remodelling around the implant. A design optimisation algorithm based on strain energy density criterion, combined with the finite element analysis, has been used in this study. The main optimisation goal was to reduce this change and keep it close to the conditions of an intact femur. The results suggest that the anterolateral side of the bone would be the optimum location for the plate, as for the geometry, the optimum moves towards having a thick, wide and short plate. These important results could be directly applicable to orthopaedic surgeons treating a femur fracture with internal plates. Since the optimisation algorithm remains the same for any patient, this advancement provides the surgeon with a tool to minimise the post surgery remodelling by trying to maintain the natural structure of the bone.

  6. Early periprosthetic femoral bone remodelling using different bearing material combinations in total hip arthroplasties: a prospective randomised study

    Directory of Open Access Journals (Sweden)

    Nygaard M.

    2004-12-01

    Full Text Available The present study was performed to test the hypothesis that different bearing materials have an impact on femoral bone remodelling within the first year after a total hip arthroplasty. A total of 225 patients with osteoarthrosis of the hip or avascular necrosis of the femoral head were included in this randomised prospective study. All patients had an identical hybrid total hip arthroplasty (cemented BiMetric stem and cementless RingLoc acetabular cup except for the bearing materials: polyethylene-on-zirconia (n = 78, CoCr-on-CoCr (n = 71, or alumina-on-alumina (n = 76. Bone mineral density (BMD was measured with Dual-energy X-ray absorptiometry (DEXA in seven Gruen zones adjacent to the femoral implant. The DEXA scan was performed within one week after surgery and was repeated one year postoperatively. There was no significant difference in periprosthetic BMD change between the three groups. After twelve months the relative BMD decrease was highest in the proximal part of the femur, - 6.2% in the greater trochanter region and - 12.7% in the lesser trochanter region. In the distal zones the relative BMD decrease was -5.3, -4.2, -2.1, -2.3, and -5.6%, respectively. The use of different bearing materials had no significant impact on femoral bone remodelling adjacent to the cemented hip stem within one year after surgery.

  7. Long-term effects of alendronate on fracture healing and bone remodeling of femoral shaft in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    Ling-jie FU; Ting-ting TANG; Yong-qiang HAO; Ke-rong DAI

    2013-01-01

    Aim:To investigate the long-term effects of alendronate (Aln),a widely used oral bisphosphonate,on fracture healing and bone remodeling in ovariectomized rats.Methods:Adult female SD rats underwent ovariectomy,and then bilateral femoral osteotomy at 12 weeks post-ovariectomy.From d 2 post-ovariectomy,the animals were divided into 3 groups,and treated with Aln (3 mg·kg-1d-1,po) for 28 weeks (Aln/Aln),Aln for 12 weeks and saline for 16 weeks (Aln/Saline) or saline for 28 weeks (Saline/Saline).At 6 and 16 weeks post-fracture,the fracture calluses were examined with X-ray radiography,and biomechanical testing and histological analysis were performed.The calluses were labeled with tetracycline and calcein to evaluate the mineral apposition rate (MAR).Results:The fracture line was less distinct in the 2 Aln-treated groups at 6 weeks post-fracture,and disappeared in all the 3 groups at 16 weeks post-fracture.The size of the callus and radiographic density of the femora in the Aln/Aln group were the highest among the 3 groups at 6 and 16 weeks post-fracture.Similar results were observed in the ultimate load at failure and energy absorption.However,the treatment with Aln delayed endochondral ossification of the callus,and significantly increased the total sagittal-sectional area,percentage callus area and callus thickness,and decreased the MAR at 6 and 16 weeks post-fracture.Conclusion:In the ovariectomized rat model,Aln is beneficial for the mechanical properties of the callus,but delays callus remodeling by suppressing the remodeling of woven bone into lamellar bone.

  8. Tooth eruption results from bone remodelling driven by bite forces sensed by soft tissue dental follicles: a finite element analysis.

    Directory of Open Access Journals (Sweden)

    Babak Sarrafpour

    Full Text Available Intermittent tongue, lip and cheek forces influence precise tooth position, so we here examine the possibility that tissue remodelling driven by functional bite-force-induced jaw-strain accounts for tooth eruption. Notably, although a separate true 'eruptive force' is widely assumed, there is little direct evidence for such a force. We constructed a three dimensional finite element model from axial computerized tomography of an 8 year old child mandible containing 12 erupted and 8 unerupted teeth. Tissues modelled included: cortical bone, cancellous bone, soft tissue dental follicle, periodontal ligament, enamel, dentine, pulp and articular cartilage. Strain and hydrostatic stress during incisive and unilateral molar bite force were modelled, with force applied via medial and lateral pterygoid, temporalis, masseter and digastric muscles. Strain was maximal in the soft tissue follicle as opposed to surrounding bone, consistent with follicle as an effective mechanosensor. Initial numerical analysis of dental follicle soft tissue overlying crowns and beneath the roots of unerupted teeth was of volume and hydrostatic stress. To numerically evaluate biological significance of differing hydrostatic stress levels normalized for variable finite element volume, 'biological response units' in Nmm were defined and calculated by multiplication of hydrostatic stress and volume for each finite element. Graphical representations revealed similar overall responses for individual teeth regardless if incisive or right molar bite force was studied. There was general compression in the soft tissues over crowns of most unerupted teeth, and general tension in the soft tissues beneath roots. Not conforming to this pattern were the unerupted second molars, which do not erupt at this developmental stage. Data support a new hypothesis for tooth eruption, in which the follicular soft tissues detect bite-force-induced bone-strain, and direct bone remodelling at the inner

  9. Tooth eruption results from bone remodelling driven by bite forces sensed by soft tissue dental follicles: a finite element analysis.

    Science.gov (United States)

    Sarrafpour, Babak; Swain, Michael; Li, Qing; Zoellner, Hans

    2013-01-01

    Intermittent tongue, lip and cheek forces influence precise tooth position, so we here examine the possibility that tissue remodelling driven by functional bite-force-induced jaw-strain accounts for tooth eruption. Notably, although a separate true 'eruptive force' is widely assumed, there is little direct evidence for such a force. We constructed a three dimensional finite element model from axial computerized tomography of an 8 year old child mandible containing 12 erupted and 8 unerupted teeth. Tissues modelled included: cortical bone, cancellous bone, soft tissue dental follicle, periodontal ligament, enamel, dentine, pulp and articular cartilage. Strain and hydrostatic stress during incisive and unilateral molar bite force were modelled, with force applied via medial and lateral pterygoid, temporalis, masseter and digastric muscles. Strain was maximal in the soft tissue follicle as opposed to surrounding bone, consistent with follicle as an effective mechanosensor. Initial numerical analysis of dental follicle soft tissue overlying crowns and beneath the roots of unerupted teeth was of volume and hydrostatic stress. To numerically evaluate biological significance of differing hydrostatic stress levels normalized for variable finite element volume, 'biological response units' in Nmm were defined and calculated by multiplication of hydrostatic stress and volume for each finite element. Graphical representations revealed similar overall responses for individual teeth regardless if incisive or right molar bite force was studied. There was general compression in the soft tissues over crowns of most unerupted teeth, and general tension in the soft tissues beneath roots. Not conforming to this pattern were the unerupted second molars, which do not erupt at this developmental stage. Data support a new hypothesis for tooth eruption, in which the follicular soft tissues detect bite-force-induced bone-strain, and direct bone remodelling at the inner surface of the

  10. Long-term effects of alendronate on fracture healing and bone remodeling of femoral shaft in ovariectomized rats

    OpenAIRE

    Fu, Ling-jie; Tang, Ting-ting; Hao, Yong-qiang; Dai, Ke-Rong

    2013-01-01

    Aim: To investigate the long-term effects of alendronate (Aln), a widely used oral bisphosphonate, on fracture healing and bone remodeling in ovariectomized rats. Methods: Adult female SD rats underwent ovariectomy, and then bilateral femoral osteotomy at 12 weeks post-ovariectomy. From d 2 post-ovariectomy, the animals were divided into 3 groups, and treated with Aln (3 mg·kg−1·d−1, po) for 28 weeks (Aln/Aln), Aln for 12 weeks and saline for 16 weeks (Aln/Saline) or saline for 28 weeks (Sali...

  11. Mecanobiología de los huesos maxilares: II. Remodelación ósea Mechanobiology of the maxillary bones: II. Bone remodelling

    Directory of Open Access Journals (Sweden)

    J. Cano-Sánchez

    2008-04-01

    Full Text Available La mecanobiología ósea se encarga de la interacción entre las señales mecánicas y los mecanismos moleculares en las células del tejido óseo. El proceso de remodelado óseo se ve influenciado por las cargas biomecánicas a diferentes niveles estructurales. En este artículo se revisa la relación entre la carga y la expresión molecular durante el remodelado óseo e intenta describir las diversas teorías que explican la transducción de señales de carga que parecen influir en la transmisión de cargas perimplantarias.Bone mechanobiology deals with connection between mechanical signals and molecular events in cells and bone tissue. Remodelling process can be influenced by biomechanical loading in different structural levels. This review paper tries to show the connection between loading and molecular expresion during bone remodelling and describes some theories which deals with signals of transduction which seem to have some importance in perimplantary loading transmision.

  12. Dynamic remodeling of microbial biofilms by functionally distinct exopolysaccharides.

    Science.gov (United States)

    Chew, Su Chuen; Kundukad, Binu; Seviour, Thomas; van der Maarel, Johan R C; Yang, Liang; Rice, Scott A; Doyle, Patrick; Kjelleberg, Staffan

    2014-08-05

    Biofilms are densely populated communities of microbial cells protected and held together by a matrix of extracellular polymeric substances. The structure and rheological properties of the matrix at the microscale influence the retention and transport of molecules and cells in the biofilm, thereby dictating population and community behavior. Despite its importance, quantitative descriptions of the matrix microstructure and microrheology are limited. Here, particle-tracking microrheology in combination with genetic approaches was used to spatially and temporally study the rheological contributions of the major exopolysaccharides Pel and Psl in Pseudomonas aeruginosa biofilms. Psl increased the elasticity and effective cross-linking within the matrix, which strengthened its scaffold and appeared to facilitate the formation of microcolonies. Conversely, Pel reduced effective cross-linking within the matrix. Without Psl, the matrix becomes more viscous, which facilitates biofilm spreading. The wild-type biofilm decreased in effective cross-linking over time, which would be advantageous for the spreading and colonization of new surfaces. This suggests that there are regulatory mechanisms to control production of the exopolysaccharides that serve to remodel the matrix of developing biofilms. The exopolysaccharides were also found to have profound effects on the spatial organization and integration of P. aeruginosa in a mixed-species biofilm model of P. aeruginosa-Staphylococcus aureus. Pel was required for close association of the two species in mixed-species microcolonies. In contrast, Psl was important for P. aeruginosa to form single-species biofilms on top of S. aureus biofilms. Our results demonstrate that Pel and Psl have distinct physical properties and functional roles during biofilm formation. Importance: Most bacteria grow as biofilms in the environment or in association with eukaryotic hosts. Removal of biofilms that form on surfaces is a challenge in clinical

  13. Role of atrial tissue remodeling on rotor dynamics: an in vitro study.

    Science.gov (United States)

    Climent, Andreu M; Guillem, María S; Fuentes, Lucia; Lee, Peter; Bollensdorff, Christian; Fernández-Santos, María Eugenia; Suárez-Sancho, Susana; Sanz-Ruiz, Ricardo; Sánchez, Pedro Luis; Atienza, Felipe; Fernández-Avilés, Francisco

    2015-12-01

    The objective of this article is to present an in vitro model of atrial cardiac tissue that could serve to study the mechanisms of remodeling related to atrial fibrillation (AF). We analyze the modification on gene expression and modifications on rotor dynamics following tissue remodeling. Atrial murine cells (HL-1 myocytes) were maintained in culture after the spontaneous initiation of AF and analyzed at two time points: 3.1 ± 1.3 and 9.7 ± 0.5 days after AF initiation. The degree of electrophysiological remodeling (i.e., relative gene expression of key ion channels) and structural inhomogeneity was compared between early and late cell culture times both in nonfibrillating and fibrillating cell cultures. In addition, the electrophysiological characteristics of in vitro fibrillation [e.g., density of phase singularities (PS/cm(2)), dominant frequency, and rotor meandering] analyzed by means of optical mapping were compared with the degree of electrophysiological remodeling. Fibrillating cell cultures showed a differential ion channel gene expression associated with atrial tissue remodeling (i.e., decreased SCN5A, CACN1C, KCND3, and GJA1 and increased KCNJ2) not present in nonfibrillating cell cultures. Also, fibrillatory complexity was increased in late- vs. early stage cultures (1.12 ± 0.14 vs. 0.43 ± 0.19 PS/cm(2), P rotor tip meandering and increase in wavefront curvature). HL-1 cells can reproduce AF features such as electrophysiological remodeling and an increased complexity of the electrophysiological behavior associated with the fibrillation time that resembles those occurring in patients with chronic AF. PMID:26408535

  14. Effects of long term treatment with high doses of odanacatib on bone mass, bone strength, and remodeling/modeling in newly ovariectomized monkeys.

    Science.gov (United States)

    Duong, L T; Pickarski, M; Cusick, T; Chen, C M; Zhuo, Y; Scott, K; Samadfam, R; Smith, S Y; Pennypacker, B L

    2016-07-01

    The objectives here were to evaluate the effects of odanacatib (ODN) at doses exceeding the clinical exposure on biomechanical properties of lumbar vertebrae (LV), hip and central femur (CF), and compare ODN to alendronate (ALN) on bone remodeling/modeling in ovariectomized (OVX) monkeys. Ten days post-surgery, animals were treated with vehicle (VEH), ODN-L (2mg/kg/day, p.o.), ODN-H (8/4mg/kg/day), or ALN (30μg/kg/week, s.c.) for 20months. An intact group was also included. ODN-L provided systemic exposures of 1.8-fold of clinical exposure. ODN-H started at 20-fold for 5.5months, and then reduced to 7.8-fold of clinical exposure, compared to ALN at approximated clinical exposure. From cross sectional analyses, LV density and peak load in ODN at both doses or ALN were not different from VEH or Intact. However, cortical thickness of femoral neck (FN) and CF in ODN were higher (21-34%, p<0.05) than VEH, due to smaller endocortical (Ec) perimeter of FN (10-11%; p<0.05) and CF (9-12%; ODN-L, p<0.05), and larger CF periosteal (Ps) perimeter (2-12%; ODN-H, p<0.001) versus VEH. ODN groups also showed slightly higher cortical porosity and Ps non-lamellar bone in CF. ODN-H treatment resulted in higher CF peak load (p<0.05) versus VEH. For all bone sites analyzed, a positive, linear relationship (r(2)=0.46-0.69, p<0.0001) of peak load to density or structural parameters was demonstrated. No treatment-related differences in the derived intrinsic strength properties were evidenced as compared between groups. ALN reduced all remodeling surfaces without affecting Ps modeling. Trabecular and intracortical remodeling were reduced in ODN groups, similar to ALN. Ec mineralizing surface in ODN-H trended to be lower than VEH by month 20, but Ec bone formation indices in ODN groups generally were not different from VEH. Ps modeling in ODN groups was significantly higher than other treatment groups. This study overall demonstrated the bone safety profile of ODN and its unique mechanism

  15. Antioxidant impregnated ultra-high molecular weight polyethylene wear debris particles display increased bone remodeling and a superior osteogenic:osteolytic profile vs. conventional UHMWPE particles in a murine calvaria model.

    Science.gov (United States)

    Chen, Yu; Hallab, Nadim J; Liao, Yen-Shuo; Narayan, Venkat; Schwarz, Edward M; Xie, Chao

    2016-05-01

    Periprosthetic osteolysis remains a major limitation of long-term successful total hip replacements with ultra-high molecular weight polyethylene (UHMWPE) bearings. As intra and extracellular reactive oxygen species are know to contribute to wear debris-induced osteoclastic bone resorption and decreased osteoblastic bone formation, antioxidant doped UHMWPE has emerged as an approach to reduce the osteolytic potential of wear debris and maintain coupled bone remodeling. To test this hypothesis in vivo, we evaluated the effects of crosslinked UHMWPE wear debris particles (AltrX(™) ), versus similar wear particles made from COVERNOX(™) containing UHMWPE (AOX(™) ), in an established murine calvaria model. Eight-week-old female C57B/6 mice (n = 10/Group) received a pre-op micro-CT scan prior to surgical implantation of the UHMWPE particles (2mg), or surgery without particles (sham). Dynamic labeling was performed by intraperitoneal injection of calcein on day 7 and alizarin on day 9, and the calvaria were harvested for micro-CT and histology on day 10. Surprisingly, we found that AOX particles induced significantly more bone resorption (1.72-fold) and osteoclast numbers (1.99-fold) vs. AltrX (p UHMWPE particles have decreased osteolytic potential due to their increased osteogenic properties that support coupled bone remodeling. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:845-851, 2016.

  16. Prostate cancer specific integrin αvβ3 modulates bone metastatic growth and tissue remodeling

    OpenAIRE

    McCabe, NP; De, S.; Vasanji, A; Brainard, J; Byzova, TV

    2007-01-01

    The management of pain and morbidity owing to the spreading and growth of cancer within bone remains to be a paramount problem in clinical care. Cancer cells actively transform bone, however, the molecular requirements and mechanisms of this process remain unclear. This study shows that functional modulation of the αvβ3 integrin receptor in prostate cancer cells is required for progression within bone and determines tumor-induced bone tissue transformation. Using histology and quantitative mi...

  17. Multiscale molecular dynamics simulations of membrane remodeling by Bin/Amphiphysin/Rvs family proteins

    Science.gov (United States)

    Chun, Chan; Haohua, Wen; Lanyuan, Lu; Jun, Fan

    2016-01-01

    Membrane curvature is no longer thought of as a passive property of the membrane; rather, it is considered as an active, regulated state that serves various purposes in the cell such as between cells and organelle definition. While transport is usually mediated by tiny membrane bubbles known as vesicles or membrane tubules, such communication requires complex interplay between the lipid bilayers and cytosolic proteins such as members of the Bin/Amphiphysin/Rvs (BAR) superfamily of proteins. With rapid developments in novel experimental techniques, membrane remodeling has become a rapidly emerging new field in recent years. Molecular dynamics (MD) simulations are important tools for obtaining atomistic information regarding the structural and dynamic aspects of biological systems and for understanding the physics-related aspects. The availability of more sophisticated experimental data poses challenges to the theoretical community for developing novel theoretical and computational techniques that can be used to better interpret the experimental results to obtain further functional insights. In this review, we summarize the general mechanisms underlying membrane remodeling controlled or mediated by proteins. While studies combining experiments and molecular dynamics simulations recall existing mechanistic models, concurrently, they extend the role of different BAR domain proteins during membrane remodeling processes. We review these recent findings, focusing on how multiscale molecular dynamics simulations aid in understanding the physical basis of BAR domain proteins, as a representative of membrane-remodeling proteins. Project supported by the National Natural Science Foundation of China (Grant No. 21403182) and the Research Grants Council of Hong Kong, China (Grant No. CityU 21300014).

  18. Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy

    DEFF Research Database (Denmark)

    Ito, Hiromu; Koefoed, Mette; Tiyapatanaputi, Prarop;

    2005-01-01

    Structural allograft healing is limited because of a lack of vascularization and remodeling. To study this we developed a mouse model that recapitulates the clinical aspects of live autograft and processed allograft healing. Gene expression analyses showed that there is a substantial decrease...... in the genes encoding RANKL and VEGF during allograft healing. Loss-of-function studies showed that both factors are required for autograft healing. To determine whether addition of these signals could stimulate allograft vascularization and remodeling, we developed a new approach in which rAAV can be freeze...

  19. A supra-cellular model for coupling of bone resorption to formation during remodeling

    DEFF Research Database (Denmark)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Pennypacker, Brenda L;

    2014-01-01

    of the osteoclasts. Here we provide evidence supporting this hypothesis, by comparing the osteoclast-canopy interface in response to two types of bone resorption inhibitors in rabbit lumbar vertebrae. The bisphosphonate alendronate, an inhibitor leading to low bone formation levels, reduces the extent of canopy...... coverage above osteoclasts. This effect is in accordance with its toxic action on periosteoclastic cells. In contrast, odanacatib, an inhibitor preserving bone formation, increases the extent of the osteoclast-canopy interface. Interestingly, these distinct effects correlate with how fast bone formation...... osteoblasts from the canopy is induced by osteoclastic factors, thereby favoring initiation of bone formation. They lead to a model where the osteoclast-canopy interface is the physical site where coupling of bone resorption to bone formation occurs....

  20. AGE-RELATED FEATURES OF PERIPHERAL BLOOD MARKERS IN CHILDREN AND YOUNG ADULTS WITH NORMAL AND PATHOLOGICAL REMODELING OF BONE TISSUE

    Directory of Open Access Journals (Sweden)

    M. V. Dvornichenko

    2016-01-01

    Full Text Available Activities of total alkaline phosphatase (TALP and its bone isoform (BALP was greater in groups of children and adolescents in the late posttraumatic period (pattern of reparative bone remodeling and scoliosis (pathological bone remodeling, than in the control (healthy children and adolescents. The content of collagen type I degradation products (CrossLaps peripheral blood practically was unchanged. Examined group with posttraumatic period had high activity of tartrate-resistant acid phosphatase form (TRACP. TALP activity reached minimum values in all the studied groups. In the process of children growing to 15–18 years old, as compared to 7–10 years old, reducing activity of remodeling was observed under physiological (healthy donors and reparative osteogenesis. It’s changes was recorded by significant decrease of the studied indicators. On the contrary, children 15–18 years old with scoliosis had maximum of the imbalance (activation/inhibition of various signs of osteogenesis of resorptive/synthetic bone processes. Also, for this group we discovered decrease osteocalcin concentration of 4 times in comparison with the group children of 7–10 years old. The detected growth of the correlations number in the correlation matrix of bone remodeling markers in case of scoliosis proposes the reduction of adaptation reserve of 15–18 years old adolescents, suffering from dysplasia of connective tissue. Thus, the pathophysiological and clinical significance of distant markers of bone metabolism screening in peripheral blood the is ambiguous. The interpretation of these indicators is difficult and largely depends on the clinical situation and age of patients. This requires improving the diagnostic approach to assess physiological and pathological remodeling of bone tissue by means of biochemical blood indicators. 

  1. Influence of exercise on bone remodeling-related hormones and cytokines in ovariectomized rats: a model of postmenopausal osteoporosis.

    Science.gov (United States)

    Li, Lihui; Chen, Xi; Lv, Shuang; Dong, Miaomiao; Zhang, Li; Tu, Jiaheng; Yang, Jie; Zhang, Lingli; Song, Yinan; Xu, Leiting; Zou, Jun

    2014-01-01

    This study aims to explore the effects of exercise on postmenopausal osteoporosis and the mechanisms by which exercise affects bone remodeling. Sixty-three Wistar female rats were randomly divided into five groups: (1) control group, (2) sham-operated group, (3) OVX (Ovariectomy) group, (4) DES-OVX (Diethylstilbestrol-OVX) group, and (5) Ex-OVX (Exercise-OVX) group. The rat osteoporosis model was established through ovariectomy. The Ex-OVX rats were made to run 251.2 meters every day, 6 d/wk for 3 months in a running wheel. Trabecular bone volume (TBV%), total resorption surface (TRS%), trabecular formation surface (TFS%), mineralization rate (MAR), bone cortex mineralization rate (mAR), and osteoid seam width (OSW) were determined by bone histomorphometry. The mRNA and protein levels of interleukin-1β (IL-1β2), interleukin-6 (IL-6), and cyclooxygenase-2 (Cox-2) were determined by in situ hybridization and immunohistochemistry, respectively. Serum levels of estrogen estradiol (E2), calcitonin (CT), osteocalcin (BGP), and parathyroid hormone (PTH) were determined by ELISA assays. The investigation revealed that compared to the control and the sham-operated groups, the OVX group showed significantly lower levels of TBV%, E2, and CT, but much higher levels of TRS%, TFS%, MAR, OSW, BGP, and PTH. The Ex-OVX group showed increased TBV% and serum levels of E2 and CT compared to the OVX group. Ovariectomy also led to a significant increase in IL-1β mRNA and protein levels in the bone marrow and IL-6 and Cox-2 protein levels in tibias. In addition, the Ex-OVX group showed lower levels of IL-1 mRNA and protein, IL-6 mRNA, and Cox-2 mRNA and protein than those in the OVX group. The upshot of the study suggests that exercise can significantly increase bone mass in postmenopausal osteoporosis rat models by inhibiting bone resorption and increasing bone formation, especially in trabecular bones.

  2. Complete twelve month bone remodeling with a bi-phasic injectable bone substitute in benign bone tumors: a prospective pilot study

    OpenAIRE

    Kaczmarczyk, Jacek; Sowinski, Piotr; Goch, Maciej; Katulska, Katarzyna

    2015-01-01

    Background Benign primary bone tumors are commonly treated by surgery involving bone grafts or synthetic bone void fillers. Although synthetic bone grafts may provide early mechanical support while minimizing the risk of donor-site morbidity and disease transmission, difficult handling properties and less than optimal transformation to bone have limited their use. Methods In a prospective series, patients with benign bone tumors were treated by minimal invasive intervention with a bi-phasic a...

  3. Suppressive effect of compact bone-derived mesenchymal stem cells on chronic airway remodeling in murine model of asthma.

    Science.gov (United States)

    Ogulur, Ismail; Gurhan, Gulben; Aksoy, Ayca; Duruksu, Gokhan; Inci, Cigdem; Filinte, Deniz; Kombak, Faruk Erdem; Karaoz, Erdal; Akkoc, Tunc

    2014-05-01

    New therapeutic strategies are needed in the treatment of asthma besides vaccines and pharmacotherapies. For the development of novel therapies, the use of mesenchymal stem cells (MSCs) is a promising approach in regenerative medicine. Delivery of compact bone (CB) derived MSCs to the injured lungs is an alternative treatment strategy for chronic asthma. In this study, we aimed to isolate highly enriched population of MSCs from mouse CB with regenerative capacity, and to investigate the impact of these cells in airway remodeling and inflammation in experimental ovalbumin-induced mouse model of chronic asthma. mCB-MSCs were isolated, characterized, labeled with GFP and then transferred into mice with chronic asthma developed by ovalbumin (OVA) provocation. Histopathological changes including basement membrane, epithelium, subepithelial smooth thickness and goblet cell hyperplasia, and MSCs migration to lung tissues were evaluated. These histopathological alterations were increased in ovalbumin-treated mice compared to PBS group (Pasthma. The results reported here provided evidence that mCB-MSCs may be an alternative strategy for the treatment of remodeling and inflammation associated with chronic asthma. PMID:24613203

  4. In vivo effects of modification of hydroxyapatite/collagen composites with and without chondroitin sulphate on bone remodeling in the sheep tibia.

    Science.gov (United States)

    Schneiders, Wolfgang; Reinstorf, Antje; Biewener, Achim; Serra, Alexandrè; Grass, Renè; Kinscher, Michael; Heineck, Jan; Rehberg, Sebastian; Zwipp, Hans; Rammelt, Stefan

    2009-01-01

    The addition of chondroitin sulphate (CS) to bone cements with calcium phosphate has lead to an enhancement of bone remodeling and an increase in new bone formation in small animals. The goal of this study was to verify the effect of CS in bone cements in a large animal model simulating a clinically relevant situation of a segmental cortical defect of a critical size on bone-implant interaction and bone remodeling. The influence of adding CS to hydroxyapatite/collagen (HA/Col) composites on host response was assessed in a standard sheep tibia model. A midshaft defect of 3 cm was created in the tibiae of 14 adult female sheep. The defect was filled with a HA/Col cement cylinder in seven animals and with a CS-modified hydroxyapatite/collagen (HA/Col/CS) cement cylinder in seven animals. In all cases the tibia was stabilized with an interlocked universal tibial nail. The animals in each group were analyzed with X-rays, CT scans, histology, immunohistochemistry, and enzymehistochemistry, as well as histomorphometric measurements. The X-ray investigation showed a significantly earlier callus reaction around the HA/Col/CS implants compared to HA/Col alone. The amount of newly formed bone at the end point of the experiment was significantly larger around HA/Col/CS cylinders both in the CT scan and in the histomorphometric analysis. There were still TRAP-positive osteoclasts around the HA/Col implants after 3 months. The number of osteopontin-positive osteoblasts and the direct bone contact were significantly higher around HA/Col/CS implants. We conclude that addition of CS enhances bone remodeling and new bone formation around HA/Col composites.

  5. [An experimental study of the effects of stress-relaxation plate on bone remodeling].

    Science.gov (United States)

    Dai, M; Dai, K; Qui, S

    1995-11-01

    An ideal bone plate would provide rigid fixation to ensure stabilization of bone fragments at the early stage after fracture, while at the late stage osteoporosis induced by stress shielding effect of the plate should be prevented. However, there is no report of such a plate that could meet with all these requirements. Twenty-eight adult New Zealand rabbits were used in this experiment. Ordinary stainless-steel plate (no washer plate) and similar plate padded with ultrahigh molecular polyethylene washers in its screw holes (washer plate) were fixed respectively on mid-shelf of each side of tibiae. The animals were killed at 2, 4, 8, 12, 16, 20 and 24 weeks after operation, and the fixed bone segments of both tibiae were removed for light microscopy, polarized light microscopy and fluoroscopy. The results showed that the tibiae fixed with plate fixation both appeared bone resorption, but there was more severe resorption in bone with no washer plate fixation than that with washer plate fixation. Cancelization of cortical bone was seen in the former but not in the latter at 12 weeks postopertively. This demonstrated that the washer might creep and damage with fixation time, resulting in gradual decrease in the rigidity of the plate-screw system and thus reducing bone resorption as caused by stress shielding. PMID:8731919

  6. Local administration of calcitriol positively influences bone remodeling and maturation during restoration of mandibular bone defects in rats

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hongrui; Cui, Jian; Feng, Wei; Lv, Shengyu; Du, Juan; Sun, Jing; Han, Xiuchun [Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan (China); Wang, Zhenming; Lu, Xiong [Key Lab of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, Sichuan (China); Yimin [Department of Advanced Medicine, Graduate School of Medicine, Hokkaido University, Sapporo (Japan); Oda, Kimimitsu [Division of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata (Japan); Amizuka, Norio [Department of Developmental Biology of Hard Tissue, Graduate School of Dental Medicine, Hokkaido University, Sapporo (Japan); Li, Minqi, E-mail: liminqi@sdu.edu.cn [Department of Bone Metabolism, School of Stomatology Shandong University, Shandong Provincial Key Laboratory of Oral Biomedicine, Jinan (China)

    2015-04-01

    The aim of this study was to investigate the influence of calcitriol on osteoinduction following local administration into mandibular bone defects. Calcitriol-loaded absorbable collagen membrane scaffolds were prepared using the polydopamine coating method and characterized by scanning electron microscopy. Composite scaffolds were implanted into rat mandibular bone defects in the following groups: no graft material (control), bare collagen membrane (CM group), collagen membrane bearing polydopamine coating (DOP/CM group), and collagen membrane bearing polydopamine coating absorbed with calcitriol (CAL/DOP/CM group). At 1, 2, 4 and 8 weeks post-surgery, the osteogenic potential of calcitriol was examined by histological and immunohistochemical methods. Following in vivo implantation, calcitriol-loaded composite scaffolds underwent rapid degradation with pronounced replacement by new bone and induced reunion of the bone marrow cavity. Calcitriol showed strong potential in inhibiting osteoclastogenesis and promotion of osteogenic differentiation at weeks 1, and 2. Furthermore, statistical analysis revealed that the newly formed bone volume in the CAL/DOP/CM group was significantly higher than other groups at weeks 1, and 2. At weeks 4, and 8, the CAL/DOP/CM group showed more mineralized bone and uniform collagen structure. These data suggest that local administration of calcitriol is promising in promoting osteogenesis and mineralization for restoration of mandibular bone defects. - Highlights: • More information on collagen material was added in the revised manuscript. • Masson–Goldner trichrome stain was performed for histomorphometry. • More specific information on calcitriol was supplemented in the Discussion section. • The MOD of ALP and Runx2 was explained in more detail. • The inhibition of osteoclastogenesis was described more accurately in the second paragraph of the discussion.

  7. Local administration of calcitriol positively influences bone remodeling and maturation during restoration of mandibular bone defects in rats

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the influence of calcitriol on osteoinduction following local administration into mandibular bone defects. Calcitriol-loaded absorbable collagen membrane scaffolds were prepared using the polydopamine coating method and characterized by scanning electron microscopy. Composite scaffolds were implanted into rat mandibular bone defects in the following groups: no graft material (control), bare collagen membrane (CM group), collagen membrane bearing polydopamine coating (DOP/CM group), and collagen membrane bearing polydopamine coating absorbed with calcitriol (CAL/DOP/CM group). At 1, 2, 4 and 8 weeks post-surgery, the osteogenic potential of calcitriol was examined by histological and immunohistochemical methods. Following in vivo implantation, calcitriol-loaded composite scaffolds underwent rapid degradation with pronounced replacement by new bone and induced reunion of the bone marrow cavity. Calcitriol showed strong potential in inhibiting osteoclastogenesis and promotion of osteogenic differentiation at weeks 1, and 2. Furthermore, statistical analysis revealed that the newly formed bone volume in the CAL/DOP/CM group was significantly higher than other groups at weeks 1, and 2. At weeks 4, and 8, the CAL/DOP/CM group showed more mineralized bone and uniform collagen structure. These data suggest that local administration of calcitriol is promising in promoting osteogenesis and mineralization for restoration of mandibular bone defects. - Highlights: • More information on collagen material was added in the revised manuscript. • Masson–Goldner trichrome stain was performed for histomorphometry. • More specific information on calcitriol was supplemented in the Discussion section. • The MOD of ALP and Runx2 was explained in more detail. • The inhibition of osteoclastogenesis was described more accurately in the second paragraph of the discussion

  8. The osteogenetic rate in alveolar bone remodeling induced by distraction osteogenesis of the periodontal ligament

    Institute of Scientific and Technical Information of China (English)

    WANG Shuang; FENG Pei-xun; GUO Xiong; ZHOU Hong

    2006-01-01

    Objective: To observe osteogenetic rate of alveolar bone on the tension side in orthodontic tooth movement through distraction osteogenesis of the periodental ligament quantificationally. Methods:The experiment was carried in 6 dogs. The left side of jaws of each one was set as test or control side, and the other side was control or test side. On the control side, the first premorlar was moved by traditional method on the test side. A self-made distraction device was used on the test side. The newly formed alveolar bone on the tension side of moved tooth was labeled by serial tetracycline fluorochrome. Sections were observed by fluorescence microscope and pictured. Newly formed bone was measured by computer image analysis. Results: The quantity of newly formed bone was significantly different between the two methods. Newly formed bone in rapid tooth movement by distraction osteogenesis of the periodental ligament was more than that in traditional method. Conclusion: The distraction through periodental ligament could induce more rapid bone formation and excite higher osteogenetic activity than traditional method.

  9. Effects of anti-sclerostin antibody and running on bone remodeling and strength

    Directory of Open Access Journals (Sweden)

    H. Toumi

    2015-06-01

    Full Text Available Sclerostin antibody (Scl-Ab represents a promising therapeutic approach to treat patients with osteoporosis. Purpose: The aim of this study was to investigate the effects of Scl-Ab, running and a combination of both on bone formation. Methods: Sixty female Wistar rats, aged 8 months were randomly assigned to five groups (subcutaneous injections performed twice a week: (1 (Sham: sedentary rats + saline, (2 (OVX: ovariectomized rats + saline, (3 (OVX + E: OVX rats + saline + treadmill training (5 times/week, 1 h/day, (4 (OVX + E + S: OVX rats + treadmill training + 5 mg/kg Scl-Ab and (5 (OVX + S: OVX rats + 5 mg/kg Scl-Ab. After 14 weeks, body composition, whole body and femoral BMDs were determined by DXA and serum was collected for analysis of osteocalcin and NTX. Bone microarchitecture was analyzed using μCT and bone strength was assessed at the femur mid-shaft in 3-point bending. Results: Running exercise decreased fat mass as well as the bone resorption marker NTX relative to the non-exercised control groups, effects that were associated with a prevention of the deleterious effects of OVX on whole body and femoral BMDs. Scl-Ab increased the bone formation marker osteocalcin, which resulted in robust increases in BMD and femoral metaphyseal bone volume to levels greater than in the Sham group. OVX + S + E group did not further impact on bone mass relative to the OVX + S group. At the cortical femur diaphysis, Scl-Ab prevented the decreases in bone strength after OVX, while exercise did not affect cortical strength. Conclusion: We suggest that while running on a treadmill can prevent some bone loss through a modest antiresorptive effect, it did not contribute to the robust bone-forming effects of Scl-Ab when combined in an estrogen ablation model.

  10. Radiation sterilized bone response to dynamic loading

    Energy Technology Data Exchange (ETDEWEB)

    Mardas, Marcin, E-mail: marcin.mardas@skpp.edu.pl [Department of Oncology, Poznan University of Medical Sciences, ul. Szamarzewskiego 82/84, 60-569 Poznan (Poland); Kubisz, Leszek [Department of Biophysics, Poznan University of Medical Sciences, ul. Fredry 10, 61-701 Poznan (Poland); Biskupski, Piotr; Mielcarek, Slawomir [Department of Physics, Adam Mickiewicz University, ul. Umultowska 85, 61-614 Poznan (Poland); Stelmach-Mardas, Marta [Department of Bromatology, Poznan University of Medical Sciences, ul. Marcelinska 420, 60-354 Poznan (Poland); Kaluska, Iwona [Centre for Radiation Research and Technology, Institute of Nuclear Chemistry and Technology, ul. Dorodna 16, 03-195 Warsaw (Poland)

    2012-08-01

    Allogeneic bone grafts are used on a large scale in surgeries. To avoid the risk of infectious diseases, allografts should be radiation-sterilized. So far, no international consensus has been achieved regarding the optimal radiation dose. Many authors suggest that bone sterilization deteriorates bone mechanical properties. However, no data on the influence of ionizing radiation on bone dynamic mechanical properties are available. Bovine femurs from 2-year old animal were machine cut and irradiated with the doses 10, 15, 25, 35, 45 and 50 kGy. Dynamic mechanical analysis was performed at 1-10 Hz at the temperature range of 0-350 Degree-Sign C in 3-point bending configuration. No statistically significant differences in storage modulus were observed. However, there were significant decreased values of loss modulus between the samples irradiated with doses of 10 ({down_arrow}14.3%), 15, 45 and 50 kGy ({down_arrow}33.2%) and controls. It was stated that increased irradiation dose decreases the temperature where collagen denaturation process starts and increases the temperature where the collagen denaturation process finishes. It was shown that activation energy of denaturation process is significantly higher for the samples irradiated with the dose of 50 kGy (615 kJ/mol) in comparison with control samples and irradiation with other doses (100-135 kJ/mol). - Highlights: Black-Right-Pointing-Pointer We examine changes in the storage modulus and loss modulus of samples irradiated with doses of 10-50 kGy. Black-Right-Pointing-Pointer We examine changes in the denaturation temperature of samples irradiated with doses of 10-50 kGy. Black-Right-Pointing-Pointer We examine changes in the activation energy of denaturation process of samples irradiated with doses of 10-50 kGy.

  11. Study of bone remodeling of two models of femoral cementless stems by means of DEXA and finite elements

    Directory of Open Access Journals (Sweden)

    López-Prats Fernando

    2010-05-01

    Full Text Available Abstract Background A hip replacement with a cemented or cementless femoral stem produces an effect on the bone called adaptive remodelling, attributable to mechanical and biological factors. All of the cementless prostheses designs try to achieve an optimal load transfer in order to avoid stress-shielding, which produces an osteopenia. Long-term densitometric studies taken after implanting ABG-I and ABG-II stems confirm that the changes made to the design and alloy of the ABG-II stem help produce less proximal atrophy of the femur. The simulation with FE allowed us to study the biomechanical behaviour of two stems. The aim of this study was, if possible, to correlate the biological and mechanical findings. Methods Both models with prostheses ABG-I and II have been simulated in five different moments of time which coincide with the DEXA measurements: postoperative, 6 months, 1, 3 and 5 years, in addition to the healthy femur as the initial reference. For the complete comparative analysis of both stems, all of the possible combinations of bone mass (group I and group II of pacients in two controlled studies for ABG-I and II stems, respectively, prosthetic geometry (ABG-I and ABG-II and stem material (Wrought Titanium or TMZF were simulated. Results and Discussion In both groups of bone mass an increase of stress in the area of the cancellous bone is produced, which coincides with the end of the HA coating, as a consequence of the bottleneck effect which is produced in the transmission of loads, and corresponds to Gruen zones 2 and 6, where no osteopenia can be seen in contrast to zones 1 and 7. Conclusions In this study it is shown that the ABG-II stem is more effective than the ABG-I given that it generates higher tensional values on the bone, due to which proximal bone atrophy diminishes. This biomechanical behaviour with an improved transmission of loads confirmed by means of FE simulation corresponds to the biological findings obtained with

  12. Dynamic Drusen Remodelling in Participants of the Nutritional AMD Treatment-2 (NAT-2 Randomized Trial.

    Directory of Open Access Journals (Sweden)

    Giuseppe Querques

    Full Text Available To evaluate the dynamic remodeling of drusen in subjects with unilateral neovascular age-related macular degeneration (AMD receiving a three-year course of oral docosahexaenoic acid (DHA or placebo.Institutional setting.Three hundred subjects with age-related maculopathy and neovascular AMD in the fellow eye were randomly assigned to receive either 840 mg/day DHA or placebo for 3 years. Main outcome measures of this post-hoc sub-group analysis were progression of drusen number, total diameter, and total area on fundus photography, and their association with DHA supplementation, socio-demographic and genetic characteristics.Drusen progression was analyzed in 167 subjects that did not develop CNV (87 that received DHA and 80 that received placebo. None of the drusen remodeling outcomes were significantly associated with DHA supplementation. Total drusen diameter reduction in the inner subfield was significantly associated with age (older patients: r = -0.17; p = 0.003. Women showed a tendency to decreased total drusen diameter in the inner subfield with CFH polymorphism (p = 0.03, where women with TT genotype tended to have a greater reduction in drusen diameter than other genotypes (CC and CT. Drusen area in the inner subfield was more reduced in older patients (r = -0.17 and in women (p = 0.01. Drusen number showed no significant trends.Dynamic drusen remodeling with net reduction in drusen load over three years was found in patients with exudative AMD in one eye and drusen in the other eye (study-eye. This reduction was correlated with increased age and female gender, and showed a tendency to be influenced by CFH genotype, but did not appear to be affected by DHA supplementation.Controlled-Trials.com ISRCTN98246501.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  14. Influence of Transplantation of Allogenic Bone Marrow Mononuclear Cells on the Left Ventricular Remodeling of Rat after Acute Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To probe into the influence of transplantation of allogenic bone marrow mononuclear cells (BM-MNCs) on the left ventricular remodeling of rat after acute myocardial infarction (AMD,60 male Wistar rats were evenly divided into three groups at random: control group 1, control group 2and transplantation group. In control group 1, chest was opened without ligation of coronary artery;in control group 2 and transplantation group, the left anterior descending branch of coronary artery was ligated to establish AMI model. Prepared culture medium and allogenic BM-MNCs suspension were respectively implanted the surrounding area of infracted cardiac muscle via epicardium of control group 2 and transplantation group. Four weeks after the operation, the osteopontin gene (OPN mRNA, P<0.01), type Ⅰ collagen (P<0.01) and angiotensin Ⅱ (AngⅡ, P<0.01) content in the left ventricular non-infracted myocardium, and the Ang Ⅱ density in blood plasma (P<0.05) of transplantation group and control group 2 were all significantly higher than that of control group 1. In the transplantation group, the myocardial OPN mRNA, type Ⅰ collagen and Ang Ⅱ content of non-infracted zone in left ventricle, and the Ang Ⅱ concentration in blood plasma were all significantly lower than those of control group 2 (P<0.05 for all). It is concluded that allogenic BM-MNCs transplantation may ease left ventricular remodeling after AMI by inhibiting the synthesis of type Ⅰ collagen in the cardiac muscle and down-regulating the expression of Ang Ⅱ and OPN gene.

  15. An in vivo assessment of muscular activity and the importance of electrical phenomena in bone remodelling.

    OpenAIRE

    Mcdonald, F.; Houston, W J

    1990-01-01

    Modified orthopaedic pins were placed close to the medial and distal epiphyses of the tibia in 4 anaesthetised rabbits, in order to allow the application of controlled external loading cycles. Rosette strain gauges were placed at midshaft level, where the greatest compressive and tensile strains were expected during loading. Two weeks later, following stabilisation of the pins by bone healing, the animals were anaesthetised again and silver-silver chloride electrodes were attached close to th...

  16. Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis

    OpenAIRE

    Bellido, Miriam; Lugo, Laura; Roman-Blas, Jorge A; Castañeda, Santos; Caeiro, Jose R; Dapia, Sonia; Calvo, Emilio; Largo, Raquel; Herrero-Beaumont, Gabriel

    2010-01-01

    Introduction Osteoporosis (OP) increases cartilage damage in a combined rabbit model of OP and osteoarthritis (OA). Accordingly, we assessed whether microstructure impairment at subchondral bone aggravates cartilage damage in this experimental model. Methods OP was induced in 20 female rabbits, by ovariectomy and intramuscular injections of methylprednisolone hemisuccinate for four weeks. Ten healthy animals were used as controls. At week 7, OA was surgically induced in left knees of all rabb...

  17. Stiffness compatibility of coralline hydroxyapatite bone substitute under dynamic loading

    Institute of Scientific and Technical Information of China (English)

    REN ChaoFeng; HOU ZhenDe; ZHAO Wei

    2009-01-01

    When hydroxyapatite bone substitutes are implanted in human bodies, bone tissues will grow into their porous structure, which will reinforce their strength and stiffness. The concept of mechanical com-patibility of bone substitutes implies that their mechanical properties are similar to the bone tissues around, as if they were part of the bone. The mechanical compatibility of bone substitutes includes both static and dynamic behavior, due to the mechanical properties of bone depending on the strain rate. In this study, split Hopkinson pressure bar technique (SHPB) was employed to determine the dy-namic mechanical properties of coralline hydroxyapatite, bones with and bones without organic com-ponents, and their dynamic stress-strain curves of the three materials were obtained. The mechanical effects of collagens in bone were assessed, by comparing the difference between the Young's moduli of the three materials. As the implanted bone substitute becomes a part of bone, it can be regarded as an inclusion composite. The effective modulus of the composite was also evaluated in order to estimate its mechanical compatibility on stiffness. The evaluated result shows that the suitable porosity of HA is0.8, which is in favor of both static and dynamic stiffness compatibility.

  18. Stiffness compatibility of coralline hydroxyapatite bone substitute under dynamic loading

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    When hydroxyapatite bone substitutes are implanted in human bodies,bone tissues will grow into their porous structure,which will reinforce their strength and stiffness.The concept of mechanical com-patibility of bone substitutes implies that their mechanical properties are similar to the bone tissues around,as if they were part of the bone.The mechanical compatibility of bone substitutes includes both static and dynamic behavior,due to the mechanical properties of bone depending on the strain rate.In this study,split Hopkinson pressure bar technique(SHPB) was employed to determine the dy-namic mechanical properties of coralline hydroxyapatite,bones with and bones without organic com-ponents,and their dynamic stress-strain curves of the three materials were obtained.The mechanical effects of collagens in bone were assessed,by comparing the difference between the Young’s moduli of the three materials.As the implanted bone substitute becomes a part of bone,it can be regarded as an inclusion composite.The effective modulus of the composite was also evaluated in order to estimate its mechanical compatibility on stiffness.The evaluated result shows that the suitable porosity of HA is 0.8,which is in favor of both static and dynamic stiffness compatibility.

  19. Predictors of ventricular remodelling in patients with reperfused acute myocardial infarction and left ventricular dysfunction candidates for bone marrow cell therapy: insights from the BONAMI trial

    Energy Technology Data Exchange (ETDEWEB)

    Manrique, Alain [Nuclear Medicine, CHU de Caen, Caen (France); Universite de Caen Normandie, EA 4650, Caen (France); CHU de Caen et GIP Cyceron, Caen cedex 6 (France); Lemarchand, Patricia; Delasalle, Beatrice; Lamirault, Guillaume; Trochu, Jean-Noel; Le Tourneau, Thierry [L' Institut du thorax, INSERM, UMR1087, Nantes (France); CNRS, UMR 6291, Nantes (France); Universite de Nantes, Nantes (France); CHU de Nantes, Nantes (France); Lairez, Olivier; Roncalli, Jerome [Institut CARDIOMET-Toulouse, Cardiac Imaging Center, CIC Biotherapies, CHU de Toulouse, Toulouse (France); Sportouch-Duckan, Catherine; Piot, Christophe [Universite Montpellier, Institut de Genomique Fonctionnelle, INSERM U661, CNRS UMR 5203, Montpellier (France); Clinique du Millenaire, Montpellier (France); Le Corvoisier, Philippe [Hopital Henri Mondor, INSERM, Centre d' Investigation Clinique 1430 et U955 equipe 3, Creteil (France); Neuder, Yannick [CHU de Grenoble, Pole Thorax et Vaisseaux, Grenoble (France); Richardson, Marjorie [CHRU Lille, Service d' Explorations Fonctionnelles Cardiovasculaires, Hopital Cardiologique, Lille (France); Lebon, Alain [CHU de Caen, Service de Cardiologie, Caen (France); Teiger, Emmanuel [Hopital Henri Mondor, AP-HP, Unite de Cardiologie Interventionnelle et Federation de Cardiologie, Creteil (France); Hossein-Foucher, Claude [Hopital Salengro CHRU de Lille, Service de Medecine Nucleaire, Lille (France); Universite de Lille 2, UFR de Medecine, Lille (France)

    2016-04-15

    Few data are available regarding the relation of left ventricular (LV) mechanical dyssynchrony to remodelling after acute myocardial infarction (MI) and stem cell therapy. We evaluated the 1-year time course of both LV mechanical dyssynchrony and remodelling in patients enrolled in the BONAMI trial, a randomized, multicenter controlled trial assessing cell therapy in patients with reperfused MI. Patients with acute MI and ejection fraction (EF) ≤ 45 % were randomized to cell therapy or to control and underwent thallium single-photon emission computed tomography (SPECT), radionuclide angiography, and echocardiography at baseline, 3 months, and 1 year. Eighty-three patients with a comprehensive 1-year follow-up were included. LV dyssynchrony was assessed by the standard deviation (SD) of the LV phase histogram using radionuclide angiography. Remodelling was defined as a 20 % increase in LV end-systolic volume index (LVESVI) at 1 year. At baseline, LVEF, wall motion score index, and perfusion defect size were significantly impaired in the 43 patients (52 %) with LV remodelling (all p < 0.001), without significant increase in LV mechanical dyssynchrony. During follow-up, there was a progressive increase in LV SD (p = 0.01). Baseline independent predictors of LV remodelling were perfusion SPECT defect size (p = 0.001), LVEF (p = 0.01) and a history of hypertension (p = 0.043). Bone marrow cell therapy did not affect the time-course of LV remodelling and dyssynchrony. LV remodelling 1 year after reperfused MI is associated with progressive LV dyssynchrony and is related to baseline infarct size and ejection fraction, without impact of cell therapy on this process. (orig.)

  20. Mechanisms of improvement of left ventricle remodeling by transplanting two kinds of autologous bone marrow stem cells in pigs

    Institute of Scientific and Technical Information of China (English)

    LI Shu-ren; WU Di; DONG Jie; XUN Li-ying; GAO Li-hui; JIN Fu-chang; QI Xiao-yong; HU Fu-li; ZHANG Jian-qing; WANG Tian-hong; DANG Yi; MENG Cun-liang; LIU Hui-liang; LI Ying-xiao

    2008-01-01

    Background The necrosis of a large number of myocardial cells after acute myocardial infarction (AMI) results in a decrease of cardiac function and ventricle remodeling.Stem cell transplantation could improve cardiac function after AMI,but the involving mechanisms have not been completely understood.The present study aimed to investigate the effects of transplantation of autologous bone marrow mononuclear cells (BM-MNC) and rnesenchymal stem cells (MSCs) via the coronary artery on the ventricle remodeling after AMI as well as the mechanisms of the effects of transplantation of different stem cells on ventricle remodeling.Methods A total of 36 male pigs were enrolled in this study,which were divided into 4 groups: control group,simple infarct model group,BM-MNC transplantation group,and MSCs transplantation group.At 90 minutes when a miniature porcine model with AMI was established,transplantation of autologous BM-MNC ((4.7±1.7)×107) and MSCs ((6.2±1.6)×105) was performed in the coronary artery via a catheter.Ultrasound,electron microscope,immunohistochemical examination and real time reverse transcdptase-polymerase chain reaction were used respectively to observe cardiac fun~ons,counts of blood vessels of cardiac muscle,cardiac muscle nuclear factor (NF)-KB,myocardial cell apoptosis,and the expression of the mRNA of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in cardiac muscles.Multivariate Logistic regression was used to analyze the correlation factors of left ventricular end-diastolic diameter (EDD).Results The number of blood vessels in the infarct zone and around its border in the BM-MNC transplantation group was more than those in the infarct model group and MSCs group (P=0.0001) and there was less myocardial cell apoptosis in the stem cell transplantation group than that in the infarct model group (all P <0.01).The positive rate of NF-KB in the stem cell transplantation group was lower than that in the infarct model

  1. OSTEOPOROSIS AND ALZHEIMER PATHOLOGY: ROLE OF CELLULAR STRESS RESPONSE AND HORMETIC REDOX SIGNALING IN AGING AND BONE REMODELING

    Directory of Open Access Journals (Sweden)

    Vittorio eCalabrese

    2014-06-01

    Full Text Available Alzheimer’s disease (AD as well as osteoporosis are multifactorial progressive degenerative disorders characterized by low parenchymal density and microarchitectural deterioration of tissue. Though not referred to as one of the major complications of AD, osteoporosis and hip fracture are commonly observed in patients with AD, however, the mechanisms underlying this association remain poorly understood. Reactive oxygen species (ROS are generally recognized as intracellular redox signaling molecules involved in the regulation of bone metabolism, including receptor activator of nuclear factor-kB ligand (RANKL-dependent osteoclast differentiation, but they also have cytotoxic effects that include peroxidation of lipids and oxidative damage to proteins and DNA. ROS formation, which is positively implicated in cellular stress response mechanisms, is a highly regulated process controlled by a complex network of intracellular signaling pathways which regulate life span across species including vitagenes which are genes involved in preserving cellular homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose–response, has the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Here we focus on possible signaling mechanisms involved in bone remodeling and activation of vitagenes resulting in enhanced defense against energy and stress resistance homeostasis dysruption with consequent impact on

  2. Stress bone remodeling after endoprosthetic replacement of large joints and its conservative correction

    Directory of Open Access Journals (Sweden)

    M A Makarov

    2009-01-01

    Full Text Available Arthroplasty is stated to be one of the most effective surgical treatments for rheumatic diseases (RD. However, the problem is that the bad quality of bone tissue has a negative impact on the outcome of surgery. The authors have studied the time course of changes in bone mineral density (BMD after total hip arthroplasty in 81 patients with RD. All the patients underwent dual-energy X-ray densitometry by a special orthopedic program. BMD was measured in 7 areas of a femoral prosthetic component as described by T.A. Gruen et al. and that was in 3 areas of an acetabular component as proposed by J.L. DeLee и J. Charnley. The first (initial measurement was carried out a fortnight after surgery; later measurements were made following 3, 6, and 12 months. It was established that there was a progressive BMD loss after surgery; following 3 months all the areas virtually exhibited a BMD reduction that peaked by month 6. BMD loss around the endoprosthetic acetabular component was about 20 %. The use of bisphosphonates, such as ibandronate (Bonviva, one of the most potent drugs of this group, is shown to be most promising in preventing BMD loss around the prosthesis.

  3. In vitro investigations of bone remodeling on a transparent hydroxyapatite ceramic

    Energy Technology Data Exchange (ETDEWEB)

    John, A; Varma, H K; Vijayan, S [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Satelmond Palace Campus, Poojappura, Thiruvananthapuram-695012, Kerala (India); Bernhardt, A; Lode, A; Vogel, A; Burmeister, B; Hanke, Th; Gelinsky, M [Max Bergmann Center of Biomaterials, Institute of Materials Science, Technical University Dresden, Budapesterstr. 27, D-01069 Dresden (Germany); Domaschke, H, E-mail: ajkari@sctimst.ac.i, E-mail: karippacheril@gmail.co [Pediatric Clinic, University Hospital Carl Gustav Carus, Technical University Dresden, Fetscherstr. 74, D-01307 Dresden (Germany)

    2009-02-15

    The light microscopic examination of cells directly on bioceramic materials in the transmission mode is impossible because many of these materials are opaque. In order to enable direct viewing of living cells and to perform time-lapse studies, nearly transparent bioceramic materials were developed. A dense and fine-grained transparent hydroxyapatite (tHA) was processed by a gel-casting route followed by low-temperature sintering (1000 deg. C). By virtue of its transparency, direct visualization of cellular events on this material is possible in transmitted light. In this study, the interaction of different bone cell types with the tHA ceramic was envisaged. Investigation of rat calvaria osteoblasts (RCO) cultured on tHA by means of transmission light microscopy indicated good cytocompatibility of tHA. Microscopic analysis of osteogenic-induced human bone marrow stromal cells (hBMSC) on tHA and quantitative analysis of their lactate dehydrogenase (LDH) activity at different time points of culture revealed favorable proliferation as well. An increase of the alkaline phosphatase (ALP) activity indicated the differentiation of osteogenic-induced hBMSC towards the osteoblastic lineage. In addition, the differentiation of human monocytes to osteoclast-like cells could also be demonstrated on tHA and was confirmed by fluorescent microscopy imaging of multinucleated cells on the transparent material.

  4. Antioxidant impregnated ultra-high molecular weight polyethylene wear debris particles display increased bone remodeling and a superior osteogenic:osteolytic profile vs. conventional UHMWPE particles in a murine calvaria model.

    Science.gov (United States)

    Chen, Yu; Hallab, Nadim J; Liao, Yen-Shuo; Narayan, Venkat; Schwarz, Edward M; Xie, Chao

    2016-05-01

    Periprosthetic osteolysis remains a major limitation of long-term successful total hip replacements with ultra-high molecular weight polyethylene (UHMWPE) bearings. As intra and extracellular reactive oxygen species are know to contribute to wear debris-induced osteoclastic bone resorption and decreased osteoblastic bone formation, antioxidant doped UHMWPE has emerged as an approach to reduce the osteolytic potential of wear debris and maintain coupled bone remodeling. To test this hypothesis in vivo, we evaluated the effects of crosslinked UHMWPE wear debris particles (AltrX(™) ), versus similar wear particles made from COVERNOX(™) containing UHMWPE (AOX(™) ), in an established murine calvaria model. Eight-week-old female C57B/6 mice (n = 10/Group) received a pre-op micro-CT scan prior to surgical implantation of the UHMWPE particles (2mg), or surgery without particles (sham). Dynamic labeling was performed by intraperitoneal injection of calcein on day 7 and alizarin on day 9, and the calvaria were harvested for micro-CT and histology on day 10. Surprisingly, we found that AOX particles induced significantly more bone resorption (1.72-fold) and osteoclast numbers (1.99-fold) vs. AltrX (p < 0.001). However, AOX also significantly induced 1.64-fold more new bone formation vs. AltrX (p < 0.01). Moreover, while the osteolytic:osteogenic ratio of both particles was very close to 1.0, which is indicative of coupled remodeling, AOX was more osteogenic (Slope = 1.13 ± 0.10 vs. 0.97 ± 0.10). Histomorphometry of the metabolically labeled undecalcified calvaria revealed a consistent trend of greater MAR in AOX vs. AltrX. Collectively, these results demonstrate that anti-oxidant impregnated UHMWPE particles have decreased osteolytic potential due to their increased osteogenic properties that support coupled bone remodeling. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:845-851, 2016. PMID:26495749

  5. Development and application of inorganic bioactive ceramic nanocomposites for bone tissue remodeling

    International Nuclear Information System (INIS)

    The objective of the article is to study the synthesis, animal tests and results of clinical applications of the newly proposed kind of bioactive ceramics for full bone tissue restoration-inorganic composites consisting of modified phosphate ceramics, bioactive glasses and bioactive glass-ceramic-so-called SYNTHETBONE materials. Regulation of the composition and structure of the composite can serve to adjust physicochemical and biological properties of the implant with demands of a particular surgery operation and provide the best results of the operations. The presented results demonstrate ample evidence of regulations of resorption rate and mechanism of the composite, favorable biological reaction on its implantation and prove its advantages and high efficiency in numerous surgery operations.

  6. Long-Term Administration of High-Fat Diet Corrects Abnormal Bone Remodeling in the Tibiae of Interleukin-6-Deficient Mice.

    Science.gov (United States)

    Feng, Wei; Liu, Bo; Liu, Di; Hasegawa, Tomoka; Wang, Wei; Han, Xiuchun; Cui, Jian; Yimin; Oda, Kimimitsu; Amizuka, Norio; Li, Minqi

    2016-01-01

    In this study, we aimed to evaluate the influence of diet-induced obesity on IL-6 deficiency-induced bone remodeling abnormality. Seven-week-old IL-6(-/-) mice and their wild type (WT) littermates were fed a standard diet (SD) or high-fat diet (HFD) for 25 weeks. Lipid formation and bone metabolism in mice tibiae were investigated by histochemical analysis. Both IL-6(-/-) and WT mice fed the HFD showed notable body weight gain, thickened cortical bones, and adipose accumulation in the bone marrow. Notably, the HFD normalized the bone phenotype of IL-6(-/-) mice to that of their WT counterpart, as characterized by a decrease in bone mass and the presence of an obliquely arranged, plate-like morphology in the trabecular bone. Alkaline phosphatase and osteocalcin expressions were attenuated in both genotypes after HFD feeding, especially for the IL-6(-/-) mice. Meanwhile, tartrate-resistant acid phosphatase staining was inhibited, osteoclast apoptosis rate down-regulated (revealed by TUNEL assay), and the proportion of cathepsin K (CK)-positive osteoclasts significantly increased in IL-6(-/-) mice on a HFD as compared with IL-6(-/-) mice on standard chow. Our results demonstrate that HFD-induced obesity reverses IL-6 deficiency-associated bone metabolic disorders by suppressing osteoblast activity, upregulating osteoclastic activity, and inhibiting osteoclast apoptosis. PMID:26416243

  7. Remodelación ósea a través del Modelo de Stanford // Bone remodeling through the Stanford´s Model.

    Directory of Open Access Journals (Sweden)

    H. Figueredo-Losada

    2009-09-01

    Full Text Available El material óseo es radicalmente distinto a cualquier otro material tratado por la mecánica clásica,su estructura es heterogénea y anisótropa, y sus propiedades mecánicas varían no solo entredistintos individuos, sino también, para un mismo hueso. En los tratamientos e intervencionesquirúrgicas donde está presente la readaptación, el crecimiento inducido del hueso puede sermodelado mediante el empleo de los criterios de remodelación ósea interna propuesto por algunosautores (Cowin y R. Huiskes, R. Carter, Doblare y García, Jacob y Beaupré y otros.En este trabajo se toma el modelo de remodelación ósea propuesto por Jacob (1994 y seimplementa con la utilización del programa Abaqus 6.4 utilizando una subrutina de usuario (UMAT,se aplico a un modelo 2D de hueso genérico con un sistema de cargas para comprobar los efectosde la remodelación y las variaciones de los valores de densidad. Como parte del trabajo fueroncreados dos programas para el procesamiento de los datos, para un análisis de resultados fuera delvisualizador del Abaqus, logrando una apreciación cualitativamente y cuantitativamente de losresultados.Palabras claves: remodelación ósea, elementos finitos, biomecánica._____________________________________________________________________________AbstractThe bone material is radically different to any other material tried by the classic mechanics, itsstructure is heterogeneous and anisótropic, and its mechanical properties not vary alone amongdifferent individuals, but also, for oneself bone. In the medical treatments and surgicalinterventions where it is present the readaptation, the induced growth of the bone can be modeledby means of the employment of the approaches of remodeling bone intern proposed by someauthors (Cowin and R. Huiskes, R. Crankcase, I will Doblare & García, Jacob & Beaupré and other.In this work it takes the pattern of bone remodelling proposed by Jacob (1994 and it isimplemented with the use of

  8. Can Na18F PET/CT Be Used to Study Bone Remodeling in the Tibia When Patients Are Being Treated with a Taylor Spatial Frame?

    Directory of Open Access Journals (Sweden)

    Henrik Lundblad

    2014-01-01

    Full Text Available Monitoring and quantifying bone remodeling are of interest, for example, in correction osteotomies, delayed fracture healing pseudarthrosis, bone lengthening, and other instances. Seven patients who had operations to attach an Ilizarov-derived Taylor Spatial Frame to the tibia gave informed consent. Each patient was examined by Na18F PET/CT twice, at approximately six weeks and three months after the operation. A validated software tool was used for the following processing steps. The first and second CT volumes were aligned in 3D and the respective PET volumes were aligned accordingly. In the first PET volume spherical volumes of interest (VOIs were delineated for the crural fracture and normal bone and transferred to the second PET volume for SUVmax evaluation. This method potentially provides clinical insight into questions such as, when has the bone remodeling progressed well enough to safely remove the TSF? and when is intervention required, in a timelier manner than current methods? For example, in two patients who completed treatment, the SUVmax between the first and second PET/CT examination decreased by 42% and 13%, respectively. Further studies in a larger patient population are needed to verify these preliminary results by correlating regional Na18F PET measurements to clinical and radiological findings.

  9. Graft Remodeling following Transcrestal Sinus Floor Elevation via the Gel-Pressure Technique (GPT and Pasteous Nano-Crystalline Hydroxyapatite Bone Substitute

    Directory of Open Access Journals (Sweden)

    Bernhard Pommer

    2015-06-01

    Full Text Available Bone grafting of the maxillary sinus is attempted to compensate for sinus pneumatization and permit reliable insertion of endosseous dental implants for prosthetic rehabilitation. The aim of the present clinical investigation was to study bone regeneration four months after transcrestal sinus floor elevation via the Gel-Pressure Technique (GPT and application of pasteous nano-crystalline hydroxyapatite bone substitute. A total of 25 patients with deficient alveolar ridges in the posterior maxilla (mean residual bone height: 4.7 ± 1.8 mm were subjected to 32 flapless transcrestal sinus floor augmentations and simultaneous insertion of 40 implants. Sinus membrane elevation height averaged 11.2 ± 2.7 mm and minimal vertical graft resorption of 0.1 mm was observed after four months. Radiographic bone density averaged 460 Hounsfield units in regions adjacent to the native jawbone (1 to 7 mm distance, while reduction of bone density by −7.2%, −11.3%, −14.8%, −19.6% and −22.7% was recorded in more apical regions of 8, 9, 10, 11, and ≥12 mm distance to the original sinus floor, respectively. The results suggest that graft remodeling is completed up to a distance of 7 mm within a healing period of four months after sinus augmentation using nano-crystalline hydroxyapatite bone substitute material.

  10. Liquid scintillation based quantitative measurement of dual radioisotopes ({sup 3}H and {sup 45}Ca) in biological samples for bone remodeling studies

    Energy Technology Data Exchange (ETDEWEB)

    Hui, Susanta K., E-mail: huixx019@umn.edu [Department of Therapeutic Radiology, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 494, Minneapolis, MN 55455 (United States); Sharma, M. [Department of Therapeutic Radiology, University of Minnesota, 420 Delaware Street SE, Mayo Mail Code 494, Minneapolis, MN 55455 (United States); Bhattacharyya, M.H. [Department of Medicine and Orthopaedic Surgery, Medical College of Georgia, Augusta, GA 30912 (United States)

    2012-01-15

    Acute and prolonged bone complications associated with radiation and chemotherapy in cancer survivors underscore the importance of establishing a laboratory-based complementary dual-isotope tool to evaluate short- as well as long-term bone remodeling in an in vivo model. To address this need, a liquid scintillation dual-label method was investigated using different scintillation cocktails for quantitative measurement of {sup 3}H-tetracycline ({sup 3}H-TC) and {sup 45}Ca as markers of bone turnover in mice. Individual samples were prepared over a wide range of known {sup 45}Ca/{sup 3}H activity ratios. Results showed that {sup 45}Ca/{sup 3}H activity ratios determined experimentally by the dual-label method were comparable to the known activity ratios (percentage difference {approx}2%), but large variations were found in samples with {sup 45}Ca/{sup 3}H activity ratios in range of 2-10 (percentage difference {approx}20-30%). Urine and fecal samples from mice administered with both {sup 3}H-TC and {sup 45}Ca were analyzed with the dual-label method. Positive correlations between {sup 3}H and {sup 45}Ca in urine (R=0.93) and feces (R=0.83) indicate that {sup 3}H-TC and {sup 45}Ca can be interchangeably used to monitor longitudinal in vivo skeletal remodeling. - Highlights: Black-Right-Pointing-Pointer Liquid scintillation cocktails support accurate dual-label analysis of {sup 3}H and {sup 45}Ca. Black-Right-Pointing-Pointer {sup 3}H-tetracycline and {sup 45}Ca were highly correlated in mice urine and feces. Black-Right-Pointing-Pointer {sup 3}H-tetracylcine and {sup 45}Ca can be used to monitor in vivo temporal bone remodeling.

  11. Recombinant Bone Morphogenetic Protein 2 Stimulates the Remodeling Chitosan-Based Porous Scaffold Into Hyaline-like Cartilage: Study in Heterotopic Implantation

    Directory of Open Access Journals (Sweden)

    Nurshat M. Gaifullin

    2013-09-01

    Full Text Available To study the morphology of remodeling the chitosan-based three-dimensional porous scaffold, containing bone morphogenetic protein-2 (BMP-2 for chondroinduction, the experiments with heterotopic implantation using 28 Wistar rats were carried out. Scaffolds with growth factor (n=12 or without it (n=12, against intact control (n=4 were implanted subcutaneously. Classical methods of histology and morphometry as well as immune histochemical markers (CD-68, CD-31, MMP-9, TIMP-1, and osteonectin expression, one used to investigate zone of remodeling in euthanized animals at 4 and 8 weeks after implantation. The BMP-2 application provides more intensive and rapid new cartilage formation from the scaffold matter. The additional chondroinductive effect proved more intensive settlement and proliferation of chondral cells in the regenerate, expression of chondral phenotype with the building the hyaline-like matrix, and the supporting necessary balance between the matrix metalloproteinases and their tissue inhibitors.

  12. 骨涎蛋白在不同类型种植体骨界面改建中的变化%Expression of bone sialoprotein in the process of implant-bone interface remodeling with different implants

    Institute of Scientific and Technical Information of China (English)

    袁林; 曹凯华; 童心

    2012-01-01

    AIM: To compare the expression of bone sialoprotein (BSP) in different implant-bone interface after loading of submerged and nonsubmcrged implant dentures. METHODS: Eight adult inbred beagle dogs were used to build the animal model. 3 submerged and 3 nonsubmerged implants were implanted into each side of the mandible respectively. The first implant at each side served as control and no denture was made. The remaining implants were fixed by metal full crown. 2,4,8, and 12 weeks after crown restoration, 2 dogs were sacrificed respectively. The corresponding mandible bone segments were taken. Buccolingual longitudinal paraffin sections, about 10 mm to each implant, were made (the thickness of each piece was 4 p.m). Immunohistochemistry was used to observe the dynamic expression of bone sialoprotein in the implant-bone interface. RESULTS: In the two control groups (without loading), weak expression of BSP in the implant梑one interface was observed. The expression level was not significantly changed at different time points. In the two experimental groups (with loading), strong BSP expression in the implant-bone interface was observed and BSP expression enhanced with loading time. Peak expression was at 8-week and afterwards, BSP ex- pression decreased and returned to the level of the control group at 12-week. No obvious difference of BSP expression in the implant-bone interface was observed between the submerged and nonsubmerged implants at the same time points. CONCLUSION; The mechanical loads from the submerged and nonsubmerged implant denture both can stimulate the expression of BSP in the implant-bone interface, promoting the interface remodeling. Furthermore, there is no distinct difference in the implant-bone interface remodeling after loading of submerged and nonsubmerged implants.%目的:比较埋植型与非埋植型种植体在义齿修复受载后,种植体-骨界面中骨涎蛋白表达的变化.方法:选用纯系Beagle犬8只,在其下颌左右两侧分

  13. Bone morphogenic protein-2 regulates the myogenic differentiation of PMVECs in CBDL rat serum-induced pulmonary microvascular remodeling

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chang; Chen, Lin; Zeng, Jing; Cui, Jian; Ning, Jiao-nin [Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038 (China); Wang, Guan-song [Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037 (China); Belguise, Karine; Wang, Xiaobo [Université P. Sabatier Toulouse III and CNRS, LBCMCP, 31062 Toulouse Cedex 9 (France); Qian, Gui-sheng [Institute of Respiratory Disease, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037 (China); Lu, Kai-zhi [Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038 (China); Yi, Bin, E-mail: yibin1974@163.com [Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing 400038 (China)

    2015-08-01

    Hepatopulmonary syndrome (HPS) is characterized by an arterial oxygenation defect induced by intrapulmonary vasodilation (IPVD) that increases morbidity and mortality. In our previous study, it was determined that both the proliferation and the myogenic differentiation of pulmonary microvascular endothelial cells (PMVECs) play a key role in the development of IPVD. However, the molecular mechanism underlying the relationship between IPVD and the myogenic differentiation of PMVECs remains unknown. Additionally, it has been shown that bone morphogenic protein-2 (BMP2), via the control of protein expression, may regulate cell differentiation including cardiomyocyte differentiation, neuronal differentiation and odontoblastic differentiation. In this study, we observed that common bile duct ligation (CBDL)-rat serum induced the upregulation of the expression of several myogenic proteins (SM-α-actin, calponin, SM-MHC) and enhanced the expression levels of BMP2 mRNA and protein in PMVECs. We also observed that both the expression levels of Smad1/5 and the activation of phosphorylated Smad1/5 were significantly elevated in PMVECs following exposure to CBDL-rat serum, which was accompanied by the down-regulation of Smurf1. The blockage of the BMP2/Smad signaling pathway with Noggin inhibited the myogenic differentiation of PMVECs, a process that was associated with relatively low expression levels of both SM-α-actin and calponin in the setting of CBDL-rat serum exposure, although SM-MHC expression was not affected. These findings suggested that the BMP2/Smad signaling pathway is involved in the myogenic differentiation of the PMVECs. In conclusion, our data highlight the pivotal role of BMP2 in the CBDL-rat serum-induced myogenic differentiation of PMVECs via the activation of both Smad1 and Smad5 and the down-regulation of Smurf1, which may represent a potential therapy for HPS-induced pulmonary vascular remodeling. - Highlights: • CBDL-rat serum promotes the myogenic

  14. Experiment K-310: The effect of space flight on ostenogenesis and dentinogenesis in the mandible of rats. Supplement 1: The effects of space flight on alveolar bone modeling and remodeling in the rat mandible

    Science.gov (United States)

    Van, P. T.; Vignery, A.; Bacon, R.

    1981-01-01

    The histomorphometric study of alveolar bone, a non-weight-bearing bone submitted mainly to the mechanical stimulations of mastication, showed that space flight decreases the remodeling activity but does not induce a negative balance between resorption and formation. The most dramatic effect of space flight has been observed along the periosteal surface, and especially in areas not covered with masticatory muscles, where bone formation almost stopped completely during the flight period. This bone, having been submitted to the same mechanical forces in the flight animals and the controls, leads to the conclusion that factors other than mechanical loading might be involved in the decreased bone formation during flight.

  15. The Dynamic Change of TGF-β1 in the Myocardial Remodeling of Rat after Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    GUO Zhangqiang; LIAO Yuhua; CHENG Xiang; LI Bin; LIU Ying; GE Hongxia; ZHANG Ling; WANG Min; GUO Heping

    2006-01-01

    To observe the dynamic changes of the TGF-β1 expressed in the infarct and non-infarcted region of rat heart during the ventricular remodeling (day 3, 7, 28, 180), myocardial infarction rat model was made and relationship between the cytokine and indicator of myocardial remodeling was analyzed. After the detection of hemodynamic parameter was performed by the Powerlab devices, the size of myocardial infarction and the morphology change was detected by TTC and HE, respectively.The relative levels of mRNA of TGF- β 1, collagen type Ⅰ, Ⅲ, and fetal gene beta-MHC were detected by RT-PCR. The distribution of TGF- β1 protein in the myocardium was detected by immunohistochemistry. The results showed that the size of infarction was higher than that of the sham operated groups in the infarcted group (44.5±0.5 vs 0). The difference in hemodynamic parameters between the infarcted group and sham operated group was significant (P<0.01). HE staining showed that inflammatory cells were accumulated in the infarcted region at the beginning of the 3rd day,which lasted 4 weeks. Then, it decreased gradually. β-MHC in the non-infarcted region rose from the 3rd day, reaching its peak at the 4th week, and it decreased gradually. The ratio of the collagen type Ⅰ/Ⅲ showed similar changes as compared with the sham operated groups (P<0.01). And the relative mRNA levels in the non-infarcted group were significantly higher than that in the infarcted and sham operated group (P<0.01) at day 180. Linear regression analysis indicated that the TGF-β1 was positively correlated with the ventricular remodeling. It was concluded that the cytokine TGF- β1 participates in the process of the myocardial remodeling, which could be a strategy in the interference of myocardial remodeling.

  16. Histochemical examination of the effects of high-dose 1,25(OH)2D3 on bone remodeling in young growing rats.

    Science.gov (United States)

    Sun, Jing; Sun, Bao; Wang, Wei; Han, Xiuchun; Liu, Hongrui; Du, Juan; Feng, Wei; Liu, Bo; Amizuka, Norio; Li, Minqi

    2016-08-01

    Vitamin D has an anabolic effect on bone developmental processes and is involved in maintaining skeletal integrity. In recent years, pediatric cases of vitamin D intoxication have attracted attention. Therefore, the aim of this study was to investigate the influence of long-term administration of physiologically-high-dose calcitriol (1,25(OH)2D3) on bone remodeling in young developing rats. Neonatal rats received once-daily subcutaneous injection of calcitriol (250 ng/kg body weight), or PBS only as a control, for 3 weeks. At 1, 2 and 4 weeks' post-administration, rats were sacrificed and fixed by transcardial perfusion with 4 % paraformaldehyde, following which tibiae were extracted for histochemical analysis. Compared with the control group, the number of tartrate-resistant acid phosphatase- and Cathepsin K-positive osteoclasts were significantly increased, and the expression of alkaline phosphatase in osteoblasts was decreased in trabecular bone of rats administered high-dose 1,25(OH)2D3, leading to decreased trabecular bone volume. In addition, the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) was increased, while that of osteoprotegerin was weaker in osteoblasts in the experimental group compared with the control group. Moreover, there was weaker immunoreactivity for EphrinB2 in osteoclasts and EphB4 in osteoblasts of trabecular bone in the experimental group compared with the control group. These findings suggest that long-term use of physiologically-high dose calcitriol may result in bone loss through RANKL/RANK/osteoprotegerin and EphrinB2-EphB4 signaling pathways, and that these negative effects could continue after drug withdrawal. Therefore, optimal limits for vitamin D administration need to be established for children and adolescents. PMID:27255234

  17. Hollow-Bone-Graft Dynamic Hip Screw Can Fix and Promote Bone Union after Femoral Neck Fracture: an Experimental Research

    OpenAIRE

    SHEN, Jia-zuo; YAO, Jian-fei; LIN, Da-sheng; Lian, Ke-jian; Ding, Zhen-qi; Lin, Bin; GUO, Zhi-min; Zhang, Ming-Hua; Li, Qiang; LI, Lin; Qi, Peng

    2012-01-01

    Background: Delayed bone union, nonunion or osteonecrosis often occur after femoral neck fractures in young adults. Secondary bone healing requires strong internal fixation, intramedullary pressure reduction and early functional exercise. Objective: To compare bone healing of femoral neck fractures treated with hollow-bone-graft dynamic hip screws (Hb-DHS) and standard dynamic hip screws (DHS) in an animal model. Design: Testing of specifically designed fixation devices in a pig animal model....

  18. Hollow-Bone-Graft Dynamic Hip Screw Can Fix and Promote Bone Union after Femoral Neck Fracture: an Experimental Research

    OpenAIRE

    Jia-zuo SHEN, Jian-fei YAO, Da-sheng LIN, Ke-jian LIAN, Zhen-qi DING, Bin LIN, Zhi-min GUO, Ming-hua ZHANG, Qiang LI, Lin LI, Peng QI

    2012-01-01

    Background: Delayed bone union, nonunion or osteonecrosis often occur after femoral neck fractures in young adults. Secondary bone healing requires strong internal fixation, intramedullary pressure reduction and early functional exercise.Objective: To compare bone healing of femoral neck fractures treated with hollow-bone-graft dynamic hip screws (Hb-DHS) and standard dynamic hip screws (DHS) in an animal model.Design: Testing of specifically designed fixation devices in a pig animal model.In...

  19. Vascular remodeling and mobilization of bone marrow-derived cells in cuff-induced vascular injury in LDL receptor knockout muce

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background Vascular remodeling is an important pathologic process in vascular injury for various vascular disorders such as atherosclerosis,postangioplasty restenosis and transplant arteriopathy.Recently,pathologic change and the role of bone marrow derived cells were wildly studied in atherosclerosis and restenosis.But the manner of lesion formation in neointima and cell recruitment in vascular remodeling lesion in the present of hypercholesterolemia is not Vet fully understood. Methods Double-transgenic mice knockout of LDL receptor gene (LDL-/-) and expressing ubiquitously green fluorescent protein (GFP) were obtained by cross-breeding LDL-/-mice with the GFP-expressing transgenic mice. LDL-/- mice (22-24 weeks of age) fed high fat diet containing 1.25% (w/w) cholesterol were subjected to 9Gy irradiation and received bone marrow (BM) cells from the double-transgenic mice.Four weeks later,a nonconstrictive cuff was Dlaced around the right femoral artery.After another 2 weeks,both right and left femoral arteries were harvested and subjected to histochemical analysis.Apoptosis was analyzed in situ using TUNEL assay.Resuits Two weeks after cuff placement,atherosclerotic lesions developed in the intima consisting of a massive accumulation of foam cells, The tissue stained with anti-α smooth muscle actin (SMA) antibody,showed a number of SMA-positive cells in the intimal lesion area.They were also positive for GFP,indicating that BM-derived cells can differentiate to SMCs in the intima in cuff-induced vascular remodeling lesions.Numerous small vessels in the adventitia as well as the endothelial lining of the intima were positive both for CD31 and GFP.The intima and media showed a larae number of TUNEL-positive signals after 2 weeks cuff injury,indicating the presence of apoptosis in vascular remodelina.Conclusions Atherosclerotic lesions in mice can be developed in the intima after 2 weeks of cuff-induced vascular inJury under the hypercholesterolemic conditions

  20. In vitro assessment of biomaterial-induced remodeling of subchondral and cancellous bone for the early intervention of joint degeneration with focus on the spinal disc

    Science.gov (United States)

    McCanless, Jonathan D.

    Osteoarthritis-associated pain of the spinal disc, knee, and hip derives from degeneration of cartilagenous tissues in these joints. Traditional therapies have focused on these cartilage (and disc specific nucleus pulposus) changes as a means of treatment through tissue grafting, regenerative synthetic implants, non-regenerative space filling implants, arthroplasty, and arthrodesis. Although such approaches may seem apparent upon initial consideration of joint degeneration, tissue pathology has shown changes in the underlying bone and vascular bed precede the onset of cartilaginous changes. It is hypothesized that these changes precedent joint degeneration and as such may provide a route for early prevention. The current work proposes an injectable biomaterial-based therapy within these subchondral and cancellous bone regions as a means of preventing or reversing osteoarthritis. Two human concentrated platelet releasate-containing alginate hydrogel/beta-tricalcium phosphate composites have been developed for this potential biomaterial application. The undertaking of assessing these materials through bench-, in vitro, and ex vivo work is described herein. These studies showed the capability of the biomaterials to initiate a wound healing response in monocytes, angiogenic and differentiation behavior in immature endothelial cells, and early osteochondral differentiation in mesenchymal stem cells. These cellular activities are associated with fracture healing and endochondral bone formation, demonstrating the potential of the biomaterials to induce osseous and vascular tissue remodeling underlying osteoarthritic joints as a novel therapy for a disease with rapidly growing healthcare costs.

  1. Cabozantinib inhibits growth of androgen-sensitive and castration-resistant prostate cancer and affects bone remodeling.

    Science.gov (United States)

    Nguyen, Holly M; Ruppender, Nazanin; Zhang, Xiaotun; Brown, Lisha G; Gross, Ted S; Morrissey, Colm; Gulati, Roman; Vessella, Robert L; Schimmoller, Frauke; Aftab, Dana T; Corey, Eva

    2013-01-01

    Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease. PMID:24205338

  2. Cabozantinib inhibits growth of androgen-sensitive and castration-resistant prostate cancer and affects bone remodeling.

    Directory of Open Access Journals (Sweden)

    Holly M Nguyen

    Full Text Available Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa, cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemistry and tissue microarrays containing normal prostate, primary PCa, and soft tissue and bone metastases, our data show that levels of MET, P-MET, and VEGFR2 are increasing during PCa progression. Our data also show that the expression of cabozantinib targets are particularly pronounced in bone metastases. To evaluate cabozantinib efficacy on PCa growth in the bone environment and in soft tissues we used androgen-sensitive LuCaP 23.1 and castration-resistant C4-2B PCa tumors. In vivo, cabozantinib inhibited the growth of PCa in bone as well as growth of subcutaneous tumors. Furthermore, cabozantinib treatment attenuated the bone response to the tumor and resulted in increased normal bone volume. In summary, the expression pattern of cabozantinib targets in primary and castration-resistant metastatic PCa, and its efficacy in two different models of PCa suggest that this agent has a strong potential for the effective treatment of PCa at different stages of the disease.

  3. Effects of Gastric Bypass and Gastric Banding on Bone Remodeling in Obese Patients with Type 2 Diabetes

    DEFF Research Database (Denmark)

    Yu, Elaine W; Wewalka, Marlene; Ding, Su-Ann;

    2016-01-01

    CONTEXT: Roux-en-Y gastric bypass (RYGB) leads to high-turnover bone loss, but little is known about skeletal effects of laparoscopic adjustable gastric banding (LAGB) or mechanisms underlying bone loss after bariatric surgery. OBJECTIVE: To evaluate effects of RYGB and LAGB on fasting...

  4. Bone marrow mesenchymal stem cell transplantation combined with perindopril treatment attenuates infarction remodelling in a rat model of acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    WANG Jian-an; LUO Rong-hua; ZHANG Xing; XIE Xiao-jie; HU Xin-yang; HE Ai-na; CHEN Jie; LI Jia-hui

    2006-01-01

    Objective: This study was performed to evaluate whether implantation of mesenchymal stem cell (MSC) would reduce left ventricular remodelling from the molecular mechanisms compared with angiotensin-converting enzyme inhibitors (ACEIs) perindopril into ischemic myocardium after acute myocardial infarction. Methods: Forty rats were divided into four groups: control, MSC, ACEI, MSC+ACEI groups. Bone marrow stem cell derived rat was injected immediately into a zone made ischemic by coronary artery ligation in MSC group and MSC+ACEI group. Phosphate-buffered saline (PBS) was injected into control group. Perindopril was administered p.o. to ACEI group and MSC+ACEI group. Six weeks after implantation, the rats were killed and heart sample was collected. Fibrillar collagen was observed by meliorative Masson's trichome stain. Western Blotting was employed to evaluate the protein expression of matrix metalloproteinase (MMP)-2, matrix metalloproteinase (MMP)-9 in infarction zone. The transcriptional level of MMP2, MMP9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1in infarction area was detected by reverse transcriptase PCR (RT-PCR) analysis. Results: The fibrillar collagen area, the protein expression of MMP2, MMP9 and the transcriptional level of MMP2, MMP9 mRNA in infarction zone reduced in MSC group,ACEI group, and MSC+ACEI group. No significant difference was detected in the expression of TIMP1 mRNA among the 4groups. Conclusion: Both MSC and ACEI could reduce infarction remodelling by altering collagen metabolism.

  5. Dynamic behavior and microstructural properties of cancellous bone

    CERN Document Server

    Laporte, Sébastien; Bousson, Valérie; Pattofatto, Stephane

    2009-01-01

    The aim of the presented study is to identify some properties of the dynamic behavior of the cancellous bone and to identify the link between this mechanical behavior and the microstructural properties. 7 cylinders of bovine cancellous bone (diameter 41 mm, thickness 14 mm) were tested in quasi static loading (0.001 s-1), 8 in dynamic loading (1000 s-1) and 10 in dynamic loading (1500 s-1) with a confinement system. All the specimens were submitted to imaging before the tests (pQCT) in order to indentify two microstructural properties: Bone Volume / Total Volume ? BV/TV ? and Trabeculae Thickness ? Tb.Th. The behavior of bovine cancellous bone under compression exhibits a foam-type behavior over the whole range of strain rates explored in this study. The results show that for the quasi-static tests only the stresses are correlated with BV/TV. For the unconfined dynamic tests, the yield stress is correlated to BV/TV and the plateau stress to BV/TV and Tb.Th. For the confined tests, only the plateau stress is c...

  6. Skeletal remodeling dynamics: New approaches with imaging instrumentation. [Laser confocal microscopy:a2

    Energy Technology Data Exchange (ETDEWEB)

    Parks, N.J.; Pinkerton, K.E.; Seibert, J.A.; Pool, R.R.

    1991-01-01

    This report of progress and future objectives timetable is based on an included schematic of goals and objectives and the project abstract which is included as Appendix 1. Five matters are summarized in the order of (1) novel methods of calcified bone confocal microscopy and reconstruction image analysis of decalcified beagle and human cortical bone serial sections, (2) macroscopic cross-correlation of beagle and human cortical and cancellous bone fractions with CT analysis, (3) guidance to the most radiobiologically important skeletal regions of interest with the just completed {sup 90}Sr bone tumor map from life time beagle studies, (4) deposition patterns of radioactive agents that participate in apatite crystal nucleation processes in bone and leave radiation-excited electrons trapped in bone mineral, and (5) the budget period timetable. The discovery that beta particles from {sup 166}Ho (T{sub {1/2}} =26 hr, {beta}{sub max} = 1.8 MeV) phosphonic acid bone agents leave detectable, long-lived, electron paramagnetic resonance signals in bone is included in Appendix 2 as a joint report.

  7. Genetic manipulation of the ghrelin signaling system in male mice reveals bone compartment specificity of acylated and unacylated ghrelin in the regulation of bone remodeling

    Science.gov (United States)

    Ghrelin receptor-deficient (Ghsr-/-) mice that lack acylated ghrelin (AG) signaling retain a metabolic response to unacylated ghrelin (UAG). Recently, we showed that Ghsr-deficiency affects bone metabolism. The aim of this study was to further establish the impact of AG and UAG on bone metabolism. W...

  8. Demineralization–remineralization dynamics in teeth and bone

    Science.gov (United States)

    Abou Neel, Ensanya Ali; Aljabo, Anas; Strange, Adam; Ibrahim, Salwa; Coathup, Melanie; Young, Anne M; Bozec, Laurent; Mudera, Vivek

    2016-01-01

    Biomineralization is a dynamic, complex, lifelong process by which living organisms control precipitations of inorganic nanocrystals within organic matrices to form unique hybrid biological tissues, for example, enamel, dentin, cementum, and bone. Understanding the process of mineral deposition is important for the development of treatments for mineralization-related diseases and also for the innovation and development of scaffolds. This review provides a thorough overview of the up-to-date information on the theories describing the possible mechanisms and the factors implicated as agonists and antagonists of mineralization. Then, the role of calcium and phosphate ions in the maintenance of teeth and bone health is described. Throughout the life, teeth and bone are at risk of demineralization, with particular emphasis on teeth, due to their anatomical arrangement and location. Teeth are exposed to food, drink, and the microbiota of the mouth; therefore, they have developed a high resistance to localized demineralization that is unmatched by bone. The mechanisms by which demineralization–remineralization process occurs in both teeth and bone and the new therapies/technologies that reverse demineralization or boost remineralization are also scrupulously discussed. Technologies discussed include composites with nano- and micron-sized inorganic minerals that can mimic mechanical properties of the tooth and bone in addition to promoting more natural repair of surrounding tissues. Turning these new technologies to products and practices would improve health care worldwide.

  9. [Biochemical markers of bone remodeling: pre-analytical variations and guidelines for their use. SFBC (Société Française de Biologie Clinique) Work Group. Biochemical markers of bone remodeling].

    Science.gov (United States)

    Garnero, P; Bianchi, F; Carlier, M C; Genty, V; Jacob, N; Kamel, S; Kindermans, C; Plouvier, E; Pressac, M; Souberbielle, J C

    2000-01-01

    Biochemical markers of bone turnover have been developed over the past 20 years that are more specific for bone tissue than conventional ones such as total alkaline phosphatase and urinary hydroxyproline. They have been widely used in clinical research and in clinical trials of new therapies as secondary end points of treatment efficacy. Most of the interest has been devoted to their use in postmenopausal osteoporosis, a condition characterized by subtle modifications of bone metabolism that cannot be detected readily by conventional markers of bone turnover. Although several recent studies have suggested that biochemical markers may be used for the management of the individual patient in routine clinical practice, this has not been clearly defined and is a matter of debate. Because of the crucial importance to clarify this issue, the Société Francaise de Biologie Clinique prompted an expert committee to summarize the available data and to make recommendations. The following paper includes a review on the biochemical and analytical aspects of the markers of bone formation and resorption and on the sources of variability such as sex, age, menstrual cycle, pregnancy and lactation, physical activity, seasonal variation and effects of diseases and treatments. We will also describe the effects of pre-analytical factors on the measurements of the different markers. Finally based on that review, we will make practical recommendations for the use of these markers in order to minimize the variability of the measurements and improve the clinical interpretation of the data.

  10. What Is Bone?

    Science.gov (United States)

    ... by your browser. Home Bone Basics What Is Bone? Publication available in: PDF (57 KB) Related Resources ... Men, and Osteoporosis Osteoporosis Prevention For Your Information Bone Remodeling Throughout life, bone is constantly renewed through ...

  11. Cabozantinib Inhibits Growth of Androgen-Sensitive and Castration-Resistant Prostate Cancer and Affects Bone Remodeling

    OpenAIRE

    Nguyen, Holly M.; Nazanin Ruppender; Xiaotun Zhang; Lisha G. Brown; Gross, Ted S.; Colm Morrissey; Roman Gulati; Vessella, Robert L.; Frauke Schimmoller; Aftab, Dana T.; Eva Corey

    2013-01-01

    Cabozantinib is an inhibitor of multiple receptor tyrosine kinases, including MET and VEGFR2. In a phase II clinical trial in advanced prostate cancer (PCa), cabozantinib treatment improved bone scans in 68% of evaluable patients. Our studies aimed to determine the expression of cabozantinib targets during PCa progression and to evaluate its efficacy in hormone-sensitive and castration-resistant PCa in preclinical models while delineating its effects on tumor and bone. Using immunohistochemis...

  12. Enhancement of local bone remodeling in osteoporotic rabbits by biomimic multilayered structures on Ti6Al4V implants.

    Science.gov (United States)

    Huang, Ling; Luo, Zhong; Hu, Yan; Shen, Xinkun; Li, Menghuan; Li, Liqi; Zhang, Yuan; Yang, Weihu; Liu, Peng; Cai, Kaiyong

    2016-06-01

    To enhance long-term survival of titanium implants in patients with osteoporosis, chitosan/gelatin multilayers containing bone morphogenetic protein 2(BMP2) and an antiosteoporotic agent of calcitonin (CT) are deposited on the Ti6Al4V (TC4) implants through layer-by-layer (LBL) electrostatic assembly technique. Here, the obtained titanium alloy implant (TC4/LBL/CT/BMP2) can regulate the release of loaded calcitonin and BMP2 agents in a sustaining manner to accelerate the bone formation and simultaneously inhibit bone resorption. In vitro results show that the bone-related cells on TC4/LBL/CT/BMP2 present the lowest production level of tartrate resistant acid phosphatase (TRAP) but the highest (p strength and favorable bone-implant osseointegration. Overall, this study establishes a simple and profound methodology to fabricate a biofunctional TC4 implant for the treatment of local osteoporotic fractures in vivo. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1437-1451, 2016. PMID:26822259

  13. Demineralization–remineralization dynamics in teeth and bone

    Directory of Open Access Journals (Sweden)

    Abou Neel EA

    2016-09-01

    Full Text Available Ensanya Ali Abou Neel,1–3 Anas Aljabo,3 Adam Strange,3 Salwa Ibrahim,3 Melanie Coathup,4 Anne M Young,3 Laurent Bozec,3 Vivek Mudera4 1Division of Biomaterials, Operative Dentistry Department, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia; 2Biomaterials Department, Faculty of Dentistry, Tanta University, Tanta, Egypt; 3Department of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute, London, UK; 4UCL Institute of Orthopaedics and Musculoskeletal Sciences, Royal National Orthopaedic Hospital, Stanmore, London, UK Abstract: Biomineralization is a dynamic, complex, lifelong process by which living organisms control precipitations of inorganic nanocrystals within organic matrices to form unique hybrid biological tissues, for example, enamel, dentin, cementum, and bone. Understanding the process of mineral deposition is important for the development of treatments for mineralization-related diseases and also for the innovation and development of scaffolds. This review provides a thorough overview of the up-to-date information on the theories describing the possible mechanisms and the factors implicated as agonists and antagonists of mineralization. Then, the role of calcium and phosphate ions in the maintenance of teeth and bone health is described. Throughout the life, teeth and bone are at risk of demineralization, with particular emphasis on teeth, due to their anatomical arrangement and location. Teeth are exposed to food, drink, and the microbiota of the mouth; therefore, they have developed a high resistance to localized demineralization that is unmatched by bone. The mechanisms by which demineralization–remineralization process occurs in both teeth and bone and the new therapies/technologies that reverse demineralization or boost remineralization are also scrupulously discussed. Technologies discussed include composites with nano- and micron-sized inorganic minerals that can mimic mechanical properties

  14. Bone marrow mononuclear cells induce beneficial remodeling and reduce diastolic dysfunction in the left ventricle of hypertensive SS/MCWi rats.

    Science.gov (United States)

    Parker, Sarah J; Didier, Daniela N; Karcher, Jamie R; Stodola, Timothy J; Endres, Bradley; Greene, Andrew S

    2012-10-01

    Bone marrow mononuclear cells (BMMNCs) increase capillary density and reduce fibrosis in rodents after myocardial infarction, resulting in an overall improvement in left ventricular function. Little is known about the effectiveness of BMMNC therapy in hypertensive heart disease. In the current study, we show that delivery of BMMNCs from hypertension protected SS-13(BN)/MCWi donor rats, but not BMMNC from hypertension susceptible SS/MCWi donor rats, resulted in 57.2 and 83.4% reductions in perivascular and interstitial fibrosis, respectively, as well as a 60% increase in capillary-to-myocyte count in the left ventricles (LV) of hypertensive SS/MCWi recipients. These histological changes were associated with improvements in LV compliance and relaxation (103 and 46.4% improvements, respectively). Furthermore, improved diastolic function in hypertensive SS/MCWi rats receiving SS-13(BN)/MCWi derived BMMNCs was associated with lower clinical indicators of heart failure, including reductions in end diastolic pressure (65%) and serum brain natriuretic peptide levels (49.9%) with no improvements observed in rats receiving SS/MCWi BMMNCs. SS/MCWi rats had a lower percentage of endothelial progenitor cells in their bone marrow relative to SS-13(BN)/MCWi rats. These results suggest that administration of BMMNCs can prevent or reverse pathological remodeling in hypertensive heart disease, which contributes to ameliorating diastolic dysfunction and associated symptomology. Furthermore, the health and hypertension susceptibility of the BMMNC donor are important factors influencing therapeutic efficacy, possibly via differences in the cellular composition of bone marrow.

  15. Simulated bone remodeling around two types of osseointegrated implants for direct fixation of upper-leg prostheses

    NARCIS (Netherlands)

    Tomaszewski, P.K.; Verdonschot, N.; Bulstra, S.K.; Rietman, J.S.; Verkerke, G.J.

    2012-01-01

    Direct attachment of an upper leg prosthesis to the skeletal system by a percutaneous implant is an alternative solution to the traditional socket fixation. In this study, we investigated long-term periprosthetic bone changes around two types of fixation implants using two different initial conditio

  16. Changes of blood parameters associated with bone remodeling following experimentally induced fatty liver disorder in laying hens

    Science.gov (United States)

    Studies have demonstrated that obesity and osteoporosis are two linked disorders in humans. This study examined if excessive lipid consumption affects bone metabolism in laying hens. One hundred 63-week-old laying hens were randomly divided into two treatments, i.e., fed with a regular diet (control...

  17. Multiple verification in computational modeling of bone pathologies

    CERN Document Server

    Liò, Pietro; Paoletti, Nicola; 10.4204/EPTCS.67.8

    2011-01-01

    We introduce a model checking approach to diagnose the emerging of bone pathologies. The implementation of a new model of bone remodeling in PRISM has led to an interesting characterization of osteoporosis as a defective bone remodeling dynamics with respect to other bone pathologies. Our approach allows to derive three types of model checking-based diagnostic estimators. The first diagnostic measure focuses on the level of bone mineral density, which is currently used in medical practice. In addition, we have introduced a novel diagnostic estimator which uses the full patient clinical record, here simulated using the modeling framework. This estimator detects rapid (months) negative changes in bone mineral density. Independently of the actual bone mineral density, when the decrease occurs rapidly it is important to alarm the patient and monitor him/her more closely to detect insurgence of other bone co-morbidities. A third estimator takes into account the variance of the bone density, which could address the...

  18. Detection of fungi colony growth on bones by dynamic speckle

    Science.gov (United States)

    Vincitorio, F. M.; Budini, N.; Mulone, C.; Spector, M.; Freyre, C.; López Díaz, A. J.; Ramil, A.

    2013-11-01

    In this work we have studied the dynamic speckle patterns of mucor fungi colonies, which were inoculated on different samples. We were interested in analyzing the development of fungi colonies in bones, since during the last two years, a series of infections by mucor fungi have been reported on patients from different hospitals in Argentina. Coincidentally, all of these infections appeared on patients that were subjected to a surgical intervention for implantation of a titanium prosthesis. Apparently, the reason of the infection was a deficient sterilization process in conjunction with an accidental contamination. We observed that fungi growth, activity and death can be distinguished by means of the dynamic speckle technique.

  19. Controlling dynamic mechanical properties and degradation of composites for bone regeneration by means of filler content

    NARCIS (Netherlands)

    Barbieri, Davide; de Bruijn, Joost D.; Luo, Xiaoman; Fare, Silvia; Grijpma, Dirk W.; Yuan, Huipin

    2013-01-01

    Bone tissue is a dynamic composite system that adapts itself, in response to the surrounding daily (cyclic) mechanical stimuli, through an equilibrium between growth and resorption processes. When there is need of synthetic bone grafts, the biggest issue is to support bone regeneration without causi

  20. Large Artery Remodeling and Dynamics following Simulated Microgravity by Prolonged Head-Down Tilt Bed Rest in Humans

    Directory of Open Access Journals (Sweden)

    Carlo Palombo

    2015-01-01

    Full Text Available The effects of simulated microgravity on the static and dynamic properties of large arteries are still mostly unknown. The present study evaluated, using an integrated vascular approach, changes in structure and function of the common carotid and femoral arteries (CCA and CFA after prolonged head-down tilt bed rest (HDTBR. Ten healthy men were enrolled in a 5-week HDTBR study endorsed by the Italian Space Agency (ASI. Arterial geometry, flow, stiffness, and shear rate were evaluated by ultrasound. Local carotid pulse pressure and wave reflection were studied by applanation tonometry. After five weeks of HDTBR, CFA showed a decrease in lumen diameter without significant changes in wall thickness (IMT, resulting in an inward remodeling. Local carotid pulse pressure decreased and carotid-to-brachial pressure amplification increased. The ratio of systolic-to-diastolic volumetric flow in CFA decreased, whereas in CCA it tended to increase. Indices of arterial stiffness and shear rate did not change during HDTBR, either in CCA or CFA. In summary, prolonged HDTBR has a different impact on CCA and CFA structure and flow, probably depending on the characteristics of the vascular bed perfused.

  1. Hollow-Bone-Graft Dynamic Hip Screw Can Fix and Promote Bone Union after Femoral Neck Fracture: an Experimental Research

    Directory of Open Access Journals (Sweden)

    Jia-zuo SHEN, Jian-fei YAO, Da-sheng LIN, Ke-jian LIAN, Zhen-qi DING, Bin LIN, Zhi-min GUO, Ming-hua ZHANG, Qiang LI, Lin LI, Peng QI

    2012-01-01

    Full Text Available Background: Delayed bone union, nonunion or osteonecrosis often occur after femoral neck fractures in young adults. Secondary bone healing requires strong internal fixation, intramedullary pressure reduction and early functional exercise.Objective: To compare bone healing of femoral neck fractures treated with hollow-bone-graft dynamic hip screws (Hb-DHS and standard dynamic hip screws (DHS in an animal model.Design: Testing of specifically designed fixation devices in a pig animal model.Interventions/Methods: We designed Hb-DHS and DHS devices appropriate to the femoral neck and head of experimental animals and used them in eight pigs (4-month-old, male or female, 30-40 kg/each. Under anesthesia, we induced medium neck type, Garden III type femoral neck fractures in each pig with fracture gaps of 0.5 mm and then fixed each left femur with Hb-DHS and each right femur with DHS. We assessed the animals radiographically and by postmortem visual appraisal of evidence of bone healing 8 and 16 weeks postoperatively.Results: There were significant differences in radiographic and general findings between the Hb-DHS and DHS groups at weeks 8 and 16 postoperatively. We found statistically significant differences between the Hb-DHS and DHS groups in bone healing scores, trabecular bone volume percentage and bone mineral density as assessed on plain radiographs and computed tomography images (P < 0.05. There were also significant differences between the Hb-DHS and DHS groups in postmortem visually assessed indicators of bone healing at both 8 and 16 weeks postoperatively.Conclusions: The Hb-DHS device promotes femoral neck bone union, stimulates trabecular bone formation, increases BMD and has advantages over DHS for internal fixation of femoral neck fractures. This animal experiment will contribute to developing optimal treatment for femoral neck fractures in young adults.

  2. Bone graft revascularization strategies

    NARCIS (Netherlands)

    W.F. Willems

    2014-01-01

    Reconstruction of avascular necrotic bone by pedicled bone grafting is a well-known treatment with little basic research supporting its application. A new canine model was used to simulate carpal bone avascular necrosis. Pedicled bone grafting proved to increase bone remodeling and bone blood flow,

  3. Efecto de telmisartan sobre marcadores del remodelado óseo en pacientes hipertensos Telmisartan effect's on remodelling bone markers in hypertensive patients

    Directory of Open Access Journals (Sweden)

    J. L. Pérez-Castrillón

    2012-02-01

    remodelado aunque se observó un descenso de la glucosa en pacientes con niveles de vitamina D por encima de 20 ng/ml (135 ± 53 mg/dl vs 119 ± 39 mg/dl, p = 0,01. Los pacientes tratados con IECAS disminuyen los valores de tensión arterial sistólica pero la diastólica no muestra cambios. Conclusiones: Telmisartan tiene un efecto neutro a nivel de los marcadores del remodelado óseo.Introduction: The telmisartan is an angiotensin II receptor blocker (ARB with a few own characteristics that it allows us to obtain a few additional benefits. It displays the ability to act as a partial agonist of PPARgamma. On the other hand, PPAR gamma intervenes in the control of bone remodelling though with not concordant results. The objective of this study to value the effect of telmisartan on bone markers in hypertensive patients. Subjects: A sample of 31 hypertensive patients with hypertension were included. The dose of telmisartan was of 80 mg/24 h and the period of follow-up was 12 weeks. The control group included 32 hypertensive patients treated before with IECA (enalapril-20 mg/24 h - or quinapril - 40 mg/24 hours. The following parameters were determined P1NP, β-CTX, 25OHD and PTH , osteocalcin, insulin and adiponectin. Results: The patients treated with Telmisartan shown a significantly decrease in systolic blood pressure (156 ± 19 mmHg vs 133 ± 15 mmHg, p = 0.001 and diastolic blood pressure (92 ± 9 mmHgvs 82 ± 6 mmHg, p = 0.01 . Changes were not observed in other parameter, PTHi (48 ± 22 pg/ml vs 45 ± 22 pg/ml, p > 0.05 and 25-vitamin D (21 ± 10 ng/ml vs 25 ± 8 ng/ml, p > 0.05, CTX (0.195 ± 0.12 ng/ml vs 0.221 ± 0.13 ng/ml, p > 0.05, PINP (39 ± 20 ng/ml vs 40 ± 19 ng/ml, p > 0.05, osteocalcin (11 ± 9 ng/ml vs 11 ± 5 ng/ml, p > 0.05, glucose, adiponectin, insulin and HOMA. When the patients divided in two groups depending on the levels of vitamin D (insufficient and not insufficient, with a cut of 20 ng/ml, there was changes on bone markers but a decrease of the

  4. OPG/RANKL/RANK系统参与牙槽骨吸收及重建过程作用初探%Role of OPG/RANKL/RANK system during alveolar bone resorption and remodeling

    Institute of Scientific and Technical Information of China (English)

    陈莉丽; 黄玫; 雷利红; 吴燕岷

    2013-01-01

    alveolar bone resorption model with the injection of E-LPS. Immunohistochemical S-P method was used to investigate the expression of OPG, RANKL and RANK in the animal model. Results The expression of OPG in MC3T3-E1 cells was up-regulated after 7 days' treatment with bone resorption supernatant than in control cells (29. 636 ± 5. 652 vs 15. 568 ± 1. 229, P < 0. 01 ) , while, the RANKL expression was down-regulated (6. 806 ± 1. 738 vs 18.082 ±2. 732, P<0.01). The ratio of OPG to RANKL was up-regulated too (P < 0. 05). The OPG level in periodontal tissues of rats was decreased compared with the tissue without resorption. But the expression of RANKL was increased. Conclusion OPG/RANKL/RANK system is involved in the bone resorption and remodeling. Osteoclast bone absorbent supernatants might affect the ratio of OPG to RANKL by regulating of the differentiation and activity of osteoblast-like cells, and thus regulate the dynamic balance of bone formation and resorption.

  5. Effect of postconditioning on dynamic expression of tenascin-C and left ventricular remodeling after myocardial ischemia and reperfusion

    OpenAIRE

    Taki, Junichi; Inaki, Anri; Wakabayashi, Hiroshi; Matsunari, Ichiro; Imanaka-Yoshida, Kyoko; Ogawa, Kazuma; Hiroe, Michiaki; Shiba, Kazuhiro; Yoshida, Toshimichi; Kinuya, Seigo

    2015-01-01

    Background Tenascin-C (TNC), an extracellular matrix glycoprotein, is expressed transiently in distinct areas in association with active tissue remodeling. This study aimed to explore how ischemic postconditioning (PC) affects myocardial expression of TNC and ventricular remodeling using 125I-labeled anti-TNC antibody (125I-TNC-Ab) in a rat model of ischemia and reperfusion. Methods In control rats (n = 27), the left coronary artery (LCA) was occluded for 30 min followed by reperfusion for 1,...

  6. Dynamic Monitoring of Cellular Remodeling Induced by the Transforming Growth Factor-β1

    Directory of Open Access Journals (Sweden)

    Kubala Lukáš

    2009-01-01

    Full Text Available Abstract The plasticity of differentiated adult cells could have a great therapeutic potential, but at the same time, it is characteristic of progression of serious pathological states such as cancer and fibrosis. In this study, we report on the application of a real-time noninvasive system for dynamic monitoring of cellular plasticity. Analysis of the cell impedance profile recorded as cell index using a real-time cell analyzer revealed its significant increase after the treatment of prostate epithelial cells with the transforming growth factor-β1. Changes in the cell index profile were paralleled with cytoskeleton rebuilding and induction of epithelial–mesenchymal transition and negatively correlated with cell proliferation. This novel application of such approach demonstrated a great potential of the impedance-based system for noninvasive and real-time monitoring of cellular fate.

  7. Dynamic remodelling of synapses can occur in the absence of the parent cell body

    Directory of Open Access Journals (Sweden)

    Baxter Becki

    2007-09-01

    Full Text Available Abstract Background Retraction of nerve terminals is a characteristic feature of development, injury and insult and may herald many neurodegenerative diseases. Although morphological events have been well characterized, we know relatively little about the nature of the underlying cellular machinery. Evidence suggests a strong local component in determining which neuronal branches and synapses are lost, but a greater understanding of this basic neurological process is required. Here we test the hypothesis that nerve terminals are semi-autonomous and able to rapidly respond to local stimuli in the absence of communication with their parent cell body. Results We used an isolated preparation consisting of distal peripheral nerve stumps, associated nerve terminals and post-synaptic muscle fibres, maintained in-vitro for up to 3 hrs. In this system synapses are intact but the presynaptic nerve terminal is disconnected from its cell soma. In control preparations synapses were stable for extended periods and did not undergo Wallerian degneration. In contrast, addition of purines triggers rapid changes at synapses. Using fluorescence and electron microscopy we observe ultrastructural and gross morphological events consistent with nerve terminal retraction. We find no evidence of Wallerian or Wallerian-like degeneration in these preparations. Pharmacological experiments implicate pre-synaptic P2X7 receptor subunits as key mediators of these events. Conclusion The data presented suggest; first that isolated nerve terminals are able to regulate connectivity independent of signals from the cell body, second that synapses exist in a dynamic state, poised to shift from stability to loss by activating intrinsic mechanisms and molecules, and third that local purines acting at purinergic receptors can trigger these events. A role for ATP receptors in this is not surprising since they are frequently activated during cellular injury, when adenosine tri-phosphate is

  8. Dynamic remodeling of the plastid envelope membranes – a tool for chloroplast envelope in vivo localizations

    Directory of Open Access Journals (Sweden)

    Frederique KH Breuers

    2012-01-01

    Full Text Available Two envelope membranes delimit plastids, the defining organelles of plant cells. The inner and outer envelope membranes are unique in their protein and lipid composition. Several studies have attempted to establish the proteome of these two membranes; however, differentiating between them is difficult due to their close proximity. Here, we describe a novel approach to distinguish the localization of proteins between the two membranes using a straightforward approach based on live cell imaging coupled with transient expression. We base our approach on analyses of the distribution of GFP-fusions, which were aimed to verify outer-envelope-membrane proteomics data. To distinguish between outer envelope and inner envelope protein localization, we used AtTOC64-GFP and AtTIC40-GFP, as respective controls. During our analyses, we observed membrane proliferations and loss of chloroplast shape in conditions of protein overexpression. The morphology of the proliferations varied in correlation with the suborganellar distribution of the overexpressed proteins. In particular, while layers of membranes built up in the inner envelope membrane, the outer envelope formed long extensions into the cytosol. Using electron microscopy, we showed that these extensions were stromules, a dynamic feature of plastids. Since the behavior of the membranes is different and is related to the protein localization, we propose that in vivo studies based on the analysis of morphological differences of the membranes can be used to distinguish between inner and outer envelope localizations of proteins. To demonstrate the applicability of this approach, we demonstrated the localization of AtLACS9 to the outer envelope membrane. We also discuss protein impact on membrane behavior and regulation of protein insertion into membranes, and provide new hypotheses on the formation of stromules.

  9. OPN、BSP在非埋植型种植体非负荷期种植体周围骨组织改建过程中的表达%Expression of OPN and BSP in the remodeling bone tissue around non-sub-merged implant during unloaded period

    Institute of Scientific and Technical Information of China (English)

    曾玉; 袁林; 程峰; 杨征毅; 潘广嗣; 王涵; 孙晋; 曹依娜; 钱钧

    2014-01-01

    目的::探讨骨桥蛋白(osteopontin,OPN)与骨涎蛋白(bonesialoprotein,BSP)在非负荷期非埋植型种植体周围骨界面改建中的作用。方法:选用健康雄性杂种犬8只,在其下颌植入非埋植型种植体,分不同时期处死动物。采用免疫组化方法,对不同时期非埋植型种植体-骨界面OPN与BSP进行动态观察,研究种植体-骨界面中OPN与BSP在界面改建过程中的表达变化。结果:种植义齿植入后在非负荷期,随着种植体周围骨组织发生改建,种植体-骨界面表达OPN和BSP有明显规律性,代表其染色强度的灰度值OPN从79.53±2.33增加到122.17±0.65;BSP从79.71±0.55增加到122.82±0.85。1周时界面OPN与BSP都有表达,2周时表达达到高峰,1月时逐渐下降,3月时趋于正常(均P<0.05)。结论:非埋植型种植体在非负荷期,种植体-骨界面OPN与BSP表达的变化有明显的规律性,且OPN与BSP能促进其界面的改建。在维持种植体与骨界面之间的骨性结合形成中起重要作用。%Objective:To investigate the role of osteopontin (OPN) and bonesialoprotein (BSP) in the remodeling bone interface around non-submerged implant during unloaded period. Methods: Eight healthy male mongrel dogs were used to build the animal model. Non-submerged implants were implanted into the bilateral mandibles of the dogs.The dogs were sacrificed in different stages after the procedure.Immunohistochemistry was used to observe the dynamic expression of OPN and BSP of non-submerged implant-bone interface in different stages,so as to study the change in expression of OPN and BSP in remodeling implant-bone interface. Results:According to immunohistochemical study,implant denture remodeled along with bone tissue around the implant after being implanted during unloaded period. The expression of OPN and BSP in the implant-bone interface showed significant regularity.The gray level (representing staining intensity) of OPN was enhanced from 79

  10. Development and characterization of an injectable dextrin-based hydrogel for bone regeneration

    OpenAIRE

    Dina M. Silva; Daniella L. Morgado; Delair, T; David, L; Rouif, S.; López-Lacomba, J. L.; A C Maurício; Santos, J. D.; Gama, F. M.

    2014-01-01

    Bone is a dynamic, highly vascularized tissue that remodels itself continuously over an individual ́s lifetime. It plays several important roles in maintaining homeostasis of the body systems [ 1 , 2 ] . However, this regenerative capac ity is limited and, as in the case of large bone defects, where the template for an orchestrated regeneration is absent, surgical proce dures are needed [ 2...

  11. Osteoclasts prefer aged bone

    DEFF Research Database (Denmark)

    Henriksen, K; Leeming, Diana Julie; Byrjalsen, I;

    2007-01-01

    We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling...

  12. Integrated Multimodal Imaging of Dynamic Bone-Tumor Alterations Associated with Metastatic Prostate Cancer

    OpenAIRE

    Jean-Christophe Brisset; Hoff, Benjamin A.; Thomas L Chenevert; Jacobson, Jon A.; Boes, Jennifer L.; Stefanie Galbán; Alnawaz Rehemtulla; Timothy D. Johnson; Pienta, Kenneth J.; Galbán, Craig J.; Meyer, Charles R.; Timothy Schakel; Klaas Nicolay; Alva, Ajjai S.; Maha Hussain

    2015-01-01

    Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI a...

  13. Dynamic modeling of bone metastasis, microenvironment and therapy: Integrating parathyroid hormone (PTH) effect, anti-resorptive and anti-cancer therapy.

    Science.gov (United States)

    Coelho, Rui Moura; Lemos, João Miranda; Alho, Irina; Valério, Duarte; Ferreira, Arlindo R; Costa, Luís; Vinga, Susana

    2016-02-21

    Bone is a common site for the development of metastasis, as its microenvironment provides the necessary conditions for the growth and proliferation of cancer cells. Several mathematical models to describe the bone remodeling process and how osteoclasts and osteoblasts coupled action ensures bone homeostasis have been proposed and further extended to include the effect of cancer cells. The model proposed here includes the influence of the parathyroid hormone (PTH) as capable of triggering and regulating the bone remodeling cycle. It also considers the secretion of PTH-related protein (PTHrP) by cancer cells, which stimulates the production of receptor activator of nuclear factor kappa-B ligand (RANKL) by osteoblasts that activates osteoclasts, increasing bone resorption and the subsequent release of growth factors entrapped in the bone matrix, which induce tumor growth, giving rise to a self-perpetuating cycle known as the vicious cycle of bone metastases. The model additionally describes how the presence of metastases contributes to the decoupling between bone resorption and formation. Moreover, the effects of anti-cancer and anti-resorptive treatments, through chemotherapy and the administration of bisphosphonates or denosumab, are also included, along with their corresponding pharmacokinetics (PK) and pharmacodynamics (PD). The simulated models, available at http://sels.tecnico.ulisboa.pt/software/, are able to describe bone remodeling cycles, the growth of bone metastases and how treatment can effectively reduce tumor burden on bone and prevent loss of bone strength. PMID:26657065

  14. Integrated multimodal imaging of dynamic bone-tumor alterations associated with metastatic prostate cancer.

    Science.gov (United States)

    Brisset, Jean-Christophe; Hoff, Benjamin A; Chenevert, Thomas L; Jacobson, Jon A; Boes, Jennifer L; Galbán, Stefanie; Rehemtulla, Alnawaz; Johnson, Timothy D; Pienta, Kenneth J; Galbán, Craig J; Meyer, Charles R; Schakel, Timothy; Nicolay, Klaas; Alva, Ajjai S; Hussain, Maha; Ross, Brian D

    2015-01-01

    Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI and CT scans to simultaneously evaluate temporal changes in normal bone homeostasis along with prostate bone metatastsis to deliver an improved understanding of the spatiotemporal local microenvironment. Dynamic tumor-stromal interactions were assessed during treatment in mouse models along with a pilot prospective clinical trial with metastatic hormone sensitive and castration resistant prostate cancer patients with bone metastases. Longitudinal changes in tumor and bone imaging metrics during delivery of therapy were quantified. Studies revealed that voxel-based parametric response maps (PRM) of DW-MRI and CT scans could be used to quantify and spatially visualize dynamic changes during prostate tumor growth and in response to treatment thereby distinguishing patients with stable disease from those with progressive disease (pprostate tumor-stromal responses to therapies thus demonstrating the potential of multi-modal PRM image-based biomarkers as a novel means for assessing dynamic alterations associated with metastatic prostate cancer. These results establish an integrated and clinically translatable approach which can be readily implemented for improving the clinical management of patients with metastatic bone disease. PMID:25859981

  15. Mouse tail vertebrae adapt to cyclic mechanical loading by increasing bone formation rate and decreasing bone resorption rate as shown by time-lapsed in vivo imaging of dynamic bone morphometry.

    Science.gov (United States)

    Lambers, Floor M; Schulte, Friederike A; Kuhn, Gisela; Webster, Duncan J; Müller, Ralph

    2011-12-01

    It is known that mechanical loading leads to an increase in bone mass through a positive shift in the balance between bone formation and bone resorption. How the remodeling sites change over time as an effect of loading remains, however, to be clarified. The purpose of this paper was to investigate how bone formation and resorption sites are modulated by mechanical loading over time by using a new imaging technique that extracts three dimensional formation and resorption parameters from time-lapsed in vivo micro-computed tomography images. To induce load adaptation, the sixth caudal vertebra of C57BL/6 mice was cyclically loaded through pins in the adjacent vertebrae at either 8 N or 0 N (control) three times a week for 5 min (3000 cycles) over a total of 4 weeks. The results showed that mechanical loading significantly increased trabecular bone volume fraction by 20% (pbone formation rate was on average 23% greater (pbone resorption rate was on average 25% smaller (pbone formation rate for the 8 N group was mostly an effect of a significantly increased surface of bone formation sites (on average 16%, pbone formation packages was less affected (on average 5% greater, pbone resorption sites was significantly reduced (on average 15%, pbone increased significantly by 24% (pbone decreased significantly by 24% (ptail vertebrae adapt to mechanical loading by increasing the surface of formation sites and decreasing the surface of resorption sites, leading to an overall increase in bone strength. This new imaging technique will provide opportunities to investigate in vivo bone remodeling in the context of disease and treatment options, with the added value that both bone formation and bone resorption parameters can be nondestructively calculated over time.

  16. Myeloma cell-induced disruption of bone remodelling compartments leads to osteolytic lesions and generation of osteoclast-myeloma hybrid cells

    DEFF Research Database (Denmark)

    Andersen, Thomas L; Søe, Kent; Søndergaard, Teis Esben;

    2010-01-01

    Osteolytic lesions are a hallmark of multiple myeloma. They are due to the hyperactivity of bone resorbing osteoclasts and hypoactivity of bone forming osteoblasts, in response to neighbouring myeloma cells. This study identified a structure that deeply affects this response, because of its impact...... on the physical organisation of the myeloma cell microenvironment. The proximity between myeloma cells and osteoclasts or osteoblasts was shown to be conditioned by the recently discovered layer of flat cells that separates the osteoclasts and osteoblasts from the bone marrow, by forming a canopy over bone......, this disruption and increased proximity and density of myeloma cells coincides with key myeloma-induced bone events, such as osteolytic lesions, impaired bone formation despite increased bone resorption, and fusion of myeloma cells with osteoclasts thereby forming myeloma-osteoclast hybrid cells. These findings...

  17. Bone

    Science.gov (United States)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

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

  18. Bone

    International Nuclear Information System (INIS)

    Bone scanning provides information on the extent of primary bone tumors, on possible metastatic disease, on the presence of osteomyelitis prior to observation of roentgenographic changes so that earlier therapy is possible, on the presence of collagen diseases, on the presence of fractures not disclosed by x-ray films, and on the evaluation of aseptic necrosis. However, the total effect and contribution of bone scanning to the diagnosis, treatment, and ultimate prognosis of pediatric skeletal diseases is, as yet, unknown. (auth)

  19. Bone Regulates Glucose Metabolism as an Endocrine Organ through Osteocalcin

    OpenAIRE

    2015-01-01

    Skeleton was considered as a dynamic connective tissue, which was essential for mobility, calcium homeostasis, and hematopoietic niche. However more and more evidences indicate that skeleton works not only as a structural scaffold but also as an endocrine organ, which regulates several metabolic processes. Besides osteoprotegerin (OPG), sclerostin (SOST), and Dickopf (DKK) which play essential roles in bone formation, modelling, remodelling, and homeostasis, bone can also secret hormones, suc...

  20. The features of HPOA on dynamic bone scintigraphy: A reflection of underlying pathophysiology

    International Nuclear Information System (INIS)

    Full text: Hypertrophic pulmonary osteoarthropathy (HPOA) is the clinical syndrome of clubbing, arthritis and periostitis which may accompany a spectrum of underlying disease processes. Increased blood flow through involved extremities is an invariable accompaniment of the syndrome and it is hypothesised that the chronic increase in peripheral blood flow results in the known pathological changes of periosteal inflammation and proliferation, oedema, synovial congestion and exudation and hyperplasia of the finger pulp. The dynamic and blood pool phases of bone scintigraphy provide a unique tool for examining the vascular changes in bone and soft tissues and we describe the previously unreported features of the dynamic bone scan in HPOA. We performed three-phase bone scans on two adolescent patients with cystic fibrosis with knee discomfort. Both studies showed marked hyperaemia to the knees. On the blood pool phase, hyperaemia was seen to the tissues closely related to the periosteum of the long bones in upper and lower limbs, periarticular tissues and finger pulps. The delayed images showed the classic features of HPOA with linear uptake of tracer in the shafts and metaphyseal regions of the long bones and minor periarticular uptake of tracer. A WBC scan performed in one patient showed WBC accumulation in the periosteum of the metaphyseal regions, extending in the shafts, of the distal femurs and proximal tibias. Negligible WBC accumulation was seen in the synovium of the knees reflecting the non-inflammatory nature of the articular changes as is described in most patients with HPOA. In conclusion, the dynamic phases of the bone scan examination in HPOA reflect the pivotal underlying pathophysiological process of abnormally increased blood flow to the periosteal and periarticular tissues of involved long bones and finger pulps and further expands the known diagnostic features of this disease on bone scintigraphy

  1. Osteoclasts and early bone remodeling after orthodontic micro-implant placement%正畸微种植体植入早期骨改建中破骨细胞的观察

    Institute of Scientific and Technical Information of China (English)

    张薇; 郭佳佳; 朱文倩; 唐国华

    2013-01-01

    目的:观察微种植体植入早期破骨细胞的产生,探讨破骨细胞变化与骨改建的关系.方法:雄性新西兰兔20只随机分为4组,在胫骨近心端近骺板处植入微种植体1颗,分别于植入3、7、14、28 d后处死(每组5只).HE染色观察微种植体周围骨组织的形态学变化,抗酒石酸酸性磷酸酶(TRAP)染色标记破骨细胞并作半定量分析.采用SPSS19.0软件包对数据进行统计学分析.结果:微种植体植入3d后,种植体骨接触区可见大量红细胞、炎症细胞、间叶细胞和骨碎屑,无明显破骨细胞.7d后,编织骨新生,呈颗粒状,破骨细胞位于骨陷窝中.14 d时,大量新生的编织骨呈网格状,破骨细胞增多,骨改建明显.28 d时,编织骨成片状,与层状骨相连,破骨细胞数目减少.TRAP染色半定量分析显示,破骨细胞数目在14 d时达到高峰,各时间点间均有显著差异(P<0.01).结论:在正畸微种植体植入早期破骨细胞产生,在新骨生成的活跃阶段破骨细胞数目增多,提示破骨细胞参与微种植体周的骨改建过程.%PURPOSE:To observe the incidence of osteoclasts during early bone remodeling after orthodontic microimplant placement.METHODS:Twenty New Zealand rabbits were randomly allotted into 4 groups.One micro-implant was implanted proximal to the epiphyseal plate of the tibia.Animals were sacrificed on day 3,7,14 and 28 (n=5).The sequence of histological changes around the micro-implants were evaluated by hematoxylin and eosin (HE) staining.Osteoclasts were identified by TRAP staining.The differences of the number of the osteoclasts among each time point were analyzed by one way ANOVA with SPSS 19.0 software package.RESULTS:After 3 days of implantation,a large number of erythrocytes,inflammatory cells,mesenchymal cells and bone debris were seen at the implant bone interfaces.Few osteoclasts were observed.On day 7,granular woven bone was formed and some osteoclasts were found in the Howship

  2. Integrated multimodal imaging of dynamic bone-tumor alterations associated with metastatic prostate cancer.

    Directory of Open Access Journals (Sweden)

    Jean-Christophe Brisset

    Full Text Available Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI and CT scans to simultaneously evaluate temporal changes in normal bone homeostasis along with prostate bone metatastsis to deliver an improved understanding of the spatiotemporal local microenvironment. Dynamic tumor-stromal interactions were assessed during treatment in mouse models along with a pilot prospective clinical trial with metastatic hormone sensitive and castration resistant prostate cancer patients with bone metastases. Longitudinal changes in tumor and bone imaging metrics during delivery of therapy were quantified. Studies revealed that voxel-based parametric response maps (PRM of DW-MRI and CT scans could be used to quantify and spatially visualize dynamic changes during prostate tumor growth and in response to treatment thereby distinguishing patients with stable disease from those with progressive disease (p<0.05. These studies suggest that PRM imaging biomarkers are useful for detection of the impact of prostate tumor-stromal responses to therapies thus demonstrating the potential of multi-modal PRM image-based biomarkers as a novel means for assessing dynamic alterations associated with metastatic prostate cancer. These results establish an integrated and clinically translatable approach which can be readily implemented for improving the clinical management of patients with metastatic bone disease.

  3. Marcadores del remodelamiento óseo en saliva y su correlación con los niveles sanguíneos en ratas Bone remodeling markers in saliva as compared to serum in rats

    Directory of Open Access Journals (Sweden)

    Pellegrini Gretel

    2006-06-01

    Full Text Available Si bien es conocida la utilidad de marcadores óseos en suero u orina para determinar cambios en el remodelamiento óseo, la misma no ha sido totalmente estudiada en saliva. Este trabajo evalúa la correlación entre dos marcadores del recambio óseo: la fosfatasa alcalina ósea (isoforma ósea, FAO y el telopéptido C-terminal del colágeno tipo I (CTX, medidos simultáneamente en suero y saliva de ratas Wistar (250 a 300 g, SHAM (n=12 y ovariectomizadas (OVX (n=12. Luego de una semana de la cirugía se extrajo sangre en ayunas y saliva total estimulada donde se evaluó CTX (ELISA, RatLabs, Osteometer Bio Tech, Dinamarca y FAO (Wiener, colorimetría. En el suero, tanto CTX (ng/ml como FAO (UI/l en ratas OVX fueron significativamente mayores que en ratas SHAM (15.3±4.0 vs. 21.8±6.4, pBone markers are useful tools to measure bone remodeling; currently they are assessed in serum and urinary samples; however there is little information concerning their measurement in saliva. The present experimental study evaluates the possibility to measure collagen type I carboxiterminal telopeptide (CTX and bone alkaline phosphatase (b-AP in saliva, its correlation with serum samples in normal conditions and in the increase of the bone remodeling due to estrogen deficiency. Twenty four normal adult Wistar rats (300±20 g [12 SHAM and 12 rats after 1 week of bilateral ovariectomy (OVX] were studied. Fasting serum and total saliva after stimulation with pilocarpine were collected. In both samples were measured: CTX (ng/ml by ELISA (RatLabs, Osteometer Bio Tech, Denmark and b-AP (IU/L (Wiener, colorimetrically. Both CTX and b-AL in serum samples were significantly higher in OVX than in SHAM rats (15.3±4.0 vs. 21.8±6.4, p<0.05 y 71±29 vs. 104±23; p<0.01, respectively. Saliva presented the same behaviour (3.6±0.5 vs. 6.4±2.9; p<0.02 y 73±29 vs. 90±8; p<0.003, respectively. When saliva CTX and b-AP were plotted against serum concentration significant

  4. Thermally Induced Osteocyte Damage Initiates a Remodelling Signaling Cascade

    OpenAIRE

    Dolan, Eimear B.; Matthew G Haugh; Voisin, Muriel C.; David Tallon; McNamara, Laoise M.

    2015-01-01

    Thermal elevations experienced by bone during orthopaedic procedures, such as cutting and drilling, exothermal reactions from bone cement, and thermal therapies such as tumor ablation, can result in thermal damage leading to death of native bone cells (osteocytes, osteoblasts, osteoclasts and mesenchymal stem cells). Osteocytes are believed to be the orchestrators of bone remodeling, which recruit nearby osteoclast and osteoblasts to control resorption and bone growth in response to mechanica...

  5. Effect of micromorphology of cortical bone tissue on crack propagation under dynamic loading

    Science.gov (United States)

    Wang, Mayao; Gao, Xing; Abdel-Wahab, Adel; Li, Simin; Zimmermann, Elizabeth A.; Riedel, Christoph; Busse, Björn; Silberschmidt, Vadim V.

    2015-09-01

    Structural integrity of bone tissue plays an important role in daily activities of humans. However, traumatic incidents such as sports injuries, collisions and falls can cause bone fracture, servere pain and mobility loss. In addition, ageing and degenerative bone diseases such as osteoporosis can increase the risk of fracture [1]. As a composite-like material, a cortical bone tissue is capable of tolerating moderate fracture/cracks without complete failure. The key to this is its heterogeneously distributed microstructural constituents providing both intrinsic and extrinsic toughening mechanisms. At micro-scale level, cortical bone can be considered as a four-phase composite material consisting of osteons, Haversian canals, cement lines and interstitial matrix. These microstructural constituents can directly affect local distributions of stresses and strains, and, hence, crack initiation and propagation. Therefore, understanding the effect of micromorphology of cortical bone on crack initiation and propagation, especially under dynamic loading regimes is of great importance for fracture risk evaluation. In this study, random microstructures of a cortical bone tissue were modelled with finite elements for four groups: healthy (control), young age, osteoporosis and bisphosphonate-treated, based on osteonal morphometric parameters measured from microscopic images for these groups. The developed models were loaded under the same dynamic loading conditions, representing a direct impact incident, resulting in progressive crack propagation. An extended finite-element method (X-FEM) was implemented to realize solution-dependent crack propagation within the microstructured cortical bone tissues. The obtained simulation results demonstrate significant differences due to micromorphology of cortical bone, in terms of crack propagation characteristics for different groups, with the young group showing highest fracture resistance and the senior group the lowest.

  6. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

    OpenAIRE

    2015-01-01

    Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can res...

  7. Dynamic T2-mapping during magnetic resonance guided high intensity focused ultrasound ablation of bone marrow

    International Nuclear Information System (INIS)

    Focal bone tumor treatments include amputation, limb-sparing surgical excision with bone reconstruction, and high-dose external-beam radiation therapy. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is an effective non-invasive thermotherapy for palliative management of bone metastases pain. MR thermometry (MRT) measures the proton resonance frequency shift (PRFS) of water molecules and produces accurate (2, since T2 increases linearly in fat during heating. T2-mapping using dual echo times during a dynamic turbo spin-echo pulse sequence enabled rapid measurement of T2. Calibration of T2-based thermal maps involved heating the marrow in a bovine femur and simultaneously measuring T2 and temperature with a thermocouple. A positive T2 temperature dependence in bone marrow of 20 ms/°C was observed. Dynamic T2-mapping should enable accurate temperature monitoring during MR-HIFU treatment of bone marrow and shows promise for improving the safety and reducing the invasiveness of pediatric bone tumor treatments.

  8. [Pharmacology of bone anabolic agents].

    Science.gov (United States)

    Matsumoto, Toshio

    2015-10-01

    Bone is constantly remodeled to maintain its volume, structural integrity and strength Currently available bone anabolic agent is teriparatide. Teriparatide increases bone mass and strength via both remodeling-dependent and -independent mechanisms, although remodeling-dependent mechanism overweighs the other. Canonical Wnt signal plays an important role in enhancing osteoblast differentiation and bone formation, and its osteocyte-derived inhibitor, sclerostin, regulates bone formation via the regulation of Wnt signaling. Anti-sclerostin antibody stimulates Wnt signaling and enhances bone formation. Phase II clinical trials with anti-sclerostin antibodies, romosozumab and blosozumab, demonstrated a marked increase in bone mineral density after one year of treatment. The new modality of anabolic agents via remodeling-independent stimulation of bone formation may open up a new avenue for the treatment of osteoporosis.

  9. Constitutive Laws and Failure Models for Compact Bones Subjected to Dynamic Loading

    CERN Document Server

    Pithioux, M; Jean, M

    2002-01-01

    Many biological tissues, such as bones and ligaments, are fibrous. The geometrical structure of these tissues shows that they exhibit a similar hierarchy in their ultra-structure and macro-structure. The aim of this work is to develop a model to study the failure of fibrous structures subjected to dynamic loading. The important feature of this model is that it describes failure in terms of the loss of cohesion between fibres. We have developed a model based on the lamellar structure of compact bone with fibres oriented at 0 degrees, 45 degrees and 90 degrees to the longitudinal axis of the bone, and have studied the influence of the model parameters on the failure process. Bone porosity and joint stress force at failure were found to be the most significant parameters. Using least square resolution, we deduced a phenomenological model of the lamellar structure. Finally, experimental results were found to be comparable with our numerical model.

  10. Dynamic contrast-enhanced MR imaging of the water fraction of normal bone marrow and diffuse bone marrow disease

    Energy Technology Data Exchange (ETDEWEB)

    Katsuya, Tomoo; Inoue, Tomio; Ishizaka, Hiroshi; Aoki, Jun; Endo, Keigo [Gunma Univ., Maebashi (Japan). School of Medicine

    2000-10-01

    To clarify the contrast-enhancement pattern of the normal hematopoietic element by isolating the signal of the water fraction in vertebral bone marrow and to investigate whether this approach can be used to characterize bone marrow pathology in several diffuse bone marrow diseases. Two groups were examined: 30 normal healthy volunteers and 19 patients with primary diffuse bone marrow disease (aplastic anemia [n=8], myelodysplastic syndrome (MDS) [n=5], chronic myelogenic leukemia (CML) [n=4], polycythemia vera [n=2]). Isolation of the signal of hematopoietic tissue was done by the chemical-shift misregistration effect. Twenty consecutive T1-weighted midsagittal lumber vertebral images were obtained immediately after the intravenous administration of Gd-DTPA of 0.1 mmol/kg body weight, and the pattern of the time-intensity curve, the peak contrast-enhancement (CE) ratio, and the washout rate (%/min) of bone marrow in normal volunteers were compared with those in patients suffering from primary diffuse bone marrow disease. The pattern of the time-intensity curve of patients with aplastic anemia showed a low peak value followed by a slow washout. However, the pattern of time-intensity curves in patients with MDS, CML, and polycythemia vera was similar to that of normal volunteers. The peak CE ratio of the water fraction in normal marrow ranged from 0.45 to 1.26 (mean {+-}S.D.: 0.87{+-}0.18). Patients with aplastic anemia showed an abnormally lower peak CE ratio of the water fraction (mean {+-}S.D.: 0.34{+-}0.19, p<0.0001). On the other hand, the peak CE ratio of the water fraction in patients with MDS was significantly higher than that of normal volunteers (mean {+-}S.D. 1.35{+-}0.39, p<0.05). In contrast, the peak CE ratio of patients with CML or polycythemia vera did not differ significantly from that of normal volunteers. The mean washout rate of patients with aplastic anemia was significantly lower than that of normal volunteers (mean {+-}S.D.: 3.50{+-}2.51 %/min

  11. Bone Adaptation and Regeneration - New Developments

    Science.gov (United States)

    Klein-Nulend, Jenneke; Bacabac, Rommel Gaud

    Bone is a dynamic tissue that is constantly renewed and adapts to its local loading environment. Mechanical loading results in adaptive changes in bone size and shape that strengthen bone structure. The mechanisms for adaptation involve a multistep process called mechanotransduction, which is the ability of resident bone cells to perceive and translate mechanical energy into a cascade of structural and biochemical changes within the cells. The transduction of a mechanical signal to a biochemical response involves pathways within the cell membrane and cytoskeleton of the osteocytes, the professional mechansensor cells of bone. During the last decade the role of mechanosensitive osteocytes in bone metabolism and turnover, and the lacuno-canalicular porosity as the structure that mediates mechanosensing, is likely to reveal a new paradigm for understanding the bone formation response to mechanical loading, and the bone resorption response to disuse. Strain-derived fluid flow of interstitial fluid through the lacuno-canalicular porosity seems to mechanically activate the osteocytes, as well as ensures transport of cell signaling molecules, nutrients and waste products. Cell-cell signaling from the osteocyte sensor cells to the effector cells (osteoblasts or osteoclasts), and the effector cell response - either bone formation or resorption, allow an explanation of local bone gain and loss as well as remodeling in response to fatigue damage as processes supervised by mechanosensitive osteocytes. The osteogenic activity of cultured bone cells has been quantitatively correlated with varying stress stimulations highlighting the importance of the rate of loading. Theoretically a possible mechanism for the stress response by osteocytes is due to strain amplification at the pericellular matrix. Single cell studies on molecular responses of osteocytes provide insight on local architectural alignment in bone during remodeling. Alignment seems to occur as a result of the

  12. Study of Bone-screw Surface Fixation in Lumbar Dynamic Stabilization

    Directory of Open Access Journals (Sweden)

    Yun-Gang Luo

    2015-01-01

    Full Text Available Background: We aimed to use the animal model of dynamic fixation to examine the interaction of the pedicle screw surface with surrounding bone, and determine whether pedicle screws achieve good mechanical stability in the vertebrae. Methods: Twenty-four goats aged 2-3 years had Cosmic ® pedicle screws implanted into both sides of the L2-L5 pedicles. Twelve goats in the bilateral dynamic fixation group had fixation rods implanted in L2-L3 and L4-L5. Twelve goats in the unilateral dynamic fixation group had fixation rods randomly fixed on one side of the lumbar spine. The side that was not implanted with fixation rods was used as a static control group. Results: In the static control group, new bone was formed around the pedicle screw and on the screw surface. In the unilateral and bilateral dynamic fixation groups, large amounts of connective tissue formed between and around the screw threads, with no new bone formation on the screw surface; the pedicle screws were loose after the fixed rods were removed. The bone mineral density and morphological parameters of the region of interest (ROI in the unilateral and bilateral dynamic fixation group were not significantly different (P > 0.05, but were lower in the fixed groups than the static control group (P 0.05; however the maximum pull force of the fixation groups was significantly less than the static control group (P < 0.01. Conclusions: Fibrous connective tissue formed at the bone-screw interface under unilateral and bilateral pedicle dynamic fixation, and the pedicle screws lost mechanical stability in the vertebrae.

  13. Age-related skeletal dynamics and decrease in bone strength in DNA repair deficient male trichothiodystrophy mice.

    Directory of Open Access Journals (Sweden)

    Claudia Nicolaije

    Full Text Available Accumulation of DNA damage caused by oxidative stress is thought to be one of the main contributors of human tissue aging. Trichothiodystrophy (TTD mice have a mutation in the Ercc2 DNA repair gene, resulting in accumulation of DNA damage and several features of segmental accelerated aging. We used male TTD mice to study the impact of DNA repair on bone metabolism with age. Analysis of bone parameters, measured by micro-computed tomography, displayed an earlier decrease in trabecular and cortical bone as well as a loss of periosteal apposition and a reduction in bone strength in TTD mice with age compared to wild type mice. Ex vivo analysis of bone marrow differentiation potential showed an accelerated reduction in the number of osteogenic and osteoprogenitor cells with unaltered differentiation capacity. Adipocyte differentiation was normal. Early in life, osteoclast number tended to be increased while at 78 weeks it was significantly lower in TTD mice. Our findings reveal the importance of genome stability and proper DNA repair for skeletal homeostasis with age and support the idea that accumulation of damage interferes with normal skeletal maintenance, causing reduction in the number of osteoblast precursors that are required for normal bone remodeling leading to a loss of bone structure and strength.

  14. Predicting Bone Mechanical State During Recovery After Long-Duration Skeletal Unloading Using QCT and Finite Element Modeling

    Science.gov (United States)

    Chang, Katarina L.; Pennline, James A.

    2013-01-01

    During long-duration missions at the International Space Station, astronauts experience weightlessness leading to skeletal unloading. Unloading causes a lack of a mechanical stimulus that triggers bone cellular units to remove mass from the skeleton. A mathematical system of the cellular dynamics predicts theoretical changes to volume fractions and ash fraction in response to temporal variations in skeletal loading. No current model uses image technology to gather information about a skeletal site s initial properties to calculate bone remodeling changes and then to compare predicted bone strengths with the initial strength. The goal of this study is to use quantitative computed tomography (QCT) in conjunction with a computational model of the bone remodeling process to establish initial bone properties to predict changes in bone mechanics during bone loss and recovery with finite element (FE) modeling. Input parameters for the remodeling model include bone volume fraction and ash fraction, which are both computed from the QCT images. A non-destructive approach to measure ash fraction is also derived. Voxel-based finite element models (FEM) created from QCTs provide initial evaluation of bone strength. Bone volume fraction and ash fraction outputs from the computational model predict changes to the elastic modulus of bone via a two-parameter equation. The modulus captures the effect of bone remodeling and functions as the key to evaluate of changes in strength. Application of this time-dependent modulus to FEMs and composite beam theory enables an assessment of bone mechanics during recovery. Prediction of bone strength is not only important for astronauts, but is also pertinent to millions of patients with osteoporosis and low bone density.

  15. Integrated Multimodal Imaging of Dynamic Bone-Tumor Alterations Associated with Metastatic Prostate Cancer

    NARCIS (Netherlands)

    Brisset, Jean-Christophe; Hoff, Benjamin A.; Chenevert, Thomas L.; Jacobson, Jon A.; Boes, Jennifer L.; Galban, Stefanie; Rehemtulla, Alnawaz; Johnson, Timothy D.; Pienta, Kenneth J.; Galban, Craig J.; Meyer, Charles R.; Schakel, Timothy; Nicolay, Klaas; Alva, Ajjai S.; Hussain, Maha; Ross, Brian D.; Schakel, Tim

    2015-01-01

    Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellul

  16. A preliminary investigation of the dynamic viscoelastic relaxation of bovine cortical bone

    Directory of Open Access Journals (Sweden)

    Loete T.J.C.

    2015-01-01

    Full Text Available A new experimental approach is proposed to characterize the dynamic viscoelastic relaxation behaviour of cortical bone. Theoretical models are presented to show that a linear viscoelastic material, when allowed to relax between two long elastic bars, will produce stress, strain and strain rate histories that contain characteristic features. Furthermore, typical experimental results are presented to show that these characteristic features are observed during split Hopkinson bar tests on bovine cortical bone using a Cone-in-Tube striker. The interpretation of this behaviour in the context of a standard linear viscoelastic model is discussed.

  17. Therapeutic inhibition of cathepsin K—reducing bone resorption while maintaining bone formation

    OpenAIRE

    Duong, Le T.

    2012-01-01

    Osteoporosis is a disease of high bone remodeling with an imbalance of bone resorption over bone formation, resulting in decreased bone mineral density and deterioration of bone microarchitecture. From the emerging understandings of the molecular and cellular regulators of bone remodeling, potential new targets for therapeutic intervention for this disease have been identified. Cathepsin K (CatK), a cysteine protease produced by osteoclasts, is the primary enzyme mediating the degradation of ...

  18. Study of Bone-screw Surface Fixation in Lumbar Dynamic Stabilization

    Institute of Scientific and Technical Information of China (English)

    Yun-Gang Luo; Tao Yu; Guo-Min Liu; Nan Yang

    2015-01-01

    Background:We aimed to use the animal model of dynamic fixation to examine the interaction of the pedicle screw surface with surrounding bone,and determine whether pedicle screws achieve good mechanical stability in the vertebrae.Methods:Twenty-four goats aged 2-3 years had Cosmic(R) pedicle screws implanted into both sides of the L2-L5 pedicles.Twelve goats in the bilateral dynamic fixation group had fixation rods implanted in L2-L3 and L4-L5.Twelve goats in the unilateral dynamic fixation group had fixation rods randomly fixed on one side of the lumbar spine.The side that was not implanted with fixation rods was used as a static control group.Results:In the static control group,new bone was formed around the pedicle screw and on the screw surface.In the unilateral and bilateral dynamic fixation groups,large amounts of connective tissue formed between and around the screw threads,with no new bone formation on the screw surface; the pedicle screws were loose after the fixed rods were removed.The bone mineral density and morphological parameters of the region of interest (ROI) in the unilateral and bilateral dynamic fixation group were not significantly different (P > 0.05),but were lower in the fixed groups than the static control group (P < 0.05).This showed the description bone of the ROI in the static control group was greater than in the fixation groups.Under loading conditions,the pedicle screw maximum pull force was not significantly different between the bilateral and unilateral dynamic fixation groups (P > 0.05); however the maximum pull force of the fixation groups was significantly less than the static control group (P < 0.01).Conclusions:Fibrous connective tissue formed at the bone-screw interface under unilateral and bilateral pedicle dynamic fixation,and the pedicle screws lost mechanical stability in the vertebrae.

  19. Titanium-Based Biomaterials for Preventing Stress Shielding between Implant Devices and Bone

    Directory of Open Access Journals (Sweden)

    M. Niinomi

    2011-01-01

    Full Text Available β-type titanium alloys with low Young's modulus are required to inhibit bone atrophy and enhance bone remodeling for implants used to substitute failed hard tissue. At the same time, these titanium alloys are required to have high static and dynamic strength. On the other hand, metallic biomaterials with variable Young's modulus are required to satisfy the needs of both patients and surgeons, namely, low and high Young's moduli, respectively. In this paper, we have discussed effective methods to improve the static and dynamic strength while maintaining low Young's modulus for β-type titanium alloys used in biomedical applications. Then, the advantage of low Young's modulus of β-type titanium alloys in biomedical applications has been discussed from the perspective of inhibiting bone atrophy and enhancing bone remodeling. Further, we have discussed the development of β-type titanium alloys with a self-adjusting Young's modulus for use in removable implants.

  20. Dynamic contrast-enhanced MR imaging and MR-guided bone biopsy on a 0.23T open imager

    Institute of Scientific and Technical Information of China (English)

    R.K.Parkkola; K.T.Mattila; J.T.Heikkila; T.O.Ekfors; M.A.Kallajoki; M.E.SjKonmu; T.J.Vaara; H.T.Aro

    2002-01-01

    Objective:To assess the feasibility of MR-guided bone biopsies.Methods::Thirty-six consecutive patients with known or suspected benign or malignant bone lesions underwent comprehensive MR imaging.A dynamic contrast-enhanced sequence followed by stationary Ti-weighted sequences were obtained and MR-guided bone biopsy of the tumor at the site with fastest enhancement was performed using an open 0.23 T MR imager.Results:All MR-guided bone biopsies samples were estimated to be sufficient by the pathologists.The biopsy specimens were diagnostic in 34 of 36 cases.Conclusion:MR-guided bone biopsies combined with dynamic contrast-enhanced imaging are feasible and safe for the diagnostic investigation of equivocal bone lesions.

  1. Evaluation of ionizing radiation effects in bone tissue by FTIR spectroscopy and dynamic mechanical analysis

    International Nuclear Information System (INIS)

    In many medical practices the bone tissue exposure to ionizing radiation is necessary. However, this radiation can interact with bone tissue in a molecular level, causing chemical and mechanical changes related with the dose used. The aim of this study was verify the changes promoted by different doses of ionizing radiation in bone tissue using spectroscopy technique of Attenuate Total Reflectance - Fourier Transforms Infrared (ATR-FTIR) and dynamic mechanical analysis. Samples of bovine bone were irradiated using irradiator of Cobalt-60 with five different doses between 0.01 kGy, 0.1 kGy,1 kGy, 15 kGy and 75 kGy. To study the effects of ionizing irradiation on bone chemical structure the sub-bands of amide I and the crystallinity index were studied. The mechanical changes were evaluated using the elastic modulus and the damping value. To verify if the chemical changes and the bone mechanic characteristics were related, it was made one study about the correlation between the crystallinity index and the elastic modulus, between the sub-bands ratio and the damping value and between the sub-bands ratio and the elastic modulus. It was possible to evaluate the effects of different dose of ionizing radiation in bone tissue. With ATR-FTIR spectroscopy analysis, it was possible observe changes in the organic components and in the hydroxyapatite crystals organization. Changes were also observed in the mechanical properties. A good correlation between the techniques was found, however, it was not possible to establish a linear or exponential dependence between dose and effect. (author)

  2. Systemic effects of fluoxetine on the amount of tooth movement, root resorption, and alveolar bone remodeling during orthodontic force application in rat

    Directory of Open Access Journals (Sweden)

    Mehdi Rafiei

    2015-01-01

    Full Text Available Background: Antidepressant drugs such as fluoxetine are of the most commonly used drugs among the public. These drugs may impact the regulation of bone cell functioning, and thus affect orthodontic tooth movement. The aim of this study was to determine the effect of fluoxetine on tooth movements during orthodontic treatment in rats. Materials and Methods: In this study, 30 male rats were randomly assigned into two groups and injected with fluoxetine 10 mg/kg (experimental group and normal saline (control group for a period of 1-month intraperitoneally 5 times/week. Then, the rats were anesthetized and a nickel-titanium closed-coil spring was placed between the left maxillary first molar and left maxillary central incisors of all samples, and then fluoxetine (experimental group and normal saline (control group were injected for another 3 weeks by the same method. After measuring tooth movements, rats were sacrificed, and histomorphometric analyses were conducted and the obtained data were statistically analyzed using independent t-test and the significance was set at 0.05. Results: Following the fluoxetine injection, the mean amount of tooth movements in the experimental group was reduced compared to the control group, which was not statistically significant (P = 0.14. There was no significant difference between the two groups regarding bone apposition rate (P = 0.83, external root resorption rate (P = 0.1, and mean number of root resorption lacunae (P = 0.16. Conclusion: Within the limitations of this study, systemic use of fluoxetine may cause insignificant reduction of tooth movement rate in rats; however, this subject needs more evaluations.

  3. Titanium-Based Biomaterials for Preventing Stress Shielding between Implant Devices and Bone

    OpenAIRE

    Niinomi, M.; Nakai, M

    2011-01-01

    β-type titanium alloys with low Young's modulus are required to inhibit bone atrophy and enhance bone remodeling for implants used to substitute failed hard tissue. At the same time, these titanium alloys are required to have high static and dynamic strength. On the other hand, metallic biomaterials with variable Young's modulus are required to satisfy the needs of both patients and surgeons, namely, low and high Young's moduli, respectively. In this paper, we have discussed effective methods...

  4. The evolution of simulation techniques for dynamic bone tissue engineering in bioreactors.

    Science.gov (United States)

    Vetsch, Jolanda Rita; Müller, Ralph; Hofmann, Sandra

    2015-08-01

    Bone tissue engineering aims to overcome the drawbacks of current bone regeneration techniques in orthopaedics. Bioreactors are widely used in the field of bone tissue engineering, as they help support efficient nutrition of cultured cells with the possible combination of applying mechanical stimuli. Beneficial influencing parameters of in vitro cultures are difficult to find and are mostly determined by trial and error, which is associated with significant time and money spent. Mathematical simulations can support the finding of optimal parameters. Simulations have evolved over the last 20 years from simple analytical models to complex and detailed computational models. They allow researchers to simulate the mechanical as well as the biological environment experienced by cells seeded on scaffolds in a bioreactor. Based on the simulation results, it is possible to give recommendations about specific parameters for bone bioreactor cultures, such as scaffold geometries, scaffold mechanical properties, the level of applied mechanical loading or nutrient concentrations. This article reviews the evolution in simulating various aspects of dynamic bone culture in bioreactors and reveals future research directions.

  5. Diabetes mellitus induces bone marrow microangiopathy

    OpenAIRE

    Oikawa, Atsuhiko; Siragusa, Mauro; Quaini, Federico; Mangialardi, Giuseppe; Katare, Rajesh G.; Caporali, Andrea; van Buul, Jaap D.; van Alphen, Floris P. J.; Graiani, Gallia; Spinetti, Gaia; Kraenkel, Nicolle; Prezioso, Lucia; Emanueli, Costanza; Madeddu, Paolo

    2009-01-01

    The impact of diabetes on the bone marrow (BM) microenvironment was not adequately explored. We investigated whether diabetes induces microvascular remodeling with negative consequence for BM homeostasis.

  6. Cell Mechanisms of Bone Tissue Loss Under Space Flight Conditions

    Science.gov (United States)

    Rodionova, Natalia

    Investigations on the space biosatellites has shown that the bone skeleton is one of the most im-portant targets of the effect space flight factors on the organism. Bone tissue cells were studied by electron microscopy in biosamples of rats' long bones flown on the board american station "SLS-2" and in experiments with modelling of microgravity ("tail suspension" method) with using autoradiography. The analysis of data permits to suppose that the processes of remod-eling in bone tissue at microgravity include the following succession of cell-to-cell interactions. Osteocytes as mechanosensory cells are first who respond to a changing "mechanical field". The next stage is intensification of osteolytic processes in osteocytes, leading to a volume en-largement of the osteocytic lacunae and removal of the "excess bone". Then mechanical signals have been transmitted through a system of canals and processes of the osteocytic syncitium to certain superficial bone zones and are perceived by osteoblasts and bone-lining cells (superficial osteocytes), as well as by the bone-marrow stromal cells. The sensitivity of stromal cells, pre-osteoblasts and osteoblasts, under microgravity was shown in a number of works. As a response to microgravity, the system of stromal cells -preosteoblasts -osteoblasts displays retardation of proliferation, differentiation and specific functions of osteogenetic cells. This is supported by the 3H-thymidine studies of the dynamics of differentiation of osteogenetic cells in remodeling zones. But unloading is not adequate and in part of the osteocytes are apoptotic changes as shown by our electron microscopic investigations. An osteocytic apoptosis can play the role in attraction the osteoclasts and in regulation of bone remodeling. The apoptotic bodies with a liquid flow through a system of canals are transferred to the bone surface, where they fulfil the role of haemoattractants for monocytes come here and form osteoclasts. The osteoclasts destroy

  7. Chromatin remodeling agent trichostatin A: a key-factor in the hepatic differentiation of human mesenchymal stem cells derived of adult bone marrow

    Directory of Open Access Journals (Sweden)

    Vinken Mathieu

    2007-04-01

    Full Text Available Abstract Background The capability of human mesenchymal stem cells (hMSC derived of adult bone marrow to undergo in vitro hepatic differentiation was investigated. Results Exposure of hMSC to a cocktail of hepatogenic factors [(fibroblast growth factor-4 (FGF-4, hepatocyte growth factor (HGF, insulin-transferrin-sodium-selenite (ITS and dexamethasone] failed to induce hepatic differentiation. Sequential exposure to these factors (FGF-4, followed by HGF, followed by HGF+ITS+dexamethasone, however, resembling the order of secretion during liver embryogenesis, induced both glycogen-storage and cytokeratin (CK18 expression. Additional exposure of the cells to trichostatin A (TSA considerably improved endodermal differentiation, as evidenced by acquisition of an epithelial morphology, chronological expression of hepatic proteins, including hepatocyte-nuclear factor (HNF-3β, alpha-fetoprotein (AFP, CK18, albumin (ALB, HNF1α, multidrug resistance-associated protein (MRP2 and CCAAT-enhancer binding protein (C/EBPα, and functional maturation, i.e. upregulated ALB secretion, urea production and inducible cytochrome P450 (CYP-dependent activity. Conclusion hMSC are able to undergo mesenchymal-to-epithelial transition. TSA is hereby essential to promote differentiation of hMSC towards functional hepatocyte-like cells.

  8. Issues in modern bone histomorphometry☆

    OpenAIRE

    Recker, R R; Kimmel, D. B.; Dempster, D.; Weinstein, R S; Wronski, T.J.; Burr, D.B.

    2011-01-01

    This review reports on proceedings of a bone histomorphometry session conducted at the Fortieth International IBMS Sun Valley Skeletal Tissue Biology Workshop held on August 1, 2010. The session was prompted by recent technical problems encountered in conducting histomorphometry on bone biopsies from humans and animals treated with anti-remodeling agents such as bisphosphonates and RANKL antibodies. These agents reduce remodeling substantially, and thus cause problems in calculating bone remo...

  9. Dynamic Contrast Enhanced Magnetic Resonance Imaging of Diffuse Spinal Bone Marrow Infiltration in Patients with Hematological Malignancies

    OpenAIRE

    Zha, Yunfei; Li, Maojin; YANG, JIANYONG

    2010-01-01

    Objective To investigate the significance of the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) parameters of diffuse spinal bone marrow infiltration in patients with hematological malignancies. Materials and Methods Dynamic gadolinium-enhanced MR imaging of the lumbar spine was performed in 26 patients with histologically proven diffuse bone marrow infiltration, including multiple myeloma (n = 6), acute lymphoblastic leukemia (n = 6), acute myeloid leukemia (n = 5), chronic m...

  10. A replication study for genome-wide gene expression levels in two layer lines elucidates differentially expressed genes of pathways involved in bone remodeling and immune responsiveness.

    Directory of Open Access Journals (Sweden)

    Christin Habig

    Full Text Available The current replication study confirmed significant differences in gene expression profiles of the cerebrum among the two commercial layer lines Lohmann Selected Leghorn (LSL and Lohmann Brown (LB. Microarray analyses were performed for 30 LSL and another 30 LB laying hens kept in the small group housing system Eurovent German. A total of 14,103 microarray probe sets using customized Affymetrix ChiGene-1_0-st Arrays with 20,399 probe sets were differentially expressed among the two layer lines LSL and LB (FDR adjusted P-value <0.05. An at least 2-fold change in expression levels could be observed for 388 of these probe sets. In LSL, 214 of the 388 probe sets were down- and 174 were up-regulated and vice versa for the LB layer line. Among the 174 up-regulated probe sets in LSL, we identified 51 significantly enriched Gene ontology (GO terms of the biological process category. A total of 63 enriched GO-terms could be identified for the 214 down-regulated probe sets of the layer line LSL. We identified nine genes significantly differentially expressed between the two layer lines in both microarray experiments. These genes play a crucial role in protection of neuronal cells from oxidative stress, bone mineral density and immune response among the two layer lines LSL and LB. Thus, the different regulation of these genes may significantly contribute to phenotypic trait differences among these layer lines. In conclusion, these novel findings provide a basis for further research to improve animal welfare in laying hens and these layer lines may be of general interest as an animal model.

  11. Effect of Chromatin-Remodeling Agents in Hepatic Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Danna Ye

    2016-01-01

    Full Text Available Epigenetic events, including covalent histone modifications and DNA methylation, play fundamental roles in the determination of lineage-specific gene expression and cell fates. The aim of this study was to determine whether the DNA methyltransferase inhibitor (DNMTi 5-aza-2′-deoxycytidine (5-aza-dC and the histone deacetylase inhibitor (HDACi trichostatin A (TSA promote the hepatic differentiation of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs and their therapeutic effect on liver damage. 1 μM TSA and 20 μM 5-aza-dC were added to standard hepatogenic medium especially at differentiation and maturation steps and their potential function on hepatic differentiation in vitro and in vivo was determined. Exposure of rBM-MSCs to 1 μM TSA at both the differentiation and maturation steps considerably improved hepatic differentiation. TSA enhanced the development of the hepatocyte shape, promoted the chronological expression of hepatocyte-specific markers, and improved hepatic functions. In contrast, treatment of rBM-MSCs with 20 μM 5-aza-dC alone or in combination with TSA was ineffective in improving hepatic differentiation in vitro. TSA and/or 5-aza-dC derived hepatocytes-like cells failed to improve the therapeutic potential in liver damage. We conclude that HDACis enhance hepatic differentiation in a time-dependent manner, while DNMTis do not induce the hepatic differentiation of rBM-MSCs in vitro. Their in vivo function needs further investigation.

  12. Tensile material properties of human rib cortical bone under quasi-static and dynamic failure loading and influence of the bone microstucture on failure characteristics

    CERN Document Server

    Subit, Damien; Valazquez-Ameijide, Juan; Arregui-Dalmases, Carlos; Crandall, Jeff

    2011-01-01

    Finite element models of the thorax are under development to assist vehicle safety researchers with the design of countermeasures such as advanced restrain systems. Computational models have become more refined with increasing geometrical complexity as element size decreases. These finite element models can now capture small geometrical features with an attempt to predict fracture. However, the bone material properties currently available, and in particular the rate sensitivity, have been mainly determined from compression tests or tests on long bones. There is a need for a new set of material properties for the human rib cortical bone. With this objective, a new clamping technique was developed to test small bone coupons under tensile loading. Ten coupons were harvested from the cortical shell of the sixth and seventh left ribs from three cadavers. The coupons were tested to fracture under quasi-static (target strain rate of 0.07 %/s) and dynamic loading (target strain rate of 170 %/s). Prior to testing, eac...

  13. The reliability and representativity of non-dynamic bone histomorphometry in uremic osteodystrophy

    DEFF Research Database (Denmark)

    Heaf, J G; Pødenphant, J; Gammelgaard, Bente

    1993-01-01

    trabecular bone indices are reliable variables and, with the possible exception of bone mass determination, indicative of systemic bone disease. Bone aluminium concentration and cortical bone indices are unreliable measures of uremic bone disease. These reservations apply to the diagnostic use of biopsy...

  14. Biomechanical Models and Experi ments in Bone Tissue Engineering

    Institute of Scientific and Technical Information of China (English)

    Christian; ODDOU; Julien; PIERRE; Karim; OUDINA; Hervé; PETITE

    2005-01-01

    1 IntroductionThe understanding of the interactions between convective and diffusive phenomena of fluid dynamics origin, on the one side, associate reactive effects of biochemical nature, on the other, is a fundamental challenge and key problem in the context of bone tissue engineering. From the mastering of the complex biological phenomena related to the substrate degradation and remodelling of the extra cellular matrix that take place during the in vitro tissue culturing processes using cell seeded implan...

  15. The use of dynamic bone scanning in the evaluation of wrist and hand pain

    International Nuclear Information System (INIS)

    Twenty-seven patients with complaints of wrist and/or hand pain were evaluated using a quantitative technique of dynamic (blood flow analysis) and static bone scan. The patients were divided in two groups according to their clinical history. Group A included 13 patients with a history of trauma. Seven patients had scaphoid fracture and 6 of them were scanned to determine non-union and/or avascular necrosis of the joint. One patient was scanned to determine the viability of a graft for non-union fracture. In all cases the scan gave a correct diagnosis as confirmed by later x-ray changes. Six patients in this group had negative x-rays. The scan demonstrated 4 cases of occult fractures, 4 had early Kienbock's Disease (KD) and 1 a soft tissue tumor. Group B included 14 patients with no known history of trauma. Nine had positive x-rays including 3 with KD that were scanned to determine their viability for surgical replacement of the lunate. The scan could distinguish between isolated involvement of the lunate and secondary degenerative changes of the surrounding carpal bones and radiocarpal joint. Two patients with tumor were correctly diagnosed by the scan, one as benign and one malignant. Four other patients with nonspecific changes on x-ray showed early arthritis (3 cases) and a cyst of the triquetrum ( 1 case) on the bone scan. Four patients in Group B had negative x-rays and the scan showed degenerative changes (3 cases) and an occult fracture of the hamate (1 case). The use of dynamic and static bone scanning appears to be a very valuable technique in the evaluation of patients with wrist and hand pain

  16. The biomechanics of point contact-dynamic compression plate and its effects on bone perfusion

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yu-feng; LI Qi-hong; GU Zu-chao; WANG Ai-min

    2006-01-01

    Objective: To compare the mechanical properties of point contact-dynamic compression plate (PC-DCP) and its effects on cortical bone perfusion with that of dynamic compression plates (DCP) in goat tibiae.Methods: Twenty pairs of matched fresh goat tibiae were used. A transverse fracture model was established.The fractures with a 3mm interspace between the fracture ends were subject to fixations with the DCPs and the PCDCPs respectively, then the four-points bending tests and the torsion tests were conducted to compare the mechanical properties of the PC-DCP with that of DCP. Another 13sexually mature goats underwent fixations with the DCPs and the PC-DCPs, respectively, at the mid-shafts of the intact bilateral tibiae. Ischemic zones were observed at four time points (1 day, 2, 6, and 12 weeks after operation)using disulphine blue staining technique.Results: There were no significant differences in mechanical properties, such as bend- and torsionresistance, between the DCPs and the PC-DCPs. One day,2, and 6 weeks after operation, on the side of DCP fixation, outer cortical bone iscbemia under the plate persisted, and this condition did not reverse until 12 weeks after operation. However, on the side of PC-DCP fixation,cortical bone ischemia occurred only in the periphery of the screw holes and at the contact sites of the PC NUTs 1 day after operation, and it disappeared at 2 weeks after operation.Conclusions: The PC-DCP has similar biomechanical properties of the DCP, but is less detrimental to local bone blood circulation than the conventional plates.

  17. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  18. Dynamic T{sub 2}-mapping during magnetic resonance guided high intensity focused ultrasound ablation of bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Waspe, Adam C.; Looi, Thomas; Mougenot, Charles; Amaral, Joao; Temple, Michael; Sivaloganathan, Siv; Drake, James M. [Centre for Image Guided Innovation and Therapeutic Intervention, The Hospital for Sick Children, Toronto, ON, M5G 1X8 (Canada); Philips Healthcare Canada, Markham, ON, L6C 2S3 (Canada); Centre for Image Guided Innovation and Therapeutic Intervention, The Hospital for Sick Children, Toronto, ON, M5G 1X8 (Canada); Department of Applied Mathematics, University of Waterloo, Waterloo, ON, N2L 3G1 (Canada); Centre for Image Guided Innovation and Therapeutic Intervention, The Hospital for Sick Children, Toronto, ON, M5G 1X8 (Canada)

    2012-11-28

    Focal bone tumor treatments include amputation, limb-sparing surgical excision with bone reconstruction, and high-dose external-beam radiation therapy. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is an effective non-invasive thermotherapy for palliative management of bone metastases pain. MR thermometry (MRT) measures the proton resonance frequency shift (PRFS) of water molecules and produces accurate (<1 Degree-Sign C) and dynamic (<5s) thermal maps in soft tissues. PRFS-MRT is ineffective in fatty tissues such as yellow bone marrow and, since accurate temperature measurements are required in the bone to ensure adequate thermal dose, MR-HIFU is not indicated for primary bone tumor treatments. Magnetic relaxation times are sensitive to lipid temperature and we hypothesize that bone marrow temperature can be determined accurately by measuring changes in T{sub 2}, since T{sub 2} increases linearly in fat during heating. T{sub 2}-mapping using dual echo times during a dynamic turbo spin-echo pulse sequence enabled rapid measurement of T{sub 2}. Calibration of T{sub 2}-based thermal maps involved heating the marrow in a bovine femur and simultaneously measuring T{sub 2} and temperature with a thermocouple. A positive T{sub 2} temperature dependence in bone marrow of 20 ms/ Degree-Sign C was observed. Dynamic T{sub 2}-mapping should enable accurate temperature monitoring during MR-HIFU treatment of bone marrow and shows promise for improving the safety and reducing the invasiveness of pediatric bone tumor treatments.

  19. Odanacatib in postmenopausal women with low bone mineral density: a review of current clinical evidence

    OpenAIRE

    Zerbini, Cristiano A. F.; McClung, Michael R.

    2013-01-01

    Human bones are in a continuous process of remodeling that ensures renovation and maintenance of the skeletal mass. Bone remodeling has two phases that are normally coupled and balanced: bone resorption mediated by osteoclasts and bone formation mediated by osteoblasts. An increase in bone resorption over bone formation results in a progressive loss of bone mass and impairment of bone microarchitecture leading to osteoporosis and its associated fractures. Recent advances in the understanding ...

  20. Dynamic contrast-enhanced MRI in Paget's disease of bone-correlation of regional microcirculation and bone turnover

    Energy Technology Data Exchange (ETDEWEB)

    Libicher, M. [University of Cologne, Department of Radiology, Cologne (Germany); Klinikum der Universitaet zu Koeln, Radiologische Klinik, Koeln (Germany); Kasperk, C. [University of Heidelberg, Department of Medicine, Division of Osteology, Heidelberg (Germany); Daniels, M.; Hosch, W. [University of Heidelberg, Department of Radiology, Heidelberg (Germany); Kauczor, H.U.; Delorme, S. [German Cancer Research Center, Department of Radiology, Heidelberg (Germany)

    2008-05-15

    The purpose of this study was to evaluate regional microcirculation in Paget's disease of bone (PD) with dynamic contrast-enhanced MR imaging (DCE-MRI). Additionally, we correlated regional bone perfusion with alkaline phosphatase as serum marker of bone turnover. We examined 71 patients with PD (27 men, 44 women, 67{+-}10 years) localized at the axial and appendicular skeleton. Contrast uptake was analyzed using a two-compartment model with the output variables amplitude A and exchange rate constant k{sub ep}. Color-coded parametric images were generated to visualize microcirculation. Serum levels of alkaline phosphatase (AP) were compared with DCE-MRI parameters. Amplitude A and exchange rate constant k{sub ep} were significantly increased in PD compared to unaffected bone (A{sub PD} 0.81{+-}0.24 vs. A{sub control} 0.34{+-}0.1 and k{sub ep} {sub PD} 4.0 {+-}2.86 vs. k{sub ep} {sub control} 1.73 {+-}0.88, p <0.001). There was a significant correlation (r{sub s}=0.5-0.7) of DCE-MRI parameters and AP at the axial (pelvis, spine) and appendicular skeleton (femur, tibia). The long bones showed increased circulation of the advancing peripheral zones and no vascularization of the central part, which had been replaced by fatty tissue. Regional microcirculation in PD is inhomogeneous with focal areas of excessive hypervascularity, especially in the advancing peripheral zone. There is a significant correlation of bone circulation and bone turnover in PD. DCE-MRI might therefore be a diagnostic tool for monitoring therapeutic effects of bisphoshonates in Paget's disease of bone. (orig.)

  1. Alveolar bone dynamics in osteoporotic rats treated with raloxifene or alendronate: confocal microscopy analysis

    Science.gov (United States)

    Ramalho-Ferreira, Gabriel; Faverani, Leonardo Perez; Grossi-Oliveira, Gustavo Augusto; Okamoto, Tetuo; Okamoto, Roberta

    2015-03-01

    In this study, the characteristics of the alveolar bone of rats with induced osteoporosis were examined. Thirty-two rats were divided into four groups according to the induction of osteoporosis and drugs administered: OG, osteoporotic rats without treatment (negative control); SG, rats which underwent sham surgery ovariectomy (SHAM); alendronate (AG), osteoporotic rats treated with alendronate; and RG, osteoporotic rats treated with raloxifene (RG). On the 8th day after ovariectomy and SHAM surgeries, drug therapy was started with AG or RG. On the 52nd day, 20 mg/kg calcein was administered to all of the rats, and on the 80th day, 20 mg/kg alizarin red was administered. Euthanasia was performed on the 98th day. The bone area marked by fluorochromes was calculated and data were subjected to two-way ANOVA test and Tukey's post-hoc test (pbone turnover only between RG and SG (p=0.074) and AG and OG (p=0.138). All other comparisons showed significant differences (pbone turnover was observed in RG and SG groups. RG was the medication that improved the dynamics of the alveolar bone of rats with induced osteoporosis, resembling that of healthy rats.

  2. Dynamic expression of the Robo ligand Slit2 in bone marrow cell populations.

    Science.gov (United States)

    Smith-Berdan, Stephanie; Schepers, Koen; Ly, Alan; Passegué, Emmanuelle; Forsberg, E Camilla

    2012-02-15

    The bone marrow (BM) niche is essential for lifelong hematopoietic stem cell (HSC) maintenance, proliferation and differentiation. Several BM cell types, including osteoblast lineage cells (OBC), mesenchymal stem cells (MSC) and endothelial cells (EC) have been implicated in supporting HSC location and function, but the relative importance of these cell types and their secreted ligands remain controversial. We recently found that the cell surface receptors Robo4 and CXCR4 cooperate to localize HSC to BM niches. We hypothesized that Slit2, a putative ligand for Robo4, cooperates with the CXCR4 ligand SDF1 to direct HSC to specific BM niche sites. Here, we have isolated OBC, MSC and EC by flow cytometry and determined their frequency within the bone marrow and the relative mRNA levels of Slit2, SDF1 and Robo4. We found that expression of Slit2 and SDF1 were dynamically regulated in MSC and OBC-like populations following radiation, while Robo4 expression was restricted to EC. Radiation also significantly affected the cellularity and frequency of both the non-adherent and adherent cells within the BM stroma. These data support a physiological role for Slit2 in regulating the dynamic function of Robo-expressing cells within BM niches at steady state and following radiation.

  3. The Role of Musculoskeletal Dynamics and Neuromuscular Control in Stress Development in Bone

    Science.gov (United States)

    DeWoody, Yssa

    1996-01-01

    The role of forces produced by the musculotendon units in the stress development of the long bones during gait has not been fully analyzed. It is well known that the musculotendons act as actuators producing the joint torques which drive the body. Although the joint torques required to perform certain motor tasks can be recovered through a kinematic analysis, it remains a difficult problem to determine the actual forces produced by each muscle that resulted in these torques. As a consequence, few studies have focused on the role of individual muscles in the development of stress in the bone. This study takes a control theoretic approach to the problem. A seven-link, eight degrees of freedom model of the body is controlled by various muscle groups on each leg to simulate gait. The simulations incorporate Hill-type models of muscles with activation and contraction dynamics controlled through neural inputs. This direct approach allows one to know the exact muscle forces exerted by each musculotendon throughout the gait cycle as well the joint torques and reaction forces at the ankle and knee. Stress and strain computed by finite element analysis on skeletal members will be related to these derived loading conditions. Thus the role of musculoskeletal dynamics and neuromuscular control in the stress development of the tibia during gait can be analyzed.

  4. Efeitos da atividade física na densidade mineral óssea e na remodelação do tecido ósseo Efectos de la actividad física en la densidad mineral ósea y en la remodelacion del tejido óseo Effects of the physical activity on the bone mineral density and bone remodelation

    Directory of Open Access Journals (Sweden)

    Eduardo Lusa Cadore

    2005-12-01

    ón de las concentraciones de esos marcadores que puedan indicar un estado de la formación o reabsorción del hueso. Sin embargo, la inconsistencia de los resultados encontrados, sugiere que el análisis de los efectos de la actividad física en el remodelación del hueso, a través de esos marcadores, debe investigarse más. Muchas diferencias existen con respecto a la relación entre la DMO con la fuerza muscular y la composición corporal, principalmente en la determinación de cual de esos factores está más asociada con la DMO. La determinación de que tipo de actividad física es ideal para aumentar el pico de masa del hueso en la adolescencia, o incluso mantenerla después de la edad adulta, es muy importante para la prevención y el posible tratamiento de la osteoporosis.The purpose of this article is to make a review on different sportive modalities and the power training on the bone remodeling, and to discuss the possible relationship of the bone mineral density (BMD to the muscular power and body composition. Several studies indicate that the high impact physical activity or physical activities demanding a high power production may have a benefic effect on the BMD due to the deformation that occurs in such tissue during the activity. Some authors have been assessing the effects of the physical training on some biochemical markers of the bone remodeling, since the variation on the concentrations of these markers might indicate a bone turnover or reabsorption state. Nevertheless, the inconsistency of the results found suggests that the analysis of the effects of the physical activity on the bone remodeling through these markers must be further investigated. There are many discrepancies as to the relationship of the BMD to the muscular power and body composition, mainly to determine what factors are most associated to the BMD. The determination of what type of physical activity is the ideal to increase the bone mass peak during the adolescence or even aiming to

  5. Use of Spongious Bone Chips and Fascia Temporalis in Alveolar Bone Defects

    OpenAIRE

    TÜZ, Hakan H.; AKAL, Ümit K.; CAMBAZOĞLU, Mine; KİŞNİŞCİ, Reha Ş.

    2004-01-01

    Graft materials are used for inducement of regeneration in bone defects. Organic and synthetic bone graft materials facilitate remodelation or healing of the bone and induce new bone formation in the area of bone resorption caused by pathological, traumatic, and physiological reasons. The aim of this study was to evaluate the effects of spongious allogenic bone graft and fascia temporalis membranous collagen tissue on the healing of bone defects clinically and radiologically. The study was c...

  6. Dynamic Alterations in Microarchitecture, Mineralization and Mechanical Property of Subchondral Bone in Rat Medial Meniscal Tear Model of Osteoarthritis

    Directory of Open Access Journals (Sweden)

    De-Gang Yu

    2015-01-01

    Full Text Available Background: The properties of subchondral bone influence the integrity of articular cartilage in the pathogenesis of osteoarthritis (OA. However, the characteristics of subchondral bone alterations remain unresolved. The present study aimed to observe the dynamic alterations in the microarchitecture, mineralization, and mechanical properties of subchondral bone during the progression of OA. Methods: A medial meniscal tear (MMT operation was performed in 128 adult Sprague Dawley rats to induce OA. At 2, 4, 8, and 12 weeks following the MMT operation, cartilage degeneration was evaluated using toluidine blue O staining, whereas changes in the microarchitecture indices and tissue mineral density (TMD, mineral-to-collagen ratio, and intrinsic mechanical properties of subchondral bone plates (BPs and trabecular bones (Tbs were measured using micro-computed tomography scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively. Results: Cartilage degeneration occurred and worsened progressively from 2 to 12 weeks after OA induction. Microarchitecture analysis revealed that the subchondral bone shifted from bone resorption early (reduced trabecular BV/TV, trabecular number, connectivity density and trabecular thickness [Tb.Th], and increased trabecular spacing (Tb.Sp at 2 and 4 weeks to bone accretion late (increased BV/TV, Tb.Th and thickness of subchondral bone plate, and reduced Tb.Sp at 8 and 12 weeks. The TMD of both the BP and Tb displayed no significant changes at 2 and 4 weeks but decreased at 8 and 12 weeks. The mineral-to-collagen ratio showed a significant decrease from 4 weeks for the Tb and from 8 weeks for the BP after OA induction. Both the elastic modulus and hardness of the Tb showed a significant decrease from 4 weeks after OA induction. The BP showed a significant decrease in its elastic modulus from 8 weeks and its hardness from 4 weeks. Conclusion: The microarchitecture, mineralization and mechanical

  7. Effect of Epimedium-derived Phytoestrogen on Bone Turnover and Bone Microarchitecture in OVX-induced Osteoporotic Rats

    Institute of Scientific and Technical Information of China (English)

    Songlin PENG; Renyun XIA; Huang FANG; Feng LI; Anmin CHEN; Ge ZHANG; Ling QIN

    2008-01-01

    To investigate the preventive effect of epimedium-defivod phytoestrogen (PE) on osteoporosis induced by ovariectomy (OVX) in rats, 11-month-old female Wistar rats were randomly di- vided into Sham, OVX and PE groups. One week after OVX, daily oral administration of PE (0.4 g·kg-1·day·-1) started in PE group, and rats in Sham and OVX groups were given vehicle accordingly. The administrations lasted for 12 weeks. The biological markers including serum osteocalcin (OC) and urinary deoxypyridinoline (DPD) for bone turnover were evaluated at the end of the 12th week. On the 13th week, all the rats were sacrificed. The right proximal tibiae were removed, subjected to micro CT for determination of trabeonlar bone structure and then bone histomorphometry was per- formed to assess bone remodeling. The OVX rats were in a high bone turnover status as evidenced by increased bone formation markers and bone resorption markers. Treatment with PE could suppress the high bone turnover rate in OVX rats. Micro CT data revealed that PE treatment could ameliorate the deterioration of the micro-architecture of proximal tibiae induced by OVX, as demonstrated by greater bone volume, increased trabecular thickness and less trahecular separation in PE group in comparison with OVX group. The static and dynamic parameters of bone histomorphometry indi- cated that there were significant increases in bone formation variables and significant decreases in bone resorption variables between PE and OVX groups. The findings suggest that PE has a beneficial effect on trabecular bone in OVX rat model and this effect is possibly associated with stimulation of bone formation as well as inhibition of bone resorption.

  8. Limitations of Single Slice Dynamic Contrast Enhanced MR in Pharmacokinetic Modeling of Bone Sarcomas

    Energy Technology Data Exchange (ETDEWEB)

    Toms, Andoni P. (Dept. of Radiology, The Norfolk and Norwich Univ. Hospital, Norwich, Norfolk (United Kingdom)); White, Lawrence M.; Bleakney, Robert R. (Dept. of Medical Imaging, Mount Sinai Hospital, Toronto, ON (Canada)); Kandel, Rita (Dept. of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON (Canada)); Noseworthy, Michael (Health Sciences Centre, Faculty of Health Sciences, McMaster Univ., Hamilton, ON (Canada)); Lee, Shepstone (Institute of Health, Univ. of East Anglia, Norwich, Norfolk (United Kingdom)); Blackstein, Martin E. (Dept. of Oncology, Mount Sinai Hospital, Toronto, ON (Canada)); Wunder, Jay (Musculoskeletal Oncology Unit, Mount Sinai Hospital, Toronto, ON (Canada))

    2009-06-15

    Background: Single slice dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) appears to provide perfusion data about sarcomas in vivo that correlate with tumor necrosis on equivalent pathological sections. However, sarcomas are heterogeneous and therefore single slice DCE-MRI may not correlate with total tumor necrosis. Purpose: To determine whether changes in pharmacokinetic modeling of DCE-MRI, during chemotherapy for primary bone sarcomas correlated with histological measures of total tumor necrosis. Material and Methods: Twelve patients with appendicular primary bone sarcomas were included in the study. Each patient had DCE-MRI before, and after completion, of pre-operative chemotherapy. The mean arterial slope (A), endothelial permeability coefficient (Ktrans), and extravascular extracellular volume (Ve) were derived from each data set using a modified two compartment pharmacokinetic model. Total tumor necrosis rates were compared with changes in A, Ktrans, and Ve. Results: Six patients had total tumor necrosis of =90% and six had a measure of <90%. The median percentage changes in A, Ktrans, and Ve for the =90% necrosis group were -52.5% (-83 to 6), -66% (-82 to 26), and 23.5% (-26 to 40), respectively. For the <90% necrosis group, A = - 35% (-75 to 132), Ktrans= - 53 (-66 to 149) and Ve= - 14.5% (-42 to 40). One patient with >90% necrosis had increases in all three measures. Comparison of the two groups generated P-values of 0.699 for A, 0.18 for Ktrans, and 0.31 for Ve. Conclusion: There was no statistically significant correlation between changes in pharmacokinetic perfusion parameters and total tumor necrosis. When using single slice DCE-MRI heterogeneous histology of primary bone sarcomas and repair mediated angiogenesis might both be confounding factors

  9. TGF-β in cancer and bone: implications for treatment of bone metastases.

    Science.gov (United States)

    Juárez, Patricia; Guise, Theresa A

    2011-01-01

    Bone metastases are common in patients with advanced breast, prostate and lung cancer. Tumor cells co-opt bone cells to drive a feed-forward cycle which disrupts normal bone remodeling to result in abnormal bone destruction or formation and tumor growth in bone. Transforming growth factor-beta (TGF-β) is a major bone-derived factor, which contributes to this vicious cycle of bone metastasis. TGF-β released from bone matrix during osteoclastic resorption stimulates tumor cells to produce osteolytic factors further increasing bone resorption adjacent to the tumor cells. TGF-β also regulates 1) key components of the metastatic cascade such as epithelial-mesenchymal transition, tumor cell invasion, angiogenesis and immunosuppression as well as 2) normal bone remodeling and coupling of bone resorption and formation. Preclinical models demonstrate that blockade of TGF-β signaling is effective to treat and prevent bone metastases as well as to increase bone mass.

  10. Cancer to bone: a fatal attraction

    OpenAIRE

    Weilbaecher, Katherine N.; Guise, Theresa A.; McCauley, Laurie K

    2011-01-01

    When cancer metastasizes to bone, considerable pain and deregulated bone remodelling occurs, greatly diminishing the possibility of cure. Metastasizing tumour cells mobilize and sculpt the bone microenvironment to enhance tumour growth and to promote bone invasion. Understanding the crucial components of the bone microenvironment that influence tumour localization, along with the tumour-derived factors that modulate cellular and protein matrix components of bone to favour tumour expansion and...

  11. 3D video-based deformation measurement of the pelvis bone under dynamic cyclic loading

    Directory of Open Access Journals (Sweden)

    Freslier Marie

    2011-07-01

    Full Text Available Abstract Background Dynamic three-dimensional (3D deformation of the pelvic bones is a crucial factor in the successful design and longevity of complex orthopaedic oncological implants. The current solutions are often not very promising for the patient; thus it would be interesting to measure the dynamic 3D-deformation of the whole pelvic bone in order to get a more realistic dataset for a better implant design. Therefore we hypothesis if it would be possible to combine a material testing machine with a 3D video motion capturing system, used in clinical gait analysis, to measure the sub millimetre deformation of a whole pelvis specimen. Method A pelvis specimen was placed in a standing position on a material testing machine. Passive reflective markers, traceable by the 3D video motion capturing system, were fixed to the bony surface of the pelvis specimen. While applying a dynamic sinusoidal load the 3D-movement of the markers was recorded by the cameras and afterwards the 3D-deformation of the pelvis specimen was computed. The accuracy of the 3D-movement of the markers was verified with 3D-displacement curve with a step function using a manual driven 3D micro-motion-stage. Results The resulting accuracy of the measurement system depended on the number of cameras tracking a marker. The noise level for a marker seen by two cameras was during the stationary phase of the calibration procedure ± 0.036 mm, and ± 0.022 mm if tracked by 6 cameras. The detectable 3D-movement performed by the 3D-micro-motion-stage was smaller than the noise level of the 3D-video motion capturing system. Therefore the limiting factor of the setup was the noise level, which resulted in a measurement accuracy for the dynamic test setup of ± 0.036 mm. Conclusion This 3D test setup opens new possibilities in dynamic testing of wide range materials, like anatomical specimens, biomaterials, and its combinations. The resulting 3D-deformation dataset can be used for a better

  12. Dynamic gadoteridol-enhanced MR imaging in the end of growing long bone of piglets

    Institute of Scientific and Technical Information of China (English)

    LI Xiao-ming; QIU Li; LI Feng; XIONG Wei; HU Dao-yu; YU Cheng; PENG Wen-jia; HU Jun-wu; FENG Ding-yi; HU Xue-mei; LI Hong-lian

    2008-01-01

    Background It is of value to identify the non-invasive means that can accurately reflect the blood supply of epiphysis and is more sensitive in detection of early ischemia of epiphysis than the conventional gadoteridol (Gd)-enhanced SE T1WI. The aim of this study was to evaluate the blood supply of various anatomic regions at the end of normal growing long bone using dynamic Gd-enhanced MR imaging and compare the sensitivities between dynamic Gd-enhanced MR imaging and conventional Gd-enhanced SE T1WI in the detection of decreased blood perfusion of early epiphyseal ischemia.Methods Twenty-seven two-week-old piglets were used in this study. For the study of the end of normal growing long bone, unilateral MR imaging of the distal femur and proximal tibia was performed on eleven piglets. The comparison was made among various anatomic regions (physeal and epiphyseal cartilage, metaphyseal spongiosa, the secondary ossification center and metaphysis) using MRI in terms of the enhancement ratio and speed. Their relationships with the histological findings, including RBC/mm and vessel distribution, were evaluated. To examine ischemic femoral head, 16 piglets were divided into two groups, with the control group having 8 piglets (involving 16 normal hips) and an ischemicgroup having 8 piglets (involving 16 hips with hyperabduction). In the ischemic group, MR imaging was performed on the hips in the hyperabduction immobilized persistently for 30 minutes. After MRI, the piglets were allowed to ambulate freely for 1 day and the same MR scanning was then repeated in a neutral position. The difference in enhancement ratio and speed of the femoral head between the control and ischemic group were evaluated.Results With regard to the end of normal growing long bone, the enhancement ratio of the metaphyseal spongiosa was greatest among all the anatomic regions (P0.05). The enhancement speed of physis was greater than that of epiphyseal cartilage (P (R >0.75) and distribution of

  13. 山茶籽联合雌二醇对去卵巢大鼠骨重建和骨代谢酶的影响%Affect of Mountain tea seed combined Estradiol on bone remodeling in ovariectomized rats and bone metabolic enzymes

    Institute of Scientific and Technical Information of China (English)

    庞广福; 李海; 陈建海; 王金花; 黎飚

    2012-01-01

    目的:了解山茶籽联合雌二醇对去卵巢大鼠骨重建和骨代谢酶的影响,为山茶籽联合雌二醇治疗I型骨质疏松症提供实验依据.方法:将90只5月龄健康雌性大白鼠分成假手术组(sham)、去卵巢模型组(OVX)、山茶籽组、雌二醇组(E2)、小剂量山茶籽+雌二醇组(Ts+ E2),每组各18只.各实验组在第8、12、16周,随机处死6只大鼠,取左股骨切片观察骨组织,取右股骨测量骨密度,取左心血测量血清雌二醇、碱性磷酸酶.数据进行统计学分析.结果:OVX组的血清雌二醇和骨密度明显低于sham组(P<0.01),而血清碱性磷酸酶明显高于sham组(P<0.01);3个治疗组与sham组相比,各时间的血清雌二醇、碱性磷酸酶、骨密度均无显著性差异(P>0.05).结论:小剂量的雌二醇联合山茶籽对去卵巢大鼠的骨质疏松症的治疗效果与单独使用较大剂量的山茶籽或较大剂量的雌二醇的治疗效果相近.%Objective: To understand the affect of Mountain tea seed combined Estradiol on bone remodeling in ovariectomized rats and bone metabolic enzymes, and to provide experimental basis for the treatment of type I osteoporosis by Mountain tea seed combined Estra-diol. Methods: 5 -month - old healthy female rats 90 were divided into five experimental groups (n = 18) : ①sham operation group (sham); ② model group, ovariectomized (OVX); ③ Mountain tea seed group (Ts), mountain water - soluble alcohol extract tea seed fed, 10 ml/kg, d (quite crude drug 5 g/g); ④ Estradiol (E2), subcutaneous injection of Estradiol 200μg/kg, 2 times / week; ⑤Mountain tea seed + low -dose Estradiol group (Ts + E2) , subcutaneous injection of Estradiol 100 μg/kg, 2 times / week and Mountain tea seed extract water-soluble alcohol fed, 10 ml/kg, d (quite crude drug 2. 5 g/g) . At 8, 12 and 16 weeks, the experimental groups were randomly killed six rats , the left femur bone tissue slices were observed, the density measurements of

  14. Dynamic nanomechanics of individual bone marrow stromal cells and cell-matrix composites during chondrogenic differentiation.

    Science.gov (United States)

    Lee, BoBae; Han, Lin; Frank, Eliot H; Grodzinsky, Alan J; Ortiz, Christine

    2015-01-01

    Dynamic nanomechanical properties of bovine bone marrow stromal cells (BMSCs) and their newly synthesized cartilage-like matrices were studied at nanometer scale deformation amplitudes. The increase in their dynamic modulus, |E(*)| (e.g., 2.4±0.4 kPa at 1 Hz to 9.7±0.2 kPa at 316 Hz at day 21, mean±SEM), and phase angle, δ, (e.g., 15±2° at 1 Hz to 74±1° at 316 Hz at day 21) with increasing frequency were attributed to the fluid flow induced poroelasticity, governed by both the newly synthesized matrix and the intracellular structures. The absence of culture duration dependence suggested that chondrogenesis of BMSCs had not yet resulted in the formation of a well-organized matrix with a hierarchical structure similar to cartilage. BMSC-matrix composites demonstrated different poro-viscoelastic frequency-dependent mechanical behavior and energy dissipation compared to chondrocyte-matrix composites due to differences in matrix molecular constituents, structure and cell properties. This study provides important insights into the design of optimal protocols for tissue-engineered cartilage products using chondrocytes and BMSCs. PMID:25468666

  15. 基于快速生长期大鼠骨生长与重建适应模型的数字量化研究%Quantitative study of bone growth and remodeling adaptation model in rapid-growing rats

    Institute of Scientific and Technical Information of China (English)

    赵文志; 刘迎曦; 张军; 张路

    2008-01-01

    凡能够预测大鼠整个牛命周期中在不同应力环境下股骨的生长趋势.%BACKGROUND: At present, bone remodeling biological model study usually applys finite element method combing with computer technique to simulate and predict bone quantity or bone structure. In this study the author integrate inversion method with animal experiment to establish a quantification bone remodeling biological model of in vivo bone tissue in real stress environment.OBJECTIVE: To set up a quantification biological model of bone growth and remodeling adaptation, which integrates animal experiments, parameter inversion identification of mathematical functions, and technique of computer simulation. DESIGN, TIME AND SETTING: The experiment was accomplished in Animal Experiment Center of Dalian Medical University in October 2002.MATERIALS: 60 female Sprague Dawley mice of 6-week old were used in this study. Challenger double-energy X ray bone density device was provided from DMS Company, France. Sensation l6 CT machine was provided from Germany Siemens Company.METHODS: 60 mice were randomly divided into two groups: i 5 animals were in normal control groups. 45 in experiment groups. By designing a new animal experiment, we investigate the effects of stress environments on bone growth and remodeling of rapid growing rats and gather the bone mineral density (BMD) of proximal femur in the same interval for the unknown parameters (B and K) inversion of bone growth and remodeling equation to create the femur three-dimension geometrical model based on CT images. MAIN OUTCOMING MEASURES: Body weight of animal, bone density and CT imagine of proximal femur. RESULTS: Body mass in the experiment group and control group was increased with the rat growing; BMD in the control group and overloading group was also increased with the rat growing; but BMD in the unloading group was decreased in the fifth week. Inversion and experimental data showed that parameter B was rapidly decreased as

  16. In vitro study of the osteocytes response to hypoxia and their regulation of bone homeostasis

    OpenAIRE

    Montesi, Monica

    2014-01-01

    Bone remodelling is a fundamental mechanism for removing and replacing bone during adaptation of the skeleton to mechanical loads. Skeletal unloading leads to severe hypoxia (1%O2) in the bone microenvironment resulting in imbalanced bone remodelling that favours bone resorption. Hypoxia, in vivo, is a physiological condition for osteocytes, 5% O2 is more likely physiological for osteocytes than 20% O2, as osteocytes are embedded deep inside the mineralized bone matrix. Osteocytes are thought...

  17. Study of Osteoclast Adhesion to Cortical Bone Surfaces: A Correlative Microscopy Approach for Concomitant Imaging of Cellular Dynamics and Surface Modifications.

    Science.gov (United States)

    Shemesh, Michal; Addadi, Sefi; Milstein, Yonat; Geiger, Benjamin; Addadi, Lia

    2016-06-22

    Bone remodeling relies on the coordinated functioning of osteoblasts, bone-forming cells, and osteoclasts, bone-resorbing cells. The effects of specific chemical and physical bone features on the osteoclast adhesive apparatus, the sealing zone ring, and their relation to resorption functionality are still not well-understood. We designed and implemented a correlative imaging method that enables monitoring of the same area of bone surface by time-lapse light microscopy, electron microscopy, and atomic force microscopy before, during, and after exposure to osteoclasts. We show that sealing zone rings preferentially develop around surface protrusions, with lateral dimensions of several micrometers, and ∼1 μm height. Direct overlay of sealing zone rings onto resorption pits on the bone surface shows that the rings adapt to pit morphology. The correlative procedure presented here is noninvasive and performed under ambient conditions, without the need for sample labeling. It can potentially be applied to study various aspects of cell-matrix interactions. PMID:26682493

  18. Autoradiographic studies of the intensity of morphogenetic processes in the bone skeleton under modeling microgravity

    Science.gov (United States)

    Rodionova, N. V.; Zolotova-Haidamaka, N. V.; Nithevich, T. P.

    In ontogenesis the development of long skeleton bones and reconstruction of bone structures during adaptive remodeling are performed due to a combination of the bone apposition and bone resorption processes. With the use of radioactive markers of specific biosyntheses -3H-thymidine and 3H-glycine we studied the dynamics and peculiarities of these processes under hypokinesia by unloading the hind limbs of young white rats (tail suspension method) during 28 days. The radionuclides were administered in a single dose at the end of the experiment and the biomaterial was taken 1, 24, 48, 120 and 192 h. after injection. In histoautographs the counts were made of a nuclei labeling index (3H-thymidine), of the number of silver grains over the cells and in the forming bone matrix in growth and remodeling zones of the femoral bone (3H-glycine). The tendency for a reduction of a labeling index in the 3H-thymidine-labeled osteogenic cells in the periost and endost has been established. The dynamics of labeled cells following various intervals after 3H-thymidine injection testifies to a delay in the rates of osteoblasts' differentiation and their transformation to osteocytes in the experiment animals. 3H-glycine is assimilated by osteogenic cells 30 min after the radionuclide injection and following 24 h. it is already incorporated into the forming bone matrix. As a result an appositional bone addition by 192 h. the silver grains are registered in the bone matrix as "labeling lines". A lower 3H-glycine uptake by the osteogenic cells and bone matrix as compared with a control is indicative of a decrease of the osteoplastic process under hypokinesia, particulary in the periost. At the same time the resorption and remodeling bone zones reveal regions of an intensive 3H-glycine uptake after 1 and 24 h. We associate this latter fact with an activation of collagen proteins in the differentiating fibroblasts (instead of osteoblasts) in these locations. This is confirmed by our previous

  19. Changes of the intensity of morphogenetic process in the bone skeleton under lowering of gravitational loading

    Science.gov (United States)

    Vasilievna Rodionova, Natalia; Zolotova-Haidamaka, Nadezhda

    The development of long skeleton bones and reconstruction of bone structures in ontogenesis during adaptive remodeling are performed due to a combination of the bone apposition and bone resorption processes. With the use of radioactive markers of specific biosyntheses -3H- thymidine and 3H-glycine we studied the dynamics and peculiarities of these processes under modeling microgravity conditions by unloading the hind limbs of young white rats (tail suspension method) during 28 days. The radionuclides were administered in a single dose at the end of the experiment and the biomaterial was taken 1, 24, 48, 120 and 192 h. after injection. In histoautographs the counts were made of a nuclei labeling index (3H-thymidine), of the number of silver grains over the cells and in the forming bone matrix in growth and remodeling zones of the femoral bone (3H-glycine). The tendency for a reduction of a labeling index in the 3H-thymidine-labeled osteogenic cells in the periost and endost has been established. The dynamics of labeled cells following various intervals after 3H-thymidine injection testifies to a delay in the rates of osteoblasts' differentiation and their transformation to osteocytes in the experiment animals. 3H-glycine is assimilated by osteogenic cells 30 min after the radionuclide injection and following 24 h. it is already incorporated into the forming bone matrix. As a result an appositional bone addition by 192 h. the silver grains are registered in the bone matrix as "labeling lines". A lower 3H-glycine uptake by the osteogenic cells and bone matrix as compared with a control is indicative of a decrease of the osteoplastic process under hypokinesia, particulary in the periost. At the same time the resorption and remodeling bone zones reveal regions of an intensive 3H-glycine uptake after 1 and 24 h. We associate this latter fact with an activation of collagen proteins in the differentiating fibroblasts (instead of osteoblasts) in these locations. This is

  20. Buccal bone loss after immediate implantation can be reduced by the flapless approach

    Directory of Open Access Journals (Sweden)

    ARTHUR BELÉM NOVAES JR

    2011-10-01

    Full Text Available Aim: The aim of this study was to evaluate the buccal bone remodeling after immediate implantation with flap or flapless approach. Material and Methods: The mandibular bilateral premolars of 3 dogs were extracted and immediately three implants were placed in both hemi-arches of each dog. Randomly, one hemi-arch was treated with the flapless approach, while in the contra lateral hemi-arch tooth extractions and implant placement were done after mucoperiosteal flap elevation. Non-submerged healing of 12 weeks was provided for both groups. Histomorphometric analysis was done to compare buccal and lingual bone height loss, bone density and bone-to-implant contact in the groups. Fluorescence analysis was performed to investigate the dynamic of bone remodeling in the different groups. Results: There was a significant association between the surgical flap and the extent of bone resorption around immediate implants. The loss of buccal bone height was significantly lower in the flapless group when compared to the flap group (0.98 mm x 2.14 mm, respectively, p<0.05. The coronal and apical buccal bone densities of the flap group were significantly higher when compared to the lingual components, showing anatomical differences between the bone plates. Fluorescence analysis showed no major differences in bone healing between the flap and flapless groups, supporting that the higher loss of buccal bone height is linked to the anatomic characteristics of this plate and to the negative influence of the detachment of the periosteum in immediate implant therapy. Conclusion: The flapless approach for immediate post-extraction implants reduces the buccal bone height loss.

  1. Erythrocyte stiffness during morphological remodeling induced by carbon ion radiation.

    Directory of Open Access Journals (Sweden)

    Baoping Zhang

    Full Text Available The adverse effect induced by carbon ion radiation (CIR is still an unavoidable hazard to the treatment object. Thus, evaluation of its adverse effects on the body is a critical problem with respect to radiation therapy. We aimed to investigate the change between the configuration and mechanical properties of erythrocytes induced by radiation and found differences in both the configuration and the mechanical properties with involving in morphological remodeling process. Syrian hamsters were subjected to whole-body irradiation with carbon ion beams (1, 2, 4, and 6 Gy or X-rays (2, 4, 6, and 12 Gy for 3, 14 and 28 days. Erythrocytes in peripheral blood and bone marrow were collected for cytomorphological analysis. The mechanical properties of the erythrocytes were determined using atomic force microscopy, and the expression of the cytoskeletal protein spectrin-α1 was analyzed via western blotting. The results showed that dynamic changes were evident in erythrocytes exposed to different doses of carbon ion beams compared with X-rays and the control (0 Gy. The magnitude of impairment of the cell number and cellular morphology manifested the subtle variation according to the irradiation dose. In particular, the differences in the size, shape and mechanical properties of the erythrocytes were well exhibited. Furthermore, immunoblot data showed that the expression of the cytoskeletal protein spectrin-α1 was changed after irradiation, and there was a common pattern among its substantive characteristics in the irradiated group. Based on these findings, the present study concluded that CIR could induce a change in mechanical properties during morphological remodeling of erythrocytes. According to the unique characteristics of the biomechanical categories, we deduce that changes in cytomorphology and mechanical properties can be measured to evaluate the adverse effects generated by tumor radiotherapy. Additionally, for the first time, the current study

  2. Dynamic Contrast Enhanced Magnetic Resonance Imaging of Diffuse Spinal Bone Marrow Infiltration in Patients with Hematological Malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Zha, Yunfei; Li, Maojin [Renmin Hospital of Wuhan University, Wuhan (China); Yang, Jianyong [the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China)

    2010-04-15

    To investigate the significance of the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) parameters of diffuse spinal bone marrow infiltration in patients with hematological malignancies. Dynamic gadolinium-enhanced MR imaging of the lumbar spine was performed in 26 patients with histologically proven diffuse bone marrow infiltration, including multiple myeloma (n = 6), acute lymphoblastic leukemia (n = 6), acute myeloid leukemia (n = 5), chronic myeloid leukemia (n = 7), and non-Hodgkin lymphoma (n = 2). Twenty subjects whose spinal MRI was normal, made up the control group. Peak enhancement percentage (E{sub max}), enhancement slope (ES), and time to peak (TTP) were determined from a time intensity curve (TIC) of lumbar vertebral bone marrow. A comparison between baseline and follow-up MR images and its histological correlation were evaluated in 10 patients. The infiltration grade of hematopoietic marrow with plasma cells was evaluated by a histological assessment of bone marrow. Differences in E{sub max}, ES, and TTP values between the control group and the patients with diffuse bone marrow infiltration were significant (t = -11.51, -9.81 and 3.91, respectively, p < 0.01). E{sub max}, ES, and TTP values were significantly different between bone marrow infiltration groups Grade 1 and Grade 2 (Z = -2.72, -2.24 and -2.89 respectively, p < 0.05). E{sub max}, ES and TTP values were not significantly different between bone marrow infiltration groups Grade 2 and Grade 3 (Z = -1.57, -1.82 and -1.58 respectively, p > 0.05). A positive correlation was found between E{sub max}, ES values and the histological grade of bone marrow infiltration (r = 0.86 and 0.84 respectively, p < 0.01). A negative correlation was found between the TTP values and bone marrow infiltration histological grade (r = -0.54, p < 0.01). A decrease in the E{sub max} and ES values was observed with increased TTP values after treatment in all of the 10 patients who responded to treatment (t

  3. Mathematical modeling of bone marrow--peripheral blood dynamics in the disease state based on current emerging paradigms, part I.

    Science.gov (United States)

    Afenya, Evans K; Ouifki, Rachid; Camara, Baba I; Mundle, Suneel D

    2016-04-01

    Stemming from current emerging paradigms related to the cancer stem cell hypothesis, an existing mathematical model is expanded and used to study cell interaction dynamics in the bone marrow and peripheral blood. The proposed mathematical model is described by a system of nonlinear differential equations with delay, to quantify the dynamics in abnormal hematopoiesis. The steady states of the model are analytically and numerically obtained. Some conditions for the local asymptotic stability of such states are investigated. Model analyses suggest that malignancy may be irreversible once it evolves from a nonmalignant state into a malignant one and no intervention takes place. This leads to the proposition that a great deal of emphasis be placed on cancer prevention. Nevertheless, should malignancy arise, treatment programs for its containment or curtailment may have to include a maximum and extensive level of effort to protect normal cells from eventual destruction. Further model analyses and simulations predict that in the untreated disease state, there is an evolution towards a situation in which malignant cells dominate the entire bone marrow - peripheral blood system. Arguments are then advanced regarding requirements for quantitatively understanding cancer stem cell behavior. Among the suggested requirements are, mathematical frameworks for describing the dynamics of cancer initiation and progression, the response to treatment, the evolution of resistance, and malignancy prevention dynamics within the bone marrow - peripheral blood architecture. PMID:26877072

  4. Cellular Mechanisms of Multiple Myeloma Bone Disease

    OpenAIRE

    Angela Oranger; Claudia Carbone; Maddalena Izzo; Maria Grano

    2013-01-01

    Multiple myeloma (MM) is a hematologic malignancy of differentiated plasma cells that accumulates and proliferates in the bone marrow. MM patients often develop bone disease that results in severe bone pain, osteolytic lesions, and pathologic fractures. These skeletal complications have not only a negative impact on quality of life but also a possible effect in overall survival. MM osteolytic bone lesions arise from the altered bone remodeling due to both increased osteoclast activation and d...

  5. Biophotonics and Bone Biology

    Science.gov (United States)

    Zimmerli, Gregory; Fischer, David; Asipauskas, Marius; Chauhan, Chirag; Compitello, Nicole; Burke, Jamie; Tate, Melissa Knothe

    2004-01-01

    One of the more serious side effects of extended space flight is an accelerated bone loss. Rates of bone loss are highest in the weight-bearing bones of the hip and spine regions, and the average rate of bone loss as measured by bone mineral density measurements is around 1.2% per month for persons in a microgravity environment. It is well known that bone remodeling responds to mechanical forces. We are developing two-photon microscopy techniques to study bone tissue and bone cell cultures to better understand the fundamental response mechanism in bone remodeling. Osteoblast and osteoclast cell cultures are being studied, and the goal is to use molecular biology techniques in conjunction with Fluorescence Lifetime Imaging Microscopy (FLIM) to study the physiology of in-vitro cell cultures in response to various stimuli, such as fluid flow induced shear stress and mechanical stress. We have constructed a two-photon fluorescence microscope for these studies, and are currently incorporating FLIM detection. Current progress will be reviewed. This work is supported by the NASA John Glenn Biomedical Engineering Consortium.

  6. Dynamic Alterations in Microarchitecture, Mineralization and Mechanical Property of Subchondral Bone in Rat Medial Meniscal Tear Model of Osteoarthritis

    Institute of Scientific and Technical Information of China (English)

    De-Gang Yu; Shao-Bo Nie; Feng-Xiang Liu; Chuan-Long Wu; Bo Tian; Wen-Gang Wang; Xiao-Qing Wang

    2015-01-01

    Background:The properties of subchondral bone influence the integrity of articular cartilage in the pathogenesis of osteoarthritis (OA).However,the characteristics of subchondral bone alterations remain unresolved.The present study aimed to observe the dynamic alterations in the microarchitecture,mineralization,and mechanical properties of subchondral bone during the progression of OA.Methods:A medial meniscal tear (MMT) operation was performed in 128 adult Sprague Dawley rats to induce OA.At 2,4,8,and 12 weeks following the MMT operation,cartilage degeneration was evaluated using toluidine blue O staining,whereas changes in the microarchitecture indices and tissue mineral density (TMD),mineral-to-collagen ratio,and intrinsic mechanical properties of subchondral bone plates (BPs) and trabecular bones (Tbs) were measured using micro-computed tomography scanning,confocal Raman microspectroscopy and nanoindentation testing,respectively.Results:Cartilage degeneration occurred and worsened progressively from 2 to 12 weeks after OA induction.Microarchitecture analysis revealed that the subchondral bone shifted from bone resorption early (reduced trabecular BV/TV,trabecular number,connectivity density and trabecular thickness [Tb.Th],and increased trabecular spacing (Tb.Sp) at 2 and 4 weeks) to bone accretion late (increased BV/TV,Tb.Th and thickness of subchondral bone plate,and reduced Tb.Sp at 8 and 12 weeks).The TMD of both the BP and Tb displayed no significant changes at 2 and 4 weeks but decreased at 8 and 12 weeks.The mineral-to-collagen ratio showed a significant decrease from 4 weeks for the Tb and from 8 weeks for the BP after OA induction.Both the elastic modulus and hardness of the Tb showed a significant decrease from 4 weeks after OA induction.The BP showed a significant decrease in its elastic modulus from 8 weeks and its hardness from 4 weeks.Conclusion:The microarchitecture,mineralization and mechanical properties of subchondral bone changed in a time

  7. In vivo visualizing the dynamics of bone marrow stem cells in mouse retina and choroidal-retinal circulation

    Science.gov (United States)

    Wang, Heuy-Ching H.; Zwick, Harry; Edsall, Peter R.; Cheramie, Rachel D.; Lund, David J.; Stuck, Bruce

    2007-02-01

    It has recently been shown that bone marrow cells can differentiate into various lineage cells including neural cells in vitro and in vivo. Therefore it is an attractive therapeutic intervention to apply autologous bone marrow-derived stem cells that may offer neuroprotection to laser-induced retinal injuries. The purpose of this study is to develop a method with which to visualize bone marrow stem cells dynamics in mouse retinal circulation. We have used a physiological method, confocal scanning laser ophthalmoscope (SLO), to track the highly enriched stem/progenitor cells circulating in the retina. Stem cells were enriched by immunomagnetic depletion of cells committed to the T- and B lymphocytic, myeloid and erythorid lineages. CellTracker TM Green-labeled stem cells were injected into the tail veins of mice with laser-induced focal retinal injuries. Bone marrow stem cells labeled with CellTracker TM Green were visible in the retinal circulation for as long as 1 hour and 30 minutes. These studies suggest that stem cell-enriched bone marrow cells may have the ability to mobilize into laser-induced retinal injuries and possibly further proliferate, differentiate and functionally integrate into the retina.

  8. Meta analysis on therapeutic effect of bone marrow stem cell transplantation on left ventricular remodeling in patients with acute myocardial infarction%骨髓干细胞移植改善心肌梗死患者左室重构的Meta分析

    Institute of Scientific and Technical Information of China (English)

    费宇行; 裘毅钢; 李晶

    2011-01-01

    Objective To review the influence of bone marrow stem cell transplantation on left ventricular remodeling in the patients with acute myocardial infarction ( AMI ). Methods The full-text literature about the random and controlling studies on influence of bone marrow stem cell transplantation on left ventricular remodeling after AMI ventilated at home and abroad from 1966 to March 2011 were retrieved from Medline, Embase, China Journal Fulltext Database and Cochrane Library according to the inclusion and exclusion criteria. The literature was analyzed by using RevMan 5.0 software. Results There were totally 16 studies included ( 894 cases ). The results of Meta analysis showed that, compared with the control group, auto-transplantation of bone marrow stem cells decreased the left ventricular end-diastolic volume ( WMD = -7. 74; 95% CI: -11.51- -37 ;P < 0.01 ) and left ventricular end-systolic volume( WMD = -8.22;95% CI: -13.62- -4. 81 ;P <0. 01 ). The analysis of subgroup showed the decrease ofleft ventricular remodeling began from the 3rd month and continued to the 6th month and 12th month. Conclusion The transplantation of bone marrow stem cells can ameliorate left ventricular remodeling after AMI.%目的 评价骨髓干细胞移植对心肌梗死患者左室重构的影响.方法 根据纳入标准和剔除标准检索Medline、Embase、中国期刊全文数据库、Cochrane 图书馆等电子数据库,收集国内外1966~2011年3月公开发表的关于急性心肌梗死后骨髓干细胞移植对左室重构的影响的随机对照研究的全文文献,最后纳入的文献用RevMan 5.0进行分析.结果 共纳入16项研究共894例患者.Meta分析结果显示:与对照组相比,自体骨髓干细胞移植显著降低了心肌梗死患者的左室舒张末期容积(WMD=-7.74;95% CI:-11.51~-3.37;P<0.01)和左室收缩末期容积(WMD=-8.22;95% CI:-13.62~-4.81;P<0.01)的变化.在亚组分析中,从3个月起即显示出减少左室重

  9. Deregulation of Bone Forming Cells in Bone Diseases and Anabolic Effects of Strontium-Containing Agents and Biomaterials

    OpenAIRE

    Shuang Tan; Binbin Zhang; Xiaomei Zhu; Ping Ao; Huajie Guo; Weihong Yi; Guang-Qian Zhou

    2014-01-01

    Age-related bone loss and osteoporosis are associated with bone remodeling changes that are featured with decreased trabecular and periosteal bone formation relative to bone resorption. Current anticatabolic therapies focusing on the inhibition of bone resorption may not be sufficient in the prevention or reversal of age-related bone deterioration and there is a big need in promoting osteoblastogenesis and bone formation. Enhanced understanding of the network formed by key signaling pathways ...

  10. Quantification of remodeling parameter sensitivity - assessed by a computer simulation model

    DEFF Research Database (Denmark)

    Thomsen, J.S.; Mosekilde, Li.; Mosekilde, Erik

    1996-01-01

    We have used a computer simulation model to evaluate the effect of several bone remodeling parameters on vertebral cancellus bone. The menopause was chosen as the base case scenario, and the sensitivity of the model to the following parameters was investigated: activation frequency, formation bal....... However, the formation balance was responsible for the greater part of total mass loss....

  11. Probiotic use decreases intestinal inflammation and increases bone density in healthy male but not female mice.

    Science.gov (United States)

    McCabe, Laura R; Irwin, Regina; Schaefer, Laura; Britton, Robert A

    2013-08-01

    Osteoporosis can result from intestinal inflammation, as is seen with inflammatory bowel disease. Probiotics, microorganisms that provide a health benefit to the host when ingested in adequate amounts, can have anti-inflammatory properties and are currently being examined to treat inflammatory bowel disease. Here, we examined if treating healthy male mice with Lactobacillus reuteri ATCC PTA 6475 (a candidate probiotic with anti-TNFα activity) could affect intestinal TNFα levels and enhance bone density. Adult male mice were given L. reuteri 6475 orally by gavage for 3×/week for 4 weeks. Examination of jejunal and ileal RNA profiles indicates that L. reuteri suppressed basal TNFα mRNA levels in the jejunum and ileum in male mice, but surprisingly not in female mice. Next, we examined bone responses. Micro-computed tomography demonstrated that L. reuteri 6475 treatment increased male trabecular bone parameters (mineral density, bone volume fraction, trabecular number, and trabecular thickness) in the distal femur metaphyseal region as well as in the lumbar vertebrae. Cortical bone parameters were unaffected. Dynamic and static histomorphometry and serum remodeling parameters indicate that L. reuteri ingestion increases osteoblast serum markers and dynamic measures of bone formation in male mice. In contrast to male mice, L. reuteri had no effect on bone parameters in female mice. Taken together our studies indicate that femoral and vertebral bone formation increases in response to oral probiotic use, leading to increased trabecular bone volume in male mice. PMID:23389860

  12. The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

    Directory of Open Access Journals (Sweden)

    Justin W Walley

    2008-12-01

    Full Text Available Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD is required for the expression of selected genes downstream of the jasmonate (JA and ethylene (ET signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.

  13. Implementación del modelo de remodelación ósea de Komarova para el estudio de la sensibilidad del proceso de remodelamiento óseo ante cambios en factores locales Model Bone of Komarova Implementation for the sensitivity study of the process of remodelling bony before changes in local factors

    Directory of Open Access Journals (Sweden)

    Aldemar Fonseca-Velásquez

    2009-12-01

    Full Text Available En este artículo se lleva a cabo la implementación del modelo de remodelación ósea de nivel celular planteado por Komarova, usando como herramienta un diagrama de bloques funcionales. El objetivo de esta implementación es hacer un análisis de sensibilidad con respecto a la variación de los parámetros del modelo y determinar la influencia de los factores paracrinos y autocrinos en la formación de osteoclastos y osteoblastos. El modelo se implementó en el paquete comercial Simulink de Matlab R2007b. Se encontró que cada parámetro tiene un rango de funcionamiento bien determinado y que, fuera de él, la estabilidad se pierde y se establecen ganancias o pérdidas de masa ósea que se pueden atribuir a anormalidades sistémicas de los huesos. Este trabajo constituye un avance sobre el tema de remodelación ósea gracias a que, a diferencia de trabajos previos, se incluyen las variaciones de los parámetros propios del proceso de remodelación que llevan a posibles alteraciones de los procesos del metabolismo óseo, lo cual constituye un punto de partida para el estudio de enfermedades y alteraciones de la densidad del hueso, y permite iniciar el modelado de nuevas enfermedades relacionadas con los huesos, como es, por ejemplo, la metástasis ósea. Este estudio, entonces, es un avance con respecto a los trabajos presentados por Komarova y Lemaire y puede explicar fenómenos de metástasis y alteraciones metabólicas como los descritos en Manolagas.In this article the cellular level model of bone remodeling implementation raised by Komarova is carried out, using like tool a functional block diagram. The objective of this implementation is to make an analysis of sensitivity with respect to the variation of the model parameters and to determine the influence of the paracrine and autocrine factors in the osteoclasts and osteoblasts formation. The model was implemented in the commercial package Simulink with Matlab R2007b. We found that each

  14. In vitro evaluation of ionizing radiation effects in bone tissue by FTIR spectroscopy and dynamic mechanical analysis

    International Nuclear Information System (INIS)

    Ionizing radiation from gamma radiation sources or X-ray generators is frequently used in Medical Science, such as radiodiagnostic exams, radiotherapy, and sterilization of haloenxerts. Ionizing radiation is capable of breaking polypeptidic chains and causing the release of free radicals by radiolysis.of water. It interacts also with organic material at the molecular level, and it may change its mechanical properties. In the specific case of bone tissue, studies report that ionizing radiation induces changes in collagen molecules and reduces the density of intermolecular crosslinks. The aim of this study was to verify the changes promoted by different doses of ionizing radiation in bone tissue using Fourier Transform Infrared Spectroscopy (FTIR) and dynamic mechanical analysis (DMA). Samples of bovine bone were irradiated using Cobalt-60 with five different doses: 0.01 kGy, 0.1 kGy, 1 kGy, 15 kGy and 75 kGy. To study the effects of ionizing irradiation on the chemical structure of the bone, the sub-bands of amide I, the crystallinity index and relation of organic and inorganic materials, were studied. The mechanical changes were evaluated using the elastic modulus and the damping value. To verify whether the chemical changes and the mechanical characteristics of the bone were correlated, the relation between the analysis made with spectroscopic data and the mechanical analysis data was studied. It was possible to evaluate the effects of different doses of ionizing radiation in bone tissue. With ATR-FTIR spectroscopy, it was possible to observe changes in the organic components and in the hydroxyapatite crystals organization. Changes were also observed in the elastic modulus and in the damping value. High correlation with statistical significance was observed among (amide III + collagen)/v1,v3, PO43- and the delta tangent, and among 1/FHWM and the elastic modulus. (author)

  15. Tumor infiltration of bone marrow in patients with hematological malignancies: dynamic contrast-enhanced magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lei; Catherine Mandel; YANG Zhen-yan; YANG Qing; Richard Nibbs; David Westerman; Alex Pitman

    2006-01-01

    Background Conventional magnetic resonance (MR) scanning techniques can identify bone marrow (BM)containing mostly fat cells. But they are not able to differentiate BM tumor infiltration, BM fibrosis and normalred BM. This is particularly problematic in assessment of recurrent or refractory hematological malignancy. Thispilot study used dynamic contrast-enhanced MR imaging (DCE-MRI) to evaluate the bone marrow status and todetermine whether several calculated parameters derived from the DCE-MRI correlate with histologicalcharacteristics of marrow, especially with the tumor fraction (TF).Methods DCE-MRI scans were performed in 25 patients with proven or known hematological malignancy whowere about to undergo bone marrow biopsy of the posterior iliac crest. The location chosen for biopsy wasexamined with MRI approximately one hour prior to the biopsy. Time-signal intensity curves (TIC) weregenerated from the region of the iliac crest corresponding to the planned biopsy site. Enhancement parameterswere calculated, including peak enhancement ratio (PER), maximum enhancement slope (Slopemax), time to peak(TTP) and mean time (MT). The biopsy specimen was reported synoptically, with relevant reported parametersincluding cellularity and tumor fraction (TF).Results PER values were significantly higher for the bone marrow tumor infiltration group than for the normalbone marrow group (P<0.05). A significant positive correlation was found between PER and TF as well asSlopemax and TF. A negative correlation was found between TTP and TF. There was no significant difference inthe mean TTP and MT values between the BM tumor infiltration group and the normal bone marrow group.Conclusions The presence of diffuse bone marrow infiltration in patients with haematological malignanciescould be verified using DCE-MRI.

  16. [Ultrasonography and Doppler effect, an original method for the early and dynamic evaluation of bone callus].

    Science.gov (United States)

    Elanga, M; Bouche, B; Putz, P; Dumont, N

    1997-12-01

    The authors describe an original and simple method for monitoring bone healing, based upon ultrasonography and the Doppler effect. They present four cases of diaphyseal fractures followed by this method and correlated with clinical findings. This noninvasive and inexpensive method of investigation is full of prospect for the monitoring of bone healing after fracture.

  17. To Remodel or To Build?

    Science.gov (United States)

    Rosenblum, Todd

    2009-01-01

    The question of remodeling an existing house to make it wheelchair accessible or building a new barrier-free house is a difficult decision. This article presents some initial questions and considerations followed by a list of pros and cons for remodeling an existing house vs. building a new house.

  18. No-Regrets Remodeling, 2nd Edition

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-12-01

    No-Regrets Remodeling, sponsored by Oak Ridge National Laboratory, is an informative publication that walks homeowners and/or remodelers through various home remodeling projects. In addition to remodeling information, the publication provides instruction on how to incorporate energy efficiency into the remodeling process. The goal of the publication is to improve homeowner satisfaction after completing a remodeling project and to provide the homeowner with a home that saves energy and is comfortable and healthy.

  19. Femoral head vascularisation in Legg-Calve-Perthes disease: comparison of dynamic gadolinium-enhanced subtraction MRI with bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Lamer, Sylvie; Dorgeret, Sophie; Brillet, Pierre-Yves; Hassan, Max; Sebag, Guy H. [Department of Paediatric Radiology, Hopital Robert Debre, 48 boulevard Serurier, 75935 Paris Cedex (France); Lariboisiere-Saint-Louis University, Paris (France); Khairouni, Abdeslam; Mazda, Keyvan; Bacheville, Eric; Pennecot, Georges F. [Department of Paediatric Orthopaedics, Hopital Robert Debre, Paris (France); Bloch, Juliette [Department of Biostatistics, Hopital Robert Debre, Paris (France)

    2002-08-01

    Heading AbstractBackground. It has been reported that MRI using a dynamic gadolinium-enhanced subtraction technique can allow the early identification of ischaemia and the pattern of revascularisation in Legg-Calve-Perthes (LCP) disease with increased spatial and contrast resolution. Therefore, dynamic gadolinium-enhanced subtraction (DGS) MRI may be a possible non-ionising substitute for bone scintigraphy.Objective. The purpose of this prospective study was to compare DGS MRI and bone scintigraphy in the assessment of femoral head perfusion in LCP disease.Materials and methods. Twenty-six DGS MR images and bone scintigraphies of 25 hips in 23 children were obtained at different stages of LCP disease; three stage I, 12 stage II, six stage III and five stage IV (Waldenstroem classification). The extent of necrosis, epiphyseal revascularisation pathways (lateral pillar, medial pillar, and/or transphyseal perfusion) and metaphyseal changes were analysed.Results. Total agreement between both techniques was noted in the depiction of epiphyseal necrosis (kappa=1), and metaphyseal abnormalities (kappa=0.9). DGS MRI demonstrated better revascularisation in the lateral (kappa=0.62) and medial pillars (kappa=0.52). The presence of basal transphyseal reperfusion was more conspicuous with MRI.Conclusions. DGS MRI allows early detection of epiphyseal ischaemia and accurate analysis of the different revascularisation patterns. These changes are directly related to the prognosis of LCP disease and can aid therapeutic decision making. (orig.)

  20. Bone turnover in wild type and pleiotrophin-transgenic mice housed for three months in the International Space Station (ISS).

    Science.gov (United States)

    Tavella, Sara; Ruggiu, Alessandra; Giuliani, Alessandra; Brun, Francesco; Canciani, Barbara; Manescu, Adrian; Marozzi, Katia; Cilli, Michele; Costa, Delfina; Liu, Yi; Piccardi, Federica; Tasso, Roberta; Tromba, Giuliana; Rustichelli, Franco; Cancedda, Ranieri

    2012-01-01

    Bone is a complex dynamic tissue undergoing a continuous remodeling process. Gravity is a physical force playing a role in the remodeling and contributing to the maintenance of bone integrity. This article reports an investigation on the alterations of the bone microarchitecture that occurred in wild type (Wt) and pleiotrophin-transgenic (PTN-Tg) mice exposed to a near-zero gravity on the International Space Station (ISS) during the Mice Drawer System (MDS) mission, to date, the longest mice permanence (91 days) in space. The transgenic mouse strain over-expressing pleiotrophin (PTN) in bone was selected because of the PTN positive effects on bone turnover. Wt and PTN-Tg control animals were maintained on Earth either in a MDS payload or in a standard vivarium cage. This study revealed a bone loss during spaceflight in the weight-bearing bones of both strains. For both Tg and Wt a decrease of the trabecular number as well as an increase of the mean trabecular separation was observed after flight, whereas trabecular thickness did not show any significant change. Non weight-bearing bones were not affected. The PTN-Tg mice exposed to normal gravity presented a poorer trabecular organization than Wt mice, but interestingly, the expression of the PTN transgene during the flight resulted in some protection against microgravity's negative effects. Moreover, osteocytes of the Wt mice, but not of Tg mice, acquired a round shape, thus showing for the first time osteocyte space-related morphological alterations in vivo. The analysis of specific bone formation and resorption marker expression suggested that the microgravity-induced bone loss was due to both an increased bone resorption and a decreased bone deposition. Apparently, the PTN transgene protection was the result of a higher osteoblast activity in the flight mice.

  1. Comparison of a quasi-dynamic and a static extraction method for the cytotoxic evaluation of acrylic bone cements.

    Science.gov (United States)

    Hoess, A; López, A; Engqvist, H; Ott, M Karlsson; Persson, C

    2016-05-01

    In this study, two different extraction approaches were compared in order to evaluate the cytotoxicity of 7 different acrylic bone cements, mainly developed for spinal applications, to osteoblastic cells. Firstly, a static extraction was carried out continuously over 24h, a method widely used in literature. Secondly, a quasi-dynamic extraction method that allowed the investigation of time-dependent cytotoxic effects of curing acrylic bone cements to cells was introduced. In both cases the extraction of the cements was started at a very early stage of the polymerization process to simulate the conditions during clinical application. Data obtained by the quasi-dynamic extraction method suggest that the cytotoxicity of the setting materials mainly originates from the release of toxic components during the first hour of the polymerization reaction. It was also shown that a static extraction over 24h generally represents this initial stage of the curing process. Furthermore, compared to the static extraction, time-dependent cytotoxicity profiles could be detected using the quasi-dynamic extraction method. Specifically, a modification of commercial OsteopalV with castor oil as a plasticizer as well as a customized cement formulation showed clear differences in cytotoxic behavior compared to the other materials during the setting process. In addition, it was observed that unreacted monomer released from the castor oil modified cement was not the main component affecting the toxicity of the material extracts. The quasi-dynamic extraction method is a useful tool to get deeper insight into the cytotoxic potential of curing acrylic bone cements under relevant biological conditions, allowing systematic optimization of materials under development. PMID:26952424

  2. Factors affecting bone strength other than osteoporosis.

    Science.gov (United States)

    Ratti, Chiara; Vulcano, Ettore; Canton, Gianluca; Marano, Marco; Murena, Luigi; Cherubino, Paolo

    2013-10-01

    Osteoporosis is the most common cause of bone fragility, especially in post-menopausal women. Bone strength may be compromised by several other medical conditions and medications, which must be ruled out in the clinical management of patients affected by fragility fractures. Indeed, 20-30% of women and up to 50% of men affected by bone fragility are diagnosed with other conditions affecting bone strength other than osteoporosis. These conditions include disorders of bone homeostasis, impaired bone remodeling, collagen disorders, and medications qualitatively and quantitatively affecting bone strength. Proper diagnosis allows correct treatment to prevent the occurrence of fragility fractures. PMID:24046057

  3. Expression of osteopontin in the process of implant-bone interface remodeling influenced by submerged or nonsubmerged implant denture%骨桥蛋白在不同种植方式种植义齿骨界面改建中的变化及意义

    Institute of Scientific and Technical Information of China (English)

    袁林; 童心; 李方舟; 曹凯华

    2012-01-01

    目的:对比埋植型与非埋植型种植体在义齿修复受载后种植体-骨界面中骨桥蛋白表达变化的异同.方法:选用纯系动物Beagle犬8只,在其下颌分别植入埋植型与非埋植型种植体,采用固定金属全冠行种植义齿修复,分不同时期处死动物.采用免疫组化方法,对修复后不同时期埋植型与非埋植型种植体-骨界面骨桥蛋白进行动态观察,比较两者之间的异同.结果:免疫组化观察发现,种植义齿修复受载后,随着种植体周围骨组织发生改建,种植体-骨界面表达骨桥蛋白较未修复对照组明显增强.2周时界面骨桥蛋白有表达,但与对照组无差异;4周和8周时明显高于对照组,并于8周时达到高峰;12周时恢复到与对照组相近.埋植型和非埋植型种植体之间无显著差异.结论:埋植型和非埋植型种植体在义齿修复受载后,所承受的机械负荷均能经过种植体传递至周围骨组织,刺激种植体-骨界面骨桥蛋白表达.%Objective: To study the expression of osteopontin (OPN) in the process of implant- bone interface remodeling after loading of submerged or nonsubmerged implant dentures. Methods: 8 adult beagle dogs were used to build the animal model. Submerged and nonsubmerged implants were implanted into the bilateral mandible respectively. Fixed metal full crown was used to carry out the submerged and nonsubmerged implant dentures. The beagle dogs were sacrificed by steps after loading. Immunohistochemistry was used to observe the expression of osteopontin in the implant-bone interface. Results; In the group after loading of implant denture, higher expression of OPN in the implant-bone interface was observed than in the unloading control. 2 weeks after loading of implant denture, the expression of OPN in the interface was observed, but there was no statistical difference between experimental and control groups. 4 and 8 weeks after loading, the expression of OPN in the loading

  4. Atrial Electrical Remodeling and Sleep Disordered Breathing

    Directory of Open Access Journals (Sweden)

    Adrian Baranchuk; Diego Conde

    2013-08-01

    . The results of this study have shown that patients with severe SDB have a longer SAPW duration than controls (131.9 ± 10.4 vs 122.8 ± 10.5 ms; p = 0.04 and that a significant reduction of the SAPW duration occurs after treatment with C-PAP (131.9 ± 10.4 to 126.2 ± 8.8 ms; p < 0.001 (Figure 1 (4. The shortening of SAPW duration and surface P-wave duration represents more rapid inter-atrial conduction and provides evidence for reverse atrial electrical remodeling. This may indicate an additional benefit of treating patients with C-PAP, as this evidence suggests that C-PAP may improve the anatomical and electrical substrate for AFib. Reverse atrial electrical remodeling is a concept in evolution, and several cardiovascular treatments may improve atrial dynamics (5. It is of utmost importance, in the times of considering AFib ablation as first line therapy for recurrent AFib; to be familiarized with the impact of non-recognized/non-treated SDBs over the cardiac electrical system. Conventional treatment for SDB as C-PAP may also represent a benefit in terms of facilitating normal atrial conduction and reducing the risks associated with AFib.

  5. BMP-2 Is Involved in Scleral Remodeling in Myopia Development

    OpenAIRE

    Honghui Li; Dongmei Cui; Feng Zhao; Lijun Huo; Jianmin Hu; Junwen Zeng

    2015-01-01

    The development of myopia is associated with scleral remodeling, but it is unclear which factors regulate this process. This study investigated bone morphogenetic protein-2 (BMP-2) expression in the sclera of guinea pigs with lens-induced myopia (LIM) and after recovery from myopia and evaluated the effect of BMP-2 on extracellular matrix (ECM) synthesis in human scleral fibroblasts (HSFs) cultured in vitro. Lens-induced myopia was brought about in two groups of guinea pigs (the lens-induced ...

  6. Wnt and Wnt inhibitors in bone metastasis

    OpenAIRE

    Sottnik, Joseph L; Christopher L. Hall; Zhang, Jian; Evan T. Keller

    2012-01-01

    Bone metastasis is a clinically devastating development of progressive cancers including prostate carcinoma, breast carcinoma and multiple myeloma. Bone metastases are typically painful, lead to adverse skeletal-related events, such as fracture, and are highly resistant to therapy. A major contribution to the ability of cancers to successfully establish bone metastases is their ability to exploit mechanisms of normal bone remodeling. Wnts are a large family of morphogenic proteins that are cr...

  7. Noninvasive methods of measuring bone blood perfusion

    OpenAIRE

    Dyke, J. P.; Aaron, R.K.

    2010-01-01

    Measurement of bone blood flow and perfusion characteristics in a noninvasive and serial manner would be advantageous in assessing revascularization after trauma and the possible risk of avascular necrosis. Many disease states, including osteoporosis, osteoarthritis, and bone neoplasms, result in disturbed bone perfusion. A causal link between bone perfusion and remodeling has shown its importance in sustained healing and regrowth following injury. Measurement of perfusion and permeability wi...

  8. In silico multi-scale model of transport and dynamic seeding in a bone tissue engineering perfusion bioreactor.

    Science.gov (United States)

    Spencer, T J; Hidalgo-Bastida, L A; Cartmell, S H; Halliday, I; Care, C M

    2013-04-01

    Computer simulations can potentially be used to design, predict, and inform properties for tissue engineering perfusion bioreactors. In this work, we investigate the flow properties that result from a particular poly-L-lactide porous scaffold and a particular choice of perfusion bioreactor vessel design used in bone tissue engineering. We also propose a model to investigate the dynamic seeding properties such as the homogeneity (or lack of) of the cellular distribution within the scaffold of the perfusion bioreactor: a pre-requisite for the subsequent successful uniform growth of a viable bone tissue engineered construct. Flows inside geometrically complex scaffolds have been investigated previously and results shown at these pore scales. Here, it is our aim to show accurately that through the use of modern high performance computers that the bioreactor device scale that encloses a scaffold can affect the flows and stresses within the pores throughout the scaffold which has implications for bioreactor design, control, and use. Central to this work is that the boundary conditions are derived from micro computed tomography scans of both a device chamber and scaffold in order to avoid generalizations and uncertainties. Dynamic seeding methods have also been shown to provide certain advantages over static seeding methods. We propose here a novel coupled model for dynamic seeding accounting for flow, species mass transport and cell advection-diffusion-attachment tuned for bone tissue engineering. The model highlights the timescale differences between different species suggesting that traditional homogeneous porous flow models of transport must be applied with caution to perfusion bioreactors. Our in silico data illustrate the extent to which these experiments have the potential to contribute to future design and development of large-scale bioreactors.

  9. PTH(1-84) Administration in Hypoparathyroidism Transiently Reduces Bone Matrix Mineralization.

    Science.gov (United States)

    Misof, Barbara M; Roschger, Paul; Dempster, David W; Zhou, Hua; Bilezikian, John P; Klaushofer, Klaus; Rubin, Mishaela R

    2016-01-01

    Patients with hypoparathyroidism have low circulating parathyroid (PTH) levels and higher cancellous bone volume and trabecular thickness. Treatment with PTH(1-84) was shown to increase abnormally low bone remodeling dynamics. In this work, we studied the effect of 1-year or 2-year PTH(1-84) treatment on cancellous and cortical bone mineralization density distribution (Cn.BMDD and Ct.BMDD) based on quantitative backscattered electron imaging (qBEI) in paired transiliac bone biopsy samples. The study cohort comprised 30 adult hypoparathyroid patients (14 treated for 1 year; 16 treated for 2 years). At baseline, Cn.BMDD was shifted to higher mineralization densities in both treatment groups (average degree of mineralization Cn.CaMean +3.9% and +2.7%, p mineralizing surface) was predictive for Cn.BMDD outcomes in the 1-year PTH(1-84) group, but not in the 2-year PTH(1-84) group. Our findings suggest higher baseline bone matrix mineralization consistent with the decreased bone turnover in hypoparathyroidism. PTH(1-84) treatment caused differential effects dependent on treatment duration that were consistent with the histomorphometric bone formation outcomes. The greater increase in bone formation during the first year of treatment was associated with a decrease in bone matrix mineralization, suggesting that PTH(1-84) exposure to the hypoparathyroid skeleton has the greatest effects on BMDD early in treatment.

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

    International Nuclear Information System (INIS)

    Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such as dioxins. Although bone morphology, mineral density and strength are sensitive endpoints of dioxin toxicity, less is known about effects on bone microarchitecture and material properties. This study characterizes TCDD-induced modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity and for normal bone phenotype. Six AHR-knockout (Ahr−/−) and wild-type (Ahr+/+) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200 μg/kg bw. Bones were examined with micro-computed tomography, nanoindentation and biomechanical testing. Serum levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr+/+ mice, TCDD-exposure resulted in harder bone matrix, thinner and more porous cortical bone, and a more compact trabecular bone compartment. Bone remodeling markers and altered expression of a number of osteogenesis related genes indicated imbalanced bone remodeling. Untreated Ahr−/− mice displayed a slightly modified bone phenotype as compared with untreated Ahr+/+ mice, while TCDD exposure caused only a few changes in bones of Ahr−/− mice. Part of the effects of both TCDD-exposure and AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker bones and most notably, increased trabecular bone volume fraction in Ahr+/+ mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. - Highlights: • TCDD disrupts bone remodeling resulting in altered cortical and trabecular bone. • In trabecular bone an anabolic effect is observed. • Cortical bone is thinner, more porous, harder, stiffer and mechanically weaker. • AHR ablation results in increased trabecular bone and softer

  11. Bone marrow cell derived arginase I is the major source of allergen-induced lung arginase but is not required for airway hyperresponsiveness, remodeling and lung inflammatory responses in mice

    Directory of Open Access Journals (Sweden)

    Rothenberg Marc E

    2009-06-01

    Full Text Available Abstract Background Arginase is significantly upregulated in the lungs in murine models of asthma, as well as in human asthma, but its role in allergic airway inflammation has not been fully elucidated in mice. Results In order to test the hypothesis that arginase has a role in allergic airway inflammation we generated arginase I-deficient bone marrow (BM chimeric mice. Following transfer of arginase I-deficient BM into irradiated recipient mice, arginase I expression was not required for hematopoietic reconstitution and baseline immunity. Arginase I deficiency in bone marrow-derived cells decreased allergen-induced lung arginase by 85.8 ± 5.6%. In contrast, arginase II-deficient mice had increased lung arginase activity following allergen challenge to a similar level to wild type mice. BM-derived arginase I was not required for allergen-elicited sensitization, recruitment of inflammatory cells in the lung, and proliferation of cells. Furthermore, allergen-induced airway hyperresponsiveness and collagen deposition were similar in arginase-deficient and wild type mice. Additionally, arginase II-deficient mice respond similarly to their control wild type mice with allergen-induced inflammation, airway hyperresponsiveness, proliferation and collagen deposition. Conclusion Bone marrow cell derived arginase I is the predominant source of allergen-induced lung arginase but is not required for allergen-induced inflammation, airway hyperresponsiveness or collagen deposition.

  12. Impact of Cytomegalovirus and Grafts versus Host Disease on the Dynamics of CD57+CD28−CD8+ T Cells After Bone Marrow Transplant

    OpenAIRE

    Ana Verena Almeida Mendes; Esper Georges Kallas; Gil Benard; Cláudio Sérgio Pannuti; Reneé Menezes; Frederico Luiz Dulley; Thomas George Evans; Reinaldo Salomão; Clarisse Martins Machado

    2008-01-01

    OBJECTIVES: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients. METHODS: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with c...

  13. Bone Biochemistry on the International Space Station

    Science.gov (United States)

    Smith, Scott M.; Heer, Martina; Zwart, Sara R.

    2016-01-01

    Bone biochemical measures provide valuable insight into the nature and time course of microgravity effects on bone during space flight, where imaging technology cannot be employed. Increased bone resorption is a hallmark of space flight, while markers of bone formation are typically unchanged or decreased. Recent studies (after the deployment to ISS of the advanced resistive exercise device, ARED), have documented that astronauts with good nutritional intake (e.g., maintenance of body mass), good vitamin D status, and exercise maintained bone mineral density. These data are encouraging, but crewmembers exercising on the ARED do have alterations in bone biochemistry, specifically, bone resorption is still increased above preflight levels, but bone formation is also significantly increased. While this bone remodeling raises questions about the strength of the resulting bone, however documents beneficial effects of nutrition and exercise in counteracting bone loss of space flight.

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

    Science.gov (United States)

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

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

  15. Triple-phase dynamic MRI: A new clue to predict malignant transformation of giant cell tumor of bone

    International Nuclear Information System (INIS)

    Objective: Our purpose was, through the comparison of the characteristics of time–intensity curve on triple-phase dynamic contrast-enhanced MRI among groups of giant cell tumor of bone (GCTB), recurrent benign giant cell tumor of bone (RBGCTB), and secondary malignant giant cell tumor of bone (SMGCTB), to find clues to predict the malignant transformation of GCTB. Subjects and methods: 21 patients diagnosed as GCTB were included in this study. All cases took recurrence after intralesional curettage. 9 cases were confirmed as SMGCTB and 12 cases were confirmed as RBGCTB. Cases were divided into four groups: group A, GCTB (n = 9); group B, SMGCTB (n = 9); group C, GCTB (n = 12); group D, RBGCTB (n = 12). Enhancement index(EI) of lesions on DCEMRI was calculated using formula: EI(t) = [S(t) − S(0)]/S(0), where S(0) was signal intensity of lesion on non-contrast-enhanced T1-weighted images and S(t) was signal intensity of lesion on DCEMRI (t = 30, 60, 180 s). Enhancement index of each group in each phase was compared using One-Way ANOVA analysis. Slope values of time–intensity curve were compared by the same way. Results: Time–intensity curve of SMGCTB was characterized by a steep upward slope followed by an early and rapid washout phase. Time–intensity curve of GCTB and RBGCTB was characterized by a steep slope followed by a relatively slow washout phase. No significant difference in enhancement index was found in the first phase (p > 0.05). There was significant difference in the second and the third phase (p < 0.05). Enhancement index of group B (SMGCTB) was smaller. There was no difference in rising slope value (p > 0.05). Conclusions: Dynamic contrast-enhanced MRI appears a helpful method to find new clues to predict malignant transformation of GCTB

  16. Dynamic testing of old and young baboon cortical bone with numerical validation

    Science.gov (United States)

    Chocron, S.; Nicolella, D.; Nicholls, A. E.; Bredbenner, T.; Havill, L.

    2012-08-01

    Cortical bone tensile mechanical properties at quasistatic and high rates (˜300s-1) were determined ex vivo using the right femurs of 12 female baboons, (Papio hamadryas spp.) from the Texas Biomedical Research Institute/Southwest National Primate Research Center in San Antonio, Texas. The animals were divided into two age groups: a young age group (6.63 ± 0.6 years) and an old age group (26.96 ± 1.3 years). Seven specimens per group were monotonically loaded to failure to determine their mechanical properties. The quasistatic strength of the bone for the old group was just a little (but not significantly) lower than the young group. High strain rate tests performed with the Hopkinson bar indicate that baboon bone from the older group was significantly weaker under impact loads than that from the younger group. This observation is particularly important due to the similarities between baboon and human bone tissue. Typical strain rates for these tests ranged from 130s-1 to 250s-1. A full-size 3-D simulation of the Hopkinson bar test was performed to confirm that the bone specimen was under stress equilibrium and to evaluate the consistency of the modulus and strength inferred from the tests. Simulations were performed in which the modulus, strength and failure strain were varied to see the sensitivity of the results. Additionally, simplified simulations were performed to estimate the strain rate environment of a femur during a fall at an impact velocity of 5 m/s, similar to a free fall velocity from a height of 1.3 meters. The simulations confirm that strain rates obtained in the Hopkinson bar are relevant because they are similar to those expected inr such a fall.

  17. Diffusion-weighted imaging and dynamic contrast-enhanced MRI of experimental breast cancer bone metastases – A correlation study with histology

    Energy Technology Data Exchange (ETDEWEB)

    Merz, Maximilian [Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Department of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Seyler, Lisa; Bretschi, Maren; Semmler, Wolfhard [Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Bäuerle, Tobias, E-mail: tobias.baeuerle@uk-erlangen.de [Department of Medical Physics in Radiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Institute of Radiology, University Medical Center Erlangen, Palmsanlage 5, 90154 Erlangen (Germany)

    2015-04-15

    Purpose: To validate imaging parameters from diffusion-weighted imaging and dynamic contrast-enhanced MRI with immunohistology and to non-invasively assess microstructure of experimental breast cancer bone metastases. Materials and methods: Animals bearing breast cancer bone metastases were imaged in a clinical 1.5 T MRI scanner. HASTE sequences were performed to calculate apparent diffusion coefficients. Saturation recovery turbo FLASH sequences were conducted while infusing 0.1 mmol/l Gd–DTPA for dynamic contrast-enhanced MRI to quantify parameters amplitude A and exchange rate constant k{sub ep}. After imaging, bone metastases were analyzed immunohistologically. Results: We found correlations of the apparent diffusion coefficients from diffusion-weighted imaging with tumor cellularity as assessed with cell nuclei staining. Histological vessel maturity was correlated negatively with parameters A and k{sub ep} from dynamic contrast-enhanced MRI. Tumor size correlated inversely with cell density and vessel permeability as well as positively with mean vessel calibers. Parameters from the rim of bone metastases differed significantly from values of the center. Conclusion: In vivo diffusion-weighted imaging and dynamic contrast-enhanced MRI in experimental bone metastases provide information about tumor cellularity and vascularity and correlate well with immunohistology.

  18. Diffusion-weighted imaging and dynamic contrast-enhanced MRI of experimental breast cancer bone metastases – A correlation study with histology

    International Nuclear Information System (INIS)

    Purpose: To validate imaging parameters from diffusion-weighted imaging and dynamic contrast-enhanced MRI with immunohistology and to non-invasively assess microstructure of experimental breast cancer bone metastases. Materials and methods: Animals bearing breast cancer bone metastases were imaged in a clinical 1.5 T MRI scanner. HASTE sequences were performed to calculate apparent diffusion coefficients. Saturation recovery turbo FLASH sequences were conducted while infusing 0.1 mmol/l Gd–DTPA for dynamic contrast-enhanced MRI to quantify parameters amplitude A and exchange rate constant kep. After imaging, bone metastases were analyzed immunohistologically. Results: We found correlations of the apparent diffusion coefficients from diffusion-weighted imaging with tumor cellularity as assessed with cell nuclei staining. Histological vessel maturity was correlated negatively with parameters A and kep from dynamic contrast-enhanced MRI. Tumor size correlated inversely with cell density and vessel permeability as well as positively with mean vessel calibers. Parameters from the rim of bone metastases differed significantly from values of the center. Conclusion: In vivo diffusion-weighted imaging and dynamic contrast-enhanced MRI in experimental bone metastases provide information about tumor cellularity and vascularity and correlate well with immunohistology

  19. The Contribution of Experimental in vivo Models to Understanding the Mechanisms of Adaptation to Mechanical Loading in Bone.

    Science.gov (United States)

    Meakin, Lee B; Price, Joanna S; Lanyon, Lance E

    2014-01-01

    Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones' strain environment produced by direct, controlled artificial bone loading. Jiri Hert introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gages to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced. Experiments combining strain gage instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats, and mice has yielded significant insight into the control of strain-related adaptive (re)modeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice, which is now the model of choice for many studies. Together such studies have demonstrated that over the physiological strain range, bone's mechanically adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles, and that these are most effective when interrupted by short periods of rest between them.

  20. microRNAs and Cardiovascular Remodeling.

    Science.gov (United States)

    Ono, Koh

    2015-01-01

    Heart failure (HF) is associated with significant morbidity and mortality attributable largely to structural changes in the heart and with associated cardiac dysfunction. Remodeling is defined as alteration of the mass, dimensions, or shape of the heart (termed cardiac or ventricular remodeling) and vessels (vascular remodeling) in response to hemodynamic load and/or cardiovascular injury in association with neurohormonal activation. Remodeling may be described as physiologic or pathologic; alternatively, remodeling may be classified as adaptive or maladaptive. The importance of remodeling as a pathogenic mechanism has been controversial because factors leading to remodeling as well as the remodeling itself may be major determinants of patients' prognosis. The basic mechanisms of cardiovascular remodeling, and especially the roles of microRNAs in HF progression and vascular diseases, will be reviewed here.

  1. Skeleton and Glucose Metabolism: A Bone-Pancreas Loop

    OpenAIRE

    2015-01-01

    Bone has been considered a structure essential for mobility, calcium homeostasis, and hematopoietic function. Recent advances in bone biology have highlighted the importance of skeleton as an endocrine organ which regulates some metabolic pathways, in particular, insulin signaling and glucose tolerance. This review will point out the role of bone as an endocrine “gland” and, specifically, of bone-specific proteins, as the osteocalcin (Ocn), and proteins involved in bone remodeling, as osteopr...

  2. Dynamic bone study in total prosthesis of the hip (RM isoelastic type)

    International Nuclear Information System (INIS)

    Over a period of 33 months, an evaluation was made of the development of 78 asymptomatic patients (average age: 62.27 ± 8.12 years), fitted with uncemented total prostheses of the hip, and a control group of 30 patients without prostheses (average age: 64.12 ± 10 years). All of them underwent bone scintigraphy modified three times: angioscintigraphy, sequenced scintigraphy and static scintigraphy. The following areas of interest were evaluated qualitatively: in the first phase, the gluteal, articular and diaphyseal regions; in the second and third phases, the cotyloid region, the trochanter, the intermediate area of the stem and the vertex of the prosthesis. The presence of any calcifications in the articular interface was sought. The natural development of bone repair activity in patients with hip prostheses showed that the areas of maximum stress, in decreasing order, are the following regions: trochanteric, cotyloid, vertex and intermediate area of the stem; the early presence of articular calcifications was observed in 20.5% of the cases studied. On the other hand, perfusion of the periprosthetic tissue showed no significant changes with respect to the control group. On the contrary, sequential scintigraphy was very sensitive in the detection of changes in the rate of bone repair, differentiating between the post-surgical period proper and the subsequent period in which the prothesis was stabilized; this was not the case with static scintigraphy, the sensitivity of which is inferior. (author). 14 refs, 3 figs

  3. Efficient computational simulation of actin stress fiber remodeling.

    Science.gov (United States)

    Ristori, T; Obbink-Huizer, C; Oomens, C W J; Baaijens, F P T; Loerakker, S

    2016-09-01

    Understanding collagen and stress fiber remodeling is essential for the development of engineered tissues with good functionality. These processes are complex, highly interrelated, and occur over different time scales. As a result, excessive computational costs are required to computationally predict the final organization of these fibers in response to dynamic mechanical conditions. In this study, an analytical approximation of a stress fiber remodeling evolution law was derived. A comparison of the developed technique with the direct numerical integration of the evolution law showed relatively small differences in results, and the proposed method is one to two orders of magnitude faster. PMID:26823159

  4. Bone Regulates Glucose Metabolism as an Endocrine Organ through Osteocalcin

    Directory of Open Access Journals (Sweden)

    Jin Shao

    2015-01-01

    Full Text Available Skeleton was considered as a dynamic connective tissue, which was essential for mobility, calcium homeostasis, and hematopoietic niche. However more and more evidences indicate that skeleton works not only as a structural scaffold but also as an endocrine organ, which regulates several metabolic processes. Besides osteoprotegerin (OPG, sclerostin (SOST, and Dickopf (DKK which play essential roles in bone formation, modelling, remodelling, and homeostasis, bone can also secret hormones, such as osteocalcin (OCN, which promotes proliferation of β cells, insulin secretion, and insulin sensitivity. Additionally OCN can also regulate the fat cells and male gonad endocrine activity and be regulated by insulin and the neural system. In summary, skeleton has endocrine function via OCN and plays an important role in energy metabolism, especially in glucose metabolism.

  5. Acceleration and holographic studies on different types of dynamization of external fixators of the bones

    Science.gov (United States)

    Podbielska, Halina; Kasprzak, Henryk T.; Voloshin, Arkady S.; Pennig, Dietmar; von Bally, Gert

    1992-08-01

    The unilateral axially dynamic fixator (Orthofix) was mounted on a sheep tibial shaft. Three fixation modes: static, dynamic controlled, and dynamic free were examined by means of double exposure holographic interferometry. Simultaneously, the acceleration was measured by an accelerometer and displayed on the monitor together with loading characteristics. The first exposure was made before the acting force was applied to the tibia plateau. The second one after the moment when the acceleration wave started to propagate through the specimen. We stated that in the case of dynamization less torsion occurs at the fracture site. So far, we have not been able to determine any correlation between results of holographic and accelerometric measurements.

  6. In vivo CT quantification of trabecular bone dynamics in mice after sciatic neurectomy using monochromatic synchrotron radiation.

    Science.gov (United States)

    Matsumoto, Takeshi; Nishikawa, Ken; Tanaka, Masao; Uesugi, Kentaro

    2011-05-01

    We demonstrated the capability of in vivo synchrotron radiation CT (SRCT) in analyzing short-term changes in trabecular bone architecture (TBA) and the degree of bone mineralization (DBM) in small animals. Mice underwent unilateral sciatic neurectomy (SN) and sham operation on the contralateral side (SO) at 13 weeks of age. In vivo SRCT scans (11.7-μm cubic voxel) were made of both knees 7 and 17 days (group 1, n = 7) or only 17 days (group 2, n = 6) after surgery. In three mice in group 2, one knee was scanned twice on the same day in different orientations for reproducibility testing. Two scan data sets of the tibial proximal metaphysis acquired at different time points (group 1) or at the same time point (group 2) were registered for detecting differences in volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), connectivity density (Conn.D), and mean DBM (mDBM). The reproducibility test showed small errors of 25%. In group 1, Tb.Th increased but Tb.N and Conn.D decreased in both SN and SO; BV/TV and mDBM increased only in SO; accordingly, BV/TV, Tb.Th, and mDBM became lower in SN than in SO. No significant interaction between SN and irradiation was found; the SN effects on TBA and DBM were similar between groups 1 and 2, although synchrotron irradiation led to higher Tb.Th and lower Tb.N in group 1. In conclusion, in vivo SRCT has potential use for detecting short-term bone dynamics of small animals. PMID:21359625

  7. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  8. Changes in bone remodeling-related factors under estrogen and tensile stress%雌激素与机械张应力对骨重建相关因子的作用★

    Institute of Scientific and Technical Information of China (English)

    彭伟; 廖春晖; 钟小龙; 陈珊

    2013-01-01

    BACKGROUND: Alveolar bone is one of the most active areas in bone metabolism, and it is liable to be affected by estrogen in orthodontic treatment for female patients. OBJECTIVE: To investigate the effect of estrogen on receptor activator of nuclear factor kappa B ligand and osteoprotegerin secreted by human periodontal ligament fibroblasts under mechanical tensile stress. METHODS: Human periodontal ligament fibroblasts were subjected to certain tensile stress loaded by four-point bending strain system after stimulated by different concentrations of estrogen. Reverse transcription-PCR detection was used to investigate the changes of bone reconstruction related factors. RESULTS AND CONCLUSION: Compared with pure machinery stimulation, human periodontal ligament fibroblasts intervened by estrogen expressed an osteoprotegerin mRNA raised trend, and a decreased trend in the mRNA expression of receptor activator of nuclear factor kappa B ligand. Estrogen can strongly modulate the mRNA expression of osteoprotegerin and receptor activator of nuclear factor kappa B ligand in human periodontal ligament fibroblasts under mechanical tensile stress.%  背景:牙槽骨是人体骨代谢最活跃的区域之一,对于在正畸治疗过程中的女性患者容易受到雌激素水平的影响。目的:观察雌激素对机械张应力作用下的牙周膜成纤维细胞骨重建相关因子骨保护素、核因子κB 受体活化子配体 mRNA 表达水平的影响。方法:利用一定浓度雌激素干预人牙周膜成纤维细胞后使用四点弯曲加力装置对细胞进行不同时间段的机械张应力加载,并利用 RT-PCR 检测雌激素与机械张应力共同作用后牙周膜成纤维细胞骨保护素、核因子κB 受体活化子配体基因表达变化。结果与结论:雌激素刺激后再进行机械张应力加载的人牙周膜成纤维细胞跟单纯受到机械张应力作用的人牙周膜成纤维细胞相比,骨保护素 mRNA 表

  9. Altered membrane dynamics of quantum dot-conjugated integrins during osteogenic differentiation of human bone marrow derived progenitor cells.

    Science.gov (United States)

    Chen, Hongfeng; Titushkin, Igor; Stroscio, Michael; Cho, Michael

    2007-02-15

    Functionalized quantum dots offer several advantages for tracking the motion of individual molecules on the cell surface, including selective binding, precise optical identification of cell surface molecules, and detailed examination of the molecular motion without photobleaching. We have used quantum dots conjugated with integrin antibodies and performed studies to quantitatively demonstrate changes in the integrin dynamics during osteogenic differentiation of human bone marrow derived progenitor cells (BMPCs). Consistent with the unusually strong BMPC adhesion previously observed, integrins on the surface of undifferentiated BMPC were found in clusters and the lateral diffusion was slow (e.g., approximately 10(-11) cm2/s). At times as early as those after a 3-day incubation in the osteogenic differentiation media, the integrin diffusion coefficients increased by an order of magnitude, and the integrin dynamics became indistinguishable from that measured on the surface of terminally differentiated human osteoblasts. Furthermore, microfilaments in BMPCs consisted of atypically thick bundles of stress fibers that were responsible for restricting the integrin lateral mobility. Studies using laser optical tweezers showed that, unlike fully differentiated osteoblasts, the BMPC cytoskeleton is weakly associated with its cell membrane. Based on these findings, it appears likely that the altered integrin dynamics is correlated with BMPC differentiation and that the integrin lateral mobility is restricted by direct links to microfilaments.

  10. Bone response from a dynamic stimulus on a one-piece and multi-piece implant abutment and crown by finite element analysis.

    Science.gov (United States)

    Hajimiragha, Habib; Abolbashari, Mohammadreza; Nokar, Saeed; Abolbashari, AmirHossein; Abolbashari, Mehrdad

    2014-10-01

    The present study was done to evaluate the effects of different types of abutments on the rate and distribution of stress on the bone surrounding the implant by dynamic finite element analysis method. In this study two ITI abutment models-one-piece and multi-piece-along with fixture, bone, and superstructure have been simulated with the help of company-made models. The maximum Von Mises stress (MVMS) was observed in the distobuccal area of the cortical bone near the crest of implant in two implant models. In the multi-piece abutment, MVMS was higher than the one-piece model (27.9 MPa and 23.3 MPa, respectively). Based on the results of this study, it can be concluded that type of abutment influences the stress distribution in the area surrounding the implant during dynamic loading.

  11. Bone biosensors: knowing the present and predicting the future

    Science.gov (United States)

    Khashayar, Patricia; Amoabediny, Ghassem; Larijani, Bagher; Vanfleteren, Jan

    2016-02-01

    Bone is an active organ with the capacity of continuous remodeling throughout adult life. In view of the fact that the current gold standard to assess bone remodeling, bone mineral density, suffers from certain limitations, newer techniques are being developed. Currently enzyme-linked immunosorbent assay is commonly used to assess bone turnover markers; the technique, however, is expensive, time consuming and needs trained personnel. Thus, there is a growing demand to fabricate different types of biosensors to provide low cost miniaturized platforms to assess the bone remodeling process more accurately. This review focuses on the latest advancements in the field of bone biosensing technologies. Its results might help provide possible solutions for translation of this technology for point-of-care diagnostic applications.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    within strict limits throughout adult life. Here, we determined that the bone marrow microanatomy adjacent to remodeling areas is a central player in this process. By using histomorphometry and multiple immunostainings, we demonstrated in biopsies exhibiting coupled bone resorption and formation...

  13. Cilengitide inhibits metastatic bone colonization in a nude rat model.

    Science.gov (United States)

    Bretschi, Maren; Merz, Maximilian; Komljenovic, Dorde; Berger, Martin R; Semmler, Wolfhard; Bäuerle, Tobias

    2011-10-01

    Integrins αvβ3 and αvβ5 are considered to play an important role in the pathogenesis of breast cancer bone metastases. This study investigates the effects of the αvβ3/αvβ5 integrin-specific inhibitor cilengitide during early metastatic bone colonization. The impact of cilengitide on the migration, invasion and proliferation of MDA-MB-231 human breast carcinoma cells as well as on bone resorption by osteoclasts was investigated in vitro. For in vivo experiments, nude rats were treated with cilengitide for 30 days starting one day after site-specific tumor cell inoculation in the hind leg, and the course of metastatic changes in bone was followed using flat-panel volumetric computed tomography (VCT) and magnetic resonance imaging (MRI). Vascular changes in bone metastases were investigated using dynamic contrast-enhanced (DCE-) MRI-derived parameters amplitude A and exchange rate coefficient kep. In vitro, cilengitide treatment resulted in a decrease in proliferation, migration and invasion of MDA-MB-231 cells, as well as of osteoclast activity. In vivo, the development of bone metastasis in the hind leg of rats was not prevented by adjuvant cilengitide treatment, but cilengitide reduced the volumes of osteolytic lesions and respective soft tissue tumors of developing bone metastases as assessed with VCT and MRI, respectively. DCE-MRI revealed significant changes in the A and kep parameters including decreased relative blood volume and increased vessel permeability after cilengitide treatment indicating vessel remodeling. In conclusion, during early pathogenic processes of bone colonization, cilengitide treatment exerted effects on tumor cells, osteoclasts and vasculature reducing the skeletal lesion size of experimental skeletal metastases. PMID:21725616

  14. Bone health in cancer patients

    DEFF Research Database (Denmark)

    Coleman, R; Body, J J; Aapro, M;

    2014-01-01

    cancer for many patients resulting in a major reduction in skeletal complications, reduced bone pain and improved quality of life. Secondly, many of the treatments we use to treat cancer patients have effects on reproductive hormones, which are critical for the maintenance of normal bone remodelling...... in the metastatic processes required for cancer dissemination, and there are emerging data showing that, at least in some clinical situations, the use of bone-targeted treatments can reduce metastasis to bone and has potential impact on patient survival.......There are three distinct areas of cancer management that make bone health in cancer patients of increasing clinical importance. First, bone metastases are common in many solid tumours, notably those arising from the breast, prostate and lung, as well as multiple myeloma, and may cause major...

  15. Mitochondrial Protein Dynamics in Cardiac Remodeling

    OpenAIRE

    Lau, Edward

    2014-01-01

    The cardiac mitochondrial proteome contains ~1,500 distinct proteins that carry out necessary metabolic and energetic processes in the heart. To sustain cardiac function, the mitochondrial proteome must be maintained in constant renewal, or turnover, especially under stress conditions. Disruptions of protein turnover can lead to protein damage and proteotoxicity, a hallmark of many heart disease etiologies. Current quantitative proteomics experiments largely focus on the measurement of the st...

  16. 骨髓间充质干细胞移植对慢性哮喘小鼠气道炎症及气道重塑的影响%Effects of Bone Marrow-Derived Mesenchymal Stem Cells on Airway Inflammation and Airway Remodeling in Chronic Asthmatic Mice

    Institute of Scientific and Technical Information of China (English)

    戈霞晖; 白冲; 陈若华; 胡珍丽; 朱天怡; 李强

    2011-01-01

    目的 探讨同种异体骨髓间充质干细胞(BMSC)移植对慢性哮喘小鼠气道炎症和气道重塑的影响.方法 40只雌性BALB/c小鼠随机分为正常对照组、BMSC对照组、哮喘模型组和BMSC治疗组.从雄性BALB/c小鼠分离BMSC.用卵白蛋白(OVA)制备慢性哮喘模型.观察BMSC移植对慢性哮喘小鼠气道炎症和气道重塑的影响,并采用流式细胞术检测BMSC对脾组织CD4+CD25+调节性T细胞比例的影响.结果 哮喘模型组支气管上皮黏膜脱落,上皮黏膜有杯状细胞增生,部分管腔内有黏液栓塞,气道、血管旁有大量炎件浸润,以及气道平滑肌细胞增生和肥大.正常对照组及BMSC对照组无气道炎症及气道重塑的表现,而BMSC治疗组气道炎症及气道重塑明显减轻.与BMSC对照组及正常对照组比较,哮喘模型组CD4+CD25+调节性T细胞占淋巴细胞的比例显著降低(P<0.05);与哮喘模型组比较,BMSC治疗组CD4+CD25+调节性T细胞占淋巴细胞的比例明显提高(P<0.05);BMSC治疗组与正常对照组及BMSC对照组无显著差异.结论 BMSC移植能明显减轻慢性哮喘小鼠气道炎症及气道重塑程度,并能上调外周CD4+CD25+调节性T细胞的比例.%Objective To investigate the effect of allogeneic bone marrow-derived mesenchymal stem cells (BMSCs) transplantation on the airway inflammation and airway remodeling in chronic asthmatic mice. Methods Forty female BALB/c mice were equally randomized into four groups,ie. a normal control group,a BMSCs control group,an asthma model group, and a BMSCs transplantation group. BMSCs were generated from male donor mice, then the mice in the asthma model group and the BMSCs transplantation group were sensitized and challenged with OVA to establish chronic asthmatic mice model. Hematoxylin and eosin staining and Alcian blue-periodic acid-Schiff staining were used to analyze the effects on airway inflammation and airway remodeling after BMSC engraftment. The number of

  17. Preliminary study on reversing airway remodeling in asthmatic mice by bone marrow mesenchymal stem cells and its mechanism%骨髓间充质干细胞逆转支气管哮喘小鼠气道重塑及其机制的初步研究

    Institute of Scientific and Technical Information of China (English)

    刘仕欣; 颛孙永勋; 谭磊

    2016-01-01

    目的:探讨骨髓间充质干细胞逆转支气管哮喘(简称哮喘)小鼠气道炎症及对气道重塑的影响。方法采用40只雄性的 BALB/c 小鼠,随机分组为骨髓间充质干细胞对照组、骨髓间充质干细胞治疗组、哮喘模型组、正常对照组。从4周龄雄性小鼠中分离出骨髓间充质干细胞。应用卵白蛋白制备慢性哮喘小鼠模型,采用流式细胞计数法检测小鼠外周血中 CD4+、CD25+调节性 T 细胞的情况,并观察骨髓间充质干细胞抑制之后气道的重塑及气道炎症的情况。结果病理检查可见哮喘模型支气管上皮黏膜有杯状细胞增生,上皮黏膜脱落,部分管腔有大量的炎性细胞浸润,气道平滑肌细胞肥大增生。正常对照组与骨髓间充质干细胞对照组无气道重塑及炎症表现,而骨髓间充质干细胞治疗组有气道炎症并且气道重塑现象明显。哮喘模型组的 CD4+、CD25+调节性 T 细胞比例较骨髓间充质干细胞对照组及正常对照组明显降低(F =12.346、14.528,P 值均<0.05);骨髓间充质干细胞治疗组 CD4+、CD25+调节性 T 细胞比例较哮喘组明显上升(F =9.438,P <0.05);而骨髓间充质干细胞治疗组、骨髓间充质干细胞对照组、正常对照组之间差异无统计学意义。结论骨髓间充质干细胞可逆转哮喘小鼠的气道炎症和气道重塑的程度,是通过上调 CD4+、CD25+调节性 T 细胞的比例发挥作用的。%Objective To investigate the effect of bone marrow mesenchymal stem cells(MSCs)to reverse asthmatic mice airway inflammation and airway remodeling.Methods Forty male BALB/c mice were randomly divided into MSCs control group,MSCs treatment group,asthma model group and normal control group.MSCs were isolated from 4-week-old male mice.The chronic asthma mouse model was made by ovalbumin.The regulatory T cells CD4 + ,CD25 + in peripheral blood were detected by flow cytometry.And to observe the situation of airway

  18. Tooth loss and alveolar remodeling in Sinosaurus triassicus (Dinosauria: Theropoda) from the Lower Jurassic strata of the Lufeng Basin, China

    Institute of Scientific and Technical Information of China (English)

    XING LiDa; BELL Phil R; ROTHSCHILD Bruce M; RAN Hao; ZHANG JianPing; DONG ZhiMing; ZHANG Wei

    2013-01-01

    Pathological or traumatic loss of teeth often results in the resorption and remodeling of the affected alveoli in mammals.However,instances of alveolar remodeling in reptiles are rare.A remodeled alveolus in the maxilla of the Chinese theropod Sinosaurus (Lower Jurassic Lower Lufeng Formation) is the first confirmed example of such dental pathology in a dinosaur.Given the known relationship between feeding behavior and tooth damage in theropods (teeth with spalled enamel,tooth crowns embedded in bone) and the absence of dentary,maxillary,and premaxillary osteomyelitis,traumatic loss of a tooth is most likely the cause of alveolar remodeling.Based on the extent of remodeling,the injury and subsequent tooth loss were non-fatal in this individual.

  19. Scintigraphic dynamics valuation of bone metastasis in the course of the treatment of 153Sm-oksabifor

    International Nuclear Information System (INIS)

    In the present study we examined the role of bone scan with 99mTc-pyrophosphate treatment planning 153Sm-oksabifor followed by analysis of post-treatment monitoring of cancer patients with bone metastases

  20. Distinct Characteristics of Mandibular Bone Collagen Relative to Long Bone Collagen: Relevance to Clinical Dentistry

    Directory of Open Access Journals (Sweden)

    Takashi Matsuura

    2014-01-01

    Full Text Available Bone undergoes constant remodeling throughout life. The cellular and biochemical mechanisms of bone remodeling vary in a region-specific manner. There are a number of notable differences between the mandible and long bones, including developmental origin, osteogenic potential of mesenchymal stem cells, and the rate of bone turnover. Collagen, the most abundant matrix protein in bone, is responsible for determining the relative strength of particular bones. Posttranslational modifications of collagen, such as intermolecular crosslinking and lysine hydroxylation, are the most essential determinants of bone strength, although the amount of collagen is also important. In comparison to long bones, the mandible has greater collagen content, a lower amount of mature crosslinks, and a lower extent of lysine hydroxylation. The great abundance of immature crosslinks in mandibular collagen suggests that there is a lower rate of cross-link maturation. This means that mandibular collagen is relatively immature and thus more readily undergoes degradation and turnover. The greater rate of remodeling in mandibular collagen likely renders more flexibility to the bone and leaves it more suited to constant exercise. As reviewed here, it is important in clinical dentistry to understand the distinctive features of the bones of the jaw.

  1. Changes in Bone Alkaline Phosphatase and Procollagen Type-1 C-Peptide after Static and Dynamic Exercises

    Science.gov (United States)

    Kubo, Keitaro; Yuki, Kazuhito; Ikebukuro, Toshihiro

    2012-01-01

    We investigated the effects of two types of nonweight-bearing exercise on changes in bone-specific alkaline phosphatase (BAP) and pro-collagen type 1 C-peptide (P1P). BAP is a specific marker of bone synthesis, whereas P1P reflects synthesis of type 1 collagen in other organs as well as bone. Eight participants performed static and dynamic…

  2. A Novel Algorithm to Quantify Coronary Remodeling Using Inferred Normal Dimensions

    Directory of Open Access Journals (Sweden)

    Breno A. A. Falcão

    2015-01-01

    Full Text Available Background:Vascular remodeling, the dynamic dimensional change in face of stress, can assume different directions as well as magnitudes in atherosclerotic disease. Classical measurements rely on reference to segments at a distance, risking inappropriate comparison between dislike vessel portions.Objective:to explore a new method for quantifying vessel remodeling, based on the comparison between a given target segment and its inferred normal dimensions.Methods:Geometric parameters and plaque composition were determined in 67 patients using three-vessel intravascular ultrasound with virtual histology (IVUS-VH. Coronary vessel remodeling at cross-section (n = 27.639 and lesion (n = 618 levels was assessed using classical metrics and a novel analytic algorithm based on the fractional vessel remodeling index (FVRI, which quantifies the total change in arterial wall dimensions related to the estimated normal dimension of the vessel. A prediction model was built to estimate the normal dimension of the vessel for calculation of FVRI.Results:According to the new algorithm, “Ectatic” remodeling pattern was least common, “Complete compensatory” remodeling was present in approximately half of the instances, and “Negative” and “Incomplete compensatory” remodeling types were detected in the remaining. Compared to a traditional diagnostic scheme, FVRI-based classification seemed to better discriminate plaque composition by IVUS-VH.Conclusion:Quantitative assessment of coronary remodeling using target segment dimensions offers a promising approach to evaluate the vessel response to plaque growth/regression.

  3. Matrix Remodeling in Pulmonary Fibrosis and Emphysema.

    Science.gov (United States)

    Kulkarni, Tejaswini; O'Reilly, Philip; Antony, Veena B; Gaggar, Amit; Thannickal, Victor J

    2016-06-01

    Pulmonary fibrosis and emphysema are chronic lung diseases characterized by a progressive decline in lung function, resulting in significant morbidity and mortality. A hallmark of these diseases is recurrent or persistent alveolar epithelial injury, typically caused by common environmental exposures such as cigarette smoke. We propose that critical determinants of the outcome of the injury-repair processes that result in fibrosis versus emphysema are mesenchymal cell fate and associated extracellular matrix dynamics. In this review, we explore the concept that regulation of mesenchymal cells under the influence of soluble factors, in particular transforming growth factor-β1, and the extracellular matrix determine the divergent tissue remodeling responses seen in pulmonary fibrosis and emphysema. PMID:26741177

  4. Three dimensional assessment of condylar surface changes and remodeling after orthognathic surgery

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Hye; Lee, Jin Woo; Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul [Dental Research Institute, Seoul National University, Seoul (Korea, Republic of); Shin, Jae Myung [Dept. of Oral and Maxillofacial Surgery, Ilsan Paik Hospital, Inje University College of Medicine, Goyang (Korea, Republic of)

    2016-03-15

    This study was performed to evaluate condylar surface changes and remodeling after orthognathic surgery using three-dimensional computed tomography (3D CT) imaging, including comparisons between the right and left sides and between the sexes. Forty patients (20 males and 20 females) who underwent multi-detector CT examinations before and after surgery were selected. Three-dimensional images comprising thousands of points on the condylar surface were obtained before and after surgery. For the quantitative assessment of condylar surface changes, point-to-point (preoperative-to-postoperative) distances were calculated using D processing software. These point-to-point distances were converted to a color map. In order to evaluate the types of condylar remodeling, the condylar head was divided into six areas (anteromedial, anteromiddle, anterolateral, posteromedial, posteromiddle, and posterolateral areas) and each area was classified into three types of condylar remodeling (bone formation, no change, and bone resorption) based on the color map. Additionally, comparative analyses were performed between the right and left sides and according to sex. The mean of the average point-to-point distances on condylar surface was 0.11±0.03 mm. Bone resorption occurred more frequently than other types of condylar remodeling, especially in the lateral areas. However, bone formation in the anteromedial area was particularly prominent. No significant difference was found between the right and left condyles, but condylar surface changes in males were significantly larger than in females. This study revealed that condylar remodeling exhibited a tendency towards bone resorption, especially in the lateral areas. Condylar surface changes occurred, but were small.

  5. The molecular clock mediates leptin-regulated bone formation.

    Science.gov (United States)

    Fu, Loning; Patel, Millan S; Bradley, Allan; Wagner, Erwin F; Karsenty, Gerard

    2005-09-01

    The hormone leptin is a regulator of bone remodeling, a homeostatic function maintaining bone mass constant. Mice lacking molecular-clock components (Per and Cry), or lacking Per genes in osteoblasts, display high bone mass, suggesting that bone remodeling may also be subject to circadian regulation. Moreover, Per-deficient mice experience a paradoxical increase in bone mass following leptin intracerebroventricular infusion. Thus, clock genes may mediate the leptin-dependent sympathetic regulation of bone formation. We show that expression of clock genes in osteoblasts is regulated by the sympathetic nervous system and leptin. Clock genes mediate the antiproliferative function of sympathetic signaling by inhibiting G1 cyclin expression. Partially antagonizing this inhibitory loop, leptin also upregulates AP-1 gene expression, which promotes cyclin D1 expression, osteoblast proliferation, and bone formation. Thus, leptin determines the extent of bone formation by modulating, via sympathetic signaling, osteoblast proliferation through two antagonistic pathways, one of which involves the molecular clock.

  6. The Rho-GEF Kalirin regulates bone mass and the function of osteoblasts and osteoclasts

    OpenAIRE

    Huang, Su; Pierre P. Eleniste; Wayakanon, Kornchanok; Mandela, Prashant; Eipper, Betty A.; Mains, Richard E.; Allen, Matthew R; Bruzzaniti, Angela

    2013-01-01

    Bone homeostasis is maintained by the balance between bone resorption by osteoclasts and bone formation by osteoblasts. Dysregulation in the activity of the bone cells can lead to osteoporosis, a disease characterized by low bone mass and an increase in bone fragility and risk of fracture. Kalirin is a novel GTP-exchange factor protein that has been shown to play a role in cytoskeletal remodeling and dendritic spine formation in neurons. We examined Kalirin expression in skeletal tissue and f...

  7. Emerging strategies and therapies for treatment of Paget’s disease of bone

    OpenAIRE

    Brown, Jacques P.

    2011-01-01

    Laëtitia Michou, Jacques P BrownLaval University, Department of Medicine, CHUQ (CHUL) Research Centre and Division of Rheumatology, Quebec City, QC, CanadaAbstract: Paget’s disease of bone (PDB) is a progressive monostotic or polyostotic metabolic bone disease characterized by focal abnormal bone remodeling, with increased bone resorption and excessive, disorganized, new bone formation. PDB rarely occurs before middle age, and it is the second most frequent metabolic bone d...

  8. Diabetes mellitus related bone metabolism and periodontal disease

    Institute of Scientific and Technical Information of China (English)

    Ying-Ying Wu; E Xiao; Dana T Graves

    2015-01-01

    Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts.

  9. Bone Biopsy

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Bone Biopsy Bone biopsy uses a needle and imaging guidance ... limitations of Bone Biopsy? What is a Bone Biopsy? A bone biopsy is an image-guided procedure ...

  10. Bone Diseases

    Science.gov (United States)

    ... avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds ... break Osteogenesis imperfecta makes your bones brittle Paget's disease of bone makes them weak Bones can also ...

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

    Directory of Open Access Journals (Sweden)

    Tae-Ho Kim

    2016-01-01

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

  12. Bone Metabolism on ISS Missions

    Science.gov (United States)

    Smith, S. M.; Heer, M. A.; Shackelford, L. C.; Zwart, S. R.

    2014-01-01

    Spaceflight-induced bone loss is associated with increased bone resorption (1, 2), and either unchanged or decreased rates of bone formation. Resistive exercise had been proposed as a countermeasure, and data from bed rest supported this concept (3). An interim resistive exercise device (iRED) was flown for early ISS crews. Unfortunately, the iRED provided no greater bone protection than on missions where only aerobic and muscular endurance exercises were available (4, 5). In 2008, the Advanced Resistive Exercise Device (ARED), a more robust device with much greater resistance capability, (6, 7) was launched to the ISS. Astronauts who had access to ARED, coupled with adequate energy intake and vitamin D status, returned from ISS missions with bone mineral densities virtually unchanged from preflight (7). Bone biochemical markers showed that while the resistive exercise and adequate energy consumption did not mitigate the increased bone resorption, bone formation was increased (7, 8). The typical drop in circulating parathyroid hormone did not occur in ARED crewmembers. In 2014, an updated look at the densitometry data was published. This study confirmed the initial findings with a much larger set of data. In 42 astronauts (33 male, 9 female), the bone mineral density response to flight was the same for men and women (9), and those with access to the ARED did not have the typical decrease in bone mineral density that was observed in early ISS crewmembers with access to the iRED (Figure 1) (7). Biochemical markers of bone formation and resorption responded similarly in men and women. These data are encouraging, and represent the first in-flight evidence in the history of human space flight that diet and exercise can maintain bone mineral density on long-duration missions. However, the maintenance of bone mineral density through bone remodeling, that is, increases in both resorption and formation, may yield a bone with strength characteristics different from those

  13. Osteoporosis: Modern Paradigms for Last Century’s Bones

    OpenAIRE

    Kruger, Marlena C.; Wolber, Frances M.

    2016-01-01

    The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a “brittle bone” disease that occurs in post-menopausal, thin, Caucasian women wi...

  14. The contribution of experimental in vivo models to understanding the mechanisms of adaptation to mechanical loading in bone

    Directory of Open Access Journals (Sweden)

    Lee B Meakin

    2014-10-01

    Full Text Available Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading.Jiri Heřt introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gauges to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced.Experiments combining strain gauge instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats and mice has yielded significant insight into the control of strain-related adaptive (remodeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice which is now the model of choice for many studies. Together such studies have demonstrated that; over the physiological strain range, bone’s mechanically-adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles and that these are most effective when interrupted by short periods of

  15. The human tri-peptide GHK and tissue remodeling.

    Science.gov (United States)

    Pickart, Loren

    2008-01-01

    Tissue remodeling follows the initial phase of wound healing and stops inflammatory and scar-forming processes, then restores the normal tissue morphology. The human peptide Gly-(L-His)-(L-Lys) or GHK, has a copper 2+ (Cu(2+)) affinity similar to the copper transport site on albumin and forms GHK-Cu, a complex with Cu(2+). These two molecules activate a plethora of remodeling related processes: (1) chemoattraction of repair cells such as macrophages, mast cells, capillary cells; (2) anti-inflammatory actions (suppression of free radicals, thromboxane formation, release of oxidizing iron, transforming growth factor beta-1, tumor necrosis factor alpha and protein glycation while increasing superoxide dismutase, vessel vasodilation, blocking ultraviolet damage to skin keratinocytes and improving fibroblast recovery after X-ray treatments); (3) increases protein synthesis of collagen, elastin, metalloproteinases, anti-proteases, vascular endothelial growth factor, fibroblast growth factor 2, nerve growth factor, neutrotropins 3 and 4, and erythropoietin; (4) increases the proliferation of fibroblasts and keratinocytes; nerve outgrowth, angiogenesis, and hair follicle size. GHK-Cu stimulates wound healing in numerous models and in humans. Controlled studies on aged skin demonstrated that it tightens skin, improves elasticity and firmness, reduces fine lines, wrinkles, photodamage and hyperpigmentation. GHK-Cu also improves hair transplant success, protects hepatic tissue from tetrachloromethane poisoning, blocks stomach ulcer development, and heals intestinal ulcers and bone tissue. These results are beginning to define the complex biochemical processes that regulate tissue remodeling. PMID:18644225

  16. Bone histomorphometry after treatment with teriparatide (PTH 1-34) in a patient with adynamic bone disease subsequent to parathyroidectomy

    OpenAIRE

    Lehmann, Gabriele; Ott, Undine; Maiwald, Jörg; Wolf, Gunter

    2008-01-01

    A 33-year-old male patient suffered from adynamic bone disease because of parathyroidectomy due to tertiary hyperparathyroidism. Histomorphometric analysis of bone biopsies taken before and 8 months after treatment with teriparatide (human parathyroid hormone 1-34 of recombinant DNA origin) for 18 months is demonstrated. A considerable increase in mineralized bone volume and also stimulated bone remodelling were detected after treatment with teriparatide. Although teriparatide is currently on...

  17. Role of bone morphogenetic protein 2 in early acetabulum development and dysplastic acetabulum remodeling%BMP-2在髋臼软骨发育早期及发育不良髋臼软骨可逆性恢复过程中的作用研究

    Institute of Scientific and Technical Information of China (English)

    莫越强; 裴新红; 马瑞雪

    2015-01-01

    目的 研究BMP-2在髋臼软骨发育早期及发育不良髋臼软骨可逆性恢复过程中的作用.方法 通过伸髋内收、模拟襁褓体位固定新生大鼠双后肢,建立发育不良髋臼软骨模型.将髋臼标本经HE染色后观察比较正常及发育不良髋臼软骨组织形态学变化特点,同时用ELISA方法和PCR方法分别检测BMP-2、BMP-4、BMP-6、BMP-7的分泌及基因表达情况.将捆绑不同时间后的大鼠松绑,其中部分当场处死,其余大鼠继续喂养,最终至30日龄,建立发育不良髋臼软骨可逆性恢复模型.研究其髋臼软骨组织形态学恢复及BMP-2分泌变化情况.结果 正常大鼠髋臼软骨呈半圆形、容积大、表面光滑.发育不良髋臼软骨髋臼上缘肥厚,软骨发生变性,与周围组织分界不清.髋臼软骨BMP-2的分泌在正常大鼠7日龄和9日龄时出现高峰,分别为(13.7±0.29) ng/ml和(13.9±0.38) ng/ml.而在发育不良髋臼软骨中这一分泌高峰消失.在发育不良髋臼软骨可逆性恢复组,捆绑4d和6d的大鼠,BMP-2的分泌高峰出现延迟,都在15日龄时出现;而在捆绑8d及以上的大鼠,在松绑后继续喂养至30日龄,髋臼软骨组织形态无法恢复正常,并且BMP-2的分泌高峰未出现.结论 BMP-2的分泌可能是髋臼软骨早期发育情况的生物学标记之一.%Objective To explore the early-stage acetabulum development in normal and dysplastic acetabula and elucidate the function of bone morphogenetic protein 2 (BMP-2) in early acetabulum development and dysplastic acetabulum remodeling.Methods The rat model of dysplastic acetabulum was established by maintaining hips in a swaddling position.By analyzing the cartilage histologic characteristics,early-stage acetabulum developments were examined in normal and dysplastic acetabulum animals.Meantime,the mRNA expression and chondrocyte secretion of functional BMP-2,bone morphogenetic protein 4 (BMP-4),bone morphogenetic protein 6 (BMP-6) and bone

  18. Cardiac Remodeling After Atrial Fibrillation Ablation

    Directory of Open Access Journals (Sweden)

    Li-Wei Lo, MD; Shih-Ann Chen, MD

    2013-06-01

    Full Text Available Radiofrequency catheter ablation procedures are considered a reasonable option for patients with symptomatic, drug refractory atrial fibrillation (AF. Ablation procedures have been reported to effectively restore sinus rhythm and provide long-term relief of symptoms. Both electrical and structural remodeling occurs with AF. A reversal of the electrical remodeling develops within 1 week after restoration to sinus rhythm following the catheter ablation. The recovery rate is faster in the right atrium than the left atrium. Reverse structural remodeling takes longer and is still present 2 to 4 months after restoration of sinus rhythm. The left atrial transport function also improves after successful catheter ablation of AF. Left atrial strain surveys from echocardiography are able to identify patients who respond to catheter ablation with significant reverse remodeling after ablation. Pre-procedural delayed enhancement magnetic resonance imaging is also able to determine the degree of atrial fibrosis and is another tool to predict the reverse remodeling after ablation. The remodeling process is complex if recurrence develops after ablation. Recent evidence shows that a combined reverse electrical and structural remodeling occurs after ablation of chronic AF when recurrence is paroxysmal AF. Progressive electrical remodeling without any structural remodeling develops in those with recurrence involving chronic AF. Whether progressive atrial remodeling is the cause or consequence during the recurrence of AF remains obscure and requires further study.

  19. Lung tissue remodeling in the acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Souza Alba Barros de

    2003-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS is characterized by diffuse alveolar damage, and evolves progressively with three phases: exsudative, fibroproliferative, and fibrotic. In the exudative phase, there are interstitial and alveolar edemas with hyaline membrane. The fibropro­liferative phase is characterized by exudate organization and fibroelastogenesis. There is proliferation of type II pneumocytes to cover the damaged epithelial surface, followed by differentiation into type I pneumocytes. The fibroproliferative phase starts early, and its severity is related to the patient?s prognosis. The alterations observed in the phenotype of the pulmonary parenchyma cells steer the tissue remodeling towards either progressive fibrosis or the restoration of normal alveolar architecture. The fibrotic phase is characterized by abnormal and excessive deposition of extracellular matrix proteins, mainly collagen. The dynamic control of collagen deposition and degradation is regulated by metalloproteinases and their tissular regulators. The deposition of proteoglycans in the extracellular matrix of ARDS patients needs better study. The regulation of extracellular matrix remodeling, in normal conditions or in several pulmonary diseases, such as ARDS, results from a complex mechanism that integrate the transcription of elements that destroy the matrix protein and produce activation/inhibition of several cellular types of lung tissue. This review article will analyze the ECM organization in ARDS, the different pulmonary parenchyma remodeling mechanisms, and the role of cytokines in the regulation of the different matrix components during the remodeling process.

  20. The effects of dynamic and three-dimensional environments on chondrogenic differentiation of bone marrow stromal cells

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Youngmee; Kim, Sang-Heon; Kim, Soo Hyun [Biomaterials Research Center, Korea Institute of Science and Technology, PO Box 131, Cheonryang, Seoul, 130-650 (Korea, Republic of); Kim, Young Ha, E-mail: soohkim@kist.re.k [Department of Materials Science and Engineering, Gwangju Institute of Science and Technology, 261 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712 (Korea, Republic of)

    2009-10-15

    Articular cartilage is subjected to complex loading, which plays a major role in its growth, development and maintenance. Previously, we found that mechanical stimuli enhanced the development and function of engineered cartilage tissues in elastic mechano-active poly(lactide-co-caprolactone) (PLCL) scaffolds. In addition, it is well known that the three-dimensional spatial organization of cells and extracellular matrices in hydrogels is crucial to chondrogenesis. This study was conducted to enhance the chondrogenic differentiation of bone marrow stromal cells (BMSCs) in the hybrid scaffolds of fibrin gels and PLCL scaffolds in dynamic environments by compression. A highly elastic scaffold was fabricated from very elastic PLCL with 85% porosity and a 300-500{mu}m pore size using a gel-pressing method. A mixture of rabbit BMSCs and fibrin gels was then seeded onto the PLCL scaffolds and subjected to continuous compressive deformation of 5% strain at 0.1 Hz for 10 days in a chondrogenic medium containing 10 ng ml{sup -1} TGF-beta{sub 1}. The BMSCs-seeded scaffold constructs were then implanted subcutaneously into nude mice. As a control, the cell-PLCL scaffold constructs were cultured under dynamic conditions or the cell-PLCL/fibrin hybrid scaffold constructs and the cell-PLCL scaffold constructs were cultured under static conditions for 10 days in vitro. The results revealed that cells adhered onto the hybrid scaffolds of fibrin gels and PLCL scaffolds cultured under dynamic conditions. In addition, the accumulation of the extracellular matrix of cell-scaffold constructs, which was increased through mechanical stimulation, showed that chondrogenic differentiation was sustained and enhanced significantly in the stimulated hybrid scaffold constructs. Overall, the results of this study indicate that the proper periodic application of dynamic compression and the three-dimensional environments of the hybrid scaffolds composed of fibrin gels and elastic PLCL can encourage

  1. Remodelling the vascular microenvironment of glioblastoma with alpha-particles

    Science.gov (United States)

    Behling, Katja; Maguire, William F.; Di Gialleonardo, Valentina; Heeb, Lukas E.M.; Hassan, Iman F.; Veach, Darren R.; Keshari, Kayvan R.; Gutin, Philip H.; Scheinberg, David A.; McDevitt, Michael R.

    2016-01-01

    Rationale Tumors escape anti-angiogenic therapy by activation of pro-angiogenic signaling pathways. Bevacizumab is approved for the treatment of recurrent glioblastoma, but patients inevitably develop resistance to this angiogenic inhibitor. We investigated targeted α-particle therapy with 225Ac-E4G10 as an anti-vascular approach and previously showed increased survival and tumor control in a high-grade transgenic orthotopic glioblastoma model. Here we investigate changes in tumor-vascular morphology and functionality caused by 225Ac-E4G10. Methods We investigated remodeling of tumor microenvironment in transgenic Ntva glioblastoma mice using a therapeutic 7.4 kBq dose of 225Ac-E4G10. Immunofluorescence and immunohistochemical analyses imaged morphological changes in the tumor blood brain barrier microenvironment. Multi-color flow cytometry quantified the endothelial progenitor cell population in the bone marrow. Diffusion-weighted magnetic resonance imaged functional changes of the tumor vascular network. Results The mechanism of drug action is a combination of glioblastoma vascular microenvironment remodeling, edema relief, and depletion of regulatory T and endothelial progenitor cells. The primary remodeling event is the reduction of both endothelial and perivascular cell populations. Tumor-associated edema and necrosis was lessened and resulted in increased perfusion and reduced diffusion. Pharmacological uptake of dasatinib into tumor was enhanced following α-particle therapy. Conclusion Targeted anti-vascular α-particle radiation remodels the glioblastoma vascular microenvironment via a multimodal mechanism of action and provides insight into the vascular architecture of Platelet-derived growth factor driven glioblastoma. PMID:27261519

  2. Gender differences in cardiac hypertrophic remodeling.

    Science.gov (United States)

    Patrizio, Mario; Marano, Giuseppe

    2016-01-01

    Cardiac remodeling is a complex process that occurs in response to different types of cardiac injury such as ischemia and hypertension, and that involves cardiomyocytes, fibroblasts, vascular smooth muscle cells, vascular endothelial cells, and inflammatory cells. The end result is cardiomyocyte hypertrophy, fibrosis, inflammation, vascular, and electrophysiological remodeling. This paper reviews a large number of studies on the influence of gender on pathological cardiac remodeling and shows how sex differences result in different clinical outcomes and therapeutic responses, with males which generally develop greater cardiac remodeling responses than females. Although estrogens appear to have an important role in attenuating adverse cardiac remodeling, the mechanisms through which gender modulates myocardial remodeling remain to be identified. PMID:27364397

  3. Remodeling patterns of occipital growth: a preliminary report.

    Science.gov (United States)

    Kranioti, Elena F; Rosas, Antonio; García-Vargas, Samuel; Estalrrich, Almudena; Bastir, Markus; Peña-Melián, Angel

    2009-11-01

    Occipital growth depends on coordinated deposition and resorption on the external and internal surface and includes interrelated processes of movement: cortical drift, displacement, and relocation. The current work aspires to map patterns of remodeling activity on the endocranial surface of the occipital bone from childhood to adulthood using a larger study sample compared with previous studies. The study sample consists of 5 adult and 10 immature (2(1/4) to 8 years old) occipital bones from skeletal remains from the eighteenth and nineteenth century. Preparation of the samples includes the elaboration of negative impressions, positive replicas coated with gold, and observed with the reflected light microscope. Cerebellar fossae are typically resorptive in both immature and adult specimens. Cerebral fossae, on the other hand, exhibit a resorptive surface in early childhood and turn into depository around the age of 7 years, which places this transition within the age interval of the completion of cerebral development. Depository fields are also observed in adult cerebral fossae. The remodeling map presented here is consistent with the results of Mowbray (Anat Rec B New Anat 2005;283B:14-22) and differs from cellular patterns described by Enlow. Future research implicating more elements of the neurocapsule can shed light on the factors affecting and driving occipital growth.

  4. Dynamic MRI of ferumoxide-labeled bone mesenchmal stem cells after transplantation in infarcted myocardium

    International Nuclear Information System (INIS)

    Objective: To investigate the ability of magnetic resonance imaging (MRI) in tracking magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model. Methods: Adult Chinese mini-pigs (n=6) were subjected to open-chest experimental MI operation. Their autogeneic bone marrow-derived mesenchymal stem cells (MSCs) was cultured and doubly labeled with ferumoxides and DAPI. On the 14 th day after MSCs transplantation, the size and location of the myocardial infarction were assessed by using delayed-enhancement MRI (DE-MRI). Then the labeled MSCs were injected intramyocardially into peri-infarct zone and normal myocardium. At 24 hrs and 3 weeks after injection, the contrast and the volume of the MR-MSCs hypointense lesion from the MR images were acquired, and the contrast was determined using the difference in signal intensity between the hypointense and normal myocardium divided by signal intensity of the normal region. After humane euthanasia, the heart was excised and histology corresponding to MRI slices that demonstrated MR-MSCs lesions was performed. Repeated-measures ANOVA and a paired t test were used for comparison of the contrast and the volume of the MR-MSCs hypointense lesion at different time points. Comparisons between independent groups were performed with the standard Student t test. Results: The labeling efficiency of ferumoxides and DAPI was 100%. On the 14 th day after the MI operation, the average percentage of infracted myocardial area was (33.6±8.9)%. Twenty- four hours after MSCs transplantation, MSCs injection sites appeared as ovoid hypointensive lesions with sharp border on T2* images. At 24 h after injection, the signal contrast [(67.00±5.48)% vs (61.92±7.76)%,t=1.65, P=0.1158] and the size [(0.56±0.24) cm2 vs (0.52±0.25) cm2, t=0.39, P=0.7044] of the lesions showed no statistical difference between the peri-infarct zone and the normal myocardium. At 3 weeks after injection, the signal contrast decreased

  5. Vitamin D and Bone Disease

    Directory of Open Access Journals (Sweden)

    S. Christodoulou

    2013-01-01

    Full Text Available Vitamin D is important for normal development and maintenance of the skeleton. Hypovitaminosis D adversely affects calcium metabolism, osteoblastic activity, matrix ossification, bone remodeling and bone density. It is well known that Vit. D deficiency in the developing skeleton is related to rickets, while in adults is related to osteomalacia. The causes of rickets include conditions that lead to hypocalcemia and/or hypophosphatemia, either isolated or secondary to vitamin D deficiency. In osteomalacia, Vit. D deficiency leads to impairment of the mineralisation phase of bone remodeling and thus an increasing amount of the skeleton being replaced by unmineralized osteoid. The relationship between Vit. D and bone mineral density and osteoporosis are still controversial while new evidence suggests that Vit. D may play a role in other bone conditions such as osteoarthritis and stress fractures. In order to maintain a “good bone health” guidelines concerning the recommended dietary intakes should be followed and screening for Vit. D deficiency in individuals at risk for deficiency is required, followed by the appropriate action.

  6. Alveolar bone loss in osteoporosis: a loaded and cellular affair?

    Science.gov (United States)

    Jonasson, Grethe; Rythén, Marianne

    2016-01-01

    Maxillary and mandibular bone mirror skeletal bone conditions. Bone remodeling happens at endosteal surfaces where the osteoclasts and osteoblasts are situated. More surfaces means more cells and remodeling. The bone turnover rate in the mandibular alveolar process is probably the fastest in the body; thus, the first signs of osteoporosis may be revealed here. Hormones, osteoporosis, and aging influence the alveolar process and the skeletal bones similarly, but differences in loading between loaded, half-loaded, and unloaded bones are important to consider. Bone mass is redistributed from one location to another where strength is needed. A sparse trabeculation in the mandibular premolar region (large intertrabecular spaces and thin trabeculae) is a reliable sign of osteopenia and a high skeletal fracture risk. Having dense trabeculation (small intertrabecular spaces and well-mineralized trabeculae) is generally advantageous to the individual because of the low fracture risk, but may imply some problems for the clinician.

  7. Alveolar bone loss in osteoporosis: a loaded and cellular affair?

    Science.gov (United States)

    Jonasson, Grethe; Rythén, Marianne

    2016-01-01

    Maxillary and mandibular bone mirror skeletal bone conditions. Bone remodeling happens at endosteal surfaces where the osteoclasts and osteoblasts are situated. More surfaces means more cells and remodeling. The bone turnover rate in the mandibular alveolar process is probably the fastest in the body; thus, the first signs of osteoporosis may be revealed here. Hormones, osteoporosis, and aging influence the alveolar process and the skeletal bones similarly, but differences in loading between loaded, half-loaded, and unloaded bones are important to consider. Bone mass is redistributed from one location to another where strength is needed. A sparse trabeculation in the mandibular premolar region (large intertrabecular spaces and thin trabeculae) is a reliable sign of osteopenia and a high skeletal fracture risk. Having dense trabeculation (small intertrabecular spaces and well-mineralized trabeculae) is generally advantageous to the individual because of the low fracture risk, but may imply some problems for the clinician. PMID:27471408

  8. A reversal phase arrest uncoupling the bone formation and resorption contributes to the bone loss in glucocorticoid treated ovariectomised aged sheep

    DEFF Research Database (Denmark)

    Andreasen, Christina Møller; Ding, Ming; Overgaard, Søren;

    2015-01-01

    Large animals as sheep are often used as models for human osteoporosis. Our aim was therefore to determine how glucocorticoid treatment of ovariectomised sheep affects the cancellous bone, determining the cellular events within the bone remodelling process that contributes to their bone loss. Twe...

  9. New simulation model for bone formation markers in osteoporosis patients treated with once-weekly teriparatide

    Institute of Scientific and Technical Information of China (English)

    Sakae Tanaka; Taiji Adachi; Tatsuhiko Kuroda; Toshitaka Nakamura; Masataka Shiraki; Toshitsugu Sugimoto; Yasuhiro Takeuchi; Mitsuru Saito; John P Bilezikian

    2014-01-01

    Daily 20-mg and once-weekly 56.5-mg teriparatide (parathyroid hormone 1–34) treatment regimens increase bone mineral density (BMD) and prevent fractures, but changes in bone turnover markers differ between the two regimens. The aim of the present study was to explain changes in bone turnover markers using once-weekly teriparatide with a simulation model. Temporary increases in bone formation markers and subsequent decreases were observed during once-weekly teriparatide treatment for 72 weeks. These observations support the hypothesis that repeated weekly teriparatide administration stimulates bone remodeling, replacing old bone with new bone and leading to a reduction in the active remodeling surface. A simulation model was developed based on the iterative remodeling cycle that occurs on residual old bone. An increase in bone formation and a subsequent decrease were observed in the preliminary simulation. For each fitted time point, the predicted value was compared to the absolute values of the bone formation and resorption markers and lumbar BMD. The simulation model strongly matched actual changes in bone turnover markers and BMD. This simulation model indicates increased bone formation marker levels in the early stage and a subsequent decrease. It is therefore concluded that remodeling-based bone formation persisted during the entire treatment period with once-weekly teriparatide.

  10. Combining experimental and mathematical modeling to reveal mechanisms of macrophage-dependent left ventricular remodeling

    Directory of Open Access Journals (Sweden)

    Dai Qiuxia

    2011-05-01

    Full Text Available Abstract Background Progressive remodeling of the left ventricle (LV following myocardial infarction (MI can lead to congestive heart failure, but the underlying initiation factors remain poorly defined. The objective of this study, accordingly, was to determine the key factors and elucidate the regulatory mechanisms of LV remodeling using integrated computational and experimental approaches. Results By examining the extracellular matrix (ECM gene expression and plasma analyte levels in C57/BL6J mice LV post-MI and ECM gene responses to transforming growth factor (TGF-β1 in cultured cardiac fibroblasts, we found that key factors in LV remodeling included macrophages, fibroblasts, transforming growth factor-β1, matrix metalloproteinase-9 (MMP-9, and specific collagen subtypes. We established a mathematical model to study LV remodeling post-MI by quantifying the dynamic balance between ECM construction and destruction. The mathematical model incorporated the key factors and demonstrated that TGF-β1 stimuli and MMP-9 interventions with different strengths and intervention times lead to different LV remodeling outcomes. The predictions of the mathematical model fell within the range of experimental measurements for these interventions, providing validation for the model. Conclusions In conclusion, our results demonstrated that the balance between ECM synthesis and degradation, controlled by interactions of specific key factors, determines the LV remodeling outcomes. Our mathematical model, based on the balance between ECM construction and destruction, provides a useful tool for studying the regulatory mechanisms and for predicting LV remodeling outcomes.

  11. Evaluation of bone substitute materials: comparison of flat-panel based volume CT to conventional multidetector CT.

    Science.gov (United States)

    Sauerbier, Sebastian; Duttenhoefer, Fabian; Sachlos, Elefterios; Haberstroh, Jörg; Scheifele, Christian; Wrbas, Karl-Thomas; Voss, Pit Jacob; Veigel, Egle; Smedek, Jörg; Ganter, Philip; Tuna, Taskin; Gutwald, Ralf; Palmowski, Moritz

    2013-10-01

    Over the last decade tissue engineering has emerged as a key factor in bone regeneration within the field of cranio-maxillofacial surgery. Despite this in vivo analysis of tissue-engineered-constructs to monitor bone rehabilitation are difficult to conduct. Novel high-resolving flat-panel based volume CTs (fp-VCT) are increasingly used for imaging bone structures. This study compares the potential value of novel fp-VCT with conventional multidetector CT (MDCT) based on a sheep sinus floor elevation model. Calcium-hydroxyapatite reinforced collagen scaffolds were populated with autologous osteoblasts and implanted into sheep maxillary sinus. After 8, 16 and 24 weeks MDCT and fp-VCT scans were performed to investigate the volume of the augmented area; densities of cancellous and compact bone were assessed as comparative values. fp-VCT imaging resulted in higher spatial resolution, which was advantageous when separating closely related anatomical structures (i.e. trabecular and compact bone, biomaterials). Fp-VCT facilitated imaging of alterations occurring in test specimens over time. fp-VCTs therefore displayed high volume coverage, dynamic imaging potential and superior performance when investigating superfine bone structures and bone remodelling of biomaterials. Thus, fp-VCTs may be a suitable instrument for intraoperative imaging and future in vivo tissue-engineering studies.

  12. Impact of cytomegalovirus and grafts versus host disease on the dynamics of CD57+CD28-CD8+ T cells after bone marrow transplant

    Directory of Open Access Journals (Sweden)

    Ana Verena Almeida Mendes

    2008-01-01

    Full Text Available OBJECTIVES: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients. METHODS: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with cytomegalovirus antigenemia assays. RESULTS: Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05. A linear regression model demonstrated a continuous decrease in CD28+ expression and a continuous increase in CD57+ expression after bone marrow transplant. The occurrence of cytomegalovirus antigenemia was associated with a steep drop in the percentage of CD28+ cells (5.94%, p<0.01 and an increase in CD57+ lymphocytes (5.60%, p<0.01. This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients. The development of acute graft versus host disease, which occurred at an earlier time than antigenemia (day 26 vs. day 56 post- bone marrow transplant, also had an impact on the CD57+ subset, triggering an increase of 4.9% in CD57+ lymphocytes (p<0.05. CONCLUSION: We found continuous relative changes in the CD28+ and CD57+ subsets during the first 120 days post- bone marrow transplant, as part of immune system reconstitution and maturation. A clear correlation was observed between the expansion of the CD57+CD28-CD8+ T lymphocyte subpopulation and the occurrence of graft versus host disease and cytomegalovirus viremia.

  13. Bone Grafts

    Science.gov (United States)

    ... repair and rebuild diseased bones in your hips, knees, spine, and sometimes other bones and joints. Grafts can also repair bone loss caused by some types of fractures or cancers. Once your body accepts the bone ...

  14. Thrombospondin-1 regulates bone homeostasis through effects on bone matrix integrity and nitric oxide signaling in osteoclasts

    OpenAIRE

    Sarah R Amend; Uluckan, Ozge; Hurchla, Michelle; Leib, Daniel; Novack, Deborah Veis; Silva, Matthew; Frazier, William; Weilbaecher, Katherine N.

    2015-01-01

    Thrombospondin-1 (TSP1), an endogenous antiangiogenic, is a widely expressed secreted ligand with roles in migration, adhesion and proliferation and is a target for new therapeutics. While TSP1 is present in the bone matrix and several TSP1 receptors play roles in bone biology, the role of TSP1 in bone remodeling has not been fully elucidated. Bone turnover is characterized by coordinated activity of bone-forming osteoblasts (OB) and bone-resorbing osteoclasts (OC). TSP1−/− mice had increased...

  15. Bone within a bone

    Energy Technology Data Exchange (ETDEWEB)

    Williams, H.J.; Davies, A.M. E-mail: wendy.turner@roh.nhs.uk; Chapman, S

    2004-02-01

    The 'bone within a bone' appearance is a well-recognized radiological term with a variety of causes. It is important to recognize this appearance and also to be aware of the differential diagnosis. A number of common conditions infrequently cause this appearance. Other causes are rare and some remain primarily of historical interest, as they are no longer encountered in clinical practice. In this review we illustrate some of the conditions that can give the bone within a bone appearance and discuss the physiological and pathological aetiology of each where known.

  16. Study of treating tibial large bone defect with migration of lengthened bone segment in goats

    Institute of Scientific and Technical Information of China (English)

    YANG liu; LI Qi-hong; ZHOU Zhong-an; TAN Zu-jian; PENG Yi-liang

    2001-01-01

    To study the effects of migration of lengthened bone segment (MLBS) on the blood circulation and repair remodeling process at the ends of large bone defect of a long bone. Methods: A total of 18 adult goats were used and more than 35% of the original length of their left tibia was resected. Upper metaphysiotomy to lengthen upper part of the tibia was done and the lengthened bone segment was migrated to repair the large bone defect. The results were observed with X-ray films, Chinese-ink permeated transparent sections and histological study. Results: After MLBS, the defect ends of the tibia were supplied with abundant blood circulation which resulted in rapid and solid long bone healing. Conclusion: Repair of large bone defect of long bones with MLBS provides a new method for clinical practice.

  17. Modelling the anabolic response of bone using a cell population model

    OpenAIRE

    Buenzli, Pascal R.; Pivonka, Peter; Gardiner, Bruce S.; Smith, David W.

    2011-01-01

    To maintain bone mass during bone remodelling, coupling is required between bone resorption and bone formation. This coordination is achieved by a network of autocrine and paracrine signalling molecules between cells of the osteoclast lineage and cells of the osteoblastic lineage. Mathematical modelling of signalling between cells of both lineages can assist in the interpretation of experimental data, clarify signalling interactions and help develop a deeper understanding of complex bone dise...

  18. Mechanistic, mathematical model to predict the dynamics of tissue genesis in bone defects via mechanical feedback and mediation of biochemical factors.

    Directory of Open Access Journals (Sweden)

    Shannon R Moore

    2014-06-01

    Full Text Available The link between mechanics and biology in the generation and the adaptation of bone has been well studied in context of skeletal development and fracture healing. Yet, the prediction of tissue genesis within - and the spatiotemporal healing of - postnatal defects, necessitates a quantitative evaluation of mechano-biological interactions using experimental and clinical parameters. To address this current gap in knowledge, this study aims to develop a mechanistic mathematical model of tissue genesis using bone morphogenetic protein (BMP to represent of a class of factors that may coordinate bone healing. Specifically, we developed a mechanistic, mathematical model to predict the dynamics of tissue genesis by periosteal progenitor cells within a long bone defect surrounded by periosteum and stabilized via an intramedullary nail. The emergent material properties and mechanical environment associated with nascent tissue genesis influence the strain stimulus sensed by progenitor cells within the periosteum. Using a mechanical finite element model, periosteal surface strains are predicted as a function of emergent, nascent tissue properties. Strains are then input to a mechanistic mathematical model, where mechanical regulation of BMP-2 production mediates rates of cellular proliferation, differentiation and tissue production, to predict healing outcomes. A parametric approach enables the spatial and temporal prediction of endochondral tissue regeneration, assessed as areas of cartilage and mineralized bone, as functions of radial distance from the periosteum and time. Comparing model results to histological outcomes from two previous studies of periosteum-mediated bone regeneration in a common ovine model, it was shown that mechanistic models incorporating mechanical feedback successfully predict patterns (spatial and trends (temporal of bone tissue regeneration. The novel model framework presented here integrates a mechanistic feedback system based

  19. Multiscale Simulation of Protein Mediated Membrane Remodeling

    OpenAIRE

    Ayton, Gary S.; Voth, Gregory A.

    2009-01-01

    Proteins interacting with membranes can result in substantial membrane deformations and curvatures. This effect is known in its broadest terms as membrane remodeling. This review article will survey current multiscale simulation methodologies that have been employed to examine protein-mediated membrane remodeling.

  20. Chromatin Remodelers: From Function to Dysfunction

    Directory of Open Access Journals (Sweden)

    Gernot Längst

    2015-06-01

    Full Text Available Chromatin remodelers are key players in the regulation of chromatin accessibility and nucleosome positioning on the eukaryotic DNA, thereby essential for all DNA dependent biological processes. Thus, it is not surprising that upon of deregulation of those molecular machines healthy cells can turn into cancerous cells. Even though the remodeling enzymes are very abundant and a multitude of different enzymes and chromatin remodeling complexes exist in the cell, the particular remodeling complex with its specific nucleosome positioning features must be at the right place at the right time in order to ensure the proper regulation of the DNA dependent processes. To achieve this, chromatin remodeling complexes harbor protein domains that specifically read chromatin targeting signals, such as histone modifications, DNA sequence/structure, non-coding RNAs, histone variants or DNA bound interacting proteins. Recent studies reveal the interaction between non-coding RNAs and chromatin remodeling complexes showing importance of RNA in remodeling enzyme targeting, scaffolding and regulation. In this review, we summarize current understanding of chromatin remodeling enzyme targeting to chromatin and their role in cancer development.

  1. Time Simulation of Bone Adaptation

    DEFF Research Database (Denmark)

    Bagge, Mette

    1998-01-01

    The structural adaptation of a three-dimensional finite element model ofthe proximal femur is considered. Presuming the bone possesses the optimalstructure under the given loads, the bone material distribution is foundby minimizing the strain energy averaged over ten load cases with avolume...... constraint. Theoptimized design is used as a start-configuration for the remodelingsimulation.The parameter characterizing the equilibrium level where no remodeling occurs is estimated from the optimization parameters.The loads vary in magnitude, location and direction simulating timedependent loading. The...

  2. Deletion of FGFR3 in Osteoclast Lineage Cells Results in Increased Bone Mass in Mice by Inhibiting Osteoclastic Bone Resorption.

    Science.gov (United States)

    Su, Nan; Li, Xiaogang; Tang, Yubin; Yang, Jing; Wen, Xuan; Guo, Jingyuan; Tang, Junzhou; Du, Xiaolan; Chen, Lin

    2016-09-01

    Fibroblast growth factor receptor 3 (FGFR3) participates in bone remodeling. Both Fgfr3 global knockout and activated mice showed decreased bone mass with increased osteoclast formation or bone resorption activity. To clarify the direct effect of FGFR3 on osteoclasts, we specifically deleted Fgfr3 in osteoclast lineage cells. Adult mice with Fgfr3 deficiency in osteoclast lineage cells (mutant [MUT]) showed increased bone mass. In a drilled-hole defect model, the bone remodeling of the holed area in cortical bone was also impaired with delayed resorption of residual woven bone in MUT mice. In vitro assay demonstrated that there was no significant difference between the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts derived from wild-type and Fgfr3-deficient bone marrow monocytes, suggesting that FGFR3 had no remarkable effect on osteoclast formation. The bone resorption activity of Fgfr3-deficient osteoclasts was markedly decreased accompanying with downregulated expressions of Trap, Ctsk, and Mmp 9. The upregulated activity of osteoclastic bone resorption by FGF2 in vitro was also impaired in Fgfr3-deficient osteoclasts, indicating that FGFR3 may participate in the regulation of bone resorption activity of osteoclasts by FGF2. Reduced adhesion but not migration in osteoclasts with Fgfr3 deficiency may be responsible for the impaired bone resorption activity. Our study for the first time genetically shows the direct positive regulation of FGFR3 on osteoclastic bone resorption. © 2016 American Society for Bone and Mineral Research.

  3. Estradiol increases hematopoietic stem and progenitor cells independent of its actions on bone

    NARCIS (Netherlands)

    Illing, Anett; Liu, Peng; Ostermay, Susanne; Schilling, Arndt; de Haan, Gerald; Krust, Andree; Amling, Michael; Chambon, Pierre; Schinke, Thorsten; Tuckermann, Jan P.

    2012-01-01

    Hematopoietic stem and progenitor cells reside in vascular and endosteal niches in the bone marrow. Factors affecting bone remodeling were reported to influence numbers and mobilization of hematopoietic stem cells. We therefore analyzed the effects of estradiol acting anabolic on bone integrity. Her

  4. Effect of chemokine receptor CXCR4 on hypoxia-induced pulmonary hypertension and vascular remodeling in rats

    Directory of Open Access Journals (Sweden)

    Hales Charles A

    2011-02-01

    Full Text Available Abstract Background CXCR4 is the receptor for chemokine CXCL12 and reportedly plays an important role in systemic vascular repair and remodeling, but the role of CXCR4 in development of pulmonary hypertension and vascular remodeling has not been fully understood. Methods In this study we investigated the role of CXCR4 in the development of pulmonary hypertension and vascular remodeling by using a CXCR4 inhibitor AMD3100 and by electroporation of CXCR4 shRNA into bone marrow cells and then transplantation of the bone marrow cells into rats. Results We found that the CXCR4 inhibitor significantly decreased chronic hypoxia-induced pulmonary hypertension and vascular remodeling in rats and, most importantly, we found that the rats that were transplanted with the bone marrow cells electroporated with CXCR4 shRNA had significantly lower mean pulmonary pressure (mPAP, ratio of right ventricular weight to left ventricular plus septal weight (RV/(LV+S and wall thickness of pulmonary artery induced by chronic hypoxia as compared with control rats. Conclusions The hypothesis that CXCR4 is critical in hypoxic pulmonary hypertension in rats has been demonstrated. The present study not only has shown an inhibitory effect caused by systemic inhibition of CXCR4 activity on pulmonary hypertension, but more importantly also has revealed that specific inhibition of the CXCR4 in bone marrow cells can reduce pulmonary hypertension and vascular remodeling via decreasing bone marrow derived cell recruitment to the lung in hypoxia. This study suggests a novel therapeutic approach for pulmonary hypertension by inhibiting bone marrow derived cell recruitment.

  5. Repair of microdamage in osteonal cortical bone adjacent to bone screw.

    Directory of Open Access Journals (Sweden)

    Lei Wang

    Full Text Available Up to date, little is known about the repair mode of microdamage in osteonal cortical bone resulting from bone screw implantation. In this study, self-tapping titanium cortical bone screws were inserted into the tibial diaphyses of 24 adult male rabbits. The animals were sacrificed at 1 day, 2 weeks, 1 month and 2 months after surgery. Histomorphometric measurement and confocal microscopy were performed on basic fuchsin stained bone sections to examine the morphological characteristics of microdamage, bone resorption activity and spatial relationship between microdamage and bone resorption. Diffuse and linear cracks were coexisted in peri-screw bone. Intracortical bone resorption was significantly increased 2 weeks after screw installation and reach to the maximum at 1 month. There was no significant difference in bone resorption between 1-month and 2-months groups. Microdamage was significantly decreased within 1 month after surgery. Bone resorption was predisposed to occur in the region of <100 µm from the bone-screw interface, where had extensive diffuse damage mixed with linear cracks. Different patterns of resorption cavities appeared in peri-screw bone. These data suggest that 1 the complex microdamage composed of diffuse damage and linear cracks is a strong stimulator for initiating targeted bone remodeling; 2 bone resorption activities taking place on the surfaces of differently oriented Haversian and Volkmann canals work in a team for the repair of extensive microdamage; 3 targeted bone remodeling is a short-term reaction to microdamage and thereby it may not be able to remove all microdamage resulting from bone screw insertion.

  6. Skeletal Blood Flow in Bone Repair and Maintenance

    Institute of Scientific and Technical Information of China (English)

    Ryan E.Tomlinson; Matthew J.Silva

    2013-01-01

    Bone is a highly vascularized tissue, although this aspect of bone is often overlooked. In this article, the importance of blood flow in bone repair and regeneration will be reviewed. First, the skeletal vascular anato-my, with an emphasis on long bones, the distinct mechanisms for vascularizing bone tissue, and methods for remodeling existing vasculature are discussed. Next, techniques for quantifying bone blood flow are briefly summarized. Finally, the body of experimental work that demonstrates the role of bone blood flow in fracture healing, distraction osteogenesis, osteoporosis, disuse osteopenia, and bone grafting is examined. These results illustrate that adequate bone blood flow is an important clinical consideration, particularly during bone regeneration and in at-risk patient groups.

  7. Bone microenvironment-mediated resistance of cancer cells to bisphosphonates and impact on bone osteocytes/stem cells.

    Science.gov (United States)

    Alasmari, Abeer; Lin, Shih-Chun; Dibart, Serge; Salih, Erdjan

    2016-08-01

    Anti-resorptive bisphosphonates (BPs) have been clinically used to prevent cancer-bone metastasis and cancer-induced bone pathologies despite the fact that the phenotypic response of the cancer-bone interactions to BP exposure is "uncharted territory". This study offers unique insights into the interplay between cancer stem cells and osteocytes/osteoblasts and mesenchymal stem cells using a three-dimensional (3D) live cancer-bone interactive model. We provide extraordinary cryptic details of the biological events that occur as a result of alendronate (ALN) treatment using 3D live cancer-bone model systems under specific bone remodeling stages. While cancer cells are susceptible to BP treatment in the absence of bone, they are totally unaffected in the presence of bone. Cancer cells colonize live bone irrespective of whether the bone is committed to bone resorption or formation and hence, cancer-bone metastasis/interactions are though to be "independent of bone remodeling stages". In our 3D live bone model systems, ALN inhibited bone resorption at the osteoclast differentiation level through effects of mineral-bound ALN on osteocytes and osteoblasts. The mineral-bound ALN rendered bone incapable of osteoblast differentiation, while cancer cells colonize the bone with striking morphological adaptations which led to a conclusion that a direct anti-cancer effect of BPs in a "live or in vivo" bone microenvironment is implausible. The above studies were complemented with mass spectrometric analysis of the media from cancer-bone organ cultures in the absence and presence of ALN. The mineral-bound ALN impacts the bone organs by limiting transformation of mesenchymal stem cells to osteoblasts and leads to diminished endosteal cell population and degenerated osteocytes within the mineralized bone matrix. PMID:27155840

  8. Bone tissue engineering: the role of interstitial fluid flow

    Science.gov (United States)

    Hillsley, M. V.; Frangos, J. A.

    1994-01-01

    It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.

  9. Pore network microarchitecture influences human cortical bone elasticity during growth and aging.

    Science.gov (United States)

    Bala, Yohann; Lefèvre, Emmanuelle; Roux, Jean-Paul; Baron, Cécile; Lasaygues, Philippe; Pithioux, Martine; Kaftandjian, Valérie; Follet, Hélène

    2016-10-01

    Cortical porosity is a major determinant of bone strength. Haversian and Volkmann׳s canals are׳seen' as pores in 2D cross-section but fashion a dynamic network of interconnected channels in 3D, a quantifiable footprint of intracortical remodeling. Given the changes in bone remodeling across life, we hypothesized that the 3D microarchitecture of the cortical pore network influences its stiffness during growth and ageing. Cubes of cortical bone of 2 mm side-length were harvested in the distal 1/3 of the fibula in 13 growing children (mean age±SD: 13±4 yrs) and 16 adults (age: 75±13 yrs). The cubes were imaged using desktop micro-CT (8.14µm isotropic voxel size). Pores were segmented as a solid to assess pore volume fraction, number, diameter, separation, connectivity and structure model index. Elastic coefficients were derived from measurements of ultrasonic bulk compression and shear wave velocities and apparent mass density. The pore volume fraction did not significantly differ between children and adults but originates from different microarchitectural patterns. Compared to children, adults had 42% (p=0.033) higher pore number that were more connected (Connective Density: +205%, p=0.001) with a 18% (p=0.007) lower pore separation. After accounting for the contribution of pore volume fraction, axial elasticity in traction-compression mode was significantly correlated with better connectivity in growing children and with pore separation among adults. The changes in intracortical remodeling across life alter the distribution, size and connectedness of the channels from which cortical void fraction originates. These alterations in pore network microarchitecture participate in changes in compressive and shear mechanical behavior, partly in a porosity-independent manner. The assessment of pore volume fraction (i.e., porosity) provides only a limited understanding of the role of cortical void volume fraction in its mechanical properties. PMID:27389322

  10. Obesity and carotid artery remodeling

    DEFF Research Database (Denmark)

    Kozakova, M; Palombo, C; Morizzo, C;

    2015-01-01

    BACKGROUND/OBJECTIVE: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions...... and CCA LD (266 healthy subjects with wide range of body weight (24-159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese subjects...... without CV complications and 88 non-obese subjects matched for gender and age). RESULTS: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile...

  11. The Multifaceted Osteoclast; Far and Beyond Bone Resorption.

    Science.gov (United States)

    Drissi, Hicham; Sanjay, Archana

    2016-08-01

    The accepted function of the bone resorbing cell, osteoclast, has been linked to bone remodeling and pathological osteolysis. Emerging evidence points to novel functions of osteoclasts in controlling bone formation and angiogenesis. Thus, while the concept of a "clastokine" with the potential to regulate osteogenesis during remodeling did not come as a surprise, new evidence provided unique insight into the mechanisms underlying osteoclastic control of bone formation. The question still remains as to whether osteoclast precursors or a unique trap positive mononuclear cell, can govern any aspect of bone formation. The novel paradigm eloquently proposed by leaders in the field brings together the concept of clastokines and osteoclast precursor-mediated bone formation, potentially though enhanced angiogenesis. These fascinating advances in osteoclast biology have motivated this short review, in which we discuss these new roles of osteoclasts. J. Cell. Biochem. 117: 1753-1756, 2016. © 2016 Wiley Periodicals, Inc. PMID:27019318

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-15

    Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such as dioxins. Although bone morphology, mineral density and strength are sensitive endpoints of dioxin toxicity, less is known about effects on bone microarchitecture and material properties. This study characterizes TCDD-induced modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity and for normal bone phenotype. Six AHR-knockout (Ahr{sup −/−}) and wild-type (Ahr{sup +/+}) mice of both genders were exposed to TCDD weekly for 10 weeks, at a total dose of 200 μg/kg bw. Bones were examined with micro-computed tomography, nanoindentation and biomechanical testing. Serum levels of bone remodeling markers were analyzed, and the expression of genes related to osteogenic differentiation was profiled using PCR array. In Ahr{sup +/+} mice, TCDD-exposure resulted in harder bone matrix, thinner and more porous cortical bone, and a more compact trabecular bone compartment. Bone remodeling markers and altered expression of a number of osteogenesis related genes indicated imbalanced bone remodeling. Untreated Ahr{sup −/−} mice displayed a slightly modified bone phenotype as compared with untreated Ahr{sup +/+} mice, while TCDD exposure caused only a few changes in bones of Ahr{sup −/−} mice. Part of the effects of both TCDD-exposure and AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker bones and most notably, increased trabecular bone volume fraction in Ahr{sup +/+} mice. AHR is involved in bone development of a normal bone phenotype, and is crucial for manifestation of TCDD-induced bone alterations. - Highlights: • TCDD disrupts bone remodeling resulting in altered cortical and trabecular bone. • In trabecular bone an anabolic effect is observed. • Cortical bone is thinner, more porous, harder, stiffer and mechanically weaker. • AHR ablation

  13. Nonallograft osteoconductive bone graft substitutes.

    Science.gov (United States)

    Bucholz, Robert W

    2002-02-01

    An estimated 500,000 to 600,000 bone grafting procedures are done annually in the United States. Approximately (1/2) of these surgeries involve spinal arthrodesis whereas 35% to 40% are used for general orthopaedic applications. Synthetic bone graft substitutes currently represent only 10% of the bone graft market, but their share is increasing as experience and confidence in their use are accrued. Despite 15 to 20 years of clinical experience with various synthetic substitutes, there have been few welldesigned, controlled clinical trials of these implants. Synthetic bone graft substitutes consist of hydroxyapatite, tricalcium phosphate, calcium sulfate, or a combination of these minerals. Their fabrication technique, crystallinity, pore dimensions, mechanical properties, and resorption rate vary. All synthetic porous substitutes share numerous advantages over autografts and allografts including their unlimited supply, easy sterilization, and storage. However, the degree to which the substitute provides an osteoconductive structural framework or matrix for new bone ingrowth differs among implants. Disadvantages of ceramic implants include brittle handling properties, variable rates of resorption, poor performance in diaphyseal defects, and potentially adverse effects on normal bone remodeling. These inherent weaknesses have refocused their primary use to bone graft extenders and carriers for pharmaceuticals. The composition, histologic features, indications, and clinical experience of several of the synthetic bone graft substitutes approved for orthopaedic use in the United States are reviewed. PMID:11937865

  14. Investigating the Robustness and Diagnostic Potential of Extracellular Matrix Remodelling Biomarkers in Alkaptonuria

    OpenAIRE

    Genovese, F; Siebuhr, A. S.; Musa, K.; Gallagher, J.A.; Milan, A. M.; Karsdal, M.A.; Rovensky, J; Bay-Jensen, A. C.; Ranganath, L. R.

    2015-01-01

    Background and aim: Alkaptonuria (AKU) clinical manifestations resemble severe arthritis. The Suitability of Nitisinone in Alkaptonuria 1 (SONIA 1) study is a dose-finding trial for nitisinone treatment of AKU patients. We tested a panel of serum and urinary biomarkers reflecting extracellular matrix remodelling (ECMR) of cartilage, bone and connective tissue in SONIA 1 patients to identify non-invasive and diagnostic biomarkers of tissue turnover in AKU.

  15. Fibroblast cytoskeletal remodeling contributes to connective tissue tension.

    Science.gov (United States)

    Langevin, Helene M; Bouffard, Nicole A; Fox, James R; Palmer, Bradley M; Wu, Junru; Iatridis, James C; Barnes, William D; Badger, Gary J; Howe, Alan K

    2011-05-01

    The visco-elastic behavior of connective tissue is generally attributed to the material properties of the extracellular matrix rather than cellular activity. We have previously shown that fibroblasts within areolar connective tissue exhibit dynamic cytoskeletal remodeling within minutes in response to tissue stretch ex vivo and in vivo. Here, we tested the hypothesis that fibroblasts, through this cytoskeletal remodeling, actively contribute to the visco-elastic behavior of the whole tissue. We measured significantly increased tissue tension when cellular function was broadly inhibited by sodium azide and when cytoskeletal dynamics were compromised by disrupting microtubules (with colchicine) or actomyosin contractility (via Rho kinase inhibition). These treatments led to a decrease in cell body cross-sectional area and cell field perimeter (obtained by joining the end of all of a fibroblast's processes). Suppressing lamellipodia formation by inhibiting Rac-1 decreased cell body cross-sectional area but did not affect cell field perimeter or tissue tension. Thus, by changing shape, fibroblasts can dynamically modulate the visco-elastic behavior of areolar connective tissue through Rho-dependent cytoskeletal mechanisms. These results have broad implications for our understanding of the dynamic interplay of forces between fibroblasts and their surrounding matrix, as well as for the neural, vascular, and immune cell populations residing within connective tissue.

  16. Long bone histology and growth patterns in ankylosaurs: implications for life history and evolution.

    Directory of Open Access Journals (Sweden)

    Martina Stein

    Full Text Available The ankylosaurs are one of the major dinosaur groups and are characterized by unique body armor. Previous studies on other dinosaur taxa have revealed growth patterns, life history and evolutionary mechanisms based on their long bone histology. However, to date nothing is known about long bone histology in the Ankylosauria. This study is the first description of ankylosaurian long bone histology based on several limb elements, which were sampled from different individuals from the Ankylosauridae and Nodosauridae. The histology is compared to that of other dinosaur groups, including other Thyreophora and Sauropodomorpha. Ankylosaur long bone histology is characterized by a fibrolamellar bone architecture. The bone matrix type in ankylosaurs is closest to that of Stegosaurus. A distinctive mixture of woven and parallel-fibered bone together with overall poor vascularization indicates slow growth rates compared to other dinosaurian taxa. Another peculiar characteristic of ankylosaur bone histology is the extensive remodeling in derived North American taxa. In contrast to other taxa, ankylosaurs substitute large amounts of their primary tissue early in ontogeny. This anomaly may be linked to the late ossification of the ankylosaurian body armor. Metabolically driven remodeling processes must have liberated calcium to ossify the protective osteodermal structures in juveniles to subadult stages, which led to further remodeling due to increased mechanical loading. Abundant structural fibers observed in the primary bone and even in remodeled bone may have improved the mechanical properties of the Haversian bone.

  17. Remodeling of the methylation landscape in breast cancer metastasis.

    Directory of Open Access Journals (Sweden)

    Marsha Reyngold

    Full Text Available The development of breast cancer metastasis is accompanied by dynamic transcriptome changes and dramatic alterations in nuclear and chromatin structure. The basis of these changes is incompletely understood. The DNA methylome of primary breast cancers contribute to transcriptomic heterogeneity and different metastatic behavior. Therefore we sought to characterize methylome remodeling during regional metastasis. We profiled the DNA methylome and transcriptome of 44 matched primary breast tumors and regional metastases. Striking subtype-specific patterns of metastasis-associated methylome remodeling were observed, which reflected the molecular heterogeneity of breast cancers. These divergent changes occurred primarily in CpG island (CGI-poor areas. Regions of methylome reorganization shared by the subtypes were also observed, and we were able to identify a metastasis-specific methylation signature that was present across the breast cancer subclasses. These alterations also occurred outside of CGIs and promoters, including sequences flanking CGIs and intergenic sequences. Integrated analysis of methylation and gene expression identified genes whose expression correlated with metastasis-specific methylation. Together, these findings significantly enhance our understanding of the epigenetic reorganization that occurs during regional breast cancer metastasis across the major breast cancer subtypes and reveal the nature of methylome remodeling during this process.

  18. Odanacatib in postmenopausal women with low bone mineral density: a review of current clinical evidence.

    Science.gov (United States)

    Zerbini, Cristiano A F; McClung, Michael R

    2013-08-01

    Human bones are in a continuous process of remodeling that ensures renovation and maintenance of the skeletal mass. Bone remodeling has two phases that are normally coupled and balanced: bone resorption mediated by osteoclasts and bone formation mediated by osteoblasts. An increase in bone resorption over bone formation results in a progressive loss of bone mass and impairment of bone microarchitecture leading to osteoporosis and its associated fractures. Recent advances in the understanding of the molecular and cellular mechanisms involved in the remodeling process have allowed the development of new targets for osteoporosis treatment. Cathepsin K, a cysteine protease, is found in osteoclasts along the bone resorption surfaces and very efficiently degrades type I collagen, the major component of the organic bone matrix. Inhibition of cathepsin K reduces bone resorption but does not impair bone formation particularly at cortical sites. Odanacatib, a potent and highly selective cathepsin K inhibitor, showed prevention of bone loss without reduction of bone formation in preclinical and clinical trials (phase I and II). Odanacatib is currently in a phase III fracture outcome international trial for the treatment of postmenopausal osteoporosis. PMID:23904864

  19. Cartilage in facet joints of patients with ankylosing spondylitis (AS) shows signs of cartilage degeneration rather than chondrocyte hypertrophy: implications for joint remodeling in AS

    OpenAIRE

    Bleil, Janine; Sieper, Joachim; Maier, Rene; Schlichting, Uwe; Hempfing, Axel; Syrbe, Uta; Appel, Heiner

    2015-01-01

    Introduction In ankylosing spondylitis (AS), joint remodeling leading to joint ankylosis involves cartilage fusion. Here, we analyzed whether chondrocyte hypertrophy is involved in cartilage fusion and subsequent joint remodeling in AS. Methods We assessed the expression of chondrocyte hypertrophy markers runt-related transcription factor 2 (Runx2), type X collagen (COL10), matrix metalloproteinase 13 (MMP13), osteocalcin and beta-catenin and the expression of positive bone morphogenic protei...

  20. Maternal uterine vascular remodeling during pregnancy.

    Science.gov (United States)

    Osol, George; Mandala, Maurizio

    2009-02-01

    Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.

  1. Cholinergic Regulation of Airway Inflammation and Remodelling

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian

    2012-01-01

    Full Text Available Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD.

  2. Understanding the local actions of lipids in bone physiology.

    Science.gov (United States)

    During, Alexandrine; Penel, Guillaume; Hardouin, Pierre

    2015-07-01

    The adult skeleton is a metabolically active organ system that undergoes continuous remodeling to remove old and/or stressed bone (resorption) and replace it with new bone (formation) in order to maintain a constant bone mass and preserve bone strength from micro-damage accumulation. In that remodeling process, cellular balances--adipocytogenesis/osteoblastogenesis and osteoblastogenesis/osteoclastogenesis--are critical and tightly controlled by many factors, including lipids as discussed in the present review. Interest in the bone lipid area has increased as a result of in vivo evidences indicating a reciprocal relationship between bone mass and marrow adiposity. Lipids in bones are usually assumed to be present only in the bone marrow. However, the mineralized bone tissue itself also contains small amounts of lipids which might play an important role in bone physiology. Fatty acids, cholesterol, phospholipids and several endogenous metabolites (i.e., prostaglandins, oxysterols) have been purported to act on bone cell survival and functions, the bone mineralization process, and critical signaling pathways. Thus, they can be regarded as regulatory molecules important in bone health. Recently, several specific lipids derived from membrane phospholipids (i.e., sphingosine-1-phosphate, lysophosphatidic acid and different fatty acid amides) have emerged as important mediators in bone physiology and the number of such molecules will probably increase in the near future. The present paper reviews the current knowledge about: (1°) bone lipid composition in both bone marrow and mineralized tissue compartments, and (2°) local actions of lipids on bone physiology in relation to their metabolism. Understanding the roles of lipids in bone is essential to knowing how an imbalance in their signaling pathways might contribute to bone pathologies, such as osteoporosis. PMID:26118851

  3. Vibrational spectroscopy in biomedical science: bone

    Science.gov (United States)

    Gamsjäger, Sonja; Zoehrer, R.; Roschger, P.; Fratzl, P.; Klaushofer, K.; Mendelsohn, R.; Paschalis, E. P.

    2009-02-01

    Fourier transform infrared imaging (FTIR) and Raman Microspectroscopy are powerful tools for characterizing the distribution of different chemical moieties in heterogeneous materials. FTIR and Raman measurements have been adapted to assess the maturity of the mineral and the quality of the organic component (collagen and non-collagenous proteins) of the mineralized tissue in bone. Unique to the FTIRI analysis is the capability to provide the spatial distribution of two of the major collagen cross-links (pyridinoline, and dehydro-dihydroxylysinonorleucine) and through the study of normal and diseased bone, relate them to bone strength. These FTIR parameters have been validated based on analysis of model compounds. It is widely accepted that bone strength is determined by bone mass and bone quality. The latter is a multifactorial term encompassing the material and structural properties of bone, and one important aspect of the bone material properties is the organic matrix. The bone material properties can be defined by parameters of mineral and collagen, as determined by FTIR and Raman analysis. Considerably less attention has been directed at collagen, although there are several publications in the literature reporting altered collagen properties associated with fragile bone, in both animals and humans. Since bone is a heterogeneous tissue due to the remodeling process, microscopic areas may be carefully selected based on quantitative Backscattered Electron Imaging or histological staining, thus ensuring comparison of areas with similar metabolic activity and mineral content. In conclusion, FTIRI and Raman vibrational spectroscopy are proving to be powerful tools in bone-related medical research.

  4. The remodeling of the posterior edentulous mandible as illustrated by computed tomography

    International Nuclear Information System (INIS)

    The aim of this study was to analyze radiologically the location and course of the mandibular canal and to observe the alveolar and basal bone changes during the remodeling procedures of atrophic mandible. CT scanning was performed on dry 30 edentulous or partially dentulous mandibles. In 48 edentulous lower halves, measuring areas were determined by three points in the length of the mandibular canal. The distance from the mandibular canal towards cranial and caudal edges, buccal and lingual external borders of the body of the mandible were measured. A statistical comparison between the mean values of different classes of mandibular body was carried out in the selected areas.The distance between the mandibular canal and caudal borders of the body of the mandible and lingual borders dose not change in the atrophic process of mandible. The mandibular canal within the mandible courses downwards from mandibular foramen towards mesial and subsequently it gets to the mental foramen. The distance between the mandibular canal and buccal external border of basal bone changes similar to the change of cranial borders of alveolar bone in the atrophic process of mandible. CT scanning was very effective and practicable to analyze the location and course of the mandibular canal and to observe the alveolar and basal bone changes of atrophic mandible. Also more detailed investigation of basal bone changes observed during the remodeling procedures of atrophic mandibles seems reasonable to rely on the massive anthropologic collections of atrophic mandibles combined with CT scanning.

  5. The remodeling of the posterior edentulous mandible as illustrated by computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chang Seo [Dept. of of Dental Radiology, College of Dentistry, Yonsei University, Seoul (Korea, Republic of)

    1999-02-15

    The aim of this study was to analyze radiologically the location and course of the mandibular canal and to observe the alveolar and basal bone changes during the remodeling procedures of atrophic mandible. CT scanning was performed on dry 30 edentulous or partially dentulous mandibles. In 48 edentulous lower halves, measuring areas were determined by three points in the length of the mandibular canal. The distance from the mandibular canal towards cranial and caudal edges, buccal and lingual external borders of the body of the mandible were measured. A statistical comparison between the mean values of different classes of mandibular body was carried out in the selected areas.The distance between the mandibular canal and caudal borders of the body of the mandible and lingual borders dose not change in the atrophic process of mandible. The mandibular canal within the mandible courses downwards from mandibular foramen towards mesial and subsequently it gets to the mental foramen. The distance between the mandibular canal and buccal external border of basal bone changes similar to the change of cranial borders of alveolar bone in the atrophic process of mandible. CT scanning was very effective and practicable to analyze the location and course of the mandibular canal and to observe the alveolar and basal bone changes of atrophic mandible. Also more detailed investigation of basal bone changes observed during the remodeling procedures of atrophic mandibles seems reasonable to rely on the massive anthropologic collections of atrophic mandibles combined with CT scanning.

  6. The Emerging Roles of ATP-Dependent Chromatin Remodeling Enzymes in Nucleotide Excision Repair

    Directory of Open Access Journals (Sweden)

    Wioletta Czaja

    2012-09-01

    Full Text Available DNA repair in eukaryotic cells takes place in the context of chromatin, where DNA, including damaged DNA, is tightly packed into nucleosomes and higher order chromatin structures. Chromatin intrinsically restricts accessibility of DNA repair proteins to the damaged DNA and impacts upon the overall rate of DNA repair. Chromatin is highly responsive to DNA damage and undergoes specific remodeling to facilitate DNA repair. How damaged DNA is accessed, repaired and restored to the original chromatin state, and how chromatin remodeling coordinates these processes in vivo, remains largely unknown. ATP-dependent chromatin remodelers (ACRs are the master regulators of chromatin structure and dynamics. Conserved from yeast to humans, ACRs utilize the energy of ATP to reorganize packing of chromatin and control DNA accessibility by sliding, ejecting or restructuring nucleosomes. Several studies have demonstrated that ATP-dependent remodeling activity of ACRs plays important roles in coordination of spatio-temporal steps of different DNA repair pathways in chromatin. This review focuses on the role of ACRs in regulation of various aspects of nucleotide excision repair (NER in the context of chromatin. We discuss current understanding of ATP-dependent chromatin remodeling by various subfamilies of remodelers and regulation of the NER pathway in vivo.

  7. Progesterone and Bone: Actions Promoting Bone Health in Women

    Directory of Open Access Journals (Sweden)

    Vanadin Seifert-Klauss

    2010-01-01

    Full Text Available Estradiol (E2 and progesterone (P4 collaborate within bone remodelling on resorption (E2 and formation (P4. We integrate evidence that P4 may prevent and, with antiresorptives, treat women's osteoporosis. P4 stimulates osteoblast differentiation in vitro. Menarche (E2 and onset of ovulation (P4 both contribute to peak BMD. Meta-analysis of 5 studies confirms that regularly cycling premenopausal women lose bone mineral density (BMD related to subclinical ovulatory disturbances (SODs. Cyclic progestin prevents bone loss in healthy premenopausal women with amenorrhea or SOD. BMD loss is more rapid in perimenopause than postmenopause—decreased bone formation due to P4 deficiency contributes. In 4 placebo-controlled RCTs, BMD loss is not prevented by P4 in postmenopausal women with increased bone turnover. However, 5 studies of E2-MPA co-therapy show greater BMD increases versus E2 alone. P4 fracture data are lacking. P4 prevents bone loss in pre- and possibly perimenopausal women; progesterone co-therapy with antiresorptives may increase bone formation and BMD.

  8. Mechanical properties of femoral cortical bone following cemented hip replacement.

    Science.gov (United States)

    Ni, G X; Lu, W W; Chiu, P K Y; Wang, Y; Li, Z Y; Zhang, Y G; Xu, B; Deng, L F; Luk, K D K

    2007-11-01

    Femoral bone remodeling following total hip replacement is a big concern and has never been examined mechanically. In this study, six goats underwent unilateral cemented hip hemiarthroplasty with polymethyl methacrylate (PMMA) bone cement. Nine months later animals were sacrificed, and the femoral cortical bone slices at different levels were analysed using microhardness testing and microcomputed tomography (micro-CT) scanning. Implanted femurs were compared to contralateral nonimplanted femurs. Extensive bone remodeling was demonstrated at both the proximal and middle levels, but not at the distal level. Compared with the nonimplanted side, significant decreases were found in the implanted femur in cortical bone area, bone mineral density, and cortical bone hardness at the proximal level, as well as in bone mineral density and bone hardness at the middle level. However, no significant difference was observed in either variable for the distal level. In addition, similar proximal-to-distal gradient changes were revealed both in cortical bone microhardness and bone mineral density. From the mechanical point of view, the results of the present study suggested that stress shielding is an important mechanical factor associated with bone adaptation following total hip replacement. PMID:17506504

  9. [Osteoplastic effectiveness of mineralized bone matrix].

    Science.gov (United States)

    2013-01-01

    In the experiment conducted on 50 Wistar rats, the peculiarities of the reparative osteogenesis were studied using scanning electron microscopy, x-ray electron-probe microanalysis and histological techniques. Granulated mineralized bone matrix (MBM) obtained without thermal and demineralizing treatment, was implanted into the tibial defect. MBM was found to possess marked osteoinductive and osteoconductive properties. It induced a prolonged activation of reparative osteogenesis after the implantation, as well as deep bone tissue ingrowth into the implant, acceleration of organotypic remodeling of regenerated bone, intense angiogenesis and early restoration of the damaged PMID:23805618

  10. Cholinergic regulation of airway inflammation and remodelling

    NARCIS (Netherlands)

    Kolahian, Saeed; Gosens, Reinoud

    2012-01-01

    Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway disease

  11. Raise the Floor When Remodeling Science Labs

    Science.gov (United States)

    Nation's Schools, 1972

    1972-01-01

    A new remodeling idea adopts the concept of raised floor covering gas, water, electrical, and drain lines. The accessible floor has removable panels set into an adjustable support frame 24 inches above a concrete subfloor. (Author)

  12. Biomechanical evaluation of dynamic hip screw with bone cement augmentation in normal bone%骨水泥强化正常骨质DHS固定的生物力学研究

    Institute of Scientific and Technical Information of China (English)

    黎宁; 彭阿钦; 聂喜增; 李锋; 赵永涛; 毕靖博; 韩长伶

    2008-01-01

    背景:DHS是治疗股骨转子间骨折的标准内固定,对于伴有骨质疏松的骨折,容易发生拉力螺钉切割.国内外文献建议骨水泥强化DHS以达到坚强内固定,但是对于正常骨质,骨水泥强化是否有效还缺少报道.目的:选取正常骨密度的股骨转子间骨折标本,观察骨水泥强化对DHS固定的生物力学影响.设计、时间及地点:同一标本两侧对比观察实验,于2005-03/05在河北省骨科研究所生物力学实验室完成.材料:选取河北医科大学解剖教研室提供的成年男性防腐尸体双侧股骨上段标本.X射线证实无结核、畸形、肿瘤.方法:取成年男性防腐尸体双侧股骨上段标本24对48侧,制备A2型股骨转子间骨折模型.右侧标本行骨水泥强化DHS固定(在股骨头近端钉道用刮匙扩大.股骨头朝下,注入2mL低黏稠度骨水泥,拧入拉力螺钉,保持位置不变直至骨水泥凝固.置入套筒,拧紧尾钉适当加压,皮质骨螺钉固定钢板),为强化组;左侧行DHS常规固定,为对照组.两组标本进行弯曲强度试验及扭转强度试验.主要观察指标:两组标本的最大负荷及最大扭矩.结果:强化组最大负荷及最大扭矩与对照组比较,差异均无统计学意义[最大负荷分别为:(3852.1602±143.6031)N和(3702.9667±133.8601)N;最大扭矩分别为(15.5±2.6)N·m,(14.7±3.4)N·m, P>0.0⑤.结论:对于正常骨密度的股骨转子间骨折,骨水泥强化对DHS固定强度及骨折整体稳定性无显著的影响.%BACKGROUND: Dynamic hip screw (DHS) is a standard internal fixation for intertrochanteric fracture, whereas the patient combined with osteoporosis, cut-out incidence of lag screw is common. The articles in China and abroad indicate bone cement augmentation of DHS to achieve firm fixation. As for normal bone, no reports is published that whether bone cement augmentation is effective.OBJECTIVE: To investigate the biomechanics of DHS with bone cement augmentation for

  13. Remodelling of cellular excitation (reaction) and intercellular coupling (diffusion) by chronic atrial fibrillation represented by a reaction-diffusion system

    Science.gov (United States)

    Zhang, Henggui; Garratt, Clifford J.; Kharche, Sanjay; Holden, Arun V.

    2009-06-01

    Human atrial tissue is an excitable system, in which myocytes are excitable elements, and cell-to-cell electrotonic interactions are via diffusive interactions of cell membrane potentials. We developed a family of excitable system models for human atrium at cellular, tissue and anatomical levels for both normal and chronic atrial fibrillation (AF) conditions. The effects of AF-induced remodelling of cell membrane ionic channels (reaction kinetics) and intercellular gap junctional coupling (diffusion) on atrial excitability, conduction of excitation waves and dynamics of re-entrant excitation waves are quantified. Both ionic channel and gap junctional coupling remodelling have rate dependent effects on atrial propagation. Membrane channel conductance remodelling allows the propagation of activity at higher rates than those sustained in normal tissue or in tissue with gap junctional remodelling alone. Membrane channel conductance remodelling is essential for the propagation of activity at rates higher than 300/min as seen in AF. Spatially heterogeneous gap junction coupling remodelling increased the risk of conduction block, an essential factor for the genesis of re-entry. In 2D and 3D anatomical models, the dynamical behaviours of re-entrant excitation waves are also altered by membrane channel modelling. This study provides insights to understand the pro-arrhythmic effects of AF-induced reaction and diffusion remodelling in atrial tissue.

  14. Chromatin Modification and Remodeling in Heart Development

    Directory of Open Access Journals (Sweden)

    Paul Delgado-Olguín

    2006-01-01

    Full Text Available In organogenesis, cell types are specified from determined precursors as morphogenetic patterning takes place. These events are largely controlled by tissue-specific transcription factors. These transcription factors must function within the context of chromatin to activate or repress target genes. Recent evidence suggests that chromatin-remodeling and -modifying factors may have tissue-specific function. Here we review the potential roles for chromatin-remodeling and -modifying proteins in the development of the mammalian heart.

  15. Diagnostic tools assessing airway remodelling in asthma.

    Science.gov (United States)

    Manso, L; Reche, M; Padial, M A; Valbuena, T; Pascual, C

    2012-01-01

    Asthma is an inflammatory disease of the lower airways characterised by the presence of airway inflammation, reversible airflow obstruction and airway hyperresponsiveness and alterations on the normal structure of the airways, known as remodelling. Remodelling is characterised by the presence of metaplasia of mucous glands, thickening of the lamina reticularis, increased angiogenesis, subepithelial fibrosis and smooth muscle hypertrophy/hyperplasia. Several techniques are being optimised at present to achieve a suitable diagnosis for remodelling. Diagnostic tools could be divided into two groups, namely invasive and non-invasive methods. Invasive techniques bring us information about bronchial structural alterations, obtaining this information directly from pathological tissue, and permit measure histological modification placed in bronchi layers as well as inflammatory and fibrotic cell infiltration. Non-invasive techniques were developed to reduce invasive methods disadvantages and measure airway remodelling-related markers such as cytokines, inflammatory mediators and others. An exhaustive review of diagnostic tools used to analyse airway remodelling in asthma, including the most useful and usually employed methods, as well as the principal advantages and disadvantages of each of them, bring us concrete and summarised information about all techniques used to evaluate alterations on the structure of the airways. A deep knowledge of these diagnostic tools will make an early diagnosis of airway remodelling possible and, probably, early diagnosis will play an important role in the near future of asthma. PMID:22236733

  16. An experimental objective method to determine maximum output and dynamic range of an active bone conduction implant: the Bonebridge

    NARCIS (Netherlands)

    Mertens, G.; Desmet, J.; Snik, A.F.M.; Heyning, P. van de

    2014-01-01

    INTRODUCTION: Recently, a new active bone conduction implant, the Bonebridge, was introduced. This transcutaneous device is proposed as an alternative to previous percutaneous systems. The current study aims to determine the maximum output (MO) of the Bonebridge by making use of Bonebridge-generated

  17. Immunologic and inflammatory mechanisms that drive asthma progression to remodeling

    OpenAIRE

    Broide, David H.

    2008-01-01

    Although histologic features of airway remodeling have been well characterized in asthma, the immunologic and inflammatory mechanisms that drive progression of asthma to remodeling are still incompletely understood. Conceptually, airway remodeling may be due to persistent inflammation and/or aberrant tissue repair mechanisms. It is likely that several immune and inflammatory cell types and mediators are involved in mediating airway remodeling. In addition, different features of airway remodel...

  18. Inhibition of cathepsin K increases modeling-based bone formation, and improves cortical dimension and strength in adult ovariectomized monkeys.

    Science.gov (United States)

    Pennypacker, Brenda L; Chen, Charles M; Zheng, Helen; Shih, Mei-Shu; Belfast, Mary; Samadfam, Rana; Duong, Le T

    2014-08-01

    Treatment with the cathepsin K (CatK) inhibitor odanacatib (ODN) protects against bone loss and maintains normal biomechanical properties in the spine and hip of ovariectomized (OVX) preclinical models. Here, we characterized the effects of ODN on the dynamics of cortical modeling and remodeling, and dimension and strength of the central femur in adult OVX-rhesus monkeys. Animals were treated with vehicle or ODN (6 or 30 mg/kg, once per day [q.d., p.o.]) in prevention mode for 21 months. Calcein and tetracycline double-labeling were given at 12 and 21 months, and the femoral cross-sections were subjected to dynamic histomorphometric and cement line analyses. ODN treatment significantly increased periosteal and endocortical bone formation (BFR/BS), accompanied with an increase in endocortical mineralizing surface (102%, p < 0.01) with the 6 mg/kg dose. ODN at both doses reduced remodeling hemiosteon numbers by 51% and 66% (p < 0.05), respectively, and ODN 30 mg/kg numerically reduced activation frequency without affecting wall thickness. On the same endocortical surface, ODN increased all modeling-based parameters, while reducing intracortical remodeling, consistent with the observed no treatment effects on cortical porosity. ODN 30 mg/kg markedly increased cortical thickness (CtTh, p < 0.001) and reduced marrow area (p < 0.01). Lastly, ODN treatment increased femoral structural strength (p < 0.001). Peak load was positively correlated with the increases in bone mineral content (BMC) (r(2)  = 0.9057, p < 0.0001) and CtTh (r2  = 0.6866, p < 0.0001). Taken together, by reducing cortical remodeling-based and stimulating modeling-based bone formation, ODN significantly improved cortical dimension and strength in OVX monkeys. This novel mechanism of CatK inhibition in stimulating cortical formation suggests that ODN represents a novel therapeutic approach for the treatment of osteoporosis. PMID:24591096

  19. Treatment with eldecalcitol positively affects mineralization, microdamage, and collagen crosslinks in primate bone.

    Science.gov (United States)

    Saito, Mitsuru; Grynpas, Marc D; Burr, David B; Allen, Matthew R; Smith, Susan Y; Doyle, Nancy; Amizuka, Norio; Hasegawa, Tomoka; Kida, Yoshikuni; Marumo, Keishi; Saito, Hitoshi

    2015-04-01

    Eldecalcitol (ELD), an active form of vitamin D analog approved for the treatment of osteoporosis in Japan, increases lumbar spine bone mineral density (BMD), suppresses bone turnover markers, and reduces fracture risk in patients with osteoporosis. We have previously reported that treatment with ELD for 6 months improved the mechanical properties of the lumbar spine in ovariectomized (OVX) cynomolgus monkeys. ELD treatment increased lumbar BMD, suppressed bone turnover markers, and reduced histomorphometric parameters of both bone formation and resorption in vertebral trabecular bone. In this study, we elucidated the effects of ELD on bone quality (namely, mineralization, microarchitecture, microdamage, and bone collagen crosslinks) in OVX cynomolgus monkeys in comparison with OVX-vehicle control monkeys. Density fractionation of bone powder prepared from lumbar vertebrae revealed that ELD treatment shifted the distribution profile of bone mineralization to a higher density, and backscattered electron microscopic imaging showed improved trabecular bone connectivity in the ELD-treated groups. Higher doses of ELD more significantly reduced the amount of microdamage compared to OVX-vehicle controls. The fractionated bone powder samples were divided according to their density, and analyzed for collagen crosslinks. Enzymatic crosslinks were higher in both the high-density (≥2.0 mg/mL) and low-density (mineralization, but prevented non-enzymatic reaction of collagen crosslinks and accumulation of bone microdamage. Bone anti-resorptive agents such as bisphosphonates slow down bone remodeling so that bone mineralization, bone microdamage, and non-enzymatic collagen crosslinks all increase. Bone anabolic agents such as parathyroid hormone decrease bone mineralization and bone microdamage by stimulating bone remodeling. ELD did not fit into either category. Histological analysis indicated that the ELD treatment strongly suppressed bone resorption by reducing the number of

  20. Cardiac remodelling and RAS inhibition.

    Science.gov (United States)

    Ferrario, Carlos M

    2016-06-01

    Risk factors such as hypertension and diabetes are known to augment the activity and tissue expression of angiotensin II (Ang II), the major effector peptide of the renin-angiotensin system (RAS). Overstimulation of the RAS has been implicated in a chain of events that contribute to the pathogenesis of cardiovascular (CV) disease, including the development of cardiac remodelling. This chain of events has been termed the CV continuum. The concept of CV disease existing as a continuum was first proposed in 1991 and it is believed that intervention at any point within the continuum can modify disease progression. Treatment with antihypertensive agents may result in regression of left ventricular hypertrophy, with different drug classes exhibiting different degrees of efficacy. The greatest decrease in left ventricular mass is observed following treatment with angiotensin converting enzyme inhibitors (ACE-Is), which inhibit Ang II formation. Although ACE-Is and angiotensin receptor blockers (ARBs) provide significant benefits in terms of CV events and stroke, mortality remains high. This is partly due to a failure to completely suppress the RAS, and, as our knowledge has increased, an escape phenomenon has been proposed whereby the human sequence of the 12 amino acid substrate angiotensin-(1-12) is converted to Ang II by the mast cell protease, chymase. Angiotensin-(1-12) is abundant in a wide range of organs and has been shown to increase blood pressure in animal models, an effect abolished by the presence of ACE-Is or ARBs. This review explores the CV continuum, in addition to examining the influence of the RAS. We also consider novel pathways within the RAS and how new therapeutic approaches that target this are required to further reduce Ang II formation, and so provide patients with additional benefits from a more complete blockade of the RAS. PMID:27105891

  1. A quantification strategy for missing bone mass in case of osteolytic bone lesions

    Energy Technology Data Exchange (ETDEWEB)

    Fränzle, Andrea, E-mail: a.fraenzle@dkfz.de; Giske, Kristina [Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Bretschi, Maren; Bäuerle, Tobias [Department of Medical Physics in Radiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Hillengass, Jens [Department of Internal Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Bendl, Rolf [Medical Informatics, Heilbronn University, Max-Planck-Strasse 39, 74081 Heilbronn, Germany and Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2013-12-15

    Purpose: Most of the patients who died of breast cancer have developed bone metastases. To understand the pathogenesis of bone metastases and to analyze treatment response of different bone remodeling therapies, preclinical animal models are examined. In breast cancer, bone metastases are often bone destructive. To assess treatment response of bone remodeling therapies, the volumes of these lesions have to be determined during the therapy process. The manual delineation of missing structures, especially if large parts are missing, is very time-consuming and not reproducible. Reproducibility is highly important to have comparable results during the therapy process. Therefore, a computerized approach is needed. Also for the preclinical research, a reproducible measurement of the lesions is essential. Here, the authors present an automated segmentation method for the measurement of missing bone mass in a preclinical rat model with bone metastases in the hind leg bones based on 3D CT scans. Methods: The affected bone structure is compared to a healthy model. Since in this preclinical rat trial the metastasis only occurs on the right hind legs, which is assured by using vessel clips, the authors use the left body side as a healthy model. The left femur is segmented with a statistical shape model which is initialised using the automatically segmented medullary cavity. The left tibia and fibula are segmented using volume growing starting at the tibia medullary cavity and stopping at the femur boundary. Masked images of both segmentations are mirrored along the median plane and transferred manually to the position of the affected bone by rigid registration. Affected bone and healthy model are compared based on their gray values. If the gray value of a voxel indicates bone mass in the healthy model and no bone in the affected bone, this voxel is considered to be osteolytic. Results: The lesion segmentations complete the missing bone structures in a reasonable way. The mean

  2. Myocardial performance index: prediction and monitoring of remodeling and functioning of the left ventricle after first myocardial infarction

    OpenAIRE

    Ćelić Vera; Dekleva Milica; Majstorović Anka; Radivojević Nenad; Kostić Nada; Čaparević Zorica

    2010-01-01

    Introduction. Dynamic changing of left ventricular geometry and contractile state after acute myocardial infarction is responsible for various aspects of left ventricular remodeling and dysfunction. A number of studies have shown that myocardial performance index allows prediction of acute myocardial infarction complications. The objective of our study was to determine the power of myocardial performance index to predict and assess the severity of left ventricular remodeling, systolic and dia...

  3. Sonic Hedgehog-activated engineered blood vessels enhance bone tissue formation

    OpenAIRE

    N C Rivron; Raiss, C.C.; Liu, J.; Nandakumar, A.; Sticht, C; Gretz, N; Truckenmuller, R.K.; Rouwkema, J.; Blitterswijk, van, W.J.

    2012-01-01

    Large bone defects naturally regenerate via a highly vascularized tissue which progressively remodels into cartilage and bone. Current approaches in bone tissue engineering are restricted by delayed vascularization and fail to recapitulate this stepwise differentiation toward bone tissue. Here, we use the morphogen Sonic Hedgehog (Shh) to induce the in vitro organization of an endothelial capillary network in an artificial tissue. We show that endogenous Hedgehog activity regulates angiogenic...

  4. Evolving Role of Bone Biomarkers in Castration-Resistant Prostate Cancer1

    OpenAIRE

    Brown, Janet E.; Sim, Sheryl

    2010-01-01

    The preferential metastasis of prostate cancer cells to bone disrupts the process of bone remodeling and results in lesions that cause significant pain and patient morbidity. Although prostate-specific antigen (PSA) is an established biomarker in prostate cancer, it provides only limited information relating to bone metastases and the treatment of metastatic bone disease with bisphosphonates or novel noncytotoxic targeted or biological agents that may provide clinical benefits without affecti...

  5. Evolving Role of Bone Biomarkers in Castration-Resistant Prostate Cancer

    OpenAIRE

    Brown, Janet E.; Sheryl Sim

    2010-01-01

    The preferential metastasis of prostate cancer cells to bone disrupts the process of bone remodeling and results in lesions that cause significant pain and patient morbidity. Although prostate-specific antigen (PSA) is an established biomarker in prostate cancer, it provides only limited information relating to bone metastases and the treatment of metastatic bone disease with bisphosphonates or novel noncytotoxic targeted or biological agents that may provide clinical benefits without affecti...

  6. Bone volume changes after immediate implant placement with or without flap elevation.

    OpenAIRE

    Mazzocco, Fabio

    2016-01-01

    The placement of implants immediately after tooth extraction is the ideal treatment option in selected cases. However, previous studies have shown that placing an implant does not avoid the shrinkage of the alveolar ridge. The aims of the present investigation were to evaluate bone dimensions after immediate implant placement with simultaneous grafting of the buccal gap, to determine if initial buccal bone width had an influence on bone remodelling and to compare bone volume ch...

  7. Dynamics of Alloplastic Bone Grafts on an Early Stage of Corticotomy-Facilitated Orthodontic Tooth Movement in Beagle Dogs

    OpenAIRE

    Hyung-Joo Choi; Dong-Yeol Lee; Tae-Woo Kim

    2014-01-01

    Alveolar augmented corticotomy is effective in accelerating orthodontic tooth movement, but the effect only lasts for a relatively short time. Therefore, the purpose of this study was to investigate the underlying biology of the immediate periodontal response to orthodontic tooth movement after a corticotomy with alloplastic bone grafts. The results demonstrated that measurable tooth movement began as early as 3 days after the intervention in beagle dogs. Based on the results and histological...

  8. [Pulmonary arterial hypertension, bone marrow, endothelial cell precursors and serotonin].

    Science.gov (United States)

    Ayme-Dietrich, Estelle; Banas, Sophie M; Monassier, Laurent; Maroteaux, Luc

    2016-01-01

    Serotonin and bone-marrow-derived stem cells participate together in triggering pulmonary hypertension. Our work has shown that the absence of 5-HT2B receptors generates permanent changes in the composition of the blood and bone-marrow in the myeloid lineages, particularly in endothelial cell progenitors. The initial functions of 5-HT2B receptors in pulmonary arterial hypertension (PAH) are restricted to bone-marrow cells. They contribute to the differentiation/proliferation/mobilization of endothelial progenitor cells from the bone-marrow. Those bone-marrow-derived cells have a critical role in the development of pulmonary hypertension and pulmonary vascular remodeling. These data indicate that bone-marrow derived endothelial progenitors play a key role in the pathogenesis of PAH and suggest that interactions involving serotonin and bone morphogenic protein type 2 receptor (BMPR2) could take place at the level of the bone-marrow. PMID:27687599

  9. Dynamic changes in percentages of CD4+CD25+regulatory T cells and Th17 cells in process of airway remodeling in mouse model of asthma%哮喘小鼠气道重塑过程中CD4+CD25+调节性T细胞和Th17细胞表达的动态变化

    Institute of Scientific and Technical Information of China (English)

    娄春艳; 李敏; 李丽

    2015-01-01

    Objective To study the dynamic changes in Th17 cells and CD4+CD25+regulatory T cells (Treg) in the spleen and to analyze their relationship with airway remodeling. Methods A total of 48 female speciifc pathogen-free Balb/c mice were randomly divided into control and asthmatic groups. To establish the asthmatic airway remodeling model, the mice were sensitized to ovalbumin (OVA) through intraperitoneal injection of OVA and aluminum hydroxide suspension and challenged by inhalation of aerosol OVA. The matched control group was treated with normal saline instead. In 24 hours after 2-week, 4-week, and 8-week aerosol inhalation, 8 mice were randomly selected from each group and sacriifced. Then histopathological examination of the left lung was performed to measure the degree of airway remodeling. The percentages of Th17 and CD4+CD25+Treg cells in total CD4+cells from the spleen were determined by lfow cytometry. Results In the asthmatic group, the ratios of total bronchial wall area to bronchial basement membrane perimeter (WAt/Pbm) and bronchial smooth muscle area to bronchial basement membrane perimeter (WAm/Pbm) signiifcantly increased as the challenge proceeds (P<0.01). The percentage of Th17 cells derived from the cell suspension of the spleen gradually increased and it was positively correlated with the degree of asthmatic airway remodeling (P<0.01). The percentage of CD4+CD25+Treg cells from the suspension gradually decreased and it was negatively correlated with the degree of asthmatic airway remodeling (P<0.01). Conclusions In mice with asthma, as the challenge proceeds, the airway remodeling becomes more severe, the percentage of Th17 cells increases, and the percentage of CD4+CD25+Treg cells decreases. The immunological imbalance is possibly one of the important factors inducing airway remodeling.%目的:探讨哮喘小鼠Th17细胞和CD4+CD25+调节性T细胞(Treg)在脾组织中表达水平的变化规律及与气道重塑的关系

  10. Understanding coupling between bone resorption and formation

    DEFF Research Database (Denmark)

    Andersen, Thomas Levin; Abdelgawad, Mohamed Essameldim; Kristensen, Helene Bjørg;

    2013-01-01

    Bone remodeling requires bone resorption by osteoclasts, bone formation by osteoblasts, and a poorly investigated reversal phase coupling resorption to formation. Likely players of the reversal phase are the cells recruited into the lacunae vacated by the osteoclasts and presumably preparing these...... lacunae for bone formation. These cells, called herein reversal cells, cover >80% of the eroded surfaces, but their nature is not identified, and it is not known whether malfunction of these cells may contribute to bone loss in diseases such as postmenopausal osteoporosis. Herein, we combined...... histomorphometry and IHC on human iliac biopsy specimens, and showed that reversal cells are immunoreactive for factors typically expressed by osteoblasts, but not for monocytic markers. Furthermore, a subpopulation of reversal cells showed several distinctive characteristics suggestive of an arrested...

  11. Local treatment of a bone graft by soaking in zoledronic acid inhibits bone resorption and bone formation. A bone chamber study in rats

    Directory of Open Access Journals (Sweden)

    Belfrage Ola

    2012-12-01

    Full Text Available Abstract Background Bone grafts are frequently used in orthopaedic surgery. Graft remodelling is advantageous but can occur too quickly, and premature bone resorption might lead to decreased mechanical integrity of the graft. Bisphosphonates delay osteoclastic bone resorption but may also impair formation of new bone. We hypothesize that these effects are dose dependent. In the present study we evaluate different ways of applying bisphosphonates locally to the graft in a bone chamber model, and compare that with systemic treatment. Methods Cancellous bone grafts were placed in titanium chambers and implanted in the tibia of 50 male rats, randomly divided into five groups. The first group served as negative control and the grafts were rinsed in saline before implantation. In the second and third groups, the grafts were soaked in a zoledronic acid solution (0.5 mg/ml for 5 seconds and 10 minutes respectively before being rinsed in saline. In the fourth group, 8 μL of zoledronic acid solution (0.5 mg/ml was pipetted onto the freeze-dried grafts without rinsing. The fifth group served as positive control and the rats were given zoledronic acid (0.1 mg/kg systemically as a single injection two weeks after surgery. The grafts were harvested at 6 weeks and analysed with histomorphometry, evaluating the ingrowth distance of new bone into the graft as an equivalent to the anabolic osteoblast effect and the amount (bone volume/total volume; BV/TV of remaining bone in the remodelled graft as equivalent to the catabolic osteoclast effect. Results In all chambers, almost the entire graft had been revascularized but only partly remodelled at harvest. The ingrowth distance of new bone into the graft was lower in grafts soaked in zoledronic acid for 10 minutes compared to control (p = 0.007. In all groups receiving zoledronic acid, the BV/TV was higher compared to control. Conclusions This study found a strong inhibitory effect on bone resorption by

  12. A fly's view of neuronal remodeling.

    Science.gov (United States)

    Yaniv, Shiri P; Schuldiner, Oren

    2016-09-01

    Developmental neuronal remodeling is a crucial step in sculpting the final and mature brain connectivity in both vertebrates and invertebrates. Remodeling includes degenerative events, such as neurite pruning, that may be followed by regeneration to form novel connections during normal development. Drosophila provides an excellent model to study both steps of remodeling since its nervous system undergoes massive and stereotypic remodeling during metamorphosis. Although pruning has been widely studied, our knowledge of the molecular and cellular mechanisms is far from complete. Our understanding of the processes underlying regrowth is even more fragmentary. In this review, we discuss recent progress by focusing on three groups of neurons that undergo stereotypic pruning and regrowth during metamorphosis, the mushroom body γ neurons, the dendritic arborization neurons and the crustacean cardioactive peptide peptidergic neurons. By comparing and contrasting the mechanisms involved in remodeling of these three neuronal types, we highlight the common themes and differences as well as raise key questions for future investigation in the field. WIREs Dev Biol 2016, 5:618-635. doi: 10.1002/wdev.241 For further resources related to this article, please visit the WIREs website. PMID:27351747

  13. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

    ... of DXA Bone Densitometry? What is a Bone Density Scan (DXA)? Bone density scanning, also called dual-energy x-ray absorptiometry ( ... is today's established standard for measuring bone mineral density (BMD). An x-ray (radiograph) is a noninvasive ...

  14. Mechanical loading up-regulates early remodeling signals from osteocytes subjected to physical damage.

    Science.gov (United States)

    Liu, Chao; Zhang, Xiaoqing; Wu, Michael; You, Lidan

    2015-12-16

    In the mineralized bone matrix, mechanical loading causes micrometer-sized cracks. These cracks trigger targeted remodeling along the micro-crack. Physical damage to osteocytes was shown to be involved in the initiation of this remodeling process. However, the role of subsequent mechanical loading osteocyte response to physical damage is unclear. In this study, we have designed and developed an in vitro cell model to study the impact of mechanical loading on osteocytes with physical damage. Specifically, a system was developed to create sub-cellular physical damage on MLO-Y4 osteocytes in vitro. This model re-created the spatial distribution of non-viable cells and VEGF expression around microdamage as reported in vivo. Using this system, the short term (24h) effects of fluid shear stress in regulation of osteocyte response to physical damage were investigated. We have observed that the mechanical stimuli had an additive effect in terms of COX-2, VEGF mRNA expressions, as well as PGE2, VEGF concentrations in the media. Interestingly, other inflammatory signals such as IL-6 and TNF-α did not change with these stimuli, at this time point. Moreover, fluid shear also had a modulating effect in regulation of osteoclast differentiation by osteocyte with physical damage. These results show that (1) subcellular physical damage upregulates remodeling signals in osteocytes at early time point, (2) mechanical loading substantially upregulates these signals for remodeling in osteocytes with physical damage. PMID:26596719

  15. Bone Appetit: The Role of Food and Nutrition in Building and Maintaining Strong Bones

    Science.gov (United States)

    Bone is a living, dynamic, metabolically active tissue. It under goes a process of constant renewal throughout life, through a process called bone turnover in which cells called osteoclasts remove old or damaged bone, and cells called osteoblasts make new bone to replace it. A healthy, balanced di...

  16. Study on bone resorption behavior of osteoclast under drug effect using {sup 41}Ca tracing

    Energy Technology Data Exchange (ETDEWEB)

    Dong Kejun [China Institute of Atomic Energy, P.O. Box 275(50), Beijing 102413 (China); Lu Liyan [China Institute of Atomic Energy, P.O. Box 275(50), Beijing 102413 (China); CNNC Third Qinshan Nuclear Power Co. Ltd., Haiyan 314300 (China); He Ming; Ouyang Yinggen; Xue Yan; Li Chaoli; Wu Shaoyong [China Institute of Atomic Energy, P.O. Box 275(50), Beijing 102413 (China); Wang Xianggao [College of Physics Science and Technology, Guangxi University, Nanning 530004 (China); Shen Hongtao [College of Physics and Technology, Guangxi Normal University, Guilin 541004 (China); Gao Jianjun [Institute of Radiation Medicine, Fudan University, Shanghai 200032 (China); Wang Wei [China Institute of Atomic Energy, P.O. Box 275(50), Beijing 102413 (China); China National Nuclear Corporation, Beijing 100822 (China); Chen Dafu; Xing Yonggang [Beijing Research Institute of Traumatology and Orthopaedics, Beijing 100035 (China); Jian, Yuan [China Institute of Atomic Energy, P.O. Box 275(50), Beijing 102413 (China); Jiang Shan, E-mail: jiangs@ciae.ac.cn [China Institute of Atomic Energy, P.O. Box 275(50), Beijing 102413 (China)

    2013-01-15

    The mechanisms governing calcium fluxes during bone remodeling processes in Osteoporosis (OP) patients are poorly known. Understanding the changes of Osteoclasts (OC) during this dynamic transition is important to prevent and cure OP. The exploration of long-lived {sup 41}Ca (T{sub 1/2} = 1.04 Multiplication-Sign 10{sup 5} years) tracer combined with AMS measurements leads to the possibility of monitoring the bone resorption behavior of OC in OP patients. In this work, the behavior of OC with the administration of Strontium Ranelate (SR), a drug for OP, was studied by using {sup 41}Ca labeled hydroxyapatite (HAP) to simulate the bone. AMS on the HI-13 tandem accelerator at CIAE was used to determine trace amounts of {sup 41}Ca. The results show that the technique of {sup 41}Ca tracing with AMS can be used to quantitatively monitor the behavior of OC in bone resorption under the effects of drugs. Experimental details and preliminary results will be presented.

  17. Experimental xenoimplantation of antlerogenic cells into mandibular bone lesions in rabbits: two-year follow-up.

    Science.gov (United States)

    Cegielski, Marek; Dziewiszek, Wojciech; Zabel, Maciej; Dziegiel, Piotr; Kuryszko, Jan; Izykowska, Ilona; Zatoński, Maciej; Bochnia, Marek

    2010-01-01

    Different types of cells require activation, and take part in annual, dynamic growth of deer antlers. Stem cells play the most important role in this process. This report shows the results of a two-year long observation of xenogenic implant of antlerogenic stem cells (cell line MIC-1). The cells were derived from growing antler of a deer (Cervus elaphus), seeded onto Spongostan and placed in postoperative lesions of mandibular bones of 15 experimental rabbits. The healing process observed in the implantation sites in all rabbits was normal, and no local inflammatory response was ever observed. Histological and immunohistochemical evaluations were performed after 1, 2, 6, 12 and 24 months, and confirmed the participation of xenogenic cells in the regeneration processes, as well as a lack of rejection of the implants. The deficiencies in the bones were replaced by newly formed, thick fibrous bone tissue that underwent mineralization and was later remodelled into lamellar bone. The results of the experiment with rabbits allow us to believe that antlerogenic cells could be used in reconstruction of bone tissues in other species as well.

  18. Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).

    Science.gov (United States)

    McGee, Meghan E; Maki, Aaron J; Johnson, Steven E; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2008-02-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.

  19. Activation of α2A-adrenergic signal transduction in chondrocytes promotes degenerative remodelling of temporomandibular joint

    Science.gov (United States)

    Jiao, Kai; Zeng, Guang; Niu, Li-Na; Yang, Hong-xu; Ren, Gao-tong; Xu, Xin-yue; Li, Fei-fei; Tay, Franklin R.; Wang, Mei-qing

    2016-01-01

    This study tested whether activation of adrenoreceptors in chondrocytes has roles in degenerative remodelling of temporomandibular joint (TMJ) and to determine associated mechanisms. Unilateral anterior crossbite (UAC) was established to induce TMJ degeneration in rats. Saline vehicle, α2- and β-adrenoreceptor antagonists or agonists were injected locally into the TMJ area of UAC rats. Cartilage degeneration, subchondral bone microarchitecture and the expression of adrenoreceptors, aggrecans, matrix metalloproteinases (MMPs) and RANKL by chondrocytes were evaluated. Chondrocytes were stimulated by norepinephrine to investigate signal transduction of adrenoreceptors. Increased α2A-adrenoreceptor expression was observed in condylar cartilage of UAC rats, together with cartilage degeneration and subchondral bone loss. Norepinephrine depresses aggrecans expression but stimulates MMP-3, MMP-13 and RANKL production by chondrocytes through ERK1/2 and PKA pathway; these effects were abolished by an α2A-adrenoreceptor antagonist. Furthermore, inhibition of α2A-adrenoreceptor attenuated degenerative remodelling in the condylar cartilage and subchondral bone, as revealed by increased cartilage thickness, proteoglycans and aggrecan expression, and decreased MMP-3, MMP-13 and RANKL expressions in cartilage, increased BMD, BV/TV, and decreased Tb.Sp in subchondral bone. Conversely, activation of α2A-adrenoreceptor intensified aforementioned degenerative changes in UAC rats. It is concluded that activation of α2A-adrenergic signal in chondrocytes promotes TMJ degenerative remodelling by chondrocyte-mediated pro-catabolic activities. PMID:27452863

  20. Bone tissue as a systemic endocrine regulator.

    Science.gov (United States)

    Zofkova, I

    2015-01-01

    Bone is a target tissue for hormones, such as the sex steroids, parathormon, vitamin D, calcitonin, glucocorticoids, and thyroid hormones. In the last decade, other "non-classic" hormones that modulate the bone tissue have been identified. While incretins (GIP and GLP-1) inhibit bone remodeling, angiotensin acts to promote remodeling. Bone morphogenetic protein (BMP) has also been found to have anabolic effects on the skeleton by activating bone formation during embryonic development, as well as in the postnatal period of life. Bone has also been identified as an endocrine tissue that produces a number of hormones, that bind to and modulate extra-skeletal receptors. Osteocalcin occupies a central position in this context. It can increase insulin secretion, insulin sensitivity and regulate metabolism of fatty acids. Moreover, osteocalcin also influences phosphate metabolism via osteocyte-derived FGF23 (which targets the kidneys and parathyroid glands to control phosphate reabsorption and metabolism of vitamin D). Finally, osteocalcin stimulates testosterone synthesis in Leydig cells and thus may play some role in male fertility. Further studies are necessary to confirm clinically important roles for skeletal tissue in systemic regulations. PMID:25470522

  1. Low Bone Density

    Science.gov (United States)

    ... Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone density ... people with normal bone density. Detecting Low Bone Density A bone density test will determine whether you ...

  2. Bone marrow oedema associated with benign and malignant bone tumours

    Energy Technology Data Exchange (ETDEWEB)

    James, S.L.J. [Department of Radiology, Royal Orthopaedic Hospital, Birmingham, B31 2AP (United Kingdom)], E-mail: steven.james@roh.nhs.uk; Panicek, D.M. [Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (United States); Davies, A.M. [Department of Radiology, Royal Orthopaedic Hospital, Birmingham, B31 2AP (United Kingdom)

    2008-07-15

    Bone marrow oedema is associated with a wide variety of pathological processes including both benign and malignant bone tumours. This imaging finding in relation to intraosseous tumours can aid in providing a more focused differential diagnosis. In this review, we will discuss the MR imaging of bone marrow oedema surrounding intraosseous neoplasms. The different pulse sequences used in differentiating underlying tumour from surrounding oedema are discussed along with the role of dynamic contrast enhanced MRI. Benign lesions commonly associated with bone marrow oedema include osteoid osteoma, osteoblastoma, chondroblastoma and Langerhan's cell histiocytosis. Metastases and malignant primary bone tumours such as osteosarcoma, Ewing's sarcoma and chondrosarcoma may also be surrounded by bone marrow oedema. The imaging findings of these conditions are reviewed and illustrated. Finally, the importance of bone marrow oedema in assessment of post chemotherapeutic response is addressed.

  3. Evaluation of Antioxidants in Bone Mineral Density of Iranian

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Oveisi

    2011-03-01

    Full Text Available AbstractObjective(s Bone is a dynamic tissue that is continuously renewed throughout life by the process of bone remodeling. Antioxidant system might be involved in the pathogenesis of bone loss, so the aim of this study was to evaluate the total antioxidant capacity (TAC, vitamin C and vitamin E levels of plasma besides measuring enzymatic antioxidants, superoxide dismutase (SOD, catalase (CAT and glutathione reductase (GR enzymes activity in Iranian osteoporotic women comparing to the control group.Materials and MethodsBone mineral density (BMD of the femoral neck and lumbar spine was measured by dual x-ray absorptiometry. The participants were divided into groups: a total participants (-3.9 ≤ T–score ≤ 3.6 including 192 women, b the control group (T-score ≥ -1 including 76 women, c the total patients (T-score < -1 including 76 women. Then, plasma TAC, vitamin C levels, SOD and GR activities, erythrocyte CAT were measured using spectrophotometrical methods separately, and for vitamin E by HPLC analysis.ResultsComparing the control group and osteoporotic women showed that: a plasma levels for vitamin C and erythrocyte CAT were markedly lower in the patients than in the controls, but plasma activity of TAC, SOD and GR were significantly higher, respectively. b the differences were higher between control and patients with severe disease (T-score <-1.7 comparing to patients in the group with milder disease (-1.7 ≤ T-score <-1. c Femoral neck BMD adjusted with age and BMI showed a positive and significant correlation with plasma levels of vitamin C in all subjects, but this relation was reverse or negative for TAC, SOD and GR.ConclusionIt seems that a physiologic increase in the amount of some antioxidants occurs in osteoporosis; even though this amount may not be sufficient for the human body requirements.

  4. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging of bone marrow in healthy individuals

    International Nuclear Information System (INIS)

    Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) displays microcirculation and permeability by application of contrast-media and diffusion-weighted imaging (DWI) is a tool for quantification of cellularity in the investigated area. Recently published examples cover breast cancer, CNS tumors, head and neck cancer, gastrointestinal cancer, prostate cancer as well as hematologic malignancies. Purpose: To investigated the influence of age, sex, and localization of the investigated region on findings of DCE-MRI and DWI. Material and Methods: DCE-MRI-parameters amplitude A and exchange rate constant kep as well as the DWI-parameter ADC of the bone marrow of the lumbar vertebral column of 30 healthy individuals covering the typical range of age of tumor patients were evaluated. ADC was calculated using b=0 and a maximal b value of either 400 or 750 s/mm2. Results: Amplitude A of DCE-MRI decreased with age (P = 0.01) and amplitude A, exchange rate constant kep as well as ADC based on b = 400 s/mm2 and b = 750 s/mm2, respectively, decreased significantly from the first to the fifth lumbar vertebra with P = 0.02, P = 0.05, P = 0.003, and P = 0.002, respectively. Conclusion: Quantitative parameters of functional imaging techniques in bone marrow are influenced by the age of the examined individual and the anatomical location of the investigated region

  5. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders

    Directory of Open Access Journals (Sweden)

    Sung Sik eChoe

    2016-04-01

    Full Text Available The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue (WAT functions as a key energy reservoir for other organs, whereas the brown adipose tissue (BAT accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secret various hormones, cytokines, and metabolites (termed as adipokines that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic over-nutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

  6. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders.

    Science.gov (United States)

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response. PMID:27148161

  7. New aspects of vascular remodelling: the involvement of all vascular cell types.

    Science.gov (United States)

    McGrath, John C; Deighan, Clare; Briones, Ana M; Shafaroudi, Majid Malekzadeh; McBride, Melissa; Adler, Jeremy; Arribas, Silvia M; Vila, Elisabet; Daly, Craig J

    2005-07-01

    Conventionally, the architecture of arteries is based around the close-packed smooth muscle cells and extracellular matrix. However, the adventitia and endothelium are now viewed as key players in vascular growth and repair. A new dynamic picture has emerged of blood vessels in a constant state of self-maintenance. Recent work raises fundamental questions about the cellular heterogeneity of arteries and the time course and triggering of normal and pathological remodelling. A common denominator emerging in hypertensive remodelling is an early increase in adventitial cell density suggesting that adventitial cells drive remodelling and may initiate subsequent changes such as re-arrangement of smooth muscle cells and extracellular matrix. The organization of vascular smooth muscle cells follows regular arrangements that can be modelled mathematically. In hypertension, new patterns can be quantified in these terms and give insights to how structure affects function. As with smooth muscle, little is known about the organization of the vascular endothelium, or its role in vascular remodelling. Current observations suggest that there may be a close relationship between the helical organization of smooth muscle cells and the underlying pattern of endothelial cells. The function of myoendothelial connections is a topic of great current interest and may relate to the structure of the internal elastic lamina through which the connections must pass. In hypertensive remodelling this must present an organizational challenge. The objective of this paper is to show how the functions of blood vessels depend on their architecture and a continuous interaction of different cell types and extracellular proteins.

  8. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders.

    Science.gov (United States)

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

  9. Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer

    Directory of Open Access Journals (Sweden)

    Thomas R. Cox

    2011-03-01

    Full Text Available Dynamic remodeling of the extracellular matrix (ECM is essential for development, wound healing and normal organ homeostasis. Life-threatening pathological conditions arise when ECM remodeling becomes excessive or uncontrolled. In this Perspective, we focus on how ECM remodeling contributes to fibrotic diseases and cancer, which both present challenging obstacles with respect to clinical treatment, to illustrate the importance and complexity of cell-ECM interactions in the pathogenesis of these conditions. Fibrotic diseases, which include pulmonary fibrosis, systemic sclerosis, liver cirrhosis and cardiovascular disease, account for over 45% of deaths in the developed world. ECM remodeling is also crucial for tumor malignancy and metastatic progression, which ultimately cause over 90% of deaths from cancer. Here, we discuss current methodologies and models for understanding and quantifying the impact of environmental cues provided by the ECM on disease progression, and how improving our understanding of ECM remodeling in these pathological conditions is crucial for uncovering novel therapeutic targets and treatment strategies. This can only be achieved through the use of appropriate in vitro and in vivo models to mimic disease, and with technologies that enable accurate monitoring, imaging and quantification of the ECM.

  10. Dynamics of Alloplastic Bone Grafts on an Early Stage of Corticotomy-Facilitated Orthodontic Tooth Movement in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Hyung-Joo Choi

    2014-01-01

    Full Text Available Alveolar augmented corticotomy is effective in accelerating orthodontic tooth movement, but the effect only lasts for a relatively short time. Therefore, the purpose of this study was to investigate the underlying biology of the immediate periodontal response to orthodontic tooth movement after a corticotomy with alloplastic bone grafts. The results demonstrated that measurable tooth movement began as early as 3 days after the intervention in beagle dogs. Based on the results and histological findings, augmented corticotomy-facilitated orthodontic tooth movement might enhance the condition of the periodontal tissue and the stability of the outcomes of orthodontic treatment.

  11. Dynamics of alloplastic bone grafts on an early stage of corticotomy-facilitated orthodontic tooth movement in beagle dogs.

    Science.gov (United States)

    Choi, Hyung-Joo; Lee, Dong-Yeol; Kim, Tae-Woo

    2014-01-01

    Alveolar augmented corticotomy is effective in accelerating orthodontic tooth movement, but the effect only lasts for a relatively short time. Therefore, the purpose of this study was to investigate the underlying biology of the immediate periodontal response to orthodontic tooth movement after a corticotomy with alloplastic bone grafts. The results demonstrated that measurable tooth movement began as early as 3 days after the intervention in beagle dogs. Based on the results and histological findings, augmented corticotomy-facilitated orthodontic tooth movement might enhance the condition of the periodontal tissue and the stability of the outcomes of orthodontic treatment. PMID:25276787

  12. 1. Morphological Implication on Cellular Response to Mechanical Stress in Bone.

    Science.gov (United States)

    Amizuka, Norio

    2016-08-01

    In bone, there are 3 distinct cell types: an osteoblast, a bone forming cell; an osteocyte embedded in bone matrix as a consequence of being differentiated from an osteoblast; and an osteoclast, a multinucleated giant cell responsible for bone resorption. Bone is always remodeled by replacing old bone with new bone (bone remodeling), by which bone can maintain its stiffness and flexibility. However, in an osteoporotic state, the disrupted balance between bone resorption and formation results in not only markedly reduced bone mass, but also in disorganized geometry of trabecules, which can often give rise to a bone fracture. Osteocytes located in their lacunae insert their fine cytoplasmic processes into narrow passageways referred to as osteocytic canaliculi. Neighboring osteocytes connect to each other by means of a gap junction in their cytoplasmic processes. Therefore, osteocytes and their lacunae/canaliculi appear to form functional syncytium called osteocytic lacunar canalicular system (OLCS). The geometrical distribution of OLCS is poorly arranged in immature bone, while it appears well-arranged distribution in mature bone (cortical bone), in which molecular transports and sensing mechanical stress seems to be efficient, and therefore, may be able to respond to mechanical stress. In this seminar, I will introduce our recent findings on the morphology and function of OLCS which may respond to mechanical stress. PMID:27441762

  13. Bone cement and bone grafting in nail path to strengthen dynamic hip screw fixation for senile osteoporotic intertrochanteric fracture%骨水泥、钉道植骨强化动力髋螺钉固定修复老年骨质疏松性股骨转子间骨折

    Institute of Scientific and Technical Information of China (English)

    林周胜; 孙鸿涛; 夏雄智; 江成; 黎飞猛

    2015-01-01

    背景:对于老年骨质疏松性髋部骨折的动力髋螺钉固定,如能避免使用过程中造成的骨量丢失,或是采用其他手段增加固定螺钉把持力,将改善动力髋螺钉固定的治疗效果。目的:对比研究3种固定方式修复老年骨质疏松性股骨转子间骨折的效果。方法:回顾性分析近5年来采用常规动力髋螺钉内固定、骨水泥强化后动力髋螺钉固定及主钉道压配植骨配合动力髋螺钉固定3种固定方式治疗老年骨质疏松性股骨转子间骨折患者的资料,分别设为对照组、骨水泥组和植骨组。结果与结论:经固定后2年随访,植骨组、骨水泥组和对照组Harris髋关节功能评分优良率分别为95%,80%,70%。植骨组骨折临床愈合时间明显缩短(P <0.05),出现螺钉固定失败情况与骨水泥组相当。对照组较其他2组相对更多出现退钉等内固定失败情况。结果表明,与其他常规动力髋螺钉内固定、骨水泥强化后动力髋螺钉固定方式相比较,主钉道压配植骨配合动力髋螺钉内固定的疗效及安全性更好。%BACKGROUND:In dynamic hip screw fixation for treating aged osteoporotic intertrochanteric fracture, avoiding the loss of bone mass, or by other means that can increase the fixed screw pulout strength, wil improve the therapeutic effect of dynamic hip screw fixation. OBJECTIVE: To compare the effects of three kinds of repair methods on aged osteoporotic intertrochanteric fracture. METHODS:Data of aged osteoporosis intertrochanteric fracture patients, who received conventional dynamic hip screw fixation, bone cement augmentation with dynamic hip screw fixation and bone grafting with dynamic hip screw fixation, were retrospectively analyzed. They were divided into control group, bone cement group and bone grafting group. RESULTS AND CONCLUSION:After two years of folow-up, the excelent and good rates of Harris hip function were 95%, 80% and 70% in

  14. Lanthanum carbonate stimulates bone formation in a rat model of renal insufficiency with low bone turnover.

    Science.gov (United States)

    Fumoto, Toshio; Ito, Masako; Ikeda, Kyoji

    2014-09-01

    Control of phosphate is important in the management of chronic kidney disease with mineral and bone disorder (CKD-MBD), for which lanthanum carbonate, a non-calcium phosphate-binding agent, has recently been introduced; however, it remains to be determined whether it has any beneficial or deleterious effect on bone remodeling. In the present study, the effects of lanthanum carbonate were examined in an animal model that mimics low turnover bone disease in CKD, i.e., thyroparathyroidectomized (TPTX) and 5/6 nephrectomized (NX) rats undergoing a constant infusion of parathyroid hormone (PTH) and thyroxine injections (TPTX-PTH-5/6NX). Bone histomorphometry at the second lumbar vertebra and tibial metaphysis revealed that both bone formation and resorption were markedly suppressed in the TPTX-PTH-5/6NX model compared with the sham-operated control group, and treatment with lanthanum carbonate was associated with the stimulation of bone formation but not an acceleration of bone resorption. Lanthanum treatment caused a robust stimulation of bone formation with an activation of osteoblasts on the endosteal surface of femoral diaphysis, leading to an increase in cortical bone volume. Thus, lanthanum carbonate has the potential to stimulate bone formation in cases of CKD-MBD with suppressed bone turnover. PMID:24126694

  15. Characterization of bone quality in prostate cancer bone metastases using Raman spectroscopy

    Science.gov (United States)

    Bi, Xiaohong; Patil, Chetan; Morrissey, Colm; Roudier, Martine P.; Mahadevan-Jansen, Anita; Nyman, Jeffry

    2010-02-01

    Prostate cancer is the most common primary tumor in men, with a high propensity to metastasize to bone. Bone metastases in prostate cancer are associated with active pathologic bone remodeling, leading to increased mortality and morbidity. Detailed characterization of bone metastases is important in the management of prostate cancer. Raman spectroscopy was applied in this study to investigate the structure and composition of metastatic bone in prostate cancer with the ultimate goal of identifying spectral features that are related to the alterations in bone quality as the bone metastases develop. Osteoblastic-, osteolytic- and tumor-absent bone specimens from prostate cancer patients were investigated using bench-top Raman microspectroscopy. Raman derived measurements of collagen mineralization, mineral crystallinity, and carbonate substitution were calculated. The osteolytic lesions demonstrated significantly lower collagen mineralization, determined by phosphate ν1/proline, and higher carbonate substitution than normal and osteoblastic bones. Mineral crystallinity was significantly lower in both blastic and lytic specimens. In addition, a significant increase in the ratio of hydroxyproine: proline was observed in the osteoblastic specimen, indicating an increase in the content of hydroxyproline at the blastic lesions. This study demonstrate that Raman spectroscopy shows promise in determining alterations in osteoblastic and osteolytic bone metastases as well as assessing the response of metastatic bone to therapies.

  16. Evaluation of treatment response of cilengitide in an experimental model of breast cancer bone metastasis using dynamic PET with 18F-FDG.

    Science.gov (United States)

    Cheng, Caixa; Komljenovic, Dorde; Pan, Leyun; Dimitrakopoulou-Strauss, Antonia; Strauss, Ludwig; Bäuerle, Tobias

    2011-01-01

    The purpose of this study was the assessment of the feasibility of dynamic positron emission tomography (PET) studies with fluorine-18 fluorodeoxyglucose ((18)F-FDG) to quantify effects of the cyclic Arg-Gly-Asp peptide cilengitide, which targets the ανβ 3 and ανβ 5 integrin receptors in rats with breast cancer bone metastases. Rats were inoculated with MDA-MB-231 breast cancer cells, followed by the development of lytic lesions in the hind leg. Rats with lytic lesions were treated with cilengitide five times weekly on a continuous basis from days 30 to 55 after tumor cell inoculation. Dynamic PET studies with (18)F-FDG were performed in untreated (n=9), controlled (n=4) and treated rats (n=6). The data were assessed using learning-machine two-tissue compartmental analysis. The (18)F-FDG kinetic parameters obtained by two-tissue compartmental model learning-machine showed significant differences when individual parameters were compared between the control group and treated animals. Quantitative assessment of the tracer kinetics and the application of classification analysis to the data provided us with evidence to identify those tumors that demonstrated effect of cilengitide treatment. The transport rate K1 and the phosphorylation rate k3 were significantly different (P=0.033 and 0.038, respectively). Classification analysis based on support vector machines ranking feature elimination of the combination of PET parameters revealed an overall accuracy of 80.0% between treated animals and the control group. We were able to identify 83.3% treated animals compared with the control group based on k2 and VB. In conclusion, the results revealed that cilengitide treatment of experimental breast cancer bone metastases had a significant therapeutic impact on (18)F-FDG kinetics. PMID:21512659

  17. In-vivo three-dimensional carpal bone kinematics during flexion-extension and radio-ulnar deviation of the wrist: Dynamic motion versus step-wise static wrist positions.

    Science.gov (United States)

    Foumani, M; Strackee, S D; Jonges, R; Blankevoort, L; Zwinderman, A H; Carelsen, B; Streekstra, G J

    2009-12-11

    An in-vivo approach to the measurement of three-dimensional motion patterns of carpal bones in the wrist may have future diagnostic applications, particularly for ligament injuries of the wrist. Static methods to measure carpal kinematics in-vivo only provide an approximation of the true kinematics of the carpal bones. This study is aimed at finding the difference between dynamically and statically acquired carpal kinematics. For eight healthy subjects, static and a dynamic measurements of the carpal kinematics were performed for a flexion-extension and a radio-ulnar deviation movement. Dynamic scans were acquired by using a four-dimensional X-ray imaging system during an imposed cyclic motion. To assess static kinematics of the wrists, three-dimensional rotational X-ray scans were acquired during step-wise flexion-extension and radio-ulnar deviation. The helical axis rotations and the rotation components. i.e. flexion-extension, radio-ulnar deviation and pro-supination were the primary parameters. Linear mixed model statistical analysis was used to determine the significance of the difference between the dynamically and statically acquired rotations of the carpal bones. Small and in most cases negligible differences were observed between the dynamic motion and the step-wise static motion of the carpal bones. The conclusion is that in the case of individuals without any pathology of the wrist, carpal kinematics can be studied either dynamically or statically. Further research is required to investigate the dynamic in-vivo carpal kinematics in patients with dynamic wrist problems.

  18. Correlation between computer-aided dynamic gadolinium-enhanced MRI assessment of inflammation and semi-quantitative synovitis and bone marrow oedema scores of the wrist in patients with rheumatoid arthritis--a cohort study

    DEFF Research Database (Denmark)

    Boesen, Mikael; Kubassova, Olga; Bouert, Rasmus;

    2012-01-01

    Objective. To test the correlation between assessment of inflammation using dynamic contrast-enhanced MRI (DCE-MRI) analysed by a novel computer-aided approach and semi-quantitative scores of synovitis and bone marrow oedema (BME) using the OMERACT-RA MRI Scoring (RAMRIS) system, in the wrist of ...

  19. BMP-2 Is Involved in Scleral Remodeling in Myopia Development.

    Directory of Open Access Journals (Sweden)

    Honghui Li

    Full Text Available The development of myopia is associated with scleral remodeling, but it is unclear which factors regulate this process. This study investigated bone morphogenetic protein-2 (BMP-2 expression in the sclera of guinea pigs with lens-induced myopia (LIM and after recovery from myopia and evaluated the effect of BMP-2 on extracellular matrix (ECM synthesis in human scleral fibroblasts (HSFs cultured in vitro. Lens-induced myopia was brought about in two groups of guinea pigs (the lens-induced myopia and myopia recovery groups by placing -4.00 D lenses on the right eye for three weeks. The left eye served as a contralateral control. In the recovery group, the lenses were removed after one week. The refractive power and axial length of the eyes were measured, and the BMP-2 expression levels in the sclera were measured. After three weeks, the lens-induced eyes acquired relative myopia in both groups of guinea pigs. Immunostaining of the eyeballs revealed significantly decreased BMP-2 expression in the posterior sclera of the myopic eyes compared to the contralateral eyes. One week after lens removal, BMP-2 expression recovered, and no differences were observed between the experimental and contralateral eyes in the recovery group. HSFs were cultured with BMP-2 or transforming growth factor-β1 (TGF-β1. Type I and type III collagen synthesis was significantly up-regulated following BMP-2 treatment in culture after one and two weeks, but the ratio of type III to type I collagen mRNA was not increased. Biosynthesis of glycosaminoglycan (GAG and aggrecan was increased in HSFs treated with BMP-2. Some chondrogenesis-associated genes expression increased in HSFs treated with BMP-2. From this study, we concluded that BMP-2 is involved in scleral remodeling in the development and recovery of lens-induced myopia.

  20. BMP-2 Is Involved in Scleral Remodeling in Myopia Development

    Science.gov (United States)

    Li, Honghui; Cui, Dongmei; Zhao, Feng; Huo, Lijun; Hu, Jianmin; Zeng, Junwen

    2015-01-01

    The development of myopia is associated with scleral remodeling, but it is unclear which factors regulate this process. This study investigated bone morphogenetic protein-2 (BMP-2) expression in the sclera of guinea pigs with lens-induced myopia (LIM) and after recovery from myopia and evaluated the effect of BMP-2 on extracellular matrix (ECM) synthesis in human scleral fibroblasts (HSFs) cultured in vitro. Lens-induced myopia was brought about in two groups of guinea pigs (the lens-induced myopia and myopia recovery groups) by placing -4.00 D lenses on the right eye for three weeks. The left eye served as a contralateral control. In the recovery group, the lenses were removed after one week. The refractive power and axial length of the eyes were measured, and the BMP-2 expression levels in the sclera were measured. After three weeks, the lens-induced eyes acquired relative myopia in both groups of guinea pigs. Immunostaining of the eyeballs revealed significantly decreased BMP-2 expression in the posterior sclera of the myopic eyes compared to the contralateral eyes. One week after lens removal, BMP-2 expression recovered, and no differences were observed between the experimental and contralateral eyes in the recovery group. HSFs were cultured with BMP-2 or transforming growth factor-β1 (TGF-β1). Type I and type III collagen synthesis was significantly up-regulated following BMP-2 treatment in culture after one and two weeks, but the ratio of type III to type I collagen mRNA was not increased. Biosynthesis of glycosaminoglycan (GAG) and aggrecan was increased in HSFs treated with BMP-2. Some chondrogenesis-associated genes expression increased in HSFs treated with BMP-2. From this study, we concluded that BMP-2 is involved in scleral remodeling in the development and recovery of lens-induced myopia. PMID:25965995

  1. Strategies for Energy Efficient Remodeling: SEER 2003 Case Study Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2004-11-01

    The goal of the Strategies for Energy Efficiency in Remodeling (SEER) project is to provide information, based on research and case studies, to remodelers and consumers about opportunities to increase home energy performance.

  2. Bone Cancer

    Science.gov (United States)

    ... cancer. Surgery is often the main treatment for bone cancer. Other treatments may include amputation, chemotherapy, and radiation therapy. Because bone cancer can come back after treatment, regular follow-up visits are important. NIH: National ...

  3. Bone: from a reservoir of minerals to a regulator of energy metabolism

    OpenAIRE

    Confavreux, Cyrille B.

    2011-01-01

    Besides locomotion, organ protection, and calcium–phosphorus homeostasis, the three classical functions of the skeleton, bone remodeling affects energy metabolism through uncarboxylated osteocalcin, a recently discovered hormone secreted by osteoblasts. This review traces how energy metabolism affects osteoblasts through the central control of bone mass involving leptin, serotoninergic neurons, the hypothalamus, and the sympathetic nervous system. Next, the role of osteocalcin (insulin secret...

  4. The effects of bone erosion from aortic aneurysm on the regional uptake of FDG

    DEFF Research Database (Denmark)

    Louring-Andersen, J.; Law, I.

    2008-01-01

    inflammation or malignancy. The FDG uptake was interpreted as evidence of ongoing nonmalignant bone remodeling secondary to the pulsating pressure of the aneurysm. This case demonstrates a potential pitfall in the interpretation of bone associated foci using FDG PET, and once again underlines the importance...

  5. Osteoblasts in Bone Physiology—Mini Review

    Directory of Open Access Journals (Sweden)

    Orit Rosenberg

    2012-04-01

    Full Text Available Bone structural integrity and shape are maintained by removal of old matrix by osteoclasts and in-situ synthesis of new bone by osteoblasts. These cells comprise the basic multicellular unit (BMU. Bone mass maintenance is determined by the net anabolic activity of the BMU, when the matrix elaboration of the osteoblasts equals or exceeds the bone resorption by the osteoclasts. The normal function of the BMU causes a continuous remodeling process of the bone, with deposition of bony matrix (osteoid along the vectors of the generated force by gravity and attached muscle activity. The osteoblasts are derived from mesenchymal stem cells (MSCs. Circulating hormones and locally produced cytokines and growth factors modulate the replication and differentiation of osteoclast and osteoblast progenitors. The appropriate number of the osteoblasts in the BMU is determined by the differentiation of the precursor bone-marrow stem cells into mature osteoblasts, their proliferation with subsequent maturation into metabolically active osteocytes, and osteoblast degradation by apoptosis. Thus, the two crucial points to target when planning to control the osteoblast population are the processes of cell proliferation and apoptosis, which are regulated by cellular hedgehog and Wnt pathways that involve humoral and mechanical stimulations. Osteoblasts regulate both bone matrix synthesis and mineralization directly by their own synthetic activities, and bone resorption indirectly by its paracrinic effects on osteoclasts. The overall synthetic and regulatory activities of osteoblasts govern bone tissue integrity and shape.

  6. Bone regeneration: current concepts and future directions

    Directory of Open Access Journals (Sweden)

    McGonagle Dennis

    2011-05-01

    Full Text Available Abstract Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis.

  7. Osteoporosis: Modern Paradigms for Last Century's Bones.

    Science.gov (United States)

    Kruger, Marlena C; Wolber, Frances M

    2016-01-01

    The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a "brittle bone" disease that occurs in post-menopausal, thin, Caucasian women with low calcium intakes and/or vitamin D insufficiency. However, a study of black women in Africa demonstrated that higher proportions of body fat did not protect bone health. Isoflavone interventions in Asian postmenopausal women have produced inconsistent bone health benefits, due in part to population heterogeneity in enteric bacterial metabolism of daidzein. A comparison of women and men in several Asian countries identified significant differences between countries in the rate of bone health decline, and a high incidence rate of osteoporosis in both sexes. These studies have revealed significant differences in genetic phenotypes, debunking long-held beliefs and leading to new paradigms in study design. Current studies are now being specifically designed to assess genotype differences between Caucasian, Asian, African, and other phenotypes, and exploring alternative methodology to measure bone architecture. PMID:27322315

  8. Connexin Remodeling Contributes to Atrial Fibrillation

    OpenAIRE

    Michelle M Jennings; J Kevin Donahue

    2013-01-01

    Atrial fibrillation significantly contributes to mortality and morbidity through increased risk of stroke, heart failure and myocardial infarcts. Investigations of mechanisms responsible for the development and maintenance of atrial fibrillation have highlighted the importance of gap junctional remodeling. Connexins 40 and 43, the major atrial gap junctional proteins, undergo considerable alterations in expression and localization in atrial fibrillation, creating an environment conducive to s...

  9. Revealing remodeler function: Varied and unique

    Science.gov (United States)

    Eastlund, Allen

    Chromatin remodelers perform a necessary and required function for the successful expression of our genetic code. By modifying, shifting, or ejecting nucleosomes from the chromatin structure they allow access to the underlying DNA to the rest of the cell's machinery. This research has focused on two major remodeler motors from major families of chromatin remodelers: the trimeric motor domain of RSC and the motor domain of the ISWI family, ISWI. Using primarily stopped-flow spectrofluorometry, I have categorized the time-dependent motions of these motor domains along their preferred substrate, double-stranded DNA. Combined with collected ATP utilization data, I present the subsequent analysis and associated conclusions that stem from the underlying assumptions and models. Interestingly, there is little in common between the investigated proteins aside from their favored medium. While RSC exhibits modest translocation characteristics and highly effective motion with the ability for large molecular forces, ISWI is not only structurally different but highly inefficient in its motion leading to difficulties in determining its specific translocation mechanics. While chromatin remodeling is a ubiquitous facet of eukaryotic life, there remains much to be understood about their general mechanisms.

  10. Link between vitamin D and airway remodeling

    Directory of Open Access Journals (Sweden)

    Berraies A

    2014-04-01

    Full Text Available Anissa Berraies, Kamel Hamzaoui, Agnes HamzaouiPediatric Respiratory Diseases Department, Abderrahmen Mami Hospital, Ariana, and Research Unit 12SP15 Tunis El Manar University, Tunis, TunisiaAbstract: In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma.Keywords: vitamin D, asthma, airway remodeling, airway smooth muscle, supplementation

  11. Interleukin-20 promotes airway remodeling in asthma.

    Science.gov (United States)

    Gong, Wenbin; Wang, Xin; Zhang, Yuguo; Hao, Junqing; Xing, Chunyan; Chu, Qi; Wang, Guicheng; Zhao, Jiping; Wang, Junfei; Dong, Qian; Liu, Tian; Zhang, Yuanyuan; Dong, Liang

    2014-12-01

    Previous studies have demonstrated that interleukin-20 (IL-20) is a pro-inflammatory cytokine, and it has been implicated in psoriasis, lupus nephritis, rheumatoid arthritis, atherosclerosis, and ulcerative colitis. Little is known about the effects of IL-20 in airway remodeling in asthma. The aim of our study was to demonstrate the function of IL-20 in airway remodeling in asthma. To identify the expression of IL-20 and its receptor, IL-20R1/IL-20R2, in the airway epithelium in bronchial tissues, bronchial biopsy specimens were collected from patients and mice with asthma and healthy subjects and stained with specific antibodies. To characterize the effects of IL-20 in asthmatic airway remodeling, we silenced and stimulated IL-20 in cell lines isolated from mice by shRNA and recombinant protein approaches, respectively, and detected the expression of α-SMA and FN-1 by Western blot analysis. First, overexpression of IL-20 and its receptor, IL-20R1/IL-20R2, was detected in the airway epithelium collected from patients and mice with asthma. Second, IL-20 increased the expression of fibronectin-1 and α-SMA, and silencing of IL-20 in mouse lung epithelial (MLE)-12 cells decreased the expression of fibronectin-1 and α-SMA. IL-20 may be a critical cytokine in airway remodeling in asthma. This study indicates that targeting IL-20 and/or its receptors may be a new therapeutic strategy for asthma. PMID:25028099

  12. Re-Modelling as De-Professionalisation

    Science.gov (United States)

    Thompson, Meryl

    2006-01-01

    The article sets out the consequences of the British Government's remodelling agenda and its emphasis on less demarcation, for the professional status of teachers in England. It describes how the National Agreement on Raising Standards and Tackling Workload, reached between five of the six trade unions for teachers and headteachers paves the way…

  13. Standard bone healing stages occur during delayed bone healing, albeit with a different temporal onset and spatial distribution of callus tissues

    OpenAIRE

    Peters, Anja; Schell, Hanna; Bail, Hermann J.; Hannemann, Marion; Schumann, Tanja; Duda, Georg N; Lienau, Jasmin

    2010-01-01

    Bone healing is considered as a recapitulation of a developmental program initiated at the time of injury. This study tested the hypothesis that in delayed bone healing the regular cascade of healing events, including remodeling of woven to lamellar bone, would be similar compared to standard healing, although the temporal onset would be delayed. A tibial osteotomy was performed in sheep and stabilized with a rotationally unstable fixator leading to delayed healing....

  14. ATP independent and ATP dependent chromatin remodeling in wheat

    International Nuclear Information System (INIS)

    Unraveling the biochemistry of chromatin dynamics during DNA replication, repair, recombination as well as transcription is the current challenge in biology. The nucleosomes containing histone octamer are the crucial elements responsible for winding and unwinding eukaryotic DNA. During DNA centric events, these nucleosomes translocate along the DNA with concomitant covalent modifications of histones. We explored these mechanisms in wheat seedlings after irradiation with survivable dose of 60Co-γ radiations. The histones isolated from