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Sample records for integrate bone remodelling

  1. 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

  2. The Effect of Irradiation on Bone Remodelling and the Structural Integrity of the Vertebral Column

    Science.gov (United States)

    1990-01-01

    1965. Schantz, A, AL Schiller and SP Kadish. Localized aplasia in irradiated vertebral bone marrow: A frequently overlooked gross observation. Arch...undergo the bone remodelling sequence together bone marrow-the soft, fatty substance filling the medullary cavaties and spongy extremities of the long

  3. Immunoregulation of bone remodelling.

    Science.gov (United States)

    Singh, Ajai; Mehdi, Abbass A; Srivastava, Rajeshwer N; Verma, Nar Singh

    2012-05-01

    Remodeling, a continuous physiological process maintains the strength of the bones, which maintains a delicate balance between bone formation and resorption process. This review gives an insight to the complex interaction and correlation between the bone remodeling and the corresponding changes in host immunological environment and also summarises the most recent developments occuring in the understanding of this complex field. T cells, both directly and indirectly increase the expression of receptor activator of nuclear factor kB ligand (RANKL); a vital step in the activation of osteoclasts, thus positively regulates the osteoclastogenesis. Though various cytokines, chemikines, transcription factors and co-stimulatory molecules are shared by both skeletal and immune systems, but researches are being conducted to establish and analyse their role and / or control on this complex but vital process. The understanding of this part of research may open new horizons in the management of inflammatory and autoimmune diseases, resulting into bone loss and that of osteoporosis also.

  4. Integration of a Finite Element Model with the DAP Bone Remodeling Model to Characterize Bone Response to Skeletal Loading

    Science.gov (United States)

    Werner, Christopher R.; Mulugeta, Lealem; Myers, J. G.; Pennline, J. A.

    2015-01-01

    NASA's Digital Astronaut Project (DAP) has developed a bone remodeling model that has been validated for predicting volumetric bone mineral density (vBMD) changes of trabecular and cortical bone in the absence of mechanical loading. The model was recently updated to include skeletal loading from exercise and free living activities to maintain healthy bone using a new daily load stimulus (DLS). This new formula was developed based on an extensive review of existing DLS formulas, as discussed in the abstract by Pennline et al. The DLS formula incorporated into the bone remodeling model utilizes strains and stress calculated from finite element model (FEM) of the bone region of interest. The proximal femur was selected for the initial application of the DLS formula, with a specific focus on the femoral neck. METHODS: The FEM was generated from CAD geometry of a femur using de-identified CT data. The femur was meshed using linear tetrahedral elements Figure (1) with higher mesh densities in the femoral neck region, which is the primary region of interest for the initial application of the DLS formula in concert with the DAP bone remodeling model. Nodal loads were applied to the femoral head and the greater trochanter and the base of the femur was held fixed. An L2 norm study was conducted to reduce the length of the femoral shaft without significantly impacting the stresses in the femoral neck. The material properties of the FEM of the proximal femur were separated between cortical and trabecular regions to work with the bone remodeling model. Determining the elements with cortical material properties in the FEM was based off of publicly available CT hip scans [4] that were segmented, cleaned, and overlaid onto the FEM.

  5. On the development of an integrated bone remodeling law for orthodontic tooth movements models using the Finite Element Method.

    OpenAIRE

    Mengoni, Marlène

    2012-01-01

    One of the guiding principles in orthodontics is to gradually impose progressive and irreversible bone deformations due to remodeling using specific force systems on the teeth. Bone remodeling leads the teeth into new positions with two tissues having a major influence: the periodontal ligament and the alveolar bone. Their mechanical and biological/physiological reactions to orthodontic forces are tightly linked. This mechanical biological coupling can be treated in biomechanical mod...

  6. Orchestration of bone remodeling

    NARCIS (Netherlands)

    Moester, Martiene Johanna Catharina

    2014-01-01

    In healthy individuals, a balance exists between bone formation and resorption. Disruption of this balance can lead to higher or lower bone mass, and disease such as osteoporosis. Treatment for osteoporosis generally inhibits bone resorption, but does not rebuild bone to a healthy strength. More kno

  7. Bone Remodeling Monitor

    Science.gov (United States)

    Foucar, Charlie; Goldberg, Leslie; Hon, Bodin; Moore, Shannon; Williams, Evan

    2009-01-01

    The impact of bone loss due to different mechanical loadings in microgravity is a major concern for astronauts upon reintroduction to gravitational forces in exploration missions to the Moon and Mars. it has been shown that astronauts not only lose bone at differing rates, with levels up to 2% per month, but each astronaut will respond to bone loss treatments differently. Pre- and post-flight imaging techniques and frozen urine samples for post-flight laboratory immunoassays To develop a novel, non-invasive, highly . sensitive, portable, intuitive, and low-powered device to measure bone resorption levels in 'real time' to provide rapid and Individualized feedback to maximize the efficacy of bone loss countermeasures 1. Collect urine specimen and analyze the level of bone resorption marker, DPD (deoxypridinoline) excreted. 2. Antibodies specific to DPD conjugated with nanoshells and mixed with specimen, the change in absorbance from agglutination is measured by an optical device. 3. The concentration of DPD is displayed and recorded on a PDA

  8. 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

  9. Implementation and Integration of a Finite Element Model into the Bone Remodeling Model to Characterize Skeletal Loading

    Science.gov (United States)

    Werner, C. R.; Lewandowski, B.; Boppana, A.; Pennline, J. A.

    2017-01-01

    NASA's Digital Astronaut Project is developing a bone physiology model to predict changes in bone mineral density over the course of a space mission. The model intends to predict bone loss due to exposure in microgravity as well as predicting bone maintenance due to mechanical stimulus generated by exercise countermeasures. These predictions will be used to inform exercise device efficacy and to help design exercise protocols that will maintain bone mineral density during long exposures to microgravity during spaceflight. The mechanical stimulus and the stresses that are exhibited on the bone are important factors for bone remodeling. These stresses are dependent on the types of exercise that are performed and vary throughout the bone due to the geometry. A primary area of focus for bone health is the proximal femur. This location is critical in transmitting loads between the upper and lower body and have been known to be a critical failure point in older individuals with conditions like osteoporosis.

  10. Effects of remifemin treatment on bone integrity and remodeling in rats with ovariectomy-induced osteoporosis.

    Directory of Open Access Journals (Sweden)

    Guangxia Cui

    Full Text Available This study aims to evaluate the effects of Remifemin (isopropanolic extract of Cimicifuga Racemosa on postmenopausal osteoporosis. 120 female Sprague-Dawley rats were randomly assigned to four groups: sham surgery with vehicle, ovariectomy with vehicle, ovariectomy with estradiol valerate, or ovariectomy with Remifemin. Daily oral administrations of the vehicle, estradiol valerate, or Remifemin began 2 weeks after surgery and lasted to 4, 8, or 12 weeks. Ten rats in each group were sacrificed at each timestep with assessment of bone mineral density, trabecular bone structure, and biomechanical parameters of the femur and lumbar vertebra. Bone turnover markers were evaluated 12 weeks after surgery. Both drugs prevented bone density loss in the distal end of the femur and preserved the trabecular bone structure in both the lumbar vertebra and distal end of the femur following ovariectomy. Both drugs protected bone stiffness at the tested regions and reduced bone reabsorption in ovariectomized rats. The preventive effects of Remifemin against bone-loss can rival those of estradiol valerate if treatment duration is adequately extended. In conclusion, Remifemin may demonstrate equivalent effects to estradiol valerate in terms of preventing postmenopausal osteoporosis.

  11. Effects of remifemin treatment on bone integrity and remodeling in rats with ovariectomy-induced osteoporosis.

    Science.gov (United States)

    Cui, Guangxia; Leng, Huijie; Wang, Ke; Wang, Jianwei; Zhu, Sainan; Jia, Jing; Chen, Xing; Zhang, Weiguang; Qin, Lihua; Bai, Wenpei

    2013-01-01

    This study aims to evaluate the effects of Remifemin (isopropanolic extract of Cimicifuga Racemosa) on postmenopausal osteoporosis. 120 female Sprague-Dawley rats were randomly assigned to four groups: sham surgery with vehicle, ovariectomy with vehicle, ovariectomy with estradiol valerate, or ovariectomy with Remifemin. Daily oral administrations of the vehicle, estradiol valerate, or Remifemin began 2 weeks after surgery and lasted to 4, 8, or 12 weeks. Ten rats in each group were sacrificed at each timestep with assessment of bone mineral density, trabecular bone structure, and biomechanical parameters of the femur and lumbar vertebra. Bone turnover markers were evaluated 12 weeks after surgery. Both drugs prevented bone density loss in the distal end of the femur and preserved the trabecular bone structure in both the lumbar vertebra and distal end of the femur following ovariectomy. Both drugs protected bone stiffness at the tested regions and reduced bone reabsorption in ovariectomized rats. The preventive effects of Remifemin against bone-loss can rival those of estradiol valerate if treatment duration is adequately extended. In conclusion, Remifemin may demonstrate equivalent effects to estradiol valerate in terms of preventing postmenopausal osteoporosis.

  12. 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

  13. Bone remodeling as a spatial evolutionary game.

    Science.gov (United States)

    Ryser, Marc D; Murgas, Kevin A

    2017-04-07

    Bone remodeling is a complex process involving cell-cell interactions, biochemical signaling and mechanical stimuli. Early models of the biological aspects of remodeling were non-spatial and focused on the local dynamics at a fixed location in the bone. Several spatial extensions of these models have been proposed, but they generally suffer from two limitations: first, they are not amenable to analysis and are computationally expensive, and second, they neglect the role played by bone-embedded osteocytes. To address these issues, we developed a novel model of spatial remodeling based on the principles of evolutionary game theory. The analytically tractable framework describes the spatial interactions between zones of bone resorption, bone formation and quiescent bone, and explicitly accounts for regulation of remodeling by bone-embedded, mechanotransducing osteocytes. Using tools from the theory of interacting particle systems we systematically classified the different dynamic regimes of the spatial model and identified regions of parameter space that allow for global coexistence of resorption, formation and quiescence, as observed in physiological remodeling. In coexistence scenarios, three-dimensional simulations revealed the emergence of sponge-like bone clusters. Comparison between spatial and non-spatial dynamics revealed substantial differences and suggested a stabilizing role of space. Our findings emphasize the importance of accounting for spatial structure and bone-embedded osteocytes when modeling the process of bone remodeling. Thanks to the lattice-based framework, the proposed model can easily be coupled to a mechanical model of bone loading.

  14. Bone Remodelling Markers in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    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.

  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. Interactions between remodelling, architecture and tissue properties in cancellous bone

    OpenAIRE

    Linden, Jacqueline

    2003-01-01

    textabstractThe aim of the research projects described in this thesis was to gain more insight in the regulation of bone remodeling and in the interactions between bone remodeling, architecture and bone tissue properties. The most striking changes during aging and osteoporosis take place in cancellous bone. For this reason, the research presented in this thesis focussed on bone remodeling in cancellous bone. We used computer modeling, finite element calculations and in vivo labeled bone speci...

  17. Osteoblast recruitment routes in human cancellous bone remodeling

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  18. Bone remodeling induced by dental implants of functionally graded materials.

    Science.gov (United States)

    Lin, Daniel; Li, Qing; Li, Wei; Swain, Michael

    2010-02-01

    Functionally graded material (FGM) had been developed as a potential implant material to replace titanium for its improved capability of initial osseointegration. The idea behind FGM dental implant is that its properties can be tailored in accordance with the biomechanical needs at different regions adapting to its hosting bony tissues, therefore creating an improved overall integration and stability in the entire restoration. However, there have been very few reports available so far on predicting bone remodeling induced by FGM dental implants. This article aims to evaluate bone remodeling when replacing the titanium with a hydroxyapatite/collagen (HAP/Col) FGM model. A finite element model was constructed in the buccal-lingual section of a dental implant-bone structure generated from in vivo CT scan images. The remodeling simulation was performed over a 4 year healing period. Comparisons were made between the titanium implant and various FGM implants of this model. The FGM implants showed an improved bone remodeling outcome. The study is expected to provide a basis for future development of FGM implants.

  19. Development of Bone Remodeling Model for Spaceflight Bone Physiology Analysis

    Science.gov (United States)

    Pennline, James A.; Werner, Christopher R.; Lewandowski, Beth; Thompson, Bill; Sibonga, Jean; Mulugeta, Lealem

    2015-01-01

    Current spaceflight exercise countermeasures do not eliminate bone loss. Astronauts lose bone mass at a rate of 1-2% a month (Lang et al. 2004, Buckey 2006, LeBlanc et al. 2007). This may lead to early onset osteoporosis and place the astronauts at greater risk of fracture later in their lives. NASA seeks to improve understanding of the mechanisms of bone remodeling and demineralization in 1g in order to appropriately quantify long term risks to astronauts and improve countermeasures. NASA's Digital Astronaut Project (DAP) is working with NASA's bone discipline to develop a validated computational model to augment research efforts aimed at achieving this goal.

  20. Histamine in regulation of bone remodeling processes

    Directory of Open Access Journals (Sweden)

    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.

  1. Chondromodulin I Is a Bone Remodeling Factor

    Science.gov (United States)

    Nakamichi, Yuko; Shukunami, Chisa; Yamada, Takashi; Aihara, Ken-ichi; Kawano, Hirotaka; Sato, Takashi; Nishizaki, Yuriko; Yamamoto, Yoko; Shindo, Masayo; Yoshimura, Kimihiro; Nakamura, Takashi; Takahashi, Naoyuki; Kawaguchi, Hiroshi; Hiraki, Yuji; Kato, Shigeaki

    2003-01-01

    Chondromodulin I (ChM-I) was supposed from its limited expression in cartilage and its functions in cultured chondrocytes as a major regulator in cartilage development. Here, we generated mice deficient in ChM-I by targeted disruption of the ChM-I gene. No overt abnormality was detected in endochondral bone formation during embryogenesis and cartilage development during growth stages of ChM-I−/− mice. However, a significant increase in bone mineral density with lowered bone resorption with respect to formation was unexpectedly found in adult ChM-I−/− mice. Thus, the present study established that ChM-I is a bone remodeling factor. PMID:12509461

  2. Interactions between remodelling, architecture and tissue properties in cancellous bone

    NARCIS (Netherlands)

    J.C. van der Linden (Jacqueline)

    2003-01-01

    textabstractThe aim of the research projects described in this thesis was to gain more insight in the regulation of bone remodeling and in the interactions between bone remodeling, architecture and bone tissue properties. The most striking changes during aging and osteoporosis take place in cancello

  3. Interactions between remodelling, architecture and tissue properties in cancellous bone

    NARCIS (Netherlands)

    J.C. van der Linden (Jacqueline)

    2003-01-01

    textabstractThe aim of the research projects described in this thesis was to gain more insight in the regulation of bone remodeling and in the interactions between bone remodeling, architecture and bone tissue properties. The most striking changes during aging and osteoporosis take place in cancello

  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. 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

    A remarkable property of bone remodeling is that osteoblasts form bone matrix exactly where and when osteoclasts have removed it. The bone remodeling compartment (BRC) canopies that cover bone surfaces undergoing remodeling, were proposed to be critical players in this mechanism. Here, we provide...... 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...

  6. 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...

  7. Action of Calciotropic Hormones on Bone Metabolism-Role of Vitamin D3 in Bone Remodeling Events

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    Catharine Andresen

    2006-01-01

    Full Text Available Vitamin D3 is known to have immunosuppressive effects that can be beneficial for treatment of immune disorders and transplant rejection, however therapeutic application is limited due to hypercalcemia and hypercalcuria. The goal of our studies was to explore both the acute and steady state effects of vitamin D3 on bone remodeling as potential limiting factors to broader use of vitamin D3 in the clinic. Vitamin D3 was evaluated for its skeletal effects in both thyroparathyroidectomized (TPTx and intact rat models. In TPTx rats, deprivation of thyroid and parathyroid hormones and calcitonin creates a low state of bone modeling and remodeling ideal for evaluation of changes imposed by drug intervention. The use of both models allowed for discrimination of individual (TPTx versus combined (intact effects of calciotropic hormones on bone and calcium metabolism. Our studies have confirmed the limitations of using vitamin D3 for treatment/co- treatment of immune disease in humans due to the intrinsic hypercalcemic properties of the hormone, and also highlighted the potential of vitamin D3 to negatively impact skeletal integrity due to excessive bone remodeling driven by bone resorption. Taken together our data emphasize the importance of including biomarkers of bone remodeling as an integral part of clinical and preclinical studies using vitamin D3 to treat immune disorders and suggest the need for co-treatment with an antiresorptive agent to counteract hypercalcemia and deterioration of bone.

  8. In vivo monitoring of bone architecture and remodeling after implant insertion: The different responses of cortical and trabecular bone.

    Science.gov (United States)

    Li, Zihui; Kuhn, Gisela; von Salis-Soglio, Marcella; Cooke, Stephen J; Schirmer, Michael; Müller, Ralph; Ruffoni, Davide

    2015-12-01

    The mechanical integrity of the bone-implant system is maintained by the process of bone remodeling. Specifically, the interplay between bone resorption and bone formation is of paramount importance to fully understand the net changes in bone structure occurring in the peri-implant bone, which are eventually responsible for the mechanical stability of the bone-implant system. Using time-lapsed in vivo micro-computed tomography combined with new composite material implants, we were able to characterize the spatio-temporal changes of bone architecture and bone remodeling following implantation in living mice. After insertion, implant stability was attained by a quick and substantial thickening of the cortical shell which counteracted the observed loss of trabecular bone, probably due to the disruption of the trabecular network. Within the trabecular compartment, the rate of bone formation close to the implant was transiently higher than far from the implant mainly due to an increased mineral apposition rate which indicated a higher osteoblastic activity. Conversely, in cortical bone, the higher rate of bone formation close to the implant compared to far away was mostly related to the recruitment of new osteoblasts as indicated by a prevailing mineralizing surface. The behavior of bone resorption also showed dissimilarities between trabecular and cortical bone. In the former, the rate of bone resorption was higher in the peri-implant region and remained elevated during the entire monitoring period. In the latter, bone resorption rate had a bigger value away from the implant and decreased with time. Our approach may help to tune the development of smart implants that can attain a better long-term stability by a local and targeted manipulation of the remodeling process within the cortical and the trabecular compartments and, particularly, in bone of poor health.

  9. [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.

  10. 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...

  11. Hydroxyapatite-coated uncemented hip stems and bone remodeling

    NARCIS (Netherlands)

    Wal, B.C.H. van der

    2010-01-01

    In this thesis the clinical results, the periprosthetic bone remodeling and histological analysis of an anatomical designed proximally hydroxyapatite-coated hip prosthesis were investigated to answer several research questions. In our first prospective study the characteristics of the bone remodelin

  12. Role of Cannabinoids in the Regulation of Bone Remodelling

    Directory of Open Access Journals (Sweden)

    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.

  13. A multiscale analytical approach for bone remodeling simulations: linking scales from collagen to trabeculae.

    Science.gov (United States)

    Colloca, Michele; Blanchard, Romane; Hellmich, Christian; Ito, Keita; van Rietbergen, Bert

    2014-07-01

    Bone is a dynamic and hierarchical porous material whose spatial and temporal mechanical properties can vary considerably due to differences in its microstructure and due to remodeling. Hence, a multiscale analytical approach, which combines bone structural information at multiple scales to the remodeling cellular activities, could form an efficient, accurate and beneficial framework for the prognosis of changes in bone properties due to, e.g., bone diseases. In this study, an analytical formulation of bone remodeling integrated with multiscale micromechanical models is proposed to investigate the effects of structural changes at the nanometer level (collagen scale) on those at higher levels (tissue scale). Specific goals of this study are to derive a mechanical stimulus sensed by the osteocytes using a multiscale framework, to test the accuracy of the multiscale model for the prediction of bone density, and to demonstrate its multiscale capabilities by predicting changes in bone density due to changes occurring at the molecular level. At each different level, the bone composition was modeled as a two-phase material which made it possible to: (1) find a closed-form solution for the energy-based mechanical stimulus sensed by the osteocytes and (2) describe the anisotropic elastic properties at higher levels as a function of the stiffness of the elementary components (collagen, hydroxyapatite and water) at lower levels. The accuracy of the proposed multiscale model of bone remodeling was tested first by comparing the analytical bone volume fraction predictions to those obtained from the corresponding μFE-based computational model. Differences between analytical and numerical predictions were less than 1% while the computational time was drastically reduced, namely by a factor of 1 million. In a further analysis, the effects of changes in collagen and hydroxyapatite volume fractions on the bone remodeling process were simulated, and it was found that such changes

  14. 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.

  15. A Computational Model for Simulating Spaceflight Induced Bone Remodeling

    Science.gov (United States)

    Pennline, James A.; Mulugeta, Lealem

    2014-01-01

    An overview of an initial development of a model of bone loss due to skeletal unloading in weight bearing sites is presented. The skeletal site chosen for the initial application of the model is the femoral neck region because hip fractures can be debilitating to the overall performance health of astronauts. The paper begins with the motivation for developing such a model of the time course of change in bone in order to understand the mechanism of bone demineralization experienced by astronauts in microgravity, to quantify the health risk, and to establish countermeasures. Following this, a general description of a mathematical formulation of the process of bone remodeling is discussed. Equations governing the rate of change of mineralized bone volume fraction and active osteoclast and osteoblast are illustrated. Some of the physiology of bone remodeling, the theory of how imbalance in remodeling can cause bone loss, and how the model attempts to capture this is discussed. The results of a preliminary validation analysis that was carried out are presented. The analysis compares a set of simulation results against bone loss data from control subjects who participated in two different bed rest studies. Finally, the paper concludes with outlining the current limitations and caveats of the model, and planned future work to enhance the state of the model.

  16. Localized tissue mineralization regulated by bone remodelling: A computational approach

    Science.gov (United States)

    Decco, Oscar; Adams, George; Cook, Richard B.; García Aznar, José Manuel

    2017-01-01

    Bone is a living tissue whose main mechanical function is to provide stiffness, strength and protection to the body. Both stiffness and strength depend on the mineralization of the organic matrix, which is constantly being remodelled by the coordinated action of the bone multicellular units (BMUs). Due to the dynamics of both remodelling and mineralization, each sample of bone is composed of structural units (osteons in cortical and packets in cancellous bone) created at different times, therefore presenting different levels of mineral content. In this work, a computational model is used to understand the feedback between the remodelling and the mineralization processes under different load conditions and bone porosities. This model considers that osteoclasts primarily resorb those parts of bone closer to the surface, which are younger and less mineralized than older inner ones. Under equilibrium loads, results show that bone volumes with both the highest and the lowest levels of porosity (cancellous and cortical respectively) tend to develop higher levels of mineral content compared to volumes with intermediate porosity, thus presenting higher material densities. In good agreement with recent experimental measurements, a boomerang-like pattern emerges when plotting apparent density at the tissue level versus material density at the bone material level. Overload and disuse states are studied too, resulting in a translation of the apparent–material density curve. Numerical results are discussed pointing to potential clinical applications. PMID:28306746

  17. The Digital Astronaut Project Computational Bone Remodeling Model (Beta Version) Bone Summit Summary Report

    Science.gov (United States)

    Pennline, James; Mulugeta, Lealem

    2013-01-01

    changes in bone cell populations that remove and replace bone in packets within the bone region. The DAP bone model is unique in several respects. In particular in takes former models of volume fraction changes one step higher in fidelity and separates BVF into separate equations for mineralized and osteoid volume fractions governed by a mineralization rate. This more closely follows the physiology of the remodeling unit cycles where bone is first resorbed and then followed by the action of osteoblasts to lay down collagen matrix which eventually becomes mineralized. In another respect, the modules allow the functional description of the time rate of change of other parameters and variables in the model during a computational simulation. More detailed description of the model, preliminary validation results, current limitation and caveats, and planned advancements are provided in sections 2 through 5. The DAP bone model is being developed primarily as a research tool, and not as a clinical tool like QCT. Even if it transitions to a clinical tool, it is not intended to replace QCT or any other clinical tool. Moreover, the DAP bone model does not predict bone fracture. Its purpose is to provide valuable additional data via "forward prediction" simulations for during and after spaceflight missions to gain insight on, (1) mechanisms of bone demineralization in microgravity, and (2) the volumetric changes at the various bone sites in response to in-flight and post-flight exercise countermeasures. This data can then be used as input to the Keyak [8] (or equivalent) FE analysis method to gain insight on how bone strength may change during and after flight. This information can also be useful to help optimize exercise countermeasure protocols to minimize changes in bone strength during flight, and improve regain of bone strength post-flight. To achieve this goal, the bone model will be integrated with DAP's exercise countermeasure models to simulate the effect of exercise

  18. 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.

  19. Transcriptional regulation of bone and joint remodeling by NFAT

    OpenAIRE

    2010-01-01

    Osteoporosis and arthritis are highly prevalent diseases and a significant cause of morbidity and mortality worldwide. These diseases result from aberrant tissue remodeling leading to weak, fracture-prone bones or painful, dysfunctional joints. The nuclear factor of activated T cells (NFAT) transcription factor family controls diverse biologic processes in vertebrates. Here, we review the scientific evidence that links NFAT-regulated gene transcription to bone and joint pathology. A particula...

  20. 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

  1. Bone remodelling around a cementless glenoid component

    NARCIS (Netherlands)

    Suarez, D.R.; Weinans, H.; Van Keulen, F.

    2012-01-01

    Post-operative change in the mechanical loading of bone may trigger its (mechanically induced) adaptation and hamper the mechanical stability of prostheses. This is especially important in cementless components, where the final fixation is achieved by the bone itself. The aim of this study is,

  2. Bone remodelling around a cementless glenoid component

    NARCIS (Netherlands)

    D.R. Suárez (Daniel); H.H. Weinans (Harrie); F. van Keulen (Fred)

    2012-01-01

    textabstractPost-operative change in the mechanical loading of bone may trigger its (mechanically induced) adaptation and hamper the mechanical stability of prostheses. This is especially important in cementless components, where the final fixation is achieved by the bone itself. The aim of this

  3. The Digital Astronaut Project Bone Remodeling Model

    Science.gov (United States)

    Pennline, James A.; Mulugeta, Lealem; Lewandowski, Beth E.; Thompson, William K.; Sibonga, Jean D.

    2014-01-01

    Under the conditions of microgravity, astronauts lose bone mass at a rate of 1% to 2% a month, particularly in the lower extremities such as the proximal femur: (1) The most commonly used countermeasure against bone loss has been prescribed exercise, (2) However, current exercise countermeasures do not completely eliminate bone loss in long duration, 4 to 6 months, spaceflight, (3,4) leaving the astronaut susceptible to early onset osteoporosis and a greater risk of fracture later in their lives. The introduction of the Advanced Resistive Exercise Device, coupled with improved nutrition, has further minimized the 4 to 6 month bone loss. But further work is needed to implement optimal exercise prescriptions, and (5) In this light, NASA's Digital Astronaut Project (DAP) is working with NASA physiologists to implement well-validated computational models that can help understand the mechanisms of bone demineralization in microgravity, and enhance exercise countermeasure development.

  4. 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

  5. Chondromodulin I Is a Bone Remodeling Factor

    OpenAIRE

    NAKAMICHI, YUKO; Shukunami, Chisa; Yamada, Takashi; Aihara, Ken-ichi; Kawano, Hirotaka; Sato, Takashi; Nishizaki, Yuriko; Yamamoto, Yoko; Shindo, Masayo; Yoshimura, Kimihiro; Nakamura, Takashi; Takahashi, Naoyuki; Kawaguchi, Hiroshi; Hiraki, Yuji; Kato, Shigeaki

    2003-01-01

    Chondromodulin I (ChM-I) was supposed from its limited expression in cartilage and its functions in cultured chondrocytes as a major regulator in cartilage development. Here, we generated mice deficient in ChM-I by targeted disruption of the ChM-I gene. No overt abnormality was detected in endochondral bone formation during embryogenesis and cartilage development during growth stages of ChM-I−/− mice. However, a significant increase in bone mineral density with lowered bone resorption with re...

  6. Intracortical bone remodeling variation shows strong genetic effects.

    Science.gov (United States)

    Havill, L M; Allen, M R; Harris, J A K; Levine, S M; Coan, H B; Mahaney, M C; Nicolella, D P

    2013-11-01

    Intracortical microstructure influences crack propagation and arrest within bone cortex. Genetic variation in intracortical remodeling may contribute to mechanical integrity and, therefore, fracture risk. Our aim was to determine the degree to which normal population-level variation in intracortical microstructure is due to genetic variation. We examined right femurs from 101 baboons (74 females, 27 males; aged 7-33 years) from a single, extended pedigree to determine osteon number, osteon area (On.Ar), haversian canal area, osteon population density, percent osteonal bone (%On.B), wall thickness (W.Th), and cortical porosity (Ct.Po). Through evaluation of the covariance in intracortical properties between pairs of relatives, we quantified the contribution of additive genetic effects (heritability [h (2)]) to variation in these traits using a variance decomposition approach. Significant age and sex effects account for 9 % (Ct.Po) to 21 % (W.Th) of intracortical microstructural variation. After accounting for age and sex, significant genetic effects are evident for On.Ar (h (2) = 0.79, p = 0.002), %On.B (h (2) = 0.82, p = 0.003), and W.Th (h (2) = 0.61, p = 0.013), indicating that 61-82 % of the residual variation (after accounting for age and sex effects) is due to additive genetic effects. This corresponds to 48-75 % of the total phenotypic variance. Our results demonstrate that normal, population-level variation in cortical microstructure is significantly influenced by genes. As a critical mediator of crack behavior in bone cortex, intracortical microstructural variation provides another mechanism through which genetic variation may affect fracture risk.

  7. Inflammatory and bone remodeling responses to the cytolethal distending toxins.

    Science.gov (United States)

    Belibasakis, Georgios N; Bostanci, Nagihan

    2014-04-04

    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.

  8. 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.

  9. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis.

    Science.gov (United States)

    Langdahl, Bente; Ferrari, Serge; Dempster, David W

    2016-12-01

    The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases. Bone modeling describes the process whereby bones are shaped or reshaped by the independent action of osteoblast and osteoclasts. The activities of osteoblasts and osteoclasts are not necessarily coupled anatomically or temporally. Bone modeling defines skeletal development and growth but continues throughout life. Modeling-based bone formation contributes to the periosteal expansion, just as remodeling-based resorption is responsible for the medullary expansion seen at the long bones with aging. Existing and upcoming treatments affect remodeling as well as modeling. Teriparatide stimulates bone formation, 70% of which is remodeling based and 20-30% is modeling based. The vast majority of modeling represents overflow from remodeling units rather than de novo modeling. Denosumab inhibits bone remodeling but is permissive for modeling at cortex. Odanacatib inhibits bone resorption by inhibiting cathepsin K activity, whereas modeling-based bone formation is stimulated at periosteal surfaces. Inhibition of sclerostin stimulates bone formation and histomorphometric analysis demonstrated that bone formation is predominantly modeling based. The bone-mass response to some osteoporosis treatments in humans certainly suggests that nonremodeling mechanisms contribute to this response and bone modeling may be such a mechanism. To date, this has only been demonstrated for teriparatide, however, it is clear that

  10. 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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  12. 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

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

    OpenAIRE

    2014-01-01

    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...

  14. Inflammatory and bone remodeling responses to the cytolethal distending toxins

    OpenAIRE

    2014-01-01

    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 e...

  15. Zanthoxylum piperitum reversed alveolar bone loss of periodontitis via regulation of bone remodeling-related factors.

    Science.gov (United States)

    Kim, Mi Hye; Lee, Hye Ji; Park, Jung-Chul; Hong, Jongki; Yang, Woong Mo

    2017-01-04

    Zanthoxylum piperitum (ZP) has been used to prevent toothache in East Asia. In this study, we investigated the effects of ZP on periodontitis along with alveolar bone loss. Twenty-eight male Sprague-Dawley rats were assigned into 4 groups; non-ligated (NOR), ligated and treated vehicle (CTR), ligated and treated 1mg/mL ZP (ZP1), and ligated and treated 100mg/mL ZP (ZP100). Sterilized 3-0 nylon ligature was placed into the subgingival sulcus around the both sides of mandibular first molar. After topical application of 1 and 100mg/mL ZP for 2 weeks, mandibles was removed for histology. In addition, SaOS-2 osteoblast cells were treated 1, 10 and 100μg/mL ZP for 24h to analyze the expressions of alveolar bone-related markers. Several alveolar bone resorption pits, which indicate cementum demineralization were decreased by ZP treatment. Topical ZP treatment inhibited periodontitis-induced alveolar bone loss. In addition, there were significant reduction of osteoclastic activities following topical ZP treatment in periodontium. The expression of RANKL was decreased in SaOS-2 osteoblast cells by treating ZP, while that of OPG was increased. ZP treatment increased the expressions of Runx2 and Osterix in SaOS-2 cells. In summary, ZP treatment inhibited alveolar bone loss as well as maintained the integrity of periodontal structures via regulation of bone remodeling. ZP may be a therapeutic target for treating periodontitis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  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. Early reversal cells in adult human bone remodeling

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  18. Alteration of proteoglycan sulfation affects bone growth and remodeling.

    Science.gov (United States)

    Gualeni, Benedetta; de Vernejoul, Marie-Christine; Marty-Morieux, Caroline; De Leonardis, Fabio; Franchi, Marco; Monti, Luca; Forlino, Antonella; Houillier, Pascal; Rossi, Antonio; Geoffroy, Valerie

    2013-05-01

    Diastrophic dysplasia (DTD) is a chondrodysplasia caused by mutations in the SLC26A2 gene, leading to reduced intracellular sulfate pool in chondrocytes, osteoblasts and fibroblasts. Hence, proteoglycans are undersulfated in the cartilage and bone of DTD patients. To characterize the bone phenotype of this skeletal dysplasia we used the Slc26a2 knock-in mouse (dtd mouse), that was previously validated as an animal model of DTD in humans. X-rays, bone densitometry, static and dynamic histomorphometry, and in vitro studies revealed a primary bone defect in the dtd mouse model. We showed in vivo that this primary bone defect in dtd mice is due to decreased bone accrual associated with a decreased trabecular and periosteal appositional rate at the cell level in one month-old mice. Although the osteoclast number evaluated by histomorphometry was not different in dtd compared to wild-type mice, urine analysis of deoxypyridinoline cross-links and serum levels of type I collagen C-terminal telopeptides showed a higher resorption rate in dtd mice compared to wild-type littermates. Electron microscopy studies showed that collagen fibrils in bone were thinner and less organized in dtd compared to wild-type mice. These data suggest that the low bone mass observed in mutant mice could possibly be linked to the different bone matrix compositions/organizations in dtd mice triggering changes in osteoblast and osteoclast activities. Overall, these results suggest that proteoglycan undersulfation not only affects the properties of hyaline cartilage, but can also lead to unbalanced bone modeling and remodeling activities, demonstrating the importance of proteoglycan sulfation in bone homeostasis. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. The osteocyte as an orchestrator of bone remodeling: an engineer’s perspective

    NARCIS (Netherlands)

    van Oers, R.F.M.; Klein-Nulend, J.; Bacabac, R.G.

    2014-01-01

    Bone is adapted to mechanical loading. The trabeculae in cancellous bone and the osteons in cortical bone are aligned to the mechanical loading direction. Our bones are constantly remodeled by bone-resorbing osteoclasts and bone-forming osteoblasts, cooperating in so-called basic multicellular units

  20. Interstitial fluid flow in canaliculi as a mechanical stimulus for cancellous bone remodeling: in silico validation.

    Science.gov (United States)

    Kameo, Yoshitaka; Adachi, Taiji

    2014-08-01

    Cancellous bone has a dynamic 3-dimensional architecture of trabeculae, the arrangement of which is continually reorganized via bone remodeling to adapt to the mechanical environment. Osteocytes are currently believed to be the major mechanosensory cells and to regulate osteoclastic bone resorption and osteoblastic bone formation in response to mechanical stimuli. We previously developed a mathematical model of trabecular bone remodeling incorporating the possible mechanisms of cellular mechanosensing and intercellular communication in which we assumed that interstitial fluid flow activates the osteocytes to regulate bone remodeling. While the proposed model has been validated by the simulation of remodeling of a single trabecula, it remains unclear whether it can successfully represent in silico the functional adaptation of cancellous bone with its multiple trabeculae. In the present study, we demonstrated the response of cancellous bone morphology to uniaxial or bending loads using a combination of our remodeling model with the voxel finite element method. In this simulation, cancellous bone with randomly arranged trabeculae remodeled to form a well-organized architecture oriented parallel to the direction of loading, in agreement with the previous simulation results and experimental findings. These results suggested that our mathematical model for trabecular bone remodeling enables us to predict the reorganization of cancellous bone architecture from cellular activities. Furthermore, our remodeling model can represent the phenomenological law of bone transformation toward a locally uniform state of stress or strain at the trabecular level.

  1. 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....

  2. Simulating Bone Loss in Microgravity Using Mathematical Formulations of Bone Remodeling

    Science.gov (United States)

    Pennline, James A.

    2009-01-01

    Most mathematical models of bone remodeling are used to simulate a specific bone disease, by disrupting the steady state or balance in the normal remodeling process, and to simulate a therapeutic strategy. In this work, the ability of a mathematical model of bone remodeling to simulate bone loss as a function of time under the conditions of microgravity is investigated. The model is formed by combining a previously developed set of biochemical, cellular dynamics, and mechanical stimulus equations in the literature with two newly proposed equations; one governing the rate of change of the area of cortical bone tissue in a cross section of a cylindrical section of bone and one governing the rate of change of calcium in the bone fluid. The mechanical stimulus comes from a simple model of stress due to a compressive force on a cylindrical section of bone which can be reduced to zero to mimic the effects of skeletal unloading in microgravity. The complete set of equations formed is a system of first order ordinary differential equations. The results of selected simulations are displayed and discussed. Limitations and deficiencies of the model are also discussed as well as suggestions for further research.

  3. Effects of loading frequency on the functional adaptation of trabeculae predicted by bone remodeling simulation.

    Science.gov (United States)

    Kameo, Yoshitaka; Adachi, Taiji; Hojo, Masaki

    2011-08-01

    The process of bone remodeling is regulated by metabolic activities of many bone cells. While osteoclasts and osteoblasts are responsible for bone resorption and formation, respectively, activities of these cells are believed to be controlled by a mechanosensory system of osteocytes embedded in the extracellular bone matrix. Several experimental and theoretical studies have suggested that the strain-derived interstitial fluid flow in lacuno-canalicular porosity serves as the prime mover for bone remodeling. Previously, we constructed a mathematical model for trabecular bone remodeling that interconnects the microscopic cellular activities with the macroscopic morphological changes in trabeculae through the mechanical hierarchy. This model assumes that fluid-induced shear stress acting on osteocyte processes is a driving force for bone remodeling. The validity of this model has been demonstrated with a remodeling simulation using a two-dimensional trabecular model. In this study, to investigate the effects of loading frequency, which is thought to be a significant mechanical factor in bone remodeling, we simulated morphological changes of a three-dimensional single trabecula under cyclic uniaxial loading with various frequencies. The results of the simulation show the trabecula reoriented to the loading direction with the progress of bone remodeling. Furthermore, as the imposed loading frequency increased, the diameter of the trabecula in the equilibrium state was enlarged by remodeling. These results indicate that our simulation model can successfully evaluate the relationship between loading frequency and trabecular bone remodeling. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Sclerostin Promotes Bone Remodeling in the Process of Tooth Movement

    Science.gov (United States)

    Shu, Rui; Bai, Ding; Sheu, Tzongjen; He, Yao; Yang, Xianrui; Xue, Chaoran; He, Yiruo; Zhao, Mengyuan; Han, Xianglong

    2017-01-01

    Tooth movement is a biological process of bone remodeling induced by mechanical force. Sclerostin secreted by osteocytes is mechanosensory and important in bone remodeling. However, little is known regarding the role of sclerostin in tooth movement. In this study, models of experimental tooth movement were established in rats and mice. Sclerostin expression was investigated with immunohistochemistry staining, and osteoclastic activity was analyzed with tartrate-resistant acid phosphatase (TRAP) staining. MLO-Y4 osteocyte-like cells underwent uniaxial compression and tension stress or were cultured in hypoxia conditions. Expression of sclerostin was assessed by RT-qPCR and ELISA. MLO-Y4 cells were cultured with recombinant human sclerostin (rhSCL) interference and then co-cultured with RAW264.7 osteoclast precursor cells. Expressions of RANKL and OPG were analyzed by RT-qPCR, and osteoclastic activity was assessed by TRAP staining. During tooth movement, sclerostin was expressed differently in compression and tension sites. In SOST knock-out mice, there were significantly fewer TRAP-positive cells than in WT mice during tooth movement in compression sites. In-vitro studies showed that the expression of sclerostin in MLO-Y4 osteocyte-like cells was not different under a uniaxial compression and tension force, whereas hypoxia conditions significantly increased sclerostin expression in MLO-Y4 cells. rhSCL interference increased the expression of RANKL and the RANKL/OPG ratio in MLO-Y4 cells and the osteoclastic induction ability of MLO-Y4 cells in experimental osteocyte-osteoclast co-culture. These data suggest that sclerostin plays an important role in the bone remodeling of tooth movement. PMID:28081119

  5. VEGF inhibition as possible therapy in spondyloarthritis patients: Targeting bone remodelling.

    Science.gov (United States)

    Lacout, Alexis; Carlier, Robert Yves; El Hajjam, Mostafa; Marcy, Pierre Yves

    2017-04-01

    Spondyloarthritis refers to a group of chronic inflammatory rheumatic diseases that predominantly affects the axial skeleton, causing pain and stiffness. Human bone is highly dynamic organ that interacts with a wide array cells and tissues. Process of bone remodelling relies on a delicate balance between bone formation and bone resorption, orchestrated by osteoblasts and osteoclasts. Disruption of this homeostatic balance of bone removal and replacement can manifest as inappropriate new bone formation found in spondylarthritis. We hypothesize that VEGF may promote bone remodelling, stimulate angiogenesis, and both osteoclastic and osteoblastic activity. Anti VEGF may be tested as a dedicated therapy to prevent bone remodelling in spondyloarthritis patients, namely in cases of aggressive disease. Bone remodelling could be monitored by using [18F]Fluoride PET scan.

  6. RETINOID RECEPTORS IN BONE AND THEIR ROLE IN BONE REMODELING

    Directory of Open Access Journals (Sweden)

    Petra eHenning

    2015-03-01

    Full Text Available Vitamin A (retinol is a necessary and important constituent of the body which is provided by food intake of retinyl esters and carotenoids. Vitamin A is known best for being important for vision, but in addition to the eye, vitamin A is necessary in numerous other organs in the body, including the skeleton. Vitamin A is converted to an active compound, all-trans-retinoic acid (ATRA, which is responsible for most of its biological actions. ATRA binds to intracellular nuclear receptors called retinoic acid receptors (RAR, RAR, RAR. RARs and closely related retinoid X receptors (RXR, RXR, RXR form heterodimers which bind to DNA and function as ligand activated transcription factors. It has been known for many years that hypervitaminosis A promotes skeleton fragility by increasing osteoclast formation and decreasing cortical bone mass. Some epidemiological studies have suggested that increased intake of vitamin A and increased serum levels of retinoids may decrease bone mineral density and increase fracture rate, but the literature on this is not conclusive. The current review summarizes how vitamin A is taken up by the intestine, metabolized, stored in the liver and processed to ATRA. ATRA’s effects on formation and activity of osteoclasts and osteoblasts are outlined, and a summary of clinical data pertaining to vitamin A and bone is presented.

  7. The effects of proteasome inhibitors on bone remodeling in multiple myeloma.

    Science.gov (United States)

    Zangari, Maurizio; Suva, Larry J

    2016-05-01

    Bone disease is a characteristic feature of multiple myeloma, a malignant plasma cell dyscrasia. In patients with multiple myeloma, the normal process of bone remodeling is dysregulated by aberrant bone marrow plasma cells, resulting in increased bone resorption, prevention of new bone formation, and consequent bone destruction. The ubiquitin-proteasome system, which is hyperactive in patients with multiple myeloma, controls the catabolism of several proteins that regulate bone remodeling. Clinical studies have reported that treatment with the first-in-class proteasome inhibitor bortezomib reduces bone resorption and increases bone formation and bone mineral density in patients with multiple myeloma. Since the introduction of bortezomib in 2003, several next-generation proteasome inhibitors have also been used clinically, including carfilzomib, oprozomib, ixazomib, and delanzomib. This review summarizes the available preclinical and clinical evidence regarding the effect of proteasome inhibitors on bone remodeling in multiple myeloma. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Bone remodelling in Neanderthal mandibles from the El Sidrón site (Asturias, Spain).

    Science.gov (United States)

    Martinez-Maza, Cayetana; Rosas, Antonio; García-Vargas, Samuel; Estalrrich, Almudena; de la Rasilla, Marco

    2011-08-23

    Skull morphology results from the bone remodelling mechanism that underlies the specific bone growth dynamics. Histological study of the bone surface from Neanderthal mandible specimens of El Sidrón (Spain) provides information about the distribution of the remodelling fields (bone remodelling patterns or BRP) indicative of the bone growth directions. In comparison with other primate species, BRP shows that Neanderthal mandibles from the El Sidrón (Spain) sample present a specific BRP. The interpretation of this map allows inferences concerning the growth directions that explain specific morphological traits of the Neanderthal mandible, such as its quadrangular shape and the posterior location of the mental foramen.

  9. Bone remodelling in Neanderthal mandibles from the El Sidrón site (Asturias, Spain)

    Science.gov (United States)

    Martinez-Maza, Cayetana; Rosas, Antonio; García-Vargas, Samuel; Estalrrich, Almudena; de la Rasilla, Marco

    2011-01-01

    Skull morphology results from the bone remodelling mechanism that underlies the specific bone growth dynamics. Histological study of the bone surface from Neanderthal mandible specimens of El Sidrón (Spain) provides information about the distribution of the remodelling fields (bone remodelling patterns or BRP) indicative of the bone growth directions. In comparison with other primate species, BRP shows that Neanderthal mandibles from the El Sidrón (Spain) sample present a specific BRP. The interpretation of this map allows inferences concerning the growth directions that explain specific morphological traits of the Neanderthal mandible, such as its quadrangular shape and the posterior location of the mental foramen. PMID:21307043

  10. 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

    Osteoblast recruitment during bone remodeling is obligatory to re-construct the bone resorbed by the osteoclast. This recruitment is believed to be triggered by osteoclast products and is therefore likely to start early during the remodeling cycle. Several osteoclast products with osteoblast...... 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...

  11. [Telmisartan effect's on remodelling bone markers in hypertensive patients].

    Science.gov (United States)

    Pérez-Castrillón, J L; De Luis, D; Inglada, L; Olmos Martínez, J M; Pinacho, F; Conde, R; González-Sagrado, M; Dueñas-Laita, A

    2012-01-01

    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. 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. 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 mmHg vs 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 glucose was observed in patients with levels of vitamin D over 20 ng/ml (135 ± 53 mg/dl vs 119 ± 39 mg/dl, p = 0.01). The patients treated with IECAS decreases the systolic blood pressure but the diastolic blood pressure values of arterial systolic does not show changes. Telmisartan has a neutral effect to level of the bone markers of bone remodelling.

  12. The Influence of Therapeutic Radiation on the Patterns of Bone Remodeling in Ovary-Intact and Ovariectomized Mice

    Science.gov (United States)

    Hui, Susanta K; Fairchild, Gregory R; Kidder, Louis S; Sharma, Manju; Bhattacharya, Maryka; Jackson, Scott; Le, Chap; Petryk, Anna; Islam, Mohammad Saiful; Yee, Douglas

    2013-01-01

    Purpose To characterize changes in bone remodeling associated with localized radiation that models therapeutic cancer treatment in ovary-intact and ovariectomized mice and evaluate the influence of radiation on the pattern of bone mineral remodeling. Methods Young adult, female BALB/c mice, ovary-intact (I) and ovariectomized (OVX), were used (n=71). All mice were intravenously injection with 15 μCi 45Ca. Thirty days post-45Ca administration, the hind limbs of 17 mice were exposed to a single 16 Gy radiation (R). The time course of 45Ca excretion, serum CTx and osteocalcin markers, and cancellous bone volume fraction (BV/TV) and cortical thickness (Ct.Th) of the distal femur were measured. Cellular activity and dynamic histomorphometry were performed. Results Irradiation resulted in rapid increases in fecal 45Ca excretion compared to control groups, indicating increased bone remodeling. CTX increased rapidly after irradiation, followed by an increase in osteocalcin concentration. BV/TV decreased in the ovary-intact mice following irradiation. Ct.Th increased in the OVX groups following irradiation. I+R exhibited diminished osteoblasts surface, osteoclast number and mineral apposition rate. Conclusions Our murine model showed the systemic effects (via 45Ca excretion) and local effects (via bone microarchitecture and surface activity) of clinically-relevant, therapeutic radiation exposure. Ovary-intact and ovariectomized murine models have similar 45Ca excretion but different bone microarchitecture responses. 45Ca assay effectively indicates the onset and rate of systemic bone mineral remodeling, providing real time assessment of changes in bone histomorphometric parameters. Monitoring bone health via a bone mineral marker may help identify the appropriate time for clinical intervention to preserve skeletal integrity. PMID:23314741

  13. Simulation of multi-stage nonlinear bone remodeling induced by fixed partial dentures of different configurations: a comparative clinical and numerical study.

    Science.gov (United States)

    Liao, Zhipeng; Yoda, Nobuhiro; Chen, Junning; Zheng, Keke; Sasaki, Keiichi; Swain, Michael V; Li, Qing

    2017-04-01

    This paper aimed to develop a clinically validated bone remodeling algorithm by integrating bone's dynamic properties in a multi-stage fashion based on a four-year clinical follow-up of implant treatment. The configurational effects of fixed partial dentures (FPDs) were explored using a multi-stage remodeling rule. Three-dimensional real-time occlusal loads during maximum voluntary clenching were measured with a piezoelectric force transducer and were incorporated into a computerized tomography-based finite element mandibular model. Virtual X-ray images were generated based on simulation and statistically correlated with clinical data using linear regressions. The strain energy density-driven remodeling parameters were regulated over the time frame considered. A linear single-stage bone remodeling algorithm, with a single set of constant remodeling parameters, was found to poorly fit with clinical data through linear regression (low [Formula: see text] and R), whereas a time-dependent multi-stage algorithm better simulated the remodeling process (high [Formula: see text] and R) against the clinical results. The three-implant-supported and distally cantilevered FPDs presented noticeable and continuous bone apposition, mainly adjacent to the cervical and apical regions. The bridged and mesially cantilevered FPDs showed bone resorption or no visible bone formation in some areas. Time-dependent variation of bone remodeling parameters is recommended to better correlate remodeling simulation with clinical follow-up. The position of FPD pontics plays a critical role in mechanobiological functionality and bone remodeling. Caution should be exercised when selecting the cantilever FPD due to the risk of overloading bone resorption.

  14. 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.

  15. Congenital Bone Fractures in Spinal Muscular Atrophy: Functional Role for SMN Protein in Bone Remodeling

    Science.gov (United States)

    Shanmugarajan, Srinivasan; Swoboda, Kathryn J.; Iannaccone, Susan T.; Ries, William L.; Maria, Bernard L.; Reddy, Sakamuri V.

    2009-01-01

    Spinal muscular atrophy is the second most common fatal childhood disorder. Core clinical features include muscle weakness caused by degenerating lower motor neurons and a high incidence of bone fractures and hypercalcemia. Fractures further compromise quality of life by progression of joint contractures or additional loss of motor function. Recent observations suggest that bone disease in spinal muscular atrophy may not be attributed entirely to lower motor neuron degeneration. The presence of the spinal muscular atrophy disease-determining survival motor neuron gene (SMN), SMN expression, and differential splicing in bone-resorbing osteoclasts was recently discovered. Its ubiquitous expression and the differential expression of splice variants suggest that SMN has specific roles in bone cell function. SMN protein also interacts with osteoclast stimulatory factor. Mouse models of human spinal muscular atrophy disease suggest a potential role of SMN protein in skeletal development. Dual energy x-ray absorptiometry analysis demonstrated a substantial decrease in total bone area and poorly developed caudal vertebra in the mouse model. These mice also had pelvic bone fractures. Studies delineating SMN signaling mechanisms and gene transcription in a cell-specific manner will provide important molecular insights into the pathogenesis of bone disease in children with spinal muscular atrophy. Moreover, understanding bone remodeling in spinal muscular atrophy may lead to novel therapeutic approaches to enhance skeletal health and quality of life. This article reviews the skeletal complications associated with spinal muscular atrophy and describes a functional role for SMN protein in osteoclast development and bone resorption activity. PMID:17761651

  16. Exploring the Bone Proteome to Help Explain Altered Bone Remodeling and Preservation of Bone Architecture and Strength in Hibernating Marmots.

    Science.gov (United States)

    Doherty, Alison H; Roteliuk, Danielle M; Gookin, Sara E; McGrew, Ashley K; Broccardo, Carolyn J; Condon, Keith W; Prenni, Jessica E; Wojda, Samantha J; Florant, Gregory L; Donahue, Seth W

    2016-01-01

    Periods of physical inactivity increase bone resorption and cause bone loss and increased fracture risk. However, hibernating bears, marmots, and woodchucks maintain bone structure and strength, despite being physically inactive for prolonged periods annually. We tested the hypothesis that bone turnover rates would decrease and bone structural and mechanical properties would be preserved in hibernating marmots (Marmota flaviventris). Femurs and tibias were collected from marmots during hibernation and in the summer following hibernation. Bone remodeling was significantly altered in cortical and trabecular bone during hibernation with suppressed formation and no change in resorption, unlike the increased bone resorption that occurs during disuse in humans and other animals. Trabecular bone architecture and cortical bone geometrical and mechanical properties were not different between hibernating and active marmots, but bone marrow adiposity was significantly greater in hibernators. Of the 506 proteins identified in marmot bone, 40 were significantly different in abundance between active and hibernating marmots. Monoaglycerol lipase, which plays an important role in fatty acid metabolism and the endocannabinoid system, was 98-fold higher in hibernating marmots compared with summer marmots and may play a role in regulating the changes in bone and fat metabolism that occur during hibernation.

  17. Determinants of ovine compact bone viscoelastic properties: effects of architecture, mineralization, and remodeling.

    Science.gov (United States)

    Les, C M; Spence, C A; Vance, J L; Christopherson, G T; Patel, B; Turner, A S; Divine, G W; Fyhrie, D P

    2004-09-01

    Significant decreases in ovine compact bone viscoelastic properties (specifically, stress-rate sensitivity, and damping efficiency) are associated with three years of ovariectomy and are particularly evident at higher frequencies [Proc. Orthop. Res. Soc. 27 (2002) 89]. It is unclear what materials or architectural features of bone are responsible for either the viscoelastic properties themselves, or for the changes in those properties that were observed with estrogen depletion. In this study, we examined the relationship between these viscoelastic mechanical properties and features involving bone architecture (BV/TV), materials parameters (ash density, %mineralization), and histologic evidence of remodeling (%remodeled, cement line interface). The extent of mineralization was inversely proportional to the material's efficiency in damping stress oscillations. The damping characteristics of bone material from ovariectomized animals were significantly more sensitive to variation in mineralization than was bone from control animals. At low frequencies (6 Hz or less), increased histologic evidence of remodeling was positively correlated with increased damping efficiency. However, the dramatic decreases in stress-rate sensitivity that accompanied 3-year ovariectomy were seen throughout the bone structure and occurred even in areas with little or no secondary Haversian remodeling as well as in areas of complete remodeling. Taken together, these data suggest that, while the mineral component may modify the viscoelastic behavior of bone, the basic mechanism underlying bone viscoelastic behavior, and of the changes in that behavior with estrogen depletion, reside in a non-mineral component of the bone that can be significantly altered in the absence of secondary remodeling.

  18. The effects of replacing collagen fibers with carbon nanotubes on the rate of bone remodeling process.

    Science.gov (United States)

    Jamilpour, Nima; Fereidoon, Abdolhosein; Rouhi, Gholamreza

    2011-08-01

    Application of carbon nanotubes (CNTs) instead of collagen fibers (CFs) in bone tissue is one of the proposed avenues for the enhancement of bone's mechanical properties. The mechanical behavior improvement caused by such a replacement is somehow guaranteed because of the superior mechanical properties of CNTs compared to those of CFs. But on the other side, bone is a very active and dynamic tissue, which is maintained through a lifelong coupled process of resorption and formation in order to reach an optimal configuration. Hence, the well accepted fact of the bone remodeling dependency on mechanical stimuli besides the differences in mechanical behavior of CNTs and CFs under loading can encourage one to hypothesize that such a replacement would cause an imbalance in the normal rate of bone remodeling process. Results of our finite element analysis indicate that the application of CNTs instead of CFs can cause a significant reduction in strain energy density, assumed here as the mechanical stimulus to initiate the bone remodeling process. Our results also show that this replacement may change the strain energy distribution within the bone. Based on a semi-mechanistic bone remodeling theory, it is speculated that this alteration in strain energy distribution in artificial bone can destabilize normal bone remodeling process, and therefore it is likely to cause some abnormalities in bone's mechanical and biological functions.

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

    DEFF Research Database (Denmark)

    Andersen, Mikkel R; Petersen, Michael M

    2015-01-01

    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 ...

  20. Analogy of strain energy density based bone-remodeling algorithm and structural topology optimization.

    Science.gov (United States)

    Jang, In Gwun; Kim, Il Yong; Kwak, Byung Ban

    2009-01-01

    In bone-remodeling studies, it is believed that the morphology of bone is affected by its internal mechanical loads. From the 1970s, high computing power enabled quantitative studies in the simulation of bone remodeling or bone adaptation. Among them, Huiskes et al. (1987, "Adaptive Bone Remodeling Theory Applied to Prosthetic Design Analysis," J. Biomech. Eng., 20, pp. 1135-1150) proposed a strain energy density based approach to bone remodeling and used the apparent density for the characterization of internal bone morphology. The fundamental idea was that bone density would increase when strain (or strain energy density) is higher than a certain value and bone resorption would occur when the strain (or strain energy density) quantities are lower than the threshold. Several advanced algorithms were developed based on these studies in an attempt to more accurately simulate physiological bone-remodeling processes. As another approach, topology optimization originally devised in structural optimization has been also used in the computational simulation of the bone-remodeling process. The topology optimization method systematically and iteratively distributes material in a design domain, determining an optimal structure that minimizes an objective function. In this paper, we compared two seemingly different approaches in different fields-the strain energy density based bone-remodeling algorithm (biomechanical approach) and the compliance based structural topology optimization method (mechanical approach)-in terms of mathematical formulations, numerical difficulties, and behavior of their numerical solutions. Two numerical case studies were conducted to demonstrate their similarity and difference, and then the solution convergences were discussed quantitatively.

  1. Large-scale microstructural simulation of load-adaptive bone remodeling in whole human vertebrae

    NARCIS (Netherlands)

    Badilatti, Sandro D.; Christen, Patrik; Levchuk, Alina; Hazrati Marangalou, Javad; Rietbergen, van Bert; Parkinson, Ian; Müller, Ralph

    2016-01-01

    Identification of individuals at risk of bone fractures remains challenging despite recent advances in bone strength assessment. In particular, the future degradation of the microstructure and load adaptation has been disregarded. Bone remodeling simulations have so far been restricted to small-volu

  2. 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

  3. Modalities for Visualization of Cortical Bone Remodeling: The Past, Present, and Future.

    Science.gov (United States)

    Harrison, Kimberly D; Cooper, David M L

    2015-01-01

    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 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 of 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 architecture." 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."

  4. 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

    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......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...

  5. 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.

  6. 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.

  7. 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

  8. On a new law of bone remodeling based on damage elasticity: a thermodynamic approach

    Directory of Open Access Journals (Sweden)

    Idhammad Ahmed

    2012-11-01

    Full Text Available Abstract Background Bone tissue is the main element of the human skeleton and is a dynamic tissue that is continuously renewed by bone-resorbing osteoclasts and bone-forming osteoblasts. The bone is also capable of repairing itself and adapting its structure to changes in its load environment through the process of bone remodeling. Therefore, this phenomenon has been gaining increasing interest in the last years and many laws have been developed in order to simulate this process. Results In this paper, we develop a new law of bone remodeling in the context of damaged elastic by applying the thermodynamic approach in the case of small perturbations. The model is solved numerically by a finite difference method in the one-dimensional bone structure of a n-unit elements model. Conclusion In addition, several numerical simulations are presented that confirm the accuracy and effectiveness of the model.

  9. Computation of bone remodelling after Duracon knee arthroplasty using a thermodynamic-based model.

    Science.gov (United States)

    Bougherara, H; Nazgooei, S; Sayyidmousavi, A; Marsik, F; Marík, I A

    2011-07-01

    The present study utilizes a recently developed literature model for the bone remodelling process to predict the evolution of bone density following Duracon total knee arthroplasty (TKA). In this model, which is based on chemical kinetics and irreversible thermodynamics, bone is treated as a self-organizing system capable of exchanging matter, energy, and entropy with its surroundings. Unlike previous models in which mechanical loading is regarded as the only stimulus for bone remodelling, the present model establishes a unique coupling between mechanical loading and the chemical reactions involved in the process of bone remodelling. This model was incorporated into the finite element software ANSYS by means of a macro to compute density distribution in distal femoral bone both before and after TKA. Consistent with dual-energy X-ray absorptiometry (DEXA) scans reported in the literature, the results showed that the most severe bone loss occurs in the anterior region of the distal femur and that there is more bone resorption in the lateral than the medial condyle following TKA. Furthermore, the bone density distribution predicted using the present model showed a gradual and uniform pattern and thus a more realistic bone evolution contrary to the strain energy density model, where there is no gradual bone density evolution.

  10. 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.

  11. LRP6 in mesenchymal stem cells is required for bone formation during bone growth and bone remodeling

    Institute of Scientific and Technical Information of China (English)

    Changjun Li; Bart O Williams; Xu Cao; Mei Wan

    2014-01-01

    Lipoprotein receptor-related protein 6 (LRP6) plays a critical role in skeletal development and homeostasis in adults. However, the role of LRP6 in mesenchymal stem cells (MSCs), skeletal stem cells that give rise to osteoblastic lineage, is unknown. In this study, we generated mice lacking LRP6 expression specifically in nestin1 MSCs by crossing nestin-Cre mice with LRP6flox mice and investigated the functional changes of bone marrow MSCs and skeletal alterations. Mice with LRP6 deletion in nestin1 cells demonstrated reductions in body weight and body length at 1 and 3 months of age. Bone architecture measured by microCT (mCT) showed a significant reduction in bone mass in both trabecular and cortical bone of homozygous and heterozygous LRP6 mutant mice. A dramatic reduction in the numbers of osteoblasts but much less significant reduction in the numbers of osteoclasts was observed in the mutant mice. Osterix1 osteoprogenitors and osteocalcin1 osteoblasts significantly reduced at the secondary spongiosa area, but only moderately decreased at the primary spongiosa area in mutant mice. Bone marrow MSCs from the mutant mice showed decreased colony forming, cell viability and cell proliferation. Thus, LRP6 in bone marrow MSCs is essential for their survival and proliferation, and therefore, is a key positive regulator for bone formation during skeletal growth and remodeling.

  12. Computer-simulated bone architecture in a simple bone-remodeling model based on a reaction-diffusion system.

    Science.gov (United States)

    Tezuka, Ken-ichi; Wada, Yoshitaka; Takahashi, Akiyuki; Kikuchi, Masanori

    2005-01-01

    Bone is a complex system with functions including those of adaptation and repair. To understand how bone cells can create a structure adapted to the mechanical environment, we propose a simple bone remodeling model based on a reaction-diffusion system influenced by mechanical stress. Two-dimensional bone models were created and subjected to mechanical loads. The conventional finite element method (FEM) was used to calculate stress distribution. A stress-reactive reaction-diffusion model was constructed and used to simulate bone remodeling under mechanical loads. When an external mechanical stress was applied, stimulated bone formation and subsequent activation of bone resorption produced an efficient adaptation of the internal shape of the model bone to a given stress, and demonstrated major structures of trabecular bone seen in the human femoral neck. The degree of adaptation could be controlled by modulating the diffusion constants of hypothetical local factors. We also tried to demonstrate the deformation of bone structure during osteoporosis by the modulation of a parameter affecting the balance between formation and resorption. This simple model gives us an insight into how bone cells can create an architecture adapted to environmental stress, and will serve as a useful tool to understand both physiological and pathological states of bone based on structural information.

  13. CELLULAR MECHANISMS OF BONE REMODELING DUE TO EXTERNAL OVERLOAD AND UNDER CONDITIONS OF TITAN IMPLANT OSSEOINTEGRATION

    Directory of Open Access Journals (Sweden)

    Gaifullin N.M.

    2016-04-01

    Full Text Available The goal of article concludes to describe the remodeling of the femur, caused by two processes: the increased strain on supporting tissue as a result of anterior cruciate ligament transection and stimulation by installation of endosseous titanium implants with a porous bioactive coating. The process is traced through 4, 8 and 12 weeks in 28 adult Wistar rats. To characterize the bone remodeling the classical methods of histology and morphometry as well as immune histochemistry to reveal osteonectin, tartrate-resistant acid phosphatase, endothelial marker СD31, matrix metalloproteinases MMP-2, MMP-9, and its tissue inhibitor TIMP-1, were used with necessary morphometrics. The study showed for bone remodelling caused by implants with a porous bioactive coating, to be superior to a similar process under conditions of overload on the bone after transection of the anterior cruciate ligament by its intensity and dynamics. This indicates a high osteoinductive effect of bioactive coating that allows not only to achieve full osseointegration, but also to stimulate a process of intensive remodeling of adjacent cancellous bone. The cooperative participation of cell populations as osteoblasts/osteocytes, osteoclasts, and endothelial cells with characteristic parallel intensive expression of matrix metalloproteinases MMP-2, MMP-9 and their tissue inhibitor TIMP-1, used to be main characteristics of bone remodeling in these conditions.

  14. The roles of exercise in bone remodeling and in prevention and treatment of osteoporosis.

    Science.gov (United States)

    Yuan, Yu; Chen, Xi; Zhang, Lingli; Wu, Juanni; Guo, Jianming; Zou, Dongchen; Chen, Binglin; Sun, Zhongguang; Shen, Chao; Zou, Jun

    2016-11-01

    With a rapid increase in the aging population, osteoporosis has become a global health problem. Although anti-resorption and anabolic drugs are available, osteoporosis cannot be completely cured. Exercise is an economical, efficacious, and safe way to prevent the development of osteoporosis. Recent studies have investigated the mechanisms by which exercise affects bone remodeling. Here we update the progress made on the effects of exercise on bone cells, including bone marrow mesenchymal stem cells, osteoblasts, osteocytes, and osteoclasts, as well as on bone mass, bone strength, and geometry, hoping to provide a theoretical basis to improve osteoporosis prevention and treatment with exercise.

  15. CELLULAR MECHANISMS OF BONE REMODELING DUE TO EXTERNAL OVERLOAD AND UNDER CONDITIONS OF TITAN IMPLANT OSSEOINTEGRATION

    OpenAIRE

    Gaifullin N.M.

    2016-01-01

    The goal of article concludes to describe the remodeling of the femur, caused by two processes: the increased strain on supporting tissue as a result of anterior cruciate ligament transection and stimulation by installation of endosseous titanium implants with a porous bioactive coating. The process is traced through 4, 8 and 12 weeks in 28 adult Wistar rats. To characterize the bone remodeling the classical methods of histology and morphometry as well as immune histochemistry to reveal osteo...

  16. 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.

  17. 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

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

    OpenAIRE

    2014-01-01

    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...

  19. Bone remodeling in the context of cellular and systemic regulation: the role of osteocytes and the nervous system.

    Science.gov (United States)

    Niedźwiedzki, Tadeusz; Filipowska, Joanna

    2015-10-01

    Bone is a dynamic tissue that undergoes constant remodeling. The appropriate course of this process determines development and regeneration of the skeleton. Tight molecular control of bone remodeling is vital for the maintenance of appropriate physiology and microarchitecture of the bone, providing homeostasis, also at the systemic level. The process of remodeling is regulated by a rich innervation of the skeleton, being the source of various growth factors, neurotransmitters, and hormones regulating function of the bone. Although the course of bone remodeling at the cellular level is mainly associated with the activity of osteoclasts and osteoblasts, recently also osteocytes have gained a growing interest as the principal regulators of bone turnover. Osteocytes play a significant role in the regulation of osteogenesis, releasing sclerostin (SOST), an inhibitor of bone formation. The process of bone turnover, especially osteogenesis, is also modulated by extra-skeletal molecules. Proliferation and differentiation of osteoblasts are promoted by the brain-derived serotonin and hypothetically inhibited by its intestinal equivalent. The activity of SOST and serotonin is either directly or indirectly associated with the canonical Wnt/β-catenin signaling pathway, the main regulatory pathway of osteoblasts function. The impairment of bone remodeling may lead to many skeletal diseases, such as high bone mass syndrome or osteoporosis. In this paper, we review the most recent data on the cellular and molecular mechanisms of bone remodeling control, with particular emphasis on the role of osteocytes and the nervous system in this process.

  20. The ARF Tumor Suppressor Regulates Bone Remodeling and Osteosarcoma Development in Mice

    Science.gov (United States)

    Harding, John C.; Deng, Hongju; Shea, Lauren K.; Eagleton, Mark C.; Niewiesk, Stefan; Lairmore, Michael D.; Piwnica-Worms, David; Rosol, Thomas J.; Weber, Jason D.; Ratner, Lee; Weilbaecher, Katherine N.

    2010-01-01

    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. PMID:21209895

  1. Transforming growth factor-beta1 adsorbed to tricalciumphosphate coated implants increases peri-implant bone remodeling

    DEFF Research Database (Denmark)

    Lin, M.; Overgaard, S; Glerup, H

    2001-01-01

    )-coated implants can improve mechanical fixation and bone ongrowth. The present study evaluated bone remodeling in newly formed bone and adjacent trabecular bone around TCP-coated implants with and without rhTGF-beta1 adsorption. Unloaded cylindrical grit-blasted titanium alloy implants coated with TCP were...

  2. The reversal phase of the bone-remodeling cycle

    DEFF Research Database (Denmark)

    Delaisse, Jean-Marie

    2014-01-01

    for the cells leading to osteogenesis during the reversal phase. This review aims at creating awareness of these cells and their activities in adult cancellous bone. It relates cell events (i) on the bone surface, (ii) in the mesenchymal envelope surrounding the bone marrow and appearing as a canopy above...... under the osteogenic influence of capillaries and osteoclasts, whereas bone surface cells become exposed to the eroded matrix and other osteoclast products. In several diverse pathophysiological situations, including osteoporosis, a decreased availability of osteoprogenitors from these local reservoirs...... coincides with decreased osteoblast recruitment and impaired initiation of bone formation, that is, uncoupling. Overall, this review stresses that coupling does not only depend on molecules able to activate osteogenesis, but that it also demands the presence of osteoprogenitors and ordered cell...

  3. 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

  4. Chronic alcoholism and bone remodeling processes: Caveats and considerations for the forensic anthropologist.

    Science.gov (United States)

    Michael, Amy R; Bengtson, Jennifer D

    2016-02-01

    Clinical literature provides substantial information on the effects of chronic alcohol abuse on bone remodeling and related skeletal disease processes. This biomedical information is seldom considered in detail by forensic anthropologists, who often rely on normative macroscopic models of bone remodeling and traditional macroscopic age estimation methods in the creation of biological profiles. The case study presented here considers the ways that alcoholism disrupts normal bone remodeling processes, thus skewing estimations of age-at-death. Alcoholism affects bone macroscopically, resulting in a porous appearance and an older estimation of age, while simultaneously inhibiting osteoblastic activity and resulting in a younger microscopic appearance. Forensic anthropologists must also be cognizant of pathological remodeling stemming from alcoholism in cases where trauma analysis is critical to the reconstruction of events leading up to death, as fracture healing rates can be affected. Beyond the case study, we also consider how forensic anthropologists and practitioners can recognize and account for osteological signatures of alcoholism in medico-legal contexts. In order to best estimate age at death, a combined macroscopic and microscopic approach should be employed whenever possible alcohol and drug abuse is known or suspected.

  5. 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.

  6. Does Simulated Spaceflight Modify Epigenetic Status During Bone Remodeling?

    Science.gov (United States)

    Thomas, Nicholas J.; Stevick, Rebecca J.; Tran, Luan H.; Nalavadi, Mohit O.; Almeida, Eduardo A.C.; Globus, Ruth K.; Alwood, Joshua S.

    2015-01-01

    Little is known about the effects of spaceflight conditions on epigenetics. The term epigenetics describes changes to the genome that can affect expression of a gene without changes to the sequence of DNA. Epigenetic processes are thought to underlie cellular differentiation, where transcription of specific genes occurs in response to key stimuli, and may be heritable - passing from one cell to its daughter cell. We hypothesize that the mechanical environment during spaceflight, namely microgravity-induced weightlessness or exercise regulate gene expression in the osteoblast-lineage cells both to control bone formation by osteoblasts and bone resorption by osteoclasts, which continually shapes bone structure throughout life. Similarly we intend to evaluate how radiation regulates these same bone cell activity and differentiation related genes. We further hypothesize that the regulation in bone cell gene expression is at least partially controlled through epigenetic mechanisms of methylation or small non-coding RNA (microRNAs). We have acquired preliminary data suggesting that global genome methylation is modified in response to axial compression of the tibia - a model of exercise. We intend to pursue these hypotheses wherein we will evaluate changes in gene expression and, congruently, changes in epigenetic state in bones from mice subjected to the aforementioned conditions: hindlimb unloading to simulate weightlessness, axial compression of the tibia, or radiation exposure in order to gain insight into the role of epigenetics in spaceflight-induced bone loss.

  7. Influence of ingrowth regions on bone remodelling around a cementless hip resurfacing femoral implant.

    Science.gov (United States)

    Haider, Ifaz T; Speirs, Andrew D; Beaulé, Paul E; Frei, Hanspeter

    2015-01-01

    Hip resurfacing arthroplasty is an alternative to traditional hip replacement that can conserve proximal bone stock and has gained popularity but bone resorption may limit implant survival and remains a clinical concern. The goal of this study was to analyze bone remodelling patterns around an uncemented resurfacing implant and the influence of ingrowth regions on resorption. A computed tomography-derived finite element model of a proximal femur with a virtually implanted resurfacing component was simulated under peak walking loads. Bone ingrowth was simulated by six interface conditions: fully bonded; fully friction; bonded cap with friction stem; a small bonded region at the stem-cup intersection with the remaining surface friction; fully frictional, except for a bonded band along the distal end of the cap and superior half of the cap bonded with the rest frictional. Interface condition had a large influence on remodelling patterns. Bone resorption was minimized when no ingrowth occurred at the bone-implant interface. Bonding only the superior half of the cap increased bone resorption slightly but allowed for a large ingrowth region to improve secondary stability.

  8. Twelve months of voluntary heavy alcohol consumption in male rhesus macaques suppresses intracortical bone remodeling.

    Science.gov (United States)

    Gaddini, Gino W; Grant, Kathleen A; Woodall, Andrew; Stull, Cara; Maddalozzo, Gianni F; Zhang, Bo; Turner, Russell T; Iwaniec, Urszula T

    2015-02-01

    Chronic heavy alcohol consumption is a risk factor for cortical bone fractures in males. The increase in fracture risk may be due, in part, to reduced bone quality. Intracortical (osteonal) bone remodeling is the principle mechanism for maintaining cortical bone quality. However, it is not clear how alcohol abuse impacts intracortical bone remodeling. This study investigated the effects of long-duration heavy alcohol consumption on intracortical bone remodeling in a non-human primate model. Following a 4-month induction period, male rhesus macaques (Macaca mulatta, n=21) were allowed to voluntarily self-administer water or alcohol (4% ethanol w/v) for 22h/d, 7 d/wk for 12months. Control monkeys (n=13) received water and an isocaloric maltose-dextrin solution. Tetracycline hydrochloride was administered orally 17 and 3days prior to sacrifice for determination of active mineralization sites. Animals in the alcohol group consumed 2.7±0.2g alcohol/kg/d (mean±SE) during the 12months of self-administration, resulting in a mean daily blood alcohol concentration of 77±9mg/dl from samples taken at 7h after the start of a daily session. However, blood alcohol concentration varied widely from day to day, with peak levels exceeding 250mg/dl, modeling a binge-drinking pattern of alcohol consumption. The skeletal response to alcohol was determined by densitometry, microcomputed tomography and histomorphometry. Significant differences in tibial bone mineral content, bone mineral density, and cortical bone architecture (cross-sectional volume, cortical volume, marrow volume, cortical thickness, and polar moment of inertia) in the tibial diaphysis were not detected with treatment. However, cortical porosity was lower (1.8±0.5 % versus 0.6±0.1 %, p=0.021) and labeled osteon density was lower (0.41±0.2/mm(2)versus 0.04±0.01/mm(2), premodeling. In concordance, plasma CTx was lower (2.5±0.3ng/ml versus 1.7±0.1ng/ml, p=0.028) in the alcohol group. These results suggest that

  9. 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 glucocorticoid-induced osteoporosis is associated with the absence of progression of the remodeling cycle to bone formation, i.e. uncoupling. An emerging concept explaining this critical role of canopies is that they represent a reservoir of osteoprogenitors to be delivered to reversal surfaces....... 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...

  10. 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.

  11. Impact of targeted PPAR gamma disruption on bone remodeling

    Science.gov (United States)

    Peroxisome proliferator-activated receptor gamma (PPAR gamma), known as the master regulator of adipogenesis, has been regarded as a promising target for new anti-osteoporosis therapy due to its role in regulating bone marrow mesenchymal stem/progenitor cell (BMSC) lineage commitment. However, the p...

  12. 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

  13. 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...

  14. Trabecular bone structure and strength - remodelling and repair

    DEFF Research Database (Denmark)

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

    2000-01-01

    relationship is based on the fact that trabecular bone is a porous material. To date, it has not been possible to determine or quantify the influence other factors may have in determining the strength of a loadbearing trabecular network. However, it is known that with age: 1) There is a loss of connectivity...... through osteoclastic perforations of horizontal struts. 2) There is an increase in anisotropy - again due to loss of horizontal struts, and perhaps also due to micro-modelling drift or to thickening of some vertical trabeculae. 3) The changes in the network can lead to the slenderness ratio between...... can never be isolated in vivo, other factors need to be investigated: The interplay between the cortical shell and the trabecular network; transmission of load; the interplay between soft tissues (cartilage, connective tissue, muscle) and bone; the shock absorbing capacity of the discs...

  15. 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.

  16. The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism.

    Science.gov (United States)

    Ducy, P

    2011-06-01

    Bone remodelling, which maintains bone mass constant during adulthood, is an energy-demanding process. This, together with the observation that the adipocyte-derived hormone leptin is a major inhibitor of bone remodelling, led to the hypothesis that bone cells regulate energy metabolism through an endocrine mechanism. Studies to test this hypothesis identified osteocalcin, a hormone secreted by osteoblasts, as a positive regulator of insulin secretion, insulin resistance and energy expenditure. Remarkably, insulin signalling in osteoblasts is a positive regulator of osteocalcin production and activation via its ability to indirectly enhance bone resorption by osteoclasts. In contrast, leptin is a potent inhibitor of osteocalcin function through its effect on the sympathetic tone. Hence, osteocalcin is part of a complex signalling network between bone and the organs more classically associated with the regulation of energy homeostasis, such as the pancreas and adipose tissue. This review summarises the molecular and cellular bases of the present knowledge on osteocalcin biology and discusses the potential relevance of osteocalcin to human metabolism and pathology.

  17. [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.

  18. Roles of the kidney in the formation, remodeling and repair of bone.

    Science.gov (United States)

    Wei, Kai; Yin, Zhiwei; Xie, Yuansheng

    2016-06-01

    The relationship between the kidney and bone is highly complex, and the kidney plays an important role in the regulation of bone development and metabolism. The kidney is the major organ involved in the regulation of calcium and phosphate homeostasis, which is essential for bone mineralization and development. Many substances synthesized by the kidney, such as 1,25(OH)2D3, Klotho, bone morphogenetic protein-7, and erythropoietin, are involved in different stages of bone formation, remodeling and repair. In addition, some cytokines which can be affected by the kidney, such as osteoprotegerin, sclerostin, fibroblast growth factor -23 and parathyroid hormone, also play important roles in bone metabolism. In this paper, we summarize the possible effects of these kidney-related cytokines on bone and their possible mechanisms. Most of these cytokines can interact with one another, constituting an intricate network between the kidney and bone. Therefore, kidney diseases should be considered among patients presenting with osteodystrophy and disturbances in bone and mineral metabolism, and treatment for renal dysfunction may accelerate their recovery.

  19. Moderate-intensity rotating magnetic fields do not affect bone quality and bone remodeling in hindlimb suspended rats.

    Directory of Open Access Journals (Sweden)

    Da Jing

    Full Text Available Abundant evidence has substantiated the positive effects of pulsed electromagnetic fields (PEMF and static magnetic fields (SMF on inhibiting osteopenia and promoting fracture healing. However, the osteogenic potential of rotating magnetic fields (RMF, another common electromagnetic application modality, remains poorly characterized thus far, although numerous commercial RMF treatment devices have been available on the market. Herein the impacts of RMF on osteoporotic bone microarchitecture, bone strength and bone metabolism were systematically investigated in hindlimb-unloaded (HU rats. Thirty two 3-month-old male Sprague-Dawley rats were randomly assigned to the Control (n = 10, HU (n = 10 and HU with RMF exposure (HU+RMF, n = 12 groups. Rats in the HU+RMF group were subjected to daily 2-hour exposure to moderate-intensity RMF (ranging from 0.60 T to 0.38 T at 7 Hz for 4 weeks. HU caused significant decreases in body mass and soleus muscle mass of rats, which were not obviously altered by RMF. Three-point bending test showed that the mechanical properties of femurs in HU rats, including maximum load, stiffness, energy absorption and elastic modulus were not markedly affected by RMF. µCT analysis demonstrated that 4-week RMF did not significantly prevent HU-induced deterioration of femoral trabecular and cortical bone microarchitecture. Serum biochemical analysis showed that RMF did not significantly change HU-induced decrease in serum bone formation markers and increase in bone resorption markers. Bone histomorphometric analysis further confirmed that RMF showed no impacts on bone remodeling in HU rats, as evidenced by unchanged mineral apposition rate, bone formation rate, osteoblast numbers and osteoclast numbers in cancellous bone. Together, our findings reveal that RMF do not significantly affect bone microstructure, bone mechanical strength and bone remodeling in HU-induced disuse osteoporotic rats. Our study indicates

  20. 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....

  1. The use of RANKL-coated brushite cement to stimulate bone remodelling.

    Science.gov (United States)

    Le Nihouannen, Damien; Hacking, S Adam; Gbureck, Uwe; Komarova, Svetlana V; Barralet, Jake E

    2008-08-01

    Calcium phosphate cements were first proposed as synthetic bone substitutes over two decades ago, however, they are characterised by slow chemical or cellular resorption and a slow osteointegration. In contrast, bone autograft has been shown to stimulate osteoclastogenesis and angiogenesis resulting in active bone remodelling and rapid graft incorporation. Therefore, we aimed to develop a biomaterial able to release a key stimulator of the bone remodelling process, cytokine RANKL. Cylinders of brushite cement, hydroxyapatite cement and sodium alginate were loaded with RANKL either by incorporation into the cement or by coating the material with soluble RANKL. To test the biological activity of these formulations, we assessed their effectiveness in inducing osteoclast formation from RAW 264.7 monocytic cell line. Only brushite and hydroxyapatite cements coated with RANKL allowed for retaining sufficient biological activity to induce osteoclast formation. Most efficient was coating 40 mg cylinder of brushite cement with 800 ng RANKL. We have found that RANKL-coated brushite cement exhibits osteoclastogenic activity for at least 1 month at 37 degrees C. Thus, we developed a formulation of brushite cement with RANKL - a synthetic bone graft that is similar to autografts in its ability to actively induce osteoclastogenesis.

  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. Osteoblast connexin43 modulates skeletal architecture by regulating both arms of bone remodeling.

    Science.gov (United States)

    Watkins, Marcus; Grimston, Susan K; Norris, Jin Yi; Guillotin, Bertrand; Shaw, Angela; Beniash, Elia; Civitelli, Roberto

    2011-04-15

    Connexin43 (Cx43) has an important role in skeletal homeostasis, and Cx43 gene (Gja1) mutations have been linked to oculodentodigital dysplasia (ODDD), a human disorder characterized by prominent skeletal abnormalities. To determine the function of Cx43 at early steps of osteogenesis and its role in the ODDD skeletal phenotype, we have used the Dermo1 promoter to drive Gja1 ablation or induce an ODDD mutation in the chondro-osteogenic linage. Both Gja1 null and ODDD mutant mice develop age-related osteopenia, primarily due to a progressive enlargement of the medullary cavity and cortical thinning. This phenotype is the consequence of a high bone turnover state, with increased endocortical osteoclast-mediated bone resorption and increased periosteal bone apposition. Increased bone resorption is a noncell autonomous defect, caused by exuberant stimulation of osteoclastogenesis by Cx43-deficient bone marrow stromal cells, via decreased Opg production. The latter is part of a broad defect in osteoblast differentiation and function, which also results in abnormal structural and material properties of bone leading to decreased resistance to mechanical load. Thus Cx43 in osteogenic cells is a critical regulator of both arms of the bone remodeling cycle, its absence causing structural changes remindful of aged or disused bone.

  4. 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

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

    Science.gov (United States)

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Hauge, Ellen-Margrethe; Bollerslev, Jens; Delaissé, Jean-Marie

    2015-04-01

    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 glucocorticoid-induced osteoporosis is associated with the absence of progression of the remodeling cycle to bone formation, i.e., uncoupling. An emerging concept explaining this critical role of canopies is that they represent a reservoir of osteoprogenitors to be delivered to reversal surfaces. 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 of iliac crest biopsies from patients exposed to long-term glucocorticoid treatment revealed a subpopulation of reversal surfaces corresponding to the characteristics of arrest found in postmenopausal osteoporosis. Importantly, these arrested reversal surfaces were devoid of canopy coverage in almost all biopsies, and their prevalence correlated with a deficiency in bone forming surfaces. Taken together with the other recent data, the functional link between canopies, reversal surface activity, and the extent of bone formation surface in postmenopausal- and glucocorticoid-induced osteoporosis, supports a model where bone restitution during remodeling demands recruitment of osteoprogenitors from the canopy onto reversal surfaces. These data suggest that securing the presence of functional local osteoprogenitors deserves attention in the search of strategies to prevent the bone loss that occurs during bone remodeling in pathological situations.

  6. 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.

  7. MAGED1 is a negative regulator of bone remodeling in mice.

    Science.gov (United States)

    Liu, Mei; Xu, Lijuan; Ma, Xiao; Xu, Jiake; Wang, Jing; Xian, Mengmeng; Zhou, Xiaotian; Wang, Min; Wang, Fang; Qin, An; Pan, Qiuhui; Wen, Chuanjun

    2015-10-01

    Melanoma antigen family D1 (MAGED1), an important adaptor protein, has been shown to ubiquitously express and play critical roles in many aspects of cellular events and physiological functions. However, its role in bone remodeling remains unknown. We, therefore, analyzed the bone phenotype of Maged1-deficient mice. Maged1-deficient mice displayed a significant osteoporotic phenotype with a marked decrease in bone density and deterioration of trabecular architecture. Histomorphometric analysis demonstrated an increased mineral apposition rate as well as increased osteoclast number and surface in Maged1 knockout mice. At the cellular level, Maged1-deficient osteoblasts exhibited an increased proliferation rate and accelerated differentiation. MAGED1 deficiency also caused a promotion in osteoclastogenesis, and that was attributed to the cell autonomous acceleration of differentiation in osteoclasts and an increased receptor activator of NF-κB ligand/osteoprotegerin ratio, a major index of osteoclastogenesis, in osteoblasts. Thus, we identified MAGED1 as a novel regulator of osteoblastogenesis, osteoclastogenesis, and bone remodeling in a mouse model.

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

    Directory of Open Access Journals (Sweden)

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2016-06-01

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

  11. Numerical simulation of load-induced bone structural remodelling using stress-limit criterion.

    Science.gov (United States)

    Marzban, Ali; Nayeb-Hashemi, Hamid; Vaziri, Ashkan

    2015-01-01

    A simple and efficient numerical method for predicting the remodelling of adaptive materials and structures under applied loading was presented and implemented within a finite element framework. The model uses the trajectorial architecture theory of optimisation to predict the remodelling of material microstructure and structural organisation under mechanical loading. We used the proposed model to calculate the density distribution of proximal femur in the frontal plane. The loading considered was the hip joint contact forces and muscular forces at the attachment sites of the muscles to the bone. These forces were estimated from a separate finite element calculation using a heterogeneous three-dimensional model of the proximal femur. The density distributions obtained by this procedure has a qualitative similarity with in vivo observations. Solutions displayed the characteristic high-density channels that are evident in the Dual X-ray Absorptiometry scan. There is also evidence of the intramedullary canal, as well as low-density regions in the femoral neck. Several parametric studies were carried out to highlight the advantages of the proposed method, which includes fast convergence and low-computational cost. The potential applications of the proposed method in predicting bone structural remodelling in cancer are also briefly discussed.

  12. Bone marrow-derived progenitor cells augment venous remodeling in a mouse dorsal skinfold chamber model.

    Directory of Open Access Journals (Sweden)

    Megan E Doyle

    Full Text Available The delivery of bone marrow-derived cells (BMDCs has been widely used to stimulate angiogenesis and arteriogenesis. We identified a progenitor-enriched subpopulation of BMDCs that is able to augment venular remodeling, a generally unexplored area in microvascular research. Two populations of BMDCs, whole bone marrow (WBM and Lin(-/Sca-1(+ progenitor cells, were encapsulated in sodium alginate and delivered to a mouse dorsal skinfold chamber model. Upon observation that encapsulated Sca-1(+ progenitor cells enhance venular remodeling, the cells and tissue were analyzed on structural and molecular levels. Venule walls were thickened and contained more nuclei after Sca-1(+ progenitor cell delivery. In addition, progenitors expressed mRNA transcript levels of chemokine (C-X-C motif ligand 2 (CXCL2 and interferon gamma (IFNγ that are over 5-fold higher compared to WBM. Tissues that received progenitors expressed significantly higher protein levels of vascular endothelial growth factor (VEGF, monocyte chemotactic protein-1 (MCP-1, and platelet derived growth factor-BB (PDGF-BB compared to tissues that received an alginate control construct. Nine days following cell delivery, tissue from progenitor recipients contained 39% more CD45(+ leukocytes, suggesting that these cells may enhance venular remodeling through the modulation of the local immune environment. Results show that different BMDC populations elicit different microvascular responses. In this model, Sca-1(+ progenitor cell-derived CXCL2 and IFNγ may mediate venule enlargement via modulation of the local inflammatory environment.

  13. 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

  14. 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.

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

    Science.gov (United States)

    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

    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. 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 rabbits. At 22 weeks, after sacrifice, microstructure parameters were assessed by micro-computed tomography, and osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), alkaline phosphatase (ALP) and metalloproteinase 9 (MMP9) protein expressions were evaluated by Western Blot at subchondral bone. In addition, cartilage damage was estimated using the histopathological Mankin score. Mann-Whitney and Spearman statistical tests were performed as appropriate, using SPSS software v 11.0. Significant difference was established at P fractal dimension and MMP9 expression occurred at subchondral bone of OA, OP and OPOA knees vs. controls (P < 0.05). In addition, the severity of cartilage damage was increased in OPOA knees vs. controls (P < 0.05). Remarkably, good correlations were observed between structural and remodelling parameters at subchondral bone, and furthermore, between subchondral structural parameters and cartilage Mankin score. Microstructure impairment at subchondral bone associated with an increased remodelling aggravated cartilage damage in OA rabbits with previous OP. Our results suggest that an increased subchondral bone resorption may account for the exacerbation of cartilage damage when early OA and OP coexist simultaneously in same individuals.

  16. 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 ...

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

    Science.gov (United States)

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

  18. Effect of Progressive Locomotor Treadmill Compared to Conventional Training on Bone Mineral Density and Bone Remodeling in Paraplegia

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    Ghasemi Mobarake

    2016-11-01

    Full Text Available Background The decrease in bone mass in paraplegic spinal cord injured persons increases the risk factors for fractures. Objectives The aim of the present study was to evaluate the effects of progressive locomotor treadmill training (LT on muscle mass, bone mineral density, and bone remodeling in paraplegia patients. Methods The subjects investigated in this research included seventeen paraplegic spinal cord injured persons who were divided randomly into two groups: LT group (n = 10 and conventional exercise group (n = 7. The exercise training protocol was performed during 12 weeks, 3 days a week, 60 minutes a session. LT included 15 minutes warm-up on stationary bike plus 45 minutes LT with 50 percent body-weight support and finally 10 minutes cool-down as an adjunct to a conventional physiotherapy program. 10 percent loading weight was added per week for LT. Conventional exercise training incorporated 15 minutes warm-up plus 45 minutes over-ground training such as stretch exercise and resistance training. Results The obtained results showed that there were significant differences in serum alkaline phosphatase levels (P < 0.001, osteocalcin levels (P = 0.003, bone mineral content (BMC of the femoral neck (P < 0.001, bone mineral density (BMD of femoral neck (P < 0.001, bone mineral content (BMC of the lumbar spine (P < 0.001, and bone mineral density (BMD of the lumbar spine (P = 0.000 between LT and conventional exercise regimes. Conclusions LT training, in addition to improvement of motor function and reduction of bone loss, can be prescribed as an effective exercise intervention for the treatment of osteoporosis in incomplete spinal cord injured persons.

  19. Role of Periostin in Adhesion and Migration of Bone Remodeling Cells

    Science.gov (United States)

    Cobo, Teresa; Viloria, Cristina G.; Solares, Laura; Fontanil, Tania; González-Chamorro, Elena; De Carlos, Félix; Cobo, Juan; Cal, Santiago; Obaya, Alvaro J.

    2016-01-01

    Periostin is an extracellular matrix protein highly expressed in collagen-rich tissues subjected to continuous mechanical stress. Functionally, periostin is involved in tissue remodeling and its altered function is associated to numerous pathological processes. In orthodontics, periostin plays key roles in the maintenance of dental tissues and it is mainly expressed in those areas where tension or pressing forces are taking place. In this regard, high expression of periostin is essential to promote migration and proliferation of periodontal ligament fibroblasts. However little is known about the participation of periostin in migration and adhesion processes of bone remodeling cells. In this work we employ the mouse pre-osteoblastic MC3T3-E1 and the macrophage-like RAW 264.7 cell lines to overexpress periostin and perform different cell-based assays to study changes in cell behavior. Our data indicate that periostin overexpression not only increases adhesion capacity of MC3T3-E1 cells to different matrix proteins but also hampers their migratory capacity. Changes on RNA expression profile of MC3T3-E1 cells upon periostin overexpression have been also analyzed, highlighting the alteration of genes implicated in processes such as cell migration, adhesion or bone metabolism but not in bone differentiation. Overall, our work provides new evidence on the impact of periostin in osteoblasts physiology. PMID:26809067

  20. Evaluation of volume and solitary bone cyst remodeling using conventional radiological examination

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    Glowacki, Maciej; Melzer, Piotr [Karol Marcinkowski University of Medical Sciences, Department of Paediatric Orthopaedics, Poznan (Poland); Ignys-O' Byrne, Anna [J. Strus City Hospital, Department of Radiology, Poznan (Poland); Ignys, Iwona [Karol Marcinkowski University of Medical Sciences, Department of Paediatric Gastroenterology and Metabolic Diseases, Poznan (Poland); Mankowski, Przemyslaw [Karol Marcinkowski University of Medical Sciences, Department of Paediatric Surgery, Traumatology and Urology, Poznan (Poland)

    2010-03-15

    To evaluate cyst remodeling, including complete healing and recurrence, and its relation to the cyst volume in two groups of patients, using curettage and bone grafting or methylprednisolone injection. A retrospective analysis was carried out on data from 132 patients with solitary bone cyst, where 79 (59.9%) had undergone curettage and bone grafting and 53 (40.1%) had been administered methylprednisolone injection, with a mean time to follow up of 12 years. The cyst volume was evaluated from conventional radiographs and the method originally reported by Goebel et al. to evaluate the volume of Ewing's sarcoma. The results were analyzed using the criteria of Neer et al. and Capanna et al. The mean cyst volume was 36.8 cm{sup 3}. Recurrence was noted in 16 (20.2%) patients treated with curettage and in nine (17.0%) treated with methylprednisolone. Cyst volume in patients treated with curettage and bone grafting ranged from 8.3 cm{sup 3} to 100.0 cm{sup 3} and with methylprednisolone from 14.0 cm{sup 3} to 50.6 cm{sup 3}. In neither group was the cyst volume related to recurrence. Volumes from 1.3 cm{sup 3} to 81.9 cm{sup 3} were stated for patients treated with curettage and bone grafting, when complete healing was observed; they were significantly lower than for those of the total group of patients who underwent curettage and bone grafting. 1. An association between solitary cyst volume and recurrence in patients treated with either bone curettage and grafting or methylprednisolone was not found. 2. The frequency of complete healing in patients treated with bone curettage and grafting decreased with an increase in the cyst volume. (orig.)

  1. EFFECT OF LOCATION AND BONE GRAFT REMODELING ON RESULTS OF BRISTOW-LATARJET PROCEDURE

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    D. A. Malanin

    2016-01-01

    Full Text Available Introduction. Operation Bristow-Latarjet proved itself as one of the most effective and predictable surgical treatments. despite its widespread use, there are various complications associated with improper installation of the bone block and the violation of its remodeling.Objective: To obtain new data on the effect of location and remodeling of bone graft block on functional outcome and stability of the shoulder joint in patients with recurrent anterior instability after the operation Bristow-latarjet.Material and methods. The material for the study served as the analysis of results of treatment of 64 patients with posttraumatic recurrent anterior shoulder dislocation who underwent Bristow-latarjet operation. postoperatively, assessed a provision and the degree of bone remodeling unit according to computed tomography in the sagittal, axial slices, and through 3d modeling. To evaluate the functional outcome scale were used western Ontario Shoulder Index (wOSI and Rowe scale.Results. At the level of the articular surface (congruent or flattening in the axial plane were 89% bone blocks, too medially or laterally arranged 9% and 2% grafts, respectively. On sagittal cT images in the middle third of the articular surface of the scapula was located 28% of the bone blocks at the bottom 60%, in the upper third of 12%. Analysis of the dependence of the results of treatment of graft positioning showed that patients with excellent and good summary on the scale WOSI and Rowe, had a correct location of the bone block in the middle and lower third of the articular process of the blade. It can be assumed that excessive lateralized or medialized bone block position in the axial plane of a more profound effect on the outcome than cranial displacement of the latter with the sagittal plane. Bony union of the graft was found by CT in 74% of cases, soft tissue 26%, the degree of resorption of the graft revealed 0-1 84% 2-3 degree in 26% of cases. In the last periods

  2. 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.

  3. Bone remodelling in the proximal femur after Charnley total hip arthroplasty.

    Science.gov (United States)

    Cohen, B; Rushton, N

    1995-09-01

    We measured bone mineral density (BMD) in the proximal femur by dual-energy X-ray absorptiometry (DEXA) in 20 patients after cemented total hip arthroplasty over a period of one year. We found a statistically significant reduction in periprosthetic BMD after six months on the medial side and on the lateral side adjacent to the mid and distal thirds of the prosthesis. At one year after operation there was a mean 6.7% reduction in BMD in the region of the calcar and a mean 5.3% increase in BMD in the femoral shaft distal to the tip of the implant. These changes reflect a pattern of reduced stress in the proximal femur and increased stress around the tip of the prosthesis. They support current concepts of bone remodelling in the proximal femur in response to prosthetic implantation.

  4. Long-term prediction of three-dimensional bone architecture in simulations of pre-, peri- and post-menopausal microstructural bone remodeling.

    Science.gov (United States)

    Müller, Ralph

    2005-03-01

    The mechanical behavior of trabecular bone depends on the internal bone structure. It is generally accepted now that the trabecular bone structure is a result of a load adaptive bone remodeling. The mathematical laws that relate bone remodeling to the local state of stress and strain, however, are still under investigation. The aim of this project was to investigate if changes in the trabecular architecture as observed with age-related bone loss and osteoporosis can be predicted from a computer model that simulates bone resorption after hormone depletion based on realistic models of trabecular microstructure using micro-computed tomography (muCT). A compact desktop muCT providing a nominal isotropic resolution of 14 mum was used to measure two groups of seven trabecular bone specimens from pre-menopausal and post-menopausal women respectively. A novel algorithm was developed to simulate age-related bone loss for the specimens in the first group. The algorithm, also referred to as simulated bone atrophy (SIBA), describes a truly three-dimensional approach and is based directly on cellular bone remodeling with an underlying realistic time frame. Bone resorption is controlled by osteoclastic penetration depth and bone formation is governed by the efficiency level of the osteoblasts. The simulation itself describes an iterative process with a cellular remodeling cycle of 197 days. Activation frequency is controllable and can be adjusted for the different phases of pre-, peri- and post-menopause. For our simulations, osteoblastic and osteoclastic activities were in balance until the onset of menopause, set to be at the age of 50 years. In that period, the structure remained almost constant. After the onset of menopause an imbalance in the cell activities was modeled resulting in a net bone loss. The doubling of the activation frequency in the peri-menopausal phase caused a pronounced loss. Using advanced animation tools and quantitative bone morphometry, the changes in

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

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    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.

  6. Effects of constitutive β-catenin activation on vertebral bone growth and remodeling at different postnatal stages in mice.

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    Min Jia

    Full Text Available BACKGROUND AND OBJECTIVE: The Wnt/β-catenin signaling pathway is essential for controlling bone mass; however, little is known about the variable effects of the constitutive activation of β-catenin (CA-β-catenin on bone growth and remodeling at different postnatal stages. The goal of the present study was to observe the effects of CA-β-catenin on vertebral bone growth and remodeling in mice at different postnatal stages. In particular, special attention was paid to whether CA-β-catenin has detrimental effects on these processes. METHODS: Catnblox(ex 3 mice were crossed with mice expressing the TM-inducible Cre fusion protein, which could be activated at designated time points via injection of tamoxifen. β-catenin was stabilized by tamoxifen injection 3 days, and 2, 4, 5, and 7 months after birth, and the effects lasted for one month. Radiographic imaging, micro-computed tomography, immunohistochemistry, and safranin O and tartrate-resistant acid phosphatase staining were employed to observe the effects of CA-β-catenin on vertebral bone growth and remodeling. RESULTS: CA-β-catenin in both early (3 days after birth and late stages (2, 4, 5, and 7 months after birth increased bone formation and decreased bone resorption, which together increased vertebral bone volume. However, when β-catenin was stabilized in the early stage, vertebral linear growth was retarded, and the mice demonstrated shorter statures. In addition, the newly formed bone was mainly immature and located close to the growth plate. In contrast, when β-catenin was stabilized in the late stage, vertebral linear growth was unaffected, and the newly formed bone was mainly mature and evenly distributed throughout the vertebral body. CONCLUSIONS: CA-β-catenin in both early and late stages of growth can increase vertebral bone volume, but β-catenin has differential effects on vertebral growth and remodeling when activated at different postnatal stages.

  7. Skeletal Site-specific Effects of Zoledronate on in vivo Bone Remodeling and in vitro BMSCs Osteogenic Activity

    Science.gov (United States)

    Gong, Xue; Yu, Wanlu; Zhao, Hang; Su, Jiansheng; Sheng, Qing

    2017-01-01

    Bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been associated with long-term oral or intravenous administration of nitrogen-containing bisphosphonates (BPs). However, the pathogenesis of BRONJ remains unknown, and definitively effective treatment has not yet been established. Bisphosphonate-related osteonecrosis (BRON) tends to occur in maxillofacial bones. Why this occurs is still unclear. Here we show that zoledronate (Zol) treatment suppresses alveolar bone remodeling after tooth typical clinical and radiographic hallmarks of the human BRONJ, whereas enhances peripheral bone quantity in bone remodeling following injury in the same individuals, shown as increased cortical bone thickness, increased trabecular bone formation and accelerated bone defect repair. We find that the RANKL/OPG ratio and Wnt-3a expression are suppressed at the extracted alveolar sites in Zol-treated rats compared with those at the injured sites of peripheral bones. We also show that Zol-treated bone marrow stromal cell (BMSCs) derived from jaw and peripheral bones exhibit differences in cell proliferation, alkaline phosphatase (ALP) activity, expression of osteogenic and chondrogenic related marker genes, and in vivo bone formation capacity. Hopefully, this study will help us better understand the pathogenesis of BRONJ, and deepen the theoretical research. PMID:28139685

  8. Effect of nasal salmon calcitonin on bone remodeling and bone mass in postmenopausal osteoporosis.

    Science.gov (United States)

    Thamsborg, G; Jensen, J E; Kollerup, G; Hauge, E M; Melsen, F; Sorensen, O H

    1996-02-01

    The effect of nasal salmon calcitonin (SCT) on bone has been investigated by densitometry, biochemical markers of bone turnover, and histomorphometry. 62 women (mean age 65 years) who had experienced Colles' fracture after menopause were randomized to receive either nasal salmon calcitonin (SCT) 200 IU or nasal placebo daily for 24 months. All received a daily supplement of 0.5 g calcium. There was a significant increase above baseline in the bone mineral density of the lumbar spine in the SCT group (2.5%; 95% confidence interval 0.9--4.2%) and in the placebo group (1.7%; 95% confidence interval 0.3--3.1%) after 24 months, but the difference between the groups was not significant (0.8%; 95% confidence interval -1.2-3.0%). Serum levels of osteocalcin decreased significantly below baseline in the SCT group, whereas they were unchanged in the placebo group. At months 12 and 24, serum levels of osteocalcin were significantly lower in the SCT group than in the placebo group (p transient decrease was observed in the placebo group. The differences between the groups were, however, not significant. The erosion depth was significantly lower in the SCT group than in the placebo group after 12 months (median [interquartile range]; 46.9 mu m [10.4] vs. 50.5 mu m [10.7]; p = 0.03), whereas bone volume and activation frequency did not differ between the groups. This study indicates that nasal SCT in a dose of 200 IU daily induces only a minor inhibition of bone resorption and therefore produces only a minor increase in bone mass. Furthermore, it seems that nasal SCT in a dose of 200 IU does not interfere with the recruitment of new bone multicellular units, but preferably decreases ongoing osteoclastic bone resorption.

  9. Electropolished Titanium Implants with a Mirror-Like Surface Support Osseointegration and Bone Remodelling

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    Cecilia Larsson Wexell

    2016-01-01

    Full Text Available This work characterises the ultrastructural composition of the interfacial tissue adjacent to electropolished, commercially pure titanium implants with and without subsequent anodisation, and it investigates whether a smooth electropolished surface can support bone formation in a manner similar to surfaces with a considerably thicker surface oxide layer. Screw-shaped implants were electropolished to remove all topographical remnants of the machining process, resulting in a thin spontaneously formed surface oxide layer and a smooth surface. Half of the implants were subsequently anodically oxidised to develop a thickened surface oxide layer and increased surface roughness. Despite substantial differences in the surface physicochemical properties, the microarchitecture and the composition of the newly formed bone were similar for both implant surfaces after 12 weeks of healing in rabbit tibia. A close spatial relationship was observed between osteocyte canaliculi and both implant surfaces. On the ultrastructural level, the merely electropolished surface showed the various stages of bone formation, for example, matrix deposition and mineralisation, entrapment of osteoblasts within the mineralised matrix, and their morphological transformation into osteocytes. The results demonstrate that titanium implants with a mirror-like surface and a thin, spontaneously formed oxide layer are able to support bone formation and remodelling.

  10. 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.

  11. A comparative mechanical and bone remodelling study of all-ceramic posterior inlay and onlay fixed partial dentures.

    Science.gov (United States)

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

    2012-01-01

    Comparative studies of bone remodelling and mechanical stresses between inlay and onlay fixed partial dentures (FPD) are rather limited. The purpose of this paper was to evaluate the biological consequence in posterior mandibular bone and the mechanical responses in these two different prosthetic configurations. Three-dimensional (3D) finite element analysis (FEA) models are created to explore the mechanical responses for the inlay and onlay preparations within the same oral environment. Strain induced bone remodelling was simulated under mastication. The remodelling adopted herein relates the strain in the bone to the change of Hounsfield Unit (HU) value in proportion to the surface area density (SAD) of bony morphology, which allows directly correlating to clinical computerised tomography (CT) data. The results show that both FPD designs exhibit a similar resultant change in bone mineral density (BMD) though the onlay configuration leads to a more uniform distribution of bone density. The inlay design results in higher mechanical stresses whilst allowing preservation of healthy tooth structure. This study provides an effective means to further clinical assessment and investigation into biomechanical responses and long-term restorative outcome with different FPD designs. Quantifying in vivo stress distributions associated with inlay/onlay FPDs can further supplement clinical investigations into prosthetic durability, FPD preparation techniques (i.e., taper angles, material development), consequent stress distributions and the ongoing biomechanical responses of mandibular bone. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Blood flow for bone remodelling correlates with locomotion in living and extinct birds.

    Science.gov (United States)

    Allan, Georgina H; Cassey, Phillip; Snelling, Edward P; Maloney, Shane K; Seymour, Roger S

    2014-08-15

    Nutrient arteries enter limb bones through discrete foramina on the shafts. They are required for bone remodelling in response to mechanical loading and dynamic forces imposed by locomotion. The cross-sectional area of the nutrient foramen of the femur represents an index of blood flow rate to the shaft and thus provides insight into the animal's level of activity. Morphometric data on femoral length, mass and foramen size from 100 extant bird species and eight extinct moa species were analysed allometrically and phylogenetically. The nutrient foramen blood flow index (Qi) and femur mass (Mf) increase with body mass (Mb). At 1 kg body mass, cursorial species have approximately 2.1 times higher Qi and 1.9 times heavier Mf than volant species. The scaling of Qi on Mf is independent of the primary mode of locomotion, but the ratio Qi/Mf decreases significantly in larger birds, although absolute Qi increases. The overall avian equation for Qi on Mb is not significantly different from previous data from mammals, but when differences in blood pressure are accounted for, estimated blood flow to the femur is approximately 1.9 times higher in cursorial birds than in mammals, possibly in relation to bipedalism and quadrupedalism, respectively. Femoral bone blood flow in both endothermic groups is estimated to be 50-100 times higher than in ectothermic reptiles. © 2014. Published by The Company of Biologists Ltd.

  13. Does platelet-rich plasma promote remodeling of autologous bone grafts used for augmentation of the maxillary sinus floor?

    NARCIS (Netherlands)

    Raghoebar, GM; Schortinghuis, J; Liem, RSB; Ruben, JL; van der Wal, JE; Vissink, A

    2005-01-01

    The aim of this study was to evaluate the effect of platelet-rich plasma (PRP) on remodeling of autologous bone grafts used for augmentation of the floor of the maxillary sinus. In five edentulous patients suffering from insufficient retention of their upper denture related to a severely resorbed ma

  14. 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.

  15. 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.

  16. Crosstalk of osteoblast and osteoclast precursors on mineralized collagen--towards an in vitro model for bone remodeling.

    Science.gov (United States)

    Bernhardt, A; Thieme, S; Domaschke, H; Springer, A; Rösen-Wolff, A; Gelinsky, M

    2010-12-01

    Bone remodeling and, therefore, integration of implant materials require the coordinated regulation of osteoblast and osteoclast activity. This is why the in vitro evaluation of biomaterials for bone regeneration should involve not only the analysis of osteoblast differentiation but also the formation and differentiation of osteoclasts. In the present study, we applied a material made of mineralized collagen I that mimics extracellular bone matrix to establish a culture system, which allows the cocultivation of human monocytes and human mesenchymal stem cells (hMSCs), which were differentiated into osteoclast-like cells and osteoblasts, respectively. Both cell types were cultivated on membrane-like structures from mineralized collagen. Transwell inserts were used to spatially separate the cell types but allowed exchange of soluble factors. The osteoclastogenesis and osteogenic differentiation were evaluated by analysis of gene expression, determination of alkaline phosphatase (ALP), and tartrate-resistant acidic phosphatase (TRAP) activity. Furthermore, cell morphology was studied using scanning electron and transmission electron microscopy. Osteogenically induced hMSC showed an increased specific ALP activity as well as increased gene expression of gene coding for alkaline phosphatase (ALPL), when cocultivated with differentiating osteoclasts. Adipogenic differentiation of hMSCs was suppressed by the presence of osteoclasts as indicated by a major decrease in adipocyte cell number and a decrease in gene expression of adipogenic markers. The formation of multinucleated osteoclasts seems to be decreased in the presence of osteogenically induced hMSC as indicated by electron microscopic evaluation and determination of TRAP activity. However, gene expression of osteoclast markers was not decreased in coculture with osteogenically induced hMSC.

  17. Aging and estrogen status: a possible endothelium-dependent vascular coupling mechanism in bone remodeling.

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    Rhonda D Prisby

    Full Text Available Bone loss with aging and menopause may be linked to vascular endothelial dysfunction. The purpose of the study was to determine whether putative modifications in endothelium-dependent vasodilation of the principal nutrient artery (PNA of the femur are associated with changes in trabecular bone volume (BV/TV with altered estrogen status in young (6 mon and old (24 mon female Fischer-344 rats. Animals were divided into 6 groups: 1 young intact, 2 old intact, 3 young ovariectomized (OVX, 4 old OVX, 5 young OVX plus estrogen replacement (OVX+E2, and 6 old OVX+E2. PNA endothelium-dependent vasodilation was assessed in vitro using acetylcholine. Trabecular bone volume of the distal femoral metaphysis was determined by microCT. In young rats, vasodilation was diminished by OVX and restored with estrogen replacement (intact, 82±7; OVX, 61±9; OVX+E2, 90±4%, which corresponded with similar modifications in BV/TV (intact, 28.7±1.6; OVX, 16.3±0.9; OVX+E2, 25.7±1.4%. In old animals, vasodilation was unaffected by OVX but enhanced with estrogen replacement (intact, 55±8; OVX, 59±7; OVX+E2, 92±4%. Likewise, modifications in BV/TV followed the same pattern (intact, 33.1±1.6; OVX, 34.4±3.7; OVX+E2, 42.4±2.1%. Furthermore, in old animals with low endogenous estrogen (i.e., intact and old OVX, vasodilation was correlated with BV/TV (R(2 = 0.630; P<0.001. These data demonstrate parallel effects of estrogen on vascular endothelial function and BV/TV, and provide for a possible coupling mechanism linking endothelium-dependent vasodilation to bone remodeling.

  18. Long-term Bone Remodeling in HA-coated Stems: A Radiographic Review of 208 Total Hip Arthroplasties (THAs) with 15 to 20 Years Follow-up.

    Science.gov (United States)

    Boldt, Jens G; Cartillier, Jean-Claude; Machenaud, Alain; Vidalain, Jean-Pierre

    2015-11-01

    We present a prospective study focused on radiographic long-term outcomes and bone remodeling at a mean of 17.0 years (range: 15 to 20) in 208 cementless fully HA-coated femoral stems (Corail, DePuy International Ltd, Leeds, UK). Total hip replacements in this study were performed by three members of the surgeon design group between 1986 and 1991. Radiographic evaluation focused on periprosthetic osteolysis, bone remodeling, osseous integration, subsidence, metaphyseal or diaphyseal load transfer, and femoral stress shielding. The radiographs were digitized and examined with contrast-enhancing software for analysis of the trabecular architecture. Radiographic signs of aseptic stem loosening were visible in two cases (1%). Three stems (1.4%) showed metaphyseal periprosthetic osteolysis in four of seven Gruen zones associated with eccentric polyethylene wear awaiting metaphyseal bone grafting and cup liner exchange. One stem (0.5%) was revised due to infection. No stem altered in varus or valgus alignment more than two degrees, and mean subsidence was 0.1 mm (range: 0 to 2 mm) after a mean of 17.0 years. A total of 5 stems (2.4%) required or are awaiting revision surgery. Trabecular orientation and micro-anatomy suggested main proximal load-transfer patterns in all except 3 cases (98.6%). Combined metaphyseal and diaphyseal osseointegration and bone remodeling were visible in 100 stems (48%). Diaphyseal stress shielding and cortical thickening were observed in 3 stems (1.4%). Other radiographic features are discussed in depth. This long-term study of 208 fully HA-coated Corail stems showed satisfactory osseointegration and fixation in 203 cases (97.6%) after a mean of 17.0 years follow-up. Stem failures were associated with extreme eccentric polyethylene wear.

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

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    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.

  20. Effects of resveratrol supplementation on bone growth in young rats and microarchitecture and remodeling in ageing rats.

    Science.gov (United States)

    Lee, Alice M C; Shandala, Tetyana; Nguyen, Long; Muhlhausler, Beverly S; Chen, Ke-Ming; Howe, Peter R; Xian, Cory J

    2014-12-16

    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 volume

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

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    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

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

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    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.

  3. Osteocyte apoptosis and absence of bone remodeling in human auditory ossicles and scleral ossicles of lower vertebrates: a mere coincidence or linked processes?

    Science.gov (United States)

    Palumbo, Carla; Cavani, Francesco; Sena, Paola; Benincasa, Marta; Ferretti, Marzia

    2012-03-01

    Considering the pivotal role as bone mechanosensors ascribed to osteocytes in bone adaptation to mechanical strains, the present study analyzed whether a correlation exists between osteocyte apoptosis and bone remodeling in peculiar bones, such as human auditory ossicles and scleral ossicles of lower vertebrates, which have been shown to undergo substantial osteocyte death and trivial or no bone turnover after cessation of growth. The investigation was performed with a morphological approach under LM (by means of an in situ end-labeling technique) and TEM. The results show that a large amount of osteocyte apoptosis takes place in both auditory and scleral ossicles after they reach their final size. Additionally, no morphological signs of bone remodeling were observed. These facts suggest that (1) bone remodeling is not necessarily triggered by osteocyte death, at least in these ossicles, and (2) bone remodeling does not need to mechanically adapt auditory and scleral ossicles since they appear to be continuously submitted to stereotyped stresses and strains; on the contrary, during the resorption phase, bone remodeling might severely impair the mechanical resistance of extremely small bony segments. Thus, osteocyte apoptosis could represent a programmed process devoted to make stable, when needed, bone structure and mechanical resistance.

  4. Thoracic bone remodeling after minimally invasive repair for pectus excavatum in adults and its clinical efficacy

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    Ji-fu LIU

    2012-04-01

    Full Text Available Objective To study thoracic bone remodeling after minimally invasive corrective surgery for pectus excavatum (PE in adults and ascertain its clinical efficacy. Methods A total of 82 patients aged 18 to 57 (23.5±6.1 were enrolled in this study. There were 67 male patients and 15 female patients. The symmetric type (Ⅰ type composed of 37 cases, whereas the nonsymmetric type (Ⅱ type comprised 45 cases. Haller index (HI was 3.2 to 11.8. Under general anesthesia, incisions located on looth sides of the mid-axillary line were made in all patients. The prepared supporting bar was inserted behind the sternum by videoassisted thoracoscopic monitoring (one bar for 60 patients and two bars for 22 patients. All patients were checked by chest CT scan pre-operation and 1 week post-operation to create a three-dimensional reconstruction thoracic image. In the sagittal plane, the center line of the body of the thoracic vertebrae was regarded as the incision line. The distance was measured between the sternum and the frontal edge of the body of the thoracic vertebrae. The condition of the displacement of the heart was also observed. Results When one bar was used, the middle and the inferior extremity of the mid-sternum was moved forward for 8.69 and 15.69mm, respectively, after correction. There was significant difference compared with that of the pre-operation (P < 0.01. However, the upper extremity of the mid-sternum and upper and inferior extremities of the manubrium were moved forward to 2.39, -2.38, and 1.44mm, which did not exhibit obvious difference compared with the values taken before the operation. When two bars were used for the patients, the inferior extremity of the manubrium and each of upper, middle, and inferior extremities of the mid-sternum showed a forward displacement for 10.8, 12.45, 17.61, and 20.62mm, respectively. There was significant difference compared with the pre-operative values (P < 0.001. The upper extremity of the

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

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    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.

  6. Low-dose hydrocortisone replacement therapy is associated with improved bone remodelling balance in hypopituitary male patients.

    Science.gov (United States)

    Behan, Lucy-Ann; Kelleher, Grainne; Hannon, Mark J; Brady, Jennifer J; Rogers, Bairbre; Tormey, William; Smith, D; Thompson, Christopher J; McKenna, Malachi J; Agha, Amar

    2014-01-01

    Glucocorticoid (GC) therapy is associated with adverse effects on bone metabolism, yet the effects of different GC physiological replacement regimens in hypopituitarism are not well characterised. We aimed to assess the effect of three hydrocortisone (HC) replacement dose regimens on bone turnover. An open cross-over study randomising ten hypopituitary men with severe acth deficiency to three commonly used HC dose regimens: dose A (20 mg mane and 10 mg tarde), dose B (10 mg mane and 10 mg tarde) and dose C (10 mg mane and 5 mg tarde). Following 6 weeks of each regimen, the participants underwent 24-h serum cortisol sampling and measurement of bone turnover markers: bone-specific alkaline phosphatase, procollagen type I N-propeptide (PINP), intact osteocalcin (OC(1-49)), C-terminal cross-linking telopeptide (CTX-I) and tartrate-resistant acid phosphatase 5b (TRACP5b). Bone remodelling balance was estimated as an absolute ratio (PINP:CTX-I) and as an index using standardised scores derived from the matched controls. There were significant increases in the concentrations of the formation markers PINP (P=0.045) and OC(1-49) (P=0.006) and in the PINP:CTX-I ratio (P=0.015), and a more positive bone remodelling balance index (P=0.03) was observed in patients on the lowest dose C than in those on the highest dose A. Mean 24-h cortisol concentrations correlated negatively with CTX-I (r=-0.66 and P=0.04) and TRACP5b (r=-0.74 and P=0.01) in patients on dose B and with OC(1-49) (r=-0.66 and P=0.04) and CTX-I (r=-0.81 and P<0.01) in patients on dose C. In patients receiving the lower-dose regimen, trough cortisol concentrations correlated with increased bone formation and resorption. Low-dose HC replacement (10 mg mane and 5 mg tarde) is associated with increased bone formation and a positive bone remodelling balance. This may have a long-term beneficial effect on bone health.

  7. Impaired differentiation of macrophage lineage cells attenuates bone remodeling and inflammatory angiogenesis in Ndrg1 deficient mice.

    Science.gov (United States)

    Watari, Kosuke; Shibata, Tomohiro; Nabeshima, Hiroshi; Shinoda, Ai; Fukunaga, Yuichi; Kawahara, Akihiko; Karasuyama, Kazuyuki; Fukushi, Jun-Ichi; Iwamoto, Yukihide; Kuwano, Michihiko; Ono, Mayumi

    2016-01-18

    N-myc downstream regulated gene 1 (NDRG1) is a responsible gene for a hereditary motor and sensory neuropathy-Lom (Charcot-Marie-Tooth disease type 4D). This is the first study aiming to assess the contribution of NDRG1 to differentiation of macrophage lineage cells, which has important implications for bone remodeling and inflammatory angiogenesis. Ndrg1 knockout (KO) mice exhibited abnormal curvature of the spine, high trabecular bone mass, and reduced number of osteoclasts. We observed that serum levels of macrophage colony-stimulating factor (M-CSF) and macrophage-related cytokines were markedly decreased in KO mice. Differentiation of bone marrow (BM) cells into osteoclasts, M1/M2-type macrophages and dendritic cells was all impaired. Furthermore, KO mice also showed reduced tumor growth and angiogenesis by cancer cells, accompanied by decreased infiltration of tumor-associated macrophages. The transfer of BM-derived macrophages from KO mice into BM-eradicated wild type (WT) mice induced much less tumor angiogenesis than observed in WT mice. Angiogenesis in corneas in response to inflammatory stimuli was also suppressed with decreased infiltration of macrophages. Taken together, these results indicate that NDRG1 deficiency attenuates the differentiation of macrophage lineage cells, suppressing bone remodeling and inflammatory angiogenesis. This study strongly suggests the crucial role of NDRG1 in differentiation process for macrophages.

  8. 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

    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...... osteoblast differentiation and function, which mirrored the histopathological bone changes. The differentially expressed genes belong to the bone morphogenetic pathway (BMP) and, in addition, include the osteoblast markers integrin-binding sialoprotein (Ibsp), bone gamma-carboxyglutamate protein (Bglap1...

  9. A comparative study of bone remodeling molecules expression in different types of jaw ameloblastoma.

    Science.gov (United States)

    Iakovou, Maria; Chrysomali, Evanthia; Piperi, Evangelia; Fanourakis, Galinos; Sklavounou, Alexandra; Vlachodimitropoulos, Dimitrios; Tseleni-Balafouta, Sophia

    2015-08-01

    Solid ameloblastoma demonstrates a more invasive behavior compared to unicystic. The follicular ameloblastoma is referred that may present a higher recurrence potential compared to the plexiform variant. In this study, the different ameloblastoma clinical types and histopathological variants were examined regarding the expression of bone remodeling-related molecules OPG, RANKL, and TRAIL. Immunostained sections of 29 solid and 11 unicystic ameloblastoma cases were semi-quantitatively evaluated and analyzed using Mann-Whitney or Kruskal-Wallis tests. Solid ameloblastoma showed a significantly increased OPG expression (P = 0.004) associated with the follicular (P ameloblastoma for differences by the histopathological pattern (no RANKL expression when plexiform pattern was seen compared to follicular). Comparison between the clinical types showed differences regarding the ratio of OPG/RANKL and TRAIL/RANKL expression. Higher OPG expression over RANKL was observed in 86.2% of the solid compared to 36.4% of the unicystic type. There was no difference in the ratio of TRAIL/RANKL expression in the unicystic, whereas 55.2% of the solid ameloblastomas showed a greater TRAIL expression over RANKL. Our results suggest OPG overexpression and RANKL underexpression in solid ameloblastoma; this may reflect a possible prevalence of the OPG/TRAIL over the OPG/RANKL signaling pathway, resulting in inactivation of TRAIL-induced apoptosis in ameloblastic cells. In unicystic ameloblastoma, the RANKL/OPG expression immunoprofile among histological variants is compatible with the reported biologic behavior. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. 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...... and postprandial indices of bone remodeling. DESIGN AND SETTING: Ancillary investigation of a prospective study at 2 academic institutions. PARTICIPANTS: Obese adults aged 21-65 years with type 2 diabetes who underwent RYGB (n=11) or LAGB (n=8). OUTCOMES: Serum C-terminal telopeptide (CTX), procollagen type 1 (P1......NP), and parathyroid hormone (PTH) were measured during a mixed meal tolerance test at baseline, 10 days and 1 year after surgery. Changes in 25-hydroxyvitamin D, polypeptide YY (PYY), glucagon-like peptide-1, glucose-dependent insulinotropic peptide, and insulin were also assessed. RESULTS: Fasting...

  11. 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.

  12. The differential effects of bisphosphonates, SERMS (selective estrogen receptor modulators, and parathyroid hormone on bone remodeling in osteoporosis

    Directory of Open Access Journals (Sweden)

    Silvia Migliaccio

    2007-04-01

    Full Text Available Silvia Migliaccio, Marina Brama, Giovanni SperaCattedra di Medicina Interna, Dipartimento di Fisiopatologia Medica, Università degli Studi di Roma “La Sapienza”, Italy Abstract: Osteoporosis is a skeletal metabolic disease characterized by a compromised bone fragility, leading to an increased risk of developing spontaneous and traumatic fractures. Osteoporosis is considered a multifactorial disease and fractures are the results of several different risk factors both extra- and intraskeletal. Thus bone fragility can be the end point of several different causes: a failure to reach an optimal peak bone mass during growth; b excessive bone resorption resulting in decreased bone mass and microarchitectural deterioration; c inadequate formation upon an increased resorption during the process of bone remodeling. The pharmacological therapeutical options, available to date, are directed on prevention of fractures. The aim of this paper is to describe the activities and the mechanisms of action, as known at present, of the most used therapies for osteoporosis and their clinical implications. Improvement of knowledge in this field will allow us to further improve therapeutical choices and pharmacological interventions.Keywords: Osteoporosis, estrogens, bisphosphonates, SERMS, teriparatide, mechanism of action, fracture

  13. A numerical simulation of the effect of using porous superelastic Nitinol and stiff Titanium fixation hardware on the bone remodeling

    Science.gov (United States)

    Raad, Bahram; Shayesteh Moghaddam, Narges; Elahinia, Mohammad

    2016-04-01

    The aim of this article is to investigate the effect of two different fixation hardware materials on bone remodeling after a mandibular reconstruction surgery and to restore the mandible's function, healthy appearance, mastication, swallowing, breathing, and speech. The hypothesis is that using fixation hardware with stiffness close to that of the surrounding bone will result in a more successful healing process in the mandible bone. The finite element model includes the material properties and forces of the cancellous bone, cortical bone, ligaments, muscles, and teeth. The reconstruction surgery is modeled by including the fixation hardware and the grafted bone. In the sectioned mandible, to best mimic the geometry of the mandible, two single barrel grafts are placed at the top of each other to form a double barrel graft set. Two different materials were used as the mandibular fixation parts, stiff Ti-6Al-4V, and porous superelastic Nickel-Titanium (NiTi) alloys. A comparison of these two alloys demonstrates that using porous NiTi alloy as the fixation part results in a faster healing pace. Furthermore, the density distribution in the mandibular bone after the healing process is more similar to the normal mandible density distribution. The simulations results indicate that the porous superelastic NiTi fixation hardware transfers and distributes the existing forces on the mandible bone more favorably. The probability of stress shielding and/or stress concentration decrease. This type of fixation hardware, therefore, is more appropriate for mandible bone reconstruction surgery. These predictions are in agreement with the clinical observations.

  14. 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.

  15. 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.

  16. Structural and Qualitative Bone Remodeling Around Repetitive Loaded Implants in Rabbits.

    Science.gov (United States)

    Kuroshima, Shinichiro; Yasutake, Munenori; Tsuiki, Kotaro; Nakano, Takayoshi; Sawase, Takashi

    2015-10-01

    Bone mechanical function is regulated by bone quality and bone mineral density (BMD) that reflect bone strength. The preferential alignment of biological apatite (BAp) c-axis/collagen fibers and osteocytes is a determinant factor of bone quality. However, the effect of mechanical loading on bone quality around dental implants is unclear. The aim of this study was to clarify the effects of mechanical loading on osseointegration, bone volume BMD, and bone quality around dental implants. Twenty anodized Ti-6Al-4V alloy implants (KYOCERA Co., Kyoto, Japan) were placed in the proximal tibial metaphysis of 10 rabbits. Twelve weeks after surgery, mechanical loading was applied along the long axis of the implant (50 N, 3 Hz, 1,800 cycles, 2 days/week) for 8 weeks. Osseointegration, bone volume, BMD, and bone quality were evaluated using light microscopy, microcomputed tomography, polarized light microscopy, and microbeam X-ray diffractometer. Mechanical loading increased osseointegration, bone volume, and BMD. Bone quality around dental implant was altered with increased osteocyte numbers and the preferential alignment direction and degree of BAp c-axis/collagen fibers. These findings suggest that mechanical loading effectively induces bone anabolic responses around dental implants. Altered bone quality may upregulate bone strength, contributing to long-term implant stability. © 2015 Wiley Periodicals, Inc.

  17. Implant bone integration importance in forensic identification.

    Science.gov (United States)

    De Angelis, Danilo; Cattaneo, Cristina

    2015-03-01

    Odontological identification consists of the comparison of antemortem dental information regarding a missing person with postmortem data from an unidentified corpse or human remains. Usually, the comparison concerns morphologic features that the operator chooses among all the visible characteristics because of inter-individual uniqueness; for this reason, implants can be of enormous assistance. A case concerning the recovery of a burnt oral implant, connected to a bone fragment, among 2780 charred bone fragments, suspected to have belonged to a victim of homicide, is presented to demonstrate that dental implants and their site of bone integration represent a very precious element for personal forensic identification. Because of their morphological invariability in time and because of their morphologic uniqueness, they were used as evidence to associate unidentified human charred remains to a missing person where DNA analysis failed to do so. The case illustrates the fundamental contribution, not yet described in literature, given by the clinical aspects of tooth replacement with dental implants to a forensic discipline. Clinical practitioners should therefore be aware of the great importance of their work and of dental records in a forensic identification scenario.

  18. The influence of exposure to UVβ of fluorescent light on the bone remodeling of hypoestrogenic Macaca fascicularis

    Directory of Open Access Journals (Sweden)

    I. A. Rachman

    2001-06-01

    Full Text Available The prevention of osteoporosis is a spesific problem that should be dealt with by increasing the women's lift expectation. The decrease of calcitriol and estrogen levels, which have a receptor in the osteoblast, will result in bone mineralization (due to calcitriol and the information of type 1 collagen (due to estrogen. The formation of calcitriol with the main basic materials from vitamin D3 is achieved with the aid of sunray UVβ, The changes in the lifestyle of women, which make them now accustomed to performing indoor activities and prevent them from being exposed to UVβ all day, have resulted in the decrease of vitamin D3 in calcitriol in women. In addition, when entering the menopausal age they will be threatened with early osteoporosis. The exposure to the UVβ of fluorescent light with the wave length identical to sun of 290-320 nm has long been known as a modality for treating skin diseases in the hope that the production of vitamin D3  will be increased. We exposed Macaca fascicularis, whose estrogen levels were set at normal, beginning low, beginning very low levels, to UVβ of fluorescent light. It showed that the Macaca fascicularis that were exposed to UVβ experienced an increase in osteocalcin with unchanged DPD which means that bone remodeling remains unchanged. By contrast, Macaca fascicularis with normal, beginning low, and beginning very low estrogen levels which were not exposed to UVβ were found to experience a decrease in osteocalcin and unchanged DPD levels. This means that a change has occurred in the bone remodeling toward bone resorption. (Med J Indones 2001; 10: 63-8Keywords: UVβ, osteoporosis, estrogen, vitamin D3, calcitriol, osteocalcin, DPD

  19. Changes of vessel-cells complex in zones of adaptive remodeling of the bone tissue under microgravity conditions

    Science.gov (United States)

    Rodionova, N.; Oganov, V.; Nosova, L.

    The development and differentiation of osteogenic cells in organism happen in closely topographical and functional connection with blood capillaries. We formerly proofed, that small-differentiated cells, which are in the population of perivascular cells are osteogenic cells -precursors . At the present time it is actually to clear up, how these biostructures react on conditions of less of biomechanical load on skeleton bones. We researched peculiarities of blood-bed structure and perivascular cells in metaphises of thighbones and tibial bones in rats, which were onboard the American space station SLS-2 and in experiments of modeling hypokinesia. There were used methods of cytochemistry, histology and electron microscopy. We established, that under the support and functional load decreasing in zones of bones adaptive remodeling, comparatively to control, on histosections the own volume of sinusoid capillaries reduces. The small vessels prevail here. The spaces of sinusoid capillaries are limited by 1 2 cells of the endothelia. Endotheliocytes in- general have the typical ultrastructure. Basal membranes are expressed not-distinctly. Perivascular cells don't create the unbroken layer. The population of these cells is not-homogeneous. It includes enclosed to endothelia small-differentiated forms and separating cells with sings of fibroblastic differentiation (the own volume of rough endoplasmic reticulum in cytoplasm induces). The part of these cells reacts on the alkaline phosphatase (the marker of the osteogenic differentiation). Under the conditions of support load decreasing (especially under the microgravity) there is a tendency to reducing of separating osteogenic cells number. We noted the priority of differentiating fibroblasts. It leads to further development in zones of bone remodeling of hearths of fibrous tissue, that doesn't mineralize. The obtained data are seen as one of mechanisms of osteoporosis and osteopenia development under the deficite of support

  20. Effects of BSP in osteoclastogenesis and bone remodeling%BSP在破骨细胞分化和骨改建过程中的作用

    Institute of Scientific and Technical Information of China (English)

    姜红; 张瑾

    2011-01-01

    骨涎蛋白(bone sialoprotein,BSP)作为小整合素结合配体N端联结糖蛋白家族(SIBLING)的成员,参与调控骨改建过程的多个环节,并与破骨细胞分化和过度活跃的骨吸收密切相关.该文就BSP在破骨细胞和骨改建过程中的作用及其细胞和分子生物学机制作一综述.%As a member of Small Integrin-Binding Ligand, N-linked Glycoprotein ( SIBLING) family,bone sialoprotein ( BSP) actively participates in the regulation of bone remodeling processes at multiple levels. In addition, BSP is closely associated with osteoclastogenesis and enhanced bone resorptive activity. In this review, we discuss new discoveries concerning the effect of BSP on osteoclastogenesis and bone remodeling.

  1. 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...

  2. The potentiation of Mangifera casturi bark extract on interleukin- 1β and bone morphogenic protein-2 expressions during bone remodeling after tooth extraction

    Directory of Open Access Journals (Sweden)

    Bayu Indra Sukmana

    2017-03-01

    Full Text Available Background: The main oral health problem in Indonesia is the high number of tooth decay. Tooth extraction is the treatment often received by patients who experience tooth decay and the wound caused by alveolar bone resorption. Bark of Mangifera casturi has been studied and proven to contain secondary metabolite which has the ability to increase osteoblast’s activity and suppress osteoclast’s activity. Purpose: The purpose of this study was to analyze interleukin-1 beta (IL-1β and bone morphogenic protein-2 (BMP-2 activities during bone remodeling after Mangifera casturi’s bark extract treatment. Method: This study was laboratory experimental research with randomized post-test only control group design. The Mangifera casturi bark was extracted using 96% ethanol maceration and n-hexane fractionation. This study used 40 male Wistar rats which are divided into 4 groups and the tooth extraction was performed on the rats’ right mandible incisive tooth. The four groups consisted of 6.35%, 12.7%, 25.4% extract treatment group, and a control group. Wistar’s mandibles were decapitated on the 7th and 14th day after extraction. Antibody staining on preparations for the examination of IL-1β and BMP-2 expressions was done using immunohistochemistry. Result: There was a significant difference of IL-1β and BMP-2 expressions in 6,35%, 12,7%, and 25,4% treatment groups compared to control group with p<0.05. Conclusion: Mangifera casturi’s bark extract was able to suppress the IL-1β expression and increase the BMP-2 expression during bone remodeling after tooth extraction.

  3. 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. 

  4. 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.

  5. Arteriolar and venular remodeling are differentially regulated by bone marrow-derived cell-specific CX3CR1 and CCR2 expression.

    Directory of Open Access Journals (Sweden)

    Joshua K Meisner

    Full Text Available The chemokine receptors CCR2 and CX3CR1 are critical for the recruitment of "inflammatory" and "resident" monocytes, respectively, subpopulations that differentially affect vascular remodeling in atherosclerosis. Here, we tested the hypothesis that bone marrow-derived cell (BMC-specific CCR2 and CX3CR1 differentially control venular and arteriolar remodeling. Venular and arteriolar lumenal remodeling were observed by intravital microscopy in mice with either CCR2 or CX3CR1 deficient BMCs after implantation of a dorsal skinfold window chamber, a model in which arterioles and venules lumenally enlarge in wild-type (WT mice. Arteriolar remodeling was abolished in mice with either CCR2 or CX3CR1-deficient BMCs. In contrast, the loss of CX3CR1 from BMCs, but not CCR2, significantly reduced small venule remodeling compared to WT controls. We conclude that microvascular remodeling is differentially regulated by BMC-expressed chemokine receptors. Both CCR2 and CX3CR1 regulate arteriole growth; however, only BMC-expressed CX3CR1 impacts small venule growth. These findings may provide a basis for additional investigations aimed at determining how patterns of monocyte subpopulation recruitment spatially influence microvascular remodeling.

  6. State of integral remodeling parameters of target organs in patients with essential hypertension and obesity.

    Science.gov (United States)

    Kochueva, M; Sukhonos, V; Shalimova, A; Psareva, V; Kirichenko, N

    2014-06-01

    Arterial hypertension combined with obesity is a very common form of comorbid disease in most countries all over the world. The combination of these diseases is characterized by mutual burdening of remodelling processes in important target organs, what greatly increases the risk of cardiovascular complications and death. The mechanisms of injury progression to vital organs in essential hypertension (EH) and obesity have some common features. The most important risk factors of target organs damage are hemodynamic and neurohumoral: inflammatory, effectors of the renin- angiotensin-aldosterone system, insulin resistance and others. Polyethiologic remodelling, lack of knowledge concerning violations in structural and functional status of important target organs and mechanisms of the interactions of their progression with this comorbidity require further study of these issues. The objective of the study was the comparative study of the state of integral indicators of structural and functional state of the heart, blood vessels and liver in patients with EH second stage with normal body weight and with concomitant obesity I and II degrees. This study found that the presence of obesity I and II in patients with EH stage II is associated with the concentric type of left ventricular hypertrophy, saved by its ejection fraction and impaired diastolic filling processes. For the patients with EH in the early stages of obesity the following characteristics are quite typical: considerable increase of intima media thickness in the carotid arteries, increasing the stiffness in the main arteries and liver parenchyma, impaired of the functional state of endothelial.

  7. 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.

  8. 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.

  9. In Vivo Magnetic Resonance Detects Rapid Remodeling Changes in the Topology of the Trabecular Bone Network After Menopause and the Protective Effect of Estradiol

    Science.gov (United States)

    Wehrli, Felix W; Ladinsky, Glenn A; Jones, Catherine; Benito, Maria; Magland, Jeremy; Vasilic, Branimir; Popescu, Andra M; Zemel, Babette; Cucchiara, Andrew J; Wright, Alexander C; Song, Hee K; Saha, Punam K; Peachey, Helen; Snyder, Peter J

    2008-01-01

    Introduction Estrogen depletion after menopause is accompanied by bone loss and architectural deterioration of trabecular bone. The hypothesis underlying this work is that the μMRI-based virtual bone biopsy can capture the temporal changes of scale and topology of the trabecular network and that estrogen supplementation preserves the integrity of the trabecular network. Materials and Methods Subjects studied were early postmenopausal women, 45–55 yr of age (N = 65), of whom 32 were on estrogen (estradiol group), and the remainder were not (control group). Early menopause was defined by amenorrhea for 6–24 mo and elevated serum follicle-stimulating hormone (FSH) concentration. The subjects were evaluated with three imaging modalities at baseline and 12 and 24 mo to determine the temporal changes in trabecular and cortical architecture and density. μMRI of the distal radius and tibia was performed at 137 × 137 × 410-μm3 voxel size. The resulting bone volume fraction maps were Fourier interpolated to a final voxel size of 45.7 × 45.7 × 136.7 μm3, binarized, skeletonized, and subjected to 3D digital topological analysis (DTA). Skeletonization converts trabecular rods to curves and plates to surfaces. Parameters quantifying scale included BV/TV, whereas DTA parameters included the volume densities of curves (C) and surface (S)-type voxels, as well as composite parameters: the surface/curve ratio (S/C), and erosion index (EI, ratio of the sum of parameters expected to increase with osteoclastic resorption divided by the sum of those expected to decrease). For comparison, pQCT of the same peripheral locations was conducted, and trabecular density and cortical structural parameters were measured. Areal BMD of the lumbar vertebrae and hip was also measured. Results Substantial changes in trabecular architecture of the distal tibia, in particular as they relate to topology of the network, were detected after 12 mo in the control group. S/C decreased 5.6% (p < 0

  10. 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.

  11. 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.

  12. Regulators of G protein signaling 12 (Rgs12) promotes osteoclastogenesis in bone remodeling and pathologic bone loss

    Science.gov (United States)

    Calcium (Ca2+) signaling plays a pivotal role in controlling various cellular processes such as secretion, differentiation, proliferation, motility, and cell death through the release of Ca2+ from internal stores and entry from extracellular fluid. In bone, receptor activator of NF-kB ligand (RANKL)...

  13. 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

  14. 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...

  15. 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.

  16. Research progress of the effects of ursolic acid on bone remodeling%熊果酸对骨重塑的相关研究进展

    Institute of Scientific and Technical Information of China (English)

    王玉琢; 崔聪聪; 包幸福; 姜欢; 胡敏

    2016-01-01

    The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts plays a key role in bone remodeling.Ursolic acid (UA)is a kind of pentacyclic triterpene compounds extracted from Chinese herbal medicine.It has several functions of anti-inflammatory,anti-oxidation,anti-tumor and has already got preliminary progress in the field of bone remodeling over recent years.It shows the functions of promoting bone formation and in-hibiting bone absorption.It will be the research focus to identify the mechanism,and this will be helpful to the anabolic actions of UA for osteoporosis treatment and bone remodeling.%成骨细胞参与的骨形成与破骨细胞参与的骨吸收之间的动态平衡,是骨重塑过程中的关键。熊果酸(ur-solic acid,UA)是一种从中草药中提取的五环三萜类化合物,具有抗炎、抗氧化、抗肿瘤等多种功效,在骨重塑方面的研究近年来已有了初步进展,主要表现为促进骨合成,抑制骨吸收作用,明确其机制是今后研究的重点,这将有助于UA 在治疗骨质疏松症及骨重塑方面更好地应用。

  17. The importance of the SIBLING family of proteins on skeletal mineralisation and bone remodelling.

    Science.gov (United States)

    Staines, Katherine A; MacRae, Vicky E; Farquharson, Colin

    2012-09-01

    The small integrin-binding ligand N-linked glycoprotein (SIBLING) family consists of osteopontin, bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein and matrix extracellular phosphoglycoprotein. These proteins share many structural characteristics and are primarily located in bone and dentin. Accumulating evidence has implicated the SIBLING proteins in matrix mineralisation. Therefore, in this review, we discuss the individual role that each of the SIBLING proteins has in this highly orchestrated process. In particular, we emphasise how the nature and extent of their proteolytic processing and post-translational modification affect their functional role. Finally, we describe the likely roles of the SIBLING proteins in clinical disorders of hypophosphataemia and their potential therapeutic use.

  18. Electropolished Titanium Implants with a Mirror-Like Surface Support Osseointegration and Bone Remodelling

    OpenAIRE

    Cecilia Larsson Wexell; Shah, Furqan A.; Lars Ericson; Aleksandar Matic; Anders Palmquist; Peter Thomsen

    2016-01-01

    This work characterises the ultrastructural composition of the interfacial tissue adjacent to electropolished, commercially pure titanium implants with and without subsequent anodisation, and it investigates whether a smooth electropolished surface can support bone formation in a manner similar to surfaces with a considerably thicker surface oxide layer. Screw-shaped implants were electropolished to remove all topographical remnants of the machining process, resulting in a thin spontaneously ...

  19. Small body size and extreme cortical bone remodeling indicate phyletic dwarfism in Magyarosaurus dacus (Sauropoda: Titanosauria).

    Science.gov (United States)

    Stein, Koen; Csiki, Zoltan; Rogers, Kristina Curry; Weishampel, David B; Redelstorff, Ragna; Carballido, Jose L; Sander, P Martin

    2010-05-18

    Sauropods were the largest terrestrial tetrapods (>10(5) kg) in Earth's history and grew at rates that rival those of extant mammals. Magyarosaurus dacus, a titanosaurian sauropod from the Upper Cretaceous (Maastrichtian) of Romania, is known exclusively from small individuals (dwarfism (phyletic nanism) in dinosaurs, but a recent study suggested that the small Romanian titanosaurs actually represent juveniles of a larger-bodied taxon. Here we present strong histological evidence that M. dacus was indeed a dwarf (phyletic nanoid). Bone histological analysis of an ontogenetic series of Magyarosaurus limb bones indicates that even the smallest Magyarosaurus specimens exhibit a bone microstructure identical to fully mature or old individuals of other sauropod taxa. Comparison of histologies with large-bodied sauropods suggests that Magyarosaurus had an extremely reduced growth rate, but had retained high basal metabolic rates typical for sauropods. The uniquely decreased growth rate and diminutive body size in Magyarosaurus were adaptations to life on a Cretaceous island and show that sauropod dinosaurs were not exempt from general ecological principles limiting body size.

  20. Genetic and hormonal control of bone volume, architecture, and remodeling in XXY mice.

    Science.gov (United States)

    Liu, Peter Y; Kalak, Robert; Lue, Yanhe; Jia, Yue; Erkkila, Krista; Zhou, Hong; Seibel, Markus J; Wang, Christina; Swerdloff, Ronald S; Dunstan, Colin R

    2010-10-01

    Klinefelter syndrome is the most common chromosomal aneuploidy in men (XXY karyotype, 1 in 600 live births) and results in testicular (infertility and androgen deficiency) and nontesticular (cognitive impairment and osteoporosis) deficits. The extent to which skeletal changes are due to testosterone deficiency or arise directly from gene overdosage cannot be determined easily in humans. To answer this, we generated XXY mice through a four-generation breeding scheme. Eight intact XXY and 9 XY littermate controls and 8 castrated XXY mice and 8 castrated XY littermate controls were euthanized at 1 year of age. Castration occurred 6 months prior to killing. A third group of 9 XXY and 11 XY littermates were castrated and simultaneously implanted with a 1-cm Silastic testosterone capsule 8 weeks prior to sacrifice. Tibias were harvested from all three groups and examined by micro-computed tomography and histomorphometry. Blood testosterone concentration was assayed by radioimmunoassay. Compared with intact XY controls, intact androgen-deficient XXY mice had lower bone volume (6.8% +/- 1.2% versus 8.8% +/- 1.7%, mean +/- SD, p = .01) and thinner trabeculae (50 +/- 4 µm versus 57 +/- 5 µm, p = .007). Trabecular separation (270 +/- 20 µm versus 270 +/- 20 µm) or osteoclast number relative to bone surface (2.4 +/- 1.0/mm2 versus 2.7 +/- 1.5/mm2) did not differ significantly. Testosterone-replaced XXY mice continued to show lower bone volume (5.5% +/- 2.4% versus 8.1% +/- 3.5%, p = .026). They also exhibited greater trabecular separation (380 +/- 69 µm versus 324 +/- 62 µm, p = .040) but equivalent blood testosterone concentrations (6.3 +/- 1.8 ng/mL versus 8.2 +/- 4.2 ng/mL, p = .28) compared with testosterone-replaced XY littermates. In contrast, castration alone drastically decreased bone volume (p < .001), trabecular thickness (p = .05), and trabecular separation (p

  1. 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.)

  2. 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

  3. 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

  4. 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.

  5. Bone marrow-derived cells participate in stromal remodeling of the lung following acute bacterial pneumonia in mice.

    Science.gov (United States)

    Serikov, Vladimir B; Mikhaylov, Viatcheslav M; Krasnodembskay, Anna D; Matthay, Michael A

    2008-01-01

    Bone marrow-derived cells (BMDC) have been shown to graft injured tissues, differentiate in specialized cells, and participate in repair. The importance of these processes in acute lung bacterial inflammation and development of fibrosis is unknown. The goal of this study was to investigate the temporal sequence and lineage commitment of BMDC in mouse lungs injured by bacterial pneumonia. We transplanted GFP-tagged BMDC into 5-Gy-irradiated C57BL/6 mice. After 3 months of recovery, mice were subjected to LD(50) intratracheal instillation of live E. coli (controls received saline) which produced pneumonia and subsequent areas of fibrosis. Lungs were investigated by immunohistology for up to 6 months. At the peak of lung inflammation, the predominant influx of BMDC were GFP(+) leukocytes. Postinflammatory foci of lung fibrosis were evident after 1-2 months. The fibrotic foci in lung stroma contained clusters of GFP(+) CD45(+) cells, GFP(+) vimentin-positive cells, and GFP(+) collagen I-positive fibroblasts. GFP(+) endothelial or epithelial cells were not identified. These data suggest that following 5-Gy irradiation and acute bacterial pneumonia, BMDC may temporarily participate in lung postinflammatory repair and stromal remodeling without long-term engraftment as specialized endothelial or epithelial cells.

  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. Adipokines: A Possible Contribution to Vascular and Bone Remodeling in Idiopathic Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Kochetkova, Evgenia A; Ugai, Ludmila G; Maistrovskaia, Yuliya V; Nevzorova, Vera A

    2017-04-01

    Osteoporosis is a major comorbidity of cardio-respiratory diseases, but the mechanistic links between pulmonary arterial hypertension and bone remain elusive. The purpose of the stud was to evaluate serum adipokines and endothelin-1 (ET-1) levels in the patients with idiopathic pulmonary arterial hypertension (IPAH) NYHA class III-IV and to determine its associations with bone mineral density (BMD). Pulmonary and hemodynamic parameters, BMD Z-scores at the lumbar spine (LS) and femoral neck (FN), serum leptin, adiponectin, visfatin and endothelin-1 (ET-1), were evaluated in 32 patients with IPAH NYHA class III-IV and 30 healthy volunteers. Leptin, adiponectin and ET-1 were higher in the patients with IPAH than in healthy subjects. Visfatin level showed a tendency to increase compared to that of healthy subjects (p = 0.076). The univariate analysis revealed a positive correlation between BMD Z-scores at both sites and 6-min walk test, and inverse relation with pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP). Adiponectin and visfatin showed positive correlations with PVR (p = 0.009 and p = 0.006). Serum adiponectin, visfatin and leptin were inversely associated with Z-scores. After adjusting for BMI and FMI, such associations persisted between visfatin and adiponectin levels and Z-scores at both sites. ET-1 related to mPAP, cardiac index and PVR. Negative correlation was observed between ET-1 and FN BMD (p = 0.01). Positive correlations have revealed between ET-1 and adiponectin (p = 0.02), visfatin (p = 0.004) in IPAH patients. These results provide further evidence that adipokine and endothelial dysregulation may cause not only a decrease in BMD, but also an increase in hemodynamic disorders of IPAH.

  8. Bone remodeling around the Cambridge cup: a DEXA study of 50 hips over 2 years.

    Science.gov (United States)

    Field, Richard E; Cronin, Michael D; Singh, Parminder J; Burtenshaw, Christine; Rushton, Neil

    2006-10-01

    In a prospective 2-year study we have used dual-energy X-ray absorptiometry to measure periprosthetic bone mineral density (BMD) following implantation of a novel, "physiological", acetabular component designed using composite materials. The acetabular components were implanted in hydroxyapatite (HA) and HA-removed options. They were implanted in conjunction with a cemented femoral component in 50 female patients who presented with displaced, subcapital, fractures of the neck of the femur. Regions of interest (ROI) were defined according to De Lee and Charnley. BMD during follow-up was compared with immediate postoperative values for the affected limb. The mean precision error (CV%) was 1.01%, 2.26% and 1.12%, for ROI I, II and III respectively. The mean change in BMD, for both cups, was analyzed. There was no significant difference between the BMD changes induced with the HA- and non-HA-coated cups. After an initial fall in BMD in all 3 ROI at 6 months, ROI I and ROI II showed return to baseline BMD by 2 years. ROI III showed no significant decrease in BMD beyond 6 months, but did not return to baseline levels. Statistical analysis revealed no significant decrease in BMD in ROI I and ROI II at 2 years, compared with immediate postoperative values. The changes in BMD reflect a pattern of maximally reduced stress in the non-weight-bearing zone (ROI III), with preservation of bone density in weight bearing zones ROI I and ROI II. These results support the design principles of the Cambridge cup.

  9. Manipulating the anabolic and catabolic response in bone graft remodeling: synergism by a combination of local BMP-7 and a single systemic dosis of zoledronate.

    Science.gov (United States)

    Harding, Anna Kajsa; Aspenberg, Per; Kataoka, Masashi; Bylski, David; Tägil, Magnus

    2008-09-01

    Remodeling of a bone graft can be influenced both by anabolic substances, such as a bone morphogenic protein (BMP) and by anticatabolic substances, such as the bisphosphonates. BMPs are potent bone anabolic substances, but also boost catabolism and cause resorption. Bisphosphonates inhibit osteoclast function and can be used to postpone resorption. In the present study a combination of both drugs was explored in a rat bone chamber model. Cancellous bone grafts were treated with either BMP-7 or saline and placed in a bone chamber implanted in the proximal tibia. After 2 weeks, an injection of either zoledronate 0.1 mg/kg or saline was given subcutaneously. The rats were killed after 6 weeks, and bone ingrowth distance into the graft and graft resorption were measured by histomorphometry. BMP-7 significantly (p = 0.007) increased new bone ingrowth distance into the graft from 2.0 mm (SD = 0.98 mm) in the controls to 3.1 mm (SD = 0.93 mm). If bisphosphonate was not given, most of the newly formed and old graft bone was resorbed. A single injection of zoledronate significantly (p < 0.001) increased the trabecular volume/total volume to 40% (SD = 9%) compared to 14% (SD = 10%) in the nonbisphosphonate treated. In total, the net amount of bone increased by 400% when BMP-7 and zoledronate combined was compared to saline. A bone graft can be treated with BMP-7 to increase new bone formation and at the same time be protected against premature catabolism by a single dose of a bisphosphonate. This combination might be useful in various conditions in orthopedic reconstruction. (c) 2008 Orthopaedic Research Society

  10. 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

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

    OpenAIRE

    Lee, Alice M. C.; Tetyana Shandala; Long Nguyen; Beverly S Muhlhausler; Ke-Ming Chen; Peter R Howe; Xian, Cory J.

    2014-01-01

    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...

  12. Development of LiCl-containing calcium aluminate cement for bone repair and remodeling applications.

    Science.gov (United States)

    Acuña-Gutiérrez, I O; Escobedo-Bocardo, J C; Almanza-Robles, J M; Cortés-Hernández, D A; Saldívar-Ramírez, M M G; Reséndiz-Hernández, P J; Zugasti-Cruz, A

    2017-01-01

    The effect of LiCl additions on the in vitro bioactivity, hemolysis, cytotoxicity, compressive strength and setting time of calcium aluminate cements was studied. Calcium aluminate clinker (AC) was obtained via solid state reaction from reagent grade chemicals of CaCO3 and Al2O3. Calcium aluminate cements (CAC) were prepared by mixing the clinker with water or aqueous LiCl solutions (0.01, 0.0125 or 0.015M (M)) using a w/c ratio of 0.4. After 21days of immersion in a simulated body fluid (SBF) at physiological conditions of temperature and pH, a Ca-P rich layer, identified as hydroxyapatite (HA), was formed on the cement without LiCl and on the cement prepared with 0.01M of LiCl solution. This indicates the high bioactivity of these cements. The cements setting times were significantly reduced using LiCl. The measured hemolysis percentages, all of them lower than 5%, indicated that the cements were not hemolytic. The compressive strength of the cements was not negatively affected by the LiCl additions. The obtained cement when a solution of LiCl 0.010M was added, presented high compressive strength, appropriated bioactivity, no cytotoxicity and low setting time, making this material a potentially bone cement.

  13. Rethinking the nature of fibrolamellar bone: an integrative biological revision of sauropod plexiform bone formation.

    Science.gov (United States)

    Stein, Koen; Prondvai, Edina

    2014-02-01

    palaeohistological studies, we introduce new osteohistological terms as well as revise widely used but incorrect terminology. To infer the role of woven bone in the bone formation of fast-growing tetrapods, we review some aspects of the interrelationships between the vascularity of bone tissues, basal metabolic rate, body size and growth rate. By putting our findings into the context of osteogenesis, we provide a new model for the diametrical limb bone growth of sauropods and present new implications for the evolution of fast growth in vertebrates. Since biomechanical studies of bone tissues suggest that predominant collagen fibre orientation (CFO) is controlled by endogenous, functional and perhaps phylogenetic factors, the relationship between CFO and bone growth rate as defined by Amprino's rule, which has been the basis for the biological interpretation of several osteohistological features, must be revised. Our findings draw attention to the urgent need for revising widely accepted basic concepts of palaeohistological studies, and for a more integrative approach to bone formation, biomechanics and bone microstructural features of extant and extinct vertebrates to infer life history traits of long extinct, iconic animals like dinosaurs. © 2013 The Authors. Biological Reviews © 2013 Cambridge Philosophical Society.

  14. 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.

  15. 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.

  16. Energy-restricted diet benefits body composition but degrades bone integrity in middle-aged obese female rats.

    Science.gov (United States)

    Shen, Chwan-Li; Zhu, Wenbin; Gao, Weimin; Wang, Shu; Chen, Lixia; Chyu, Ming-Chien

    2013-08-01

    This study investigates the effects of a restricted diet (RD) on body composition and musculoskeletal health along with endocrines and molecular mechanism in established mature obese rats. Twenty female rats were fed with a high-fat diet (HFD) ad libitum for 4 months and then assigned to either HFD or RD group for another 4 months. Another 10 rats were on a low-fat diet for 8 months. Outcome measures included body composition, bone mineral density, microarchitecrure, and strength; serum leptin, adiponectin, insulin-like growth factor I, and liver glutathione peroxidase activity; and protein expression and spleen tumor necrosis factor α messenger RNA expression. We hypothesized that mature obese rats on a 35% energy restriction diet for 4 months would improve body composition but degrade microstructural and mechanical properties of long bones, and such changes in musculoskeletal integrity are related to the modulation of obesity-related endocrines and proinflammation. Relative to HFD, RD benefited body composition (decreased body weight and %fat mass and increased %fat-free mass); decreased insulin-like growth factor I and leptin; elevated adiponectin, glutathione peroxidase activity and protein expression and tumor necrosis factor α messenger RNA expression; and suppressed bone formation and increased bone resorption, resulting in decreased trabecular and cortical bone volume, bone mineral density, and bone strength. Relative to low-fat diet, RD had a similar effect on body composition and serum markers but increased bone turnover rate and decreased bone mineral density and strength. Our data suggest that long-term RD has a negative impact on bone remodeling in obese female rats, probably through modification of endocrines and elevation of proinflammation. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Tendon gradient mineralization for tendon to bone interface integration.

    Science.gov (United States)

    Qu, Jin; Thoreson, Andrew R; Chen, Qingshan; An, Kai-Nan; Amadio, Peter C; Zhao, Chunfeng

    2013-11-01

    Tendon-to-bone integration is a great challenge for tendon or ligament reconstruction regardless of use of autograft or allograft tendons. We mineralized the tendon, thus transforming the tendon-to-bone into a "bone-to-bone" interface for healing. Sixty dog flexor digitorum profundus (FDP) tendons were divided randomly into five groups: (1) normal FDP tendon, (2) CaP (non-extraction and mineralization without fetuin), (3) CaPEXT (Extraction by Na2 HPO4 and mineralization without fetuin), (4) CaPFetuin (non-extraction and mineralization with fetuin), and (5) CaPEXTFetuin (extraction and mineralization with fetuin). The calcium and phosphate content significantly increased in tendons treated with combination of extraction and fetuin compared to the other treatments. Histology also revealed a dense mineral deposition throughout the tendon outer layers and penetrated into the tendon to a depth of 200 µm in a graded manner. Compressive moduli were significantly lower in the four mineralized groups compared with normal control group. No significant differences in maximum failure strength or stiffness were found in the suture pull-out test among all groups. Mineralization of tendon alters the interface from tendon to bone into mineralized tendon to bone, which may facilitate tendon-to-bone junction healing following tendon or ligament reconstruction.

  18. 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.

  19. Immunolocalization of CSF-1, RANKL and OPG in the enamel-related periodontium of the rat incisor and their implications for alveolar bone remodeling.

    Science.gov (United States)

    Neves, J S; Salmon, C R; Omar, N F; Narvaes, E A O; Gomes, J R; Novaes, P D

    2009-07-01

    The enamel-related periodontium (ERP) in rat incisors is related to bone resorption. In these teeth the face of the socket related to the enamel is continuously removed at the inner side and newly formed at the outer side. CSF-1, RANKL and OPG are regulatory molecules essential for osteoclastogenesis. To verify the effects of impeded eruption on bone remodeling, the tooth eruption was prevented by immobilization of lower rat incisor and CSF-1, RANKL and OPG distribution in the ERP was analyzed after 18 days of immobilization and in normal eruption. The region of the alveolar crest of the rat incisor was used. Immunohistochemistry and tartrate-resistant acid phosphatase (TRAP) were performed. The immunostaining of the dental follicle was quantified using Leica QWin software. Positive-TRAP osteoclasts were counted, and both groups were compared. In the normal incisor, the number of osteoclasts was significantly greater than in the immobilized tooth. In the dental follicle, there was no significant difference in the immunostaining intensity for CSF-1 and OPG between the groups (p > 0.05), but for RANKL the immobilized incisor group showed immunostaining intensity smaller than the normal incisor group (p incisor, modify the RANKL/OPG ratio, in the presence of CSF-1, altering the metabolism of cells that participate in the bone remodeling.

  20. Breast cancer osteomimicry and its role in bone specific metastasis; an integrative, systematic review of preclinical evidence.

    Science.gov (United States)

    Awolaran, Olugbenga; Brooks, Susan A; Lavender, Verna

    2016-12-01

    Metastasis accounts for most of the deaths from breast cancer and the preference of invasive breast cancer metastasising to bone has been widely reported. However, the biological basis of breast cancer osteotropism is not fully understood. This paper provides, for the first time, an integrative, systematic review of evidence of molecular factors that have functional roles in the homing of metastatic breast cancer to the bone. Pubmed, Web of Science and EBSCOhost were searched using keywords and synonyms for molecular, metastasis, breast cancer and bone to identify articles published between January 2004 and August 2016. 4491 potentially relevant citations were retrieved. 63 articles met the inclusion criteria, which were primary studies reporting evidence of molecular factors that have functional roles in predisposing breast cancer bone metastasis in vivo. 12 of those 63 articles that additionally met quality criteria were included in the review. Extracted data were tabulated and key findings that indicated biological mechanisms involved in breast cancer metastasis to bone were synthesised. 15 proteins expressed by breast cancer cells were identified as factors that mediate breast cancer bone metastasis: ICAM-1, cadherin-11, osteoactivin, bone sialoprotein, CCN3, IL-11, CCL2, CITED2, CXCR4, CTGF, OPN, CX3CR1, TWIST1, adrenomedullin and Enpp1. Upregulation or overexpression of one or more of them by breast cancer cells resulted in increased breast cancer metastasis to bone in vivo, except for CCL2 where bone-metastatic cells showed a reduced expression of this factor. All factors identified, here expressed by breast cancer cells, are proteins that are normally expressed in the bone microenvironment and linked to physiologic bone functions. All have a functional role in one of more of the following: cell proliferation and differentiation, bone mineralization and remodelling, cell adhesion and/or chemokine signalling. Six of them (cadherin-11, ICAM-1, OPN, CX3CR1

  1. Three-dimensional micro-level computational study of Wolff's law via trabecular bone remodeling in the human proximal femur using design space topology optimization.

    Science.gov (United States)

    Boyle, Christopher; Kim, Il Yong

    2011-03-15

    The law of bone remodeling, commonly referred to as Wolff's Law, asserts that the internal trabecular bone adapts to external loadings, reorienting with the principal stress trajectories to maximize mechanical efficiency creating a naturally optimum structure. The goal of the current study was to utilize an advanced structural optimization algorithm, called design space optimization (DSO), to perform a micro-level three-dimensional finite element bone remodeling simulation on the human proximal femur and analyse the results to determine the validity of Wolff's hypothesis. DSO optimizes the layout of material by iteratively distributing it into the areas of highest loading, while simultaneously changing the design domain to increase computational efficiency. The result is a "fully stressed" structure with minimized compliance and increased stiffness. The large-scale computational simulation utilized a 175 μm mesh resolution and the routine daily loading activities of walking and stair climbing. The resulting anisotropic trabecular architecture was compared to both Wolff's trajectory hypothesis and natural femur samples from literature using a variety of visualization techniques, including radiography and computed tomography (CT). The results qualitatively revealed several anisotropic trabecular regions, that were comparable to the natural human femurs. Quantitatively, the various regional bone volume fractions from the computational results were consistent with quantitative CT analyses. The global strain energy proceeded to become more uniform during optimization; implying increased mechanical efficiency was achieved. The realistic simulated trabecular geometry suggests that the DSO method can accurately predict bone adaptation due to mechanical loading and that the proximal femur is an optimum structure as the Wolff hypothesized.

  2. Tendon Gradient Mineralization for Tendon to Bone Interface Integration

    Science.gov (United States)

    Qu, Jin; Thoreson, Andrew R.; Chen, Qingshan; An, Kai-Nan; Amadio, Peter C.; Zhao, Chunfeng

    2014-01-01

    Tendon-to-bone integration is a great challenge for tendon or ligament reconstruction regardless of use of autograft or allograft tendons. We mineralized the tendon, thus transforming the tendon-to-bone into a “bone-to-bone” interface for healing. Sixty dog flexor digitorum profundus (FDP) tendons were divided randomly into 5 groups: 1) normal FDP tendon, 2) CaP (Non-extraction and mineralization without fetuin), 3) CaPEXT (Extraction by Na2HPO4 and mineralization without fetuin), 4) CaPFetuin (Non-extraction and mineralization with fetuin), and 5) CaPEXTFetuin (Extraction and mineralization with fetuin). The calcium and phosphate content significantly increased in tendons treated with combination of extraction and fetuin compared to the other treatments. Histology also revealed a dense mineral deposition throughout the tendon outer layers and penetrated into the tendon to a depth of 200 μm in a graded manner. Compressive moduli were significantly lower in the four mineralized groups compared with normal control group. No significant differences in maximum failure strength or stiffness were found in the suture pull-out test among all groups. Mineralization of tendon alters the interface from tendon to bone into mineralized tendon to bone, which may facilitate tendon-to-bone junction healing following tendon or ligament reconstruction. PMID:23939935

  3. 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

  4. Effect of reactive oxygen species on bone remodeling in the pathogenesis of osteoporosis%活性氧影响骨重建在骨质疏松发病中的作用

    Institute of Scientific and Technical Information of China (English)

    谢翠柳; 刘珂; 孟玉坤

    2013-01-01

    骨重建是成年骨组织改建的主要形式,同时受生物力学因素和非生物力学因素调控.机体内活性氧产生和清除失衡会造成氧化应激,在此状态下活性氧作为非生物力学因素参与调控的骨重建与骨质疏松的发生有密切关系.活性氧损伤骨细胞转导力学信号的能力,上调骨重建阈值,导致骨组织已经习惯的力学刺激不足以维持骨量,而发生废用型骨重建.同时,在更新骨质和修复微损伤时,活性氧抑制成骨细胞分化和骨形成,促进破骨细胞形成和骨吸收,导致负性骨重建.总的效应是骨量逐年丢失,伴随骨结构逐渐退行性变,骨质疏松随年龄的增加而加重.%Bone remodeling, regulated by both biomechanical and non-biomechanical factors, is the major form of bone tissue reconstruction in adults. The state of oxidative stress results from imbalanced generation and elimination of reactive oxygen species ( ROS ). Under this state, ROS is closely related with the development of osteoporosis and the regulation of bone remodeling as a non - biochemical factor. ROS can impair the ability of mechanical transduction of osteocytes, up-regulate the threshold of bone remodeling. As the result bone mass cannot be maintained by the mechanics stimuli accustomed in bone tissue, and the disuse-mode of bone remodeling occurs. Meanwhile, during the updating of bone mass and the repairing of micro-damage, ROS can inhibit the differentiation of osteoblasts and bone formation, whereas promote the formation of osteoclasts and bone absorption, resulting in a negative bone remodeling. In conclusion, the effect of ROS on bone remodeling results in gradual bone loss and bone micro-architectural deterioration year by year. Osteoporosis exacerbates along with the increase of age.

  5. 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.

  6. Regulation of Bone Metabolism

    Science.gov (United States)

    Shahi, Maryam; Peymani, Amir; Sahmani, Mehdi

    2017-01-01

    Bone is formed through the processes of endochondral and intramembranous ossification. In endochondral ossification primary mesenchymal cells differentiate to chondrocytes and then are progressively substituted by bone, while in intramembranous ossification mesenchymal stem cells (MSCs) differentiate directly into osteoblasts to form bone. The steps of osteogenic proliferation, differentiation, and bone homeostasis are controlled by various markers and signaling pathways. Bone needs to be remodeled to maintain integrity with osteoblasts, which are bone-forming cells, and osteoclasts, which are bone-degrading cells.In this review we considered the major factors and signaling pathways in bone formation; these include fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs), wingless-type (Wnt) genes, runt-related transcription factor 2 (RUNX2) and osteoblast-specific transcription factor (osterix or OSX). PMID:28367467

  7. Regulation of Bone Metabolism.

    Science.gov (United States)

    Shahi, Maryam; Peymani, Amir; Sahmani, Mehdi

    2017-04-01

    Bone is formed through the processes of endochondral and intramembranous ossification. In endochondral ossification primary mesenchymal cells differentiate to chondrocytes and then are progressively substituted by bone, while in intramembranous ossification mesenchymal stem cells (MSCs) differentiate directly into osteoblasts to form bone. The steps of osteogenic proliferation, differentiation, and bone homeostasis are controlled by various markers and signaling pathways. Bone needs to be remodeled to maintain integrity with osteoblasts, which are bone-forming cells, and osteoclasts, which are bone-degrading cells.In this review we considered the major factors and signaling pathways in bone formation; these include fibroblast growth factors (FGFs), bone morphogenetic proteins (BMPs), wingless-type (Wnt) genes, runt-related transcription factor 2 (RUNX2) and osteoblast-specific transcription factor (osterix or OSX).

  8. Development of an enzyme-linked immunosorbent assay for detection of chicken osteocalcin and its use in evaluation of perch effects on bone remodeling in caged White Leghorns.

    Science.gov (United States)

    Jiang, S; Cheng, H W; Hester, P Y; Hou, J-F

    2013-08-01

    Osteocalcin (OC) is a sensitive biochemical marker for evaluating bone turnover in mammals. The role of avian OC is less clear because of the need for a chicken assay. Our objectives were to develop an assay using indirect competitive ELISA for detecting chicken serum OC and use the assay to examine the effects of perches on bone remodeling in caged hens. Anti-chicken OC polyclonal antibody was produced by immunization of rabbits with a recombinant OC from Escherichia coli. Chicken OC extracted from bone was used as a coated protein, and purified chicken OC was used for calibration. The limit of detection of the developed OC ELISA was 0.13 ng/mL. The intra- and interassay CV were chickens that never had access to perches during their life cycle. Treatment 2 chickens had perches during the pullet phase (0 to 16.9 wk of age), whereas treatment 3 chickens had perches only during the egg-laying phase of the life cycle (17 to 71 wk of age). Treatment 4 chickens always had access to perches (0 to 71 wk of age). Correlation between the 2 assays was 0.62 (P chicken ELISA were higher than that detected using the Rat-Mid ELISA (P chicken ELISA assay showed that hens with perch access had higher concentrations of serum OC than hens without perches during egg laying (P = 0.04). Pullet access to perches did not affect serum OC levels in 71-wk-old hens (P = 0.15). In conclusion, a chicken OC ELISA has been validated that is sensitive and accurate with adequate discriminatory power for measuring bone remodeling in chickens.

  9. Long-term vitamin D deficiency in older adult C57BL/6 mice does not affect bone structure, remodeling and mineralization.

    Science.gov (United States)

    van der Meijden, K; Buskermolen, J; van Essen, H W; Schuurman, T; Steegenga, W T; Brouwer-Brolsma, E M; Langenbach, G E J; van Ruijven, L J; den Heijer, M; Lips, P; Bravenboer, N

    2016-11-01

    Animal models show that vitamin D deficiency may have severe consequences for skeletal health. However, most studies have been performed in young rodents for a relatively short period, while in older adult rodents the effects of long-term vitamin D deficiency on skeletal health have not been extensively studied. Therefore, the first aim of this study was to determine the effects of long-term vitamin D deficiency on bone structure, remodeling and mineralization in bones from older adult mice. The second aim was to determine the effects of long-term vitamin D deficiency on mRNA levels of genes involved in vitamin D metabolism in bones from older adult mice. Ten months old male C57BL/6 mice were fed a diet containing 0.5% calcium, 0.2% phosphate and 0 (n=8) or 1 (n=9) IU vitamin D3/gram for 14 months. At an age of 24 months, mice were sacrificed for histomorphometric and micro-computed tomography (micro-CT) analysis of humeri as well as analysis of CYP27B1, CYP24 and VDR mRNA levels in tibiae and kidneys using RT-qPCR. Plasma samples, obtained at 17 and 24 months of age, were used for measurements of 25-hydroxyvitamin D (25(OH)D) (all samples), phosphate and parathyroid hormone (PTH) (terminal samples) concentrations. At the age of 17 and 24 months, mean plasma 25(OH)D concentrations were below the detection limit (vitamin D deficient diets. Plasma phosphate and PTH concentrations did not differ between both groups. Micro-CT and histomorphometric analysis of bone mineral density, structure and remodeling did not reveal differences between control and vitamin D deficient mice. Long-term vitamin D deficiency did also not affect CYP27B1 mRNA levels in tibiae, while CYP24 mRNA levels in tibiae were below the detection threshold in both groups. VDR mRNA levels in tibiae from vitamin D deficient mice were 0.7 fold lower than those in control mice. In conclusion, long-term vitamin D deficiency in older adult C57BL/6 mice, accompanied by normal plasma PTH and phosphate

  10. Evaluation of bone tissue remodeling and mineral metabolism in elderly patients who have not been previously examined and have received no antiosteoporotic therapy

    Directory of Open Access Journals (Sweden)

    S B Malichenko

    2012-01-01

    Full Text Available Objective: to evaluate bone tissue remodeling and mineral metabolism in elderly women who have not been previously examined and have received no antiosteoporotic therapy. Patients and methods. A total of 3152 women aged 65—75 years were examined using questionnaires and tests according to international validated scales and tests. The investigators measured bone density by dual-energy X-ray absorptiometry and mineral and bone mineral parameters. Results. Most patients were ascertained to have motor and physical impairments and cognitive dysfunction; 100% of cases had risk factors for osteoporosis (OP; 32.4% had a history of atraumatic fractures; 56.4% were diagnosed as having OP during standard examinations; 72.7% needed treatment in accordance with the FRAX procedure. The sensitivity of FRAX in patients (with OP without pathological fractures, OP with a history of low-energy fractures, or osteopenia with pathological fractures requiring treatment according to these standard methods was 70.3, 71.5, and 24.3%, respectively. Conclusion. The majority of elderly (65—75-year-old women who had not been previously examined and had received no antiosteoporotic therapy were found to have bone metabolic disturbances, a history of fractures in the presence of cognitive dysfunction, impaired motor activity, lowered quality of life, and inadequate calcium intake. At the same time, FRAX is not always the method of choice.

  11. Evaluation of bone tissue remodeling and mineral metabolism in elderly patients who have not been previously examined and have received no antiosteoporotic therapy

    Directory of Open Access Journals (Sweden)

    S B Malichenko

    2012-03-01

    Full Text Available Objective: to evaluate bone tissue remodeling and mineral metabolism in elderly women who have not been previously examined and have received no antiosteoporotic therapy. Patients and methods. A total of 3152 women aged 65—75 years were examined using questionnaires and tests according to international validated scales and tests. The investigators measured bone density by dual-energy X-ray absorptiometry and mineral and bone mineral parameters. Results. Most patients were ascertained to have motor and physical impairments and cognitive dysfunction; 100% of cases had risk factors for osteoporosis (OP; 32.4% had a history of atraumatic fractures; 56.4% were diagnosed as having OP during standard examinations; 72.7% needed treatment in accordance with the FRAX procedure. The sensitivity of FRAX in patients (with OP without pathological fractures, OP with a history of low-energy fractures, or osteopenia with pathological fractures requiring treatment according to these standard methods was 70.3, 71.5, and 24.3%, respectively. Conclusion. The majority of elderly (65—75-year-old women who had not been previously examined and had received no antiosteoporotic therapy were found to have bone metabolic disturbances, a history of fractures in the presence of cognitive dysfunction, impaired motor activity, lowered quality of life, and inadequate calcium intake. At the same time, FRAX is not always the method of choice.

  12. 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

  13. 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.

  14. 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.

  15. p38α MAPK regulates proliferation and differentiation of osteoclast progenitors and bone remodeling in an aging-dependent manner

    Science.gov (United States)

    Cong, Qian; Jia, Hao; Li, Ping; Qiu, Shoutao; Yeh, James; Wang, Yibin; Zhang, Zhen-Lin; Ao, Junping; Li, Baojie; Liu, Huijuan

    2017-01-01

    Bone mass is determined by the balance between bone formation, carried out by mesenchymal stem cell-derived osteoblasts, and bone resorption, carried out by monocyte-derived osteoclasts. Here we investigated the potential roles of p38 MAPKs, which are activated by growth factors and cytokines including RANKL and BMPs, in osteoclastogenesis and bone resorption by ablating p38α MAPK in LysM+monocytes. p38α deficiency promoted monocyte proliferation but regulated monocyte osteoclastic differentiation in a cell-density dependent manner, with proliferating p38α−/− cultures showing increased differentiation. While young mutant mice showed minor increase in bone mass, 6-month-old mutant mice developed osteoporosis, associated with an increase in osteoclastogenesis and bone resorption and an increase in the pool of monocytes. Moreover, monocyte-specific p38α ablation resulted in a decrease in bone formation and the number of bone marrow mesenchymal stem/stromal cells, likely due to decreased expression of PDGF-AA and BMP2. The expression of PDGF-AA and BMP2 was positively regulated by the p38 MAPK-Creb axis in osteoclasts, with the promoters of PDGF-AA and BMP2 having Creb binding sites. These findings uncovered the molecular mechanisms by which p38α MAPK regulates osteoclastogenesis and coordinates osteoclastogenesis and osteoblastogenesis. PMID:28382965

  16. Multi-omic data integration links Deleted in Breast Cancer 1 (DBC1) Degradation to Chromatin Remodeling in Inflammatory Response

    Energy Technology Data Exchange (ETDEWEB)

    Nakayasu, Ernesto S.; Brown, Roslyn N.; Ansong, Charles; Sydor, Michael A.; Imtiaz, Sayed; Mihai, Cosmin; Sontag, Ryan L.; Hixson, Kim K.; Monroe, Matthew E.; Sobreira, Tiago; Orr, Galya; Petyuk, Vladislav A.; Yang, Feng; Smith, Richard D.; Adkins, Joshua N.

    2013-08-12

    Ubiquitination is a common protein post-translational modification that regulates many key cellular functions. Here we investigated the dynamics of ubiquitinated proteins after an inflammatory stimulation of RAW264.7 macrophage-like cells with bacterial lipopolysaccharide. We demonstrate that levels of global ubiquitination, and K48 and K63 polyubiquitination change after lipopolysaccharide stimulation. A quantitative proteomic analysis identified 1199 ubiquitinated proteins, 78 of which had significantly changed ubiquitination levels after lipopolysaccharide stimulation. We next identified a subset of proteins that were targeted for degradation after lipopolysaccharide stimulation, by integrating the ubiquitinome data with global proteomics and transcriptomics results. Using cellular assays and western blot analyses we biochemically validated DBC1, a histone deacetylase inhibitor not previously linked to inflammation, as a degradation substrate, which is targeted via an orchestrated mechanism utilizing caspases and the proteasome. The degradation of DBC1 releases histone deacetylase activity, linking lipopolysaccharide activation to chromatin remodeling in caspase- and proteasome-mediated signaling.

  17. Modularity of the rodent mandible: integrating bones, muscles, and teeth.

    Science.gov (United States)

    Zelditch, Miriam Leah; Wood, Aaron R; Bonett, Ronald M; Swiderski, Donald L

    2008-01-01

    Summary Several models explain how a complex integrated system like the rodent mandible can arise from multiple developmental modules. The models propose various integrating mechanisms, including epigenetic effects of muscles on bones. We test five for their ability to predict correlations found in the individual (symmetric) and fluctuating asymmetric (FA) components of shape variation. We also use exploratory methods to discern patterns unanticipated by any model. Two models fit observed correlation matrices from both components: (1) parts originating in same mesenchymal condensation are integrated, (2) parts developmentally dependent on the same muscle form an integrated complex as do those dependent on teeth. Another fits the correlations observed in FA: each muscle insertion site is an integrated unit. However, no model fits well, and none predicts the complex structure found in the exploratory analyses, best described as a reticulated network. Furthermore, no model predicts the correlation between proximal parts of the condyloid and coronoid, which can exceed the correlations between proximal and distal parts of the same process. Additionally, no model predicts the correlation between molar alveolus and ramus and/or angular process, one of the highest correlations found in the FA component. That correlation contradicts the basic premise of all five developmental models, yet it should be anticipated from the epigenetic effects of mastication, possibly the primary morphogenetic process integrating the jaw coupling forces generated by muscle contraction with those experienced at teeth.

  18. Relationship between 3-month changes in biochemical markers of bone remodelling and changes in bone mineral density and fracture incidence in patients treated with strontium ranelate for 3 years.

    Science.gov (United States)

    Bruyère, O; Collette, J; Rizzoli, R; Decock, C; Ortolani, S; Cormier, C; Detilleux, J; Reginster, J-Y

    2010-06-01

    From two randomised controlled trials, it is shown that 3-month changes in biochemical markers of bone formation (bone-specific alkaline phosphatase and C-terminal propeptide of type I procollagen) were associated with 3-year bone mineral density (BMD) changes, but not fracture incidence in patients treated with strontium ranelate. The purpose of this study was to assess if short-term change in biochemical markers of bone remodelling is associated with long-term BMD change and fracture incidence observed during treatment with strontium ranelate. From the SOTI and TROPOS trials, bone-specific alkaline phosphatase (BALP), C-terminal propeptide of type I procollagen (PICP), serum C-terminal telopeptides (S-CTX) and urine N-terminal telopeptides of type I collagen (U-NTX) were assessed at baseline and after 3 months. Two thousand three hundred seventy-three women were included in this study. Multiple regression analysis showed that 3-month changes in PICP and BALP but not s-CTX I nor s-NTX I were significantly (p < 0.001) associated with 3-year BMD changes at the lumbar spine and the femoral neck. Changes in s-CTX I, PICP and BALP were significantly associated with change in total proximal femur BMD. Changes in biochemical markers explain less than 8% of the BMD changes. The 3-month changes in BALP, PICP s-CTX I and s-NTX I were not significantly associated with fracture incidence. Short-term changes in biochemical markers of bone formation are associated with future BMD changes in patients treated with strontium ranelate, suggesting a bone-forming activity of this treatment, but are not appropriate to monitor the efficacy of strontium ranelate at the individual level.

  19. 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...

  20. Repeatability of quantitative parameters of 18F-fluoride PET/CT and biochemical tumour and specific bone remodelling markers in prostate cancer bone metastases.

    Science.gov (United States)

    Wassberg, Cecilia; Lubberink, Mark; Sörensen, Jens; Johansson, Silvia

    2017-12-01

    18F-fluoride PET/CT exhibits high sensitivity to delineate and measure the extent of bone metastatic disease in patients with prostate cancer. 18F-fluoride PET/CT could potentially replace traditional bone scintigraphy in clinical routine and trials. However, more studies are needed to assess repeatability and biological uptake variation. The aim of this study was to perform test-retest analysis of quantitative PET-derived parameters and blood/serum bone turnover markers at the same time point. Ten patients with prostate cancer and verified bone metastases were prospectively included. All underwent two serial 18F-fluoride PET/CT at 1 h post-injection. Up to five dominant index lesions and whole-body 18F-fluoride skeletal tumour burden were recorded per patient. Lesion-based PET parameters were SUVmax, SUVmean and functional tumour volume applying a VOI with 50% threshold (FTV50%). The total skeletal tumour burden, total lesion 18F-fluoride (TLF), was calculated using a threshold of SUV of ≥15. Blood/serum biochemical bone turnover markers obtained at the time of each PET were PSA, ALP, S-osteocalcin, S-beta-CTx, 1CTP and BAP. A total of 47 index lesions and a range of 2-122 bone metastases per patient were evaluated. Median time between 18F-fluoride PET/CT was 7 days (range 6-8 days). Repeatability coefficients were for SUVmax 26%, SUVmean 24%, FTV50% for index lesions 23% and total skeletal tumour burden (TLF) 35%. Biochemical bone marker repeatability coefficients were for PSA 19%, ALP 23%, S-osteocalcin 18%, S-beta-CTx 22%, 1CTP 18% and BAP 23%. Quantitative 18F-fluoride uptake and simultaneous biochemical bone markers measurements are reproducible for prostate cancer metastases and show similar magnitude in test-retest variation.

  1. 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

  2. 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...

  3. 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

  4. 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.

  5. Dynamic Cross Talk between S1P and CXCL12 Regulates Hematopoietic Stem Cells Migration, Development and Bone Remodeling

    Directory of Open Access Journals (Sweden)

    Karin Golan

    2013-09-01

    Full Text Available Hematopoietic stem cells (HSCs are mostly retained in a quiescent non-motile mode in their bone marrow (BM niches, shifting to a migratory cycling and differentiating state to replenish the blood with mature leukocytes on demand. The balance between the major chemo-attractants CXCL12, predominantly in the BM, and S1P, mainly in the blood, dynamically regulates HSC recruitment to the circulation versus their retention in the BM. During alarm situations, stress-signals induce a decrease in CXCL12 levels in the BM, while S1P levels are rapidly and transiently increased in the circulation, thus favoring mobilization of stem cells as part of host defense and repair mechanisms. Myeloid cytokines, including G-CSF, up-regulate S1P signaling in the BM via the PI3K pathway. Induced CXCL12 secretion from stromal cells via reactive oxygen species (ROS generation and increased S1P1 expression and ROS signaling in HSCs, all facilitate mobilization. Bone turnover is also modulated by both CXCL12 and S1P, regulating the dynamic BM stromal microenvironment, osteoclasts and stem cell niches which all functionally express CXCL12 and S1P receptors. Overall, CXCL12 and S1P levels in the BM and circulation are synchronized to mutually control HSC motility, leukocyte production and osteoclast/osteoblast bone turnover during homeostasis and stress situations.

  6. The Effects of Bone Remodeling Inhibition by Alendronate on Three-Dimensional Microarchitecture of Subchondral Bone Tissues in Guinea Pig Primary Osteoarthrosis

    DEFF Research Database (Denmark)

    Ding, Ming

    2008-01-01

    We assessed whether increase of subchondral bone density enhances cartilage stress during impact loading, leading to progressive cartilage degeneration and accelerated osteoarthrosis (OA) progression. Sixty-six male guinea pigs were randomly divided into six groups. During a 9-week treatment period...

  7. The effects of bone remodeling inhibition by alendronate on 3-D microarchitecture of subchondral bone tissues in guinea pig primary osteoarthrosis

    DEFF Research Database (Denmark)

    Ding, Ming; Danielsen, Carl Christian; Hvid, Ivan

    2008-01-01

    We assess whether increase of subchondral bone density enhances cartilage stress during impact loading leading to progressive cartilage degeneration and accelerated osteoarthrosis (OA) progression.               Sixty-six male guinea pigs were randomly divided into 6 groups. During a 9-week...

  8. Electrospun Hydroxyapatite-Containing Chitosan Nanofibers Crosslinked with Genipin for Bone Tissue Engineering

    OpenAIRE

    Frohbergh, Michael E.; Katsman, Anna; Botta, Gregory P.; Lazarovici, Phillip; Schauer, Caroline L.; Wegst, Ulrike G.K.; Lelkes, Peter I

    2012-01-01

    Reconstruction of large bone defects remains problematic in orthopedic and craniofacial clinical practice. Autografts are limited in supply and are associated with donor site morbidity while other materials show poor integration with the host’s own bone. This lack of integration is often due to the absence of periosteum, the outer layer of bone that contains osteoprogenitor cells and is critical for the growth and remodeling of bone tissue. In this study we developed a one-step platform to el...

  9. The remodeling transient and the calcium economy.

    Science.gov (United States)

    Aloia, J F; Arunabh-Talwar, S; Pollack, S; Yeh, J K

    2008-07-01

    The remodeling transient describes a change in bone mass that lasts one remodeling cycle following an intervention that disturbs the calcium economy. We demonstrated the transient in a study of the response of bone density to calcium/vitamin D3 supplementation and show the hazards of misinterpretation if the transient is not considered. The remodeling transient describes a change in bone mass that lasts for one remodeling cycle following an intervention that disturbs the calcium economy. We report an intervention with calcium and vitamin D supplementation in 208 postmenopausal African-American women where the remodeling transient was considered a priori in the study design. Both groups (calcium alone vs. calcium + 20 microg (800 IU) vitamin D3) were ensured a calcium intake in excess of 1200 mg/day. There were no differences between the two groups in changes in BMD over time. These BMD changes were therefore interpreted to reflect increased calcium intake in both groups but not any influence of vitamin D. A transient increase in bone mineral density was observed during the first year of study, followed by a decline. The remodeling period was estimated at about 9 months, which is similar to histomorphometric estimates. It is problematic to draw conclusions concerning interventions that influence the calcium economy without considering the remodeling transient in study design. Studies of agents that effect bone remodeling must be carried out for at least two remodeling cycles and appropriate techniques must be used in data analysis.

  10. Stress and the Emerging Roles of Chromatin Remodeling in Signal Integration and Stable Transmission of Reversible Phenotypes

    Science.gov (United States)

    Weaver, Ian C. G.; Korgan, Austin C.; Lee, Kristen; Wheeler, Ryan V.; Hundert, Amos S.; Goguen, Donna

    2017-01-01

    The influence of early life experience and degree of parental-infant attachment on emotional development in children and adolescents has been comprehensively studied. Structural and mechanistic insight into the biological foundation and maintenance of mammalian defensive systems (metabolic, immune, nervous and behavioral) is slowly advancing through the emerging field of developmental molecular (epi)genetics. Initial evidence revealed that differential nurture early in life generates stable differences in offspring hypothalamic-pituitary-adrenal (HPA) regulation, in part, through chromatin remodeling and changes in DNA methylation of specific genes expressed in the brain, revealing physical, biochemical and molecular paths for the epidemiological concept of gene-environment interactions. Herein, a primary molecular mechanism underpinning the early developmental programming and lifelong maintenance of defensive (emotional) responses in the offspring is the alteration of chromatin domains of specific genomic regions from a condensed state (heterochromatin) to a transcriptionally accessible state (euchromatin). Conversely, DNA methylation promotes the formation of heterochromatin, which is essential for gene silencing, genomic integrity and chromosome segregation. Therefore, inter-individual differences in chromatin modifications and DNA methylation marks hold great potential for assessing the impact of both early life experience and effectiveness of intervention programs—from guided psychosocial strategies focused on changing behavior to pharmacological treatments that target chromatin remodeling and DNA methylation enzymes to dietary approaches that alter cellular pools of metabolic intermediates and methyl donors to affect nutrient bioavailability and metabolism. In this review article, we discuss the potential molecular mechanism(s) of gene regulation associated with chromatin modeling and programming of endocrine (e.g., HPA and metabolic or cardiovascular) and

  11. The micro-architecture of human cancellous bone from fracture neck of femur patients in relation to the structural integrity and fracture toughness of the tissue

    Directory of Open Access Journals (Sweden)

    C. Greenwood

    2015-12-01

    Full Text Available Osteoporosis is clinically assessed from bone mineral density measurements using dual energy X-ray absorption (DXA. However, these measurements do not always provide an accurate fracture prediction, arguably because DXA does not grapple with ‘bone quality’, which is a combined result of microarchitecture, texture, bone tissue properties, past loading history, material chemistry and bone physiology in reaction to disease. Studies addressing bone quality are comparatively few if one considers the potential importance of this factor. They suffer due to low number of human osteoporotic specimens, use of animal proxies and/or the lack of differentiation between confounding parameters such as gender and state of diseased bone. The present study considers bone samples donated from patients (n = 37 who suffered a femoral neck fracture and in this very well defined cohort we have produced in previous work fracture toughness measurements (FT which quantify its ability to resist crack growth which reflects directly the structural integrity of the cancellous bone tissue. We investigated correlations between BV/TV and other microarchitectural parameters; we examined effects that may suggest differences in bone remodelling between males and females and compared the relationships with the FT properties. The data crucially has shown that TbTh, TbSp, SMI and TbN may provide a proxy or surrogate for BV/TV. Correlations between FT critical stress intensity values and microarchitecture parameters (BV/TV, BS/TV, TbN, BS/BV and SMI for osteoporotic cancellous tissue were observed and are for the first time reported in this study. Overall, this study has not only highlighted that the fracture model based upon BMD could potentially be improved with inclusion of other microarchitecture parameters, but has also given us clear clues as to which of them are more influential in this role.

  12. Biologic and clinical aspects of integration of different bone substitutes in oral surgery: a literature review.

    Science.gov (United States)

    Zizzari, Vincenzo Luca; Zara, Susi; Tetè, Giulia; Vinci, Raffaele; Gherlone, Enrico; Cataldi, Amelia

    2016-10-01

    Many bone substitutes have been proposed for bone regeneration, and researchers have focused on the interactions occurring between grafts and host tissue, as the biologic response of host tissue is related to the origin of the biomaterial. Bone substitutes used in oral and maxillofacial surgery could be categorized according to their biologic origin and source as autologous bone graft when obtained from the same individual receiving the graft; homologous bone graft, or allograft, when harvested from an individual other than the one receiving the graft; animal-derived heterologous bone graft, or xenograft, when derived from a species other than human; and alloplastic graft, made of bone substitute of synthetic origin. The aim of this review is to describe the most commonly used bone substitutes, according to their origin, and to focus on the biologic events that ultimately lead to the integration of a biomaterial with the host tissue.

  13. Numerical assessment of bone remodeling around conventionally and early loaded titanium and titanium-zirconium alloy dental implants.

    Science.gov (United States)

    Akça, Kıvanç; Eser, Atılım; Çavuşoğlu, Yeliz; Sağırkaya, Elçin; Çehreli, Murat Cavit

    2015-05-01

    The aim of this study was to investigate conventionally and early loaded titanium and titanium-zirconium alloy implants by three-dimensional finite element stress analysis. Three-dimensional model of a dental implant was created and a thread area was established as a region of interest in trabecular bone to study a localized part of the global model with a refined mesh. The peri-implant tissues around conventionally loaded (model 1) and early loaded (model 2) implants were implemented and were used to explore principal stresses, displacement values, and equivalent strains in the peri-implant region of titanium and titanium-zirconium implants under static load of 300 N with or without 30° inclination applied on top of the abutment surface. Under axial loading, principal stresses in both models were comparable for both implants and models. Under oblique loading, principal stresses around titanium-zirconium implants were slightly higher in both models. Comparable stress magnitudes were observed in both models. The displacement values and equivalent strain amplitudes around both implants and models were similar. Peri-implant bone around titanium and titanium-zirconium implants experiences similar stress magnitudes coupled with intraosseous implant displacement values under conventional loading and early loading simulations. Titanium-zirconium implants have biomechanical outcome comparable to conventional titanium implants under conventional loading and early loading.

  14. Open topological strings and integrable hierarchies: Remodeling the A-model

    CERN Document Server

    Brini, Andrea

    2011-01-01

    We set up, purely in A-model terms, a novel formalism for the global solution of the open and closed topological A-model on toric Calabi-Yau threefolds. The starting point is to build on recent progress in the mathematical theory of open Gromov-Witten invariants of orbifolds; we interpret the localization formulae as relating D-brane amplitudes to closed string amplitudes perturbed with twisted masses through an analogue of the "loop insertion operator" of matrix models. We first generalize this form of open/closed string duality to general toric backgrounds in all chambers of the stringy Kaehler moduli space; secondarily, we display a neat connection of the (gauged) closed string side to tau functions of 1+1 Hamiltonian integrable hierarchies, and exploit it to provide an effective computation of open string amplitudes. In doing so, we also provide a systematic treatment of the change of flat open moduli induced by a phase transition in the closed moduli space. We test our proposal in detail by providing an ...

  15. Two distinct mechanisms mediate the involvement of bone marrow cells in islet remodeling: neogenesis of insulin-producing cells and support of islet recovery.

    Science.gov (United States)

    Iskovich, Svetlana; Goldenberg-Cohen, Nitza; Sadikov, Tamila; Yaniv, Isaac; Stein, Jerry; Askenasy, Nadir

    2015-01-01

    We have recently reported that small-sized bone marrow cells (BMCs) isolated by counterflow centrifugal elutriation and depleted of lineage markers (Fr25lin(-)) have the capacity to differentiate and contribute to regeneration of injured islets. In this study, we assess some of the characteristics of these cells compared to elutriated hematopoietic progenitors (R/O) and whole BMCs in a murine model of streptozotocin-induced chemical diabetes. The GFP(bright)CD45(+) progeny of whole BMCs and R/O progenitors progressively infiltrate the pancreas with evolution of donor chimerism; are found at islet perimeter, vascular, and ductal walls; and have a modest impact on islet recovery from injury. In contrast, Fr25lin(-) cells incorporate in the islets, convert to GFP(dim)CD45(-)PDX-1(+) phenotypes, produce proinsulin, and secrete insulin with significant contribution to stabilization of glucose homeostasis. The elutriated Fr25lin(-) cells express low levels of CD45 and are negative for SCA-1 and c-kit, as removal of cells expressing these markers did not impair conversion to produce insulin. BMCs mediate two synergistic mechanisms that contribute to islet recovery from injury: support of islet remodeling by hematopoietic cells and neogenesis of insulin-producing cells from stem cells.

  16. 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.

  17. Current concept review: bone growth factors and bone remodeling%骨生长因子与骨重建研究进展

    Institute of Scientific and Technical Information of China (English)

    苏佳灿; 许硕贵; 张春才

    2001-01-01

    @@骨重建(bone remodeling)是指骨的形状、密度分布随时间的变化而改变,受到骨生长因子、年龄、局部血供、营养及力学环境等诸多因素的影响〔1〕。多种细胞因子〔1~7〕,如转化生长因子-β(Transforming Growth Factor-beta ,TGF-β)、骨形态发生蛋白(Bone Morphogenetic Proteins, BMPs)、成纤维细胞生长因子(Fibroblast Growth Factor, FGF)、胰岛素样生长因子-Ⅰ/-Ⅱ(Insulin-like Growth Factor-Ⅰ/-Ⅱ,IGF-Ⅰ/-Ⅱ)、血小板衍生生长因子(Platelet-derived Growth Factor,PDGF)、生长激素(Growth Hormone,GH)、肿瘤坏死因子-α(Tumor Necrosis Factor α,TNF-α )及β2微球蛋白(beta-2 microglobulin, β2-MG)等都参与了骨重建过程中骨细胞的增殖、分化以及基质合成的调节。笔者就上述骨生长因子对骨重建的影响作一综述。

  18. Secondary hyperparathyroidism in HIV-infected patients: relationship with bone remodeling and response to vitamin D supplementation

    Directory of Open Access Journals (Sweden)

    S Bañon

    2012-11-01

    Full Text Available Purpose of the study: Secondary hyperparathyroidism (SH is frequent in HIV-infected patients. However, the causes and consequences are not well established. The aim of our study was to determine the relationship between parathyroid hormone (PTH, vitamin D and bone mineral density (BMD in HIV-infected patients, and the effect of vitamin D replacement on PTH levels. Methods: Prospective study of 506 patients with at least two sequential serum determinations of PTH and 25-hydroxyvitamin D levels. In all cases, a bone dual X-ray absorptiometry (DEXA was performed at inclusion. Hyperparathyroidism was defined as a PTH level above 65 pg/ml. Summary of results: Mean age was 44 yrs (24–78, and 75% were male. Mean BMI was 23.7 (17.97–33.11, and only 3% were of black race. Median nadir CD4+ was 200 cells/µL (9–499, and median time of HIV infection was 15.3 yrs (1.7–25.2. At inclusion, 488 patients (86% were on HAART (31% TDF+PI, 44% TDF+NNRTI, 25% non-TDF based regimen for a median of 929.5 days (154–1969, and 40% were HCV-coinfected. Median eGFR was 97.9 ml/min (62.14–134.08. Overall, mean serum PTH was 56.3 pg/mL (27.2–95.07. SH was observed in 27% of cases, with a marked influence of seasonality (from 44% in January to 10% in August. Mean levels of vitamin D were 17.45 ng/mL (7.6–40.78, with 16% below 10 ng/ml, 59%<20 ng/ml (deficiency, 85%<30 ng/ml (insufficiency. SH was related to vitamin D deficiency (relative risk, RR, 2.44, age (RR 1.04 per year, and a higher decrease in eGFR (RR 1.03 per ml/min, after adjustment by season, antiretroviral therapy, GFR at baseline, and HCV coinfection. DEXA scan showed 18% osteoporosis and 54% osteopenia, and there was an inverse correlation between PTH levels and T and Z score in femoral neck (r=−0.14, p<0.01, higher in those patients below 40 yrs. Vitamin D supplementation in 181 patients produced a significant decrease in serum PTH (57.2 if not treated vs 50.5 pg/ml, p=0.02, 23% continues with

  19. Impact of repeated intravenous bone marrow mesenchymal stem cells infusion on myocardial collagen network remodeling in a rat model of doxorubicin-induced dilated cardiomyopathy.

    Science.gov (United States)

    Yu, Qin; Li, Qianxiao; Na, Rongmei; Li, Xiaofei; Liu, Baiting; Meng, Lili; Liutong, Hanyu; Fang, Weiyi; Zhu, Ning; Zheng, Xiaoqun

    2014-02-01

    Bone marrow mesenchymal stem cells (MSCs) transplantation improved cardiac function and reduced myocardial fibrosis in both ischemic and non-ischemic cardiomyopathies. We evaluated the effects of repeated peripheral vein injection of MSCs on collagen network remodeling and myocardial TGF-β1, AT1, CYP11B2 (aldosterone synthase) gene expressions in a rat model of doxorubicin (DOX)-induced dilated cardiomyopathy (DCM). Thirty-eight out of 53 SD rats survived at 10 weeks post-DOX injection (2.5 mg/kg/week for 6 weeks, i.p.) were divided into DCM blank (without treatment, n = 12), DCM placebo (intravenous tail injection of 0.5 mL serum-free culture medium every other day for ten times, n = 13), and DCM plus MSCs group (intravenous tail injection of 5 × 10(6) MSCs dissolved in 0.5 mL serum-free culture medium every other day for 10 times, n = 13). Ten untreated rats served as normal controls. At 20 weeks after DOX injection, echocardiography, myocardial collagen content, myocardial expressions of types I and III collagen, TGF-β1, AT1, and CYP11B2 were compared among groups. At 20 weeks post-DOX injection, 8 rats (67%) survived in DCM blank group, 9 rats (69%) survived in DCM placebo group while 13 rats (100 %) survived in DCM plus MSCs group. Left ventricular end-diastolic diameter was significantly higher and ejection fraction was significantly lower in DCM blank and DCM placebo groups compared to normal control rats, which were significantly improved in DCM plus MSCs group (all p collagen volume fraction, types I and III collagen, myocardial mRNA expressions of TGF-β1, AT1, CYP11B2, and collagen I/III ratio were all significantly lower in DCM plus MSCs group compared to DCM blank and DCM placebo groups (all p collagen network remodeling possibly through downregulating renin-angiotensin-aldosterone system in DOX-induced DCM rats.

  20. HTLV-1 Tax mediated downregulation of miRNAs associated with chromatin remodeling factors in T cells with stably integrated viral promoter.

    Directory of Open Access Journals (Sweden)

    Saifur Rahman

    Full Text Available RNA interference (RNAi is a natural cellular mechanism to silence gene expression and is predominantly mediated by microRNAs (miRNAs that target messenger RNA. Viruses can manipulate the cellular processes necessary for their replication by targeting the host RNAi machinery. This study explores the effect of human T-cell leukemia virus type 1 (HTLV-1 transactivating protein Tax on the RNAi pathway in the context of a chromosomally integrated viral long terminal repeat (LTR using a CD4(+ T-cell line, Jurkat. Transcription factor profiling of the HTLV-1 LTR stably integrated T-cell clone transfected with Tax demonstrates increased activation of substrates and factors associated with chromatin remodeling complexes. Using a miRNA microarray and bioinformatics experimental approach, Tax was also shown to downregulate the expression of miRNAs associated with the translational regulation of factors required for chromatin remodeling. These observations were validated with selected miRNAs and an HTLV-1 infected T cells line, MT-2. miR-149 and miR-873 were found to be capable of directly targeting p300 and p/CAF, chromatin remodeling factors known to play critical role in HTLV-1 pathogenesis. Overall, these results are first in line establishing HTLV-1/Tax-miRNA-chromatin concept and open new avenues toward understanding retroviral latency and/or replication in a given cell type.

  1. Bone marrow mesenchymal stem cells-conditioned medium enhances vascular remodeling after stroke in type 2 diabetic rats.

    Science.gov (United States)

    Xiang, Jie; Hu, Jinxia; Shen, Tong; Liu, Bin; Hua, Fang; Zan, Kun; Zu, Jie; Cui, Guiyun; Ye, Xinchun

    2017-03-22

    Our previous studies have found that stem cells conditioned medium (CM) facilitated functional recovery after stroke in non-diabetics. However, whether bone marrow stromal cells conditioned medium (BMSCs-CM) treatment after stroke in type 2 diabetic (T2DM) rats improve functional outcomes remains unclear. T2DM rats were induced and subjected to stroke then treated with or without BMSCs-CM. Functional outcomes and blood-brain barrier (BBB) leakage were performed, the expression of Angiopoietin (Ang) 1 and tyrosine kinase (Tie) 2 were also assessed. Our results showed that BMSCs-CM treatment significantly improved functional outcomes, decreased BBB leakage and the expression of Ang1 and Tie2 were also changed after BMSCs-CM treatment in type 2 diabetes after stroke. In conclusion, enhanced expression of Ang1 and Tie2 in ischemic brain after BMSCs-CM treatment of stroke may contribute to the improved functional recovery after stroke in type 2 diabetic rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Involvement of Toll-Like Receptor 2 and Pro-Apoptotic Signaling Pathways in Bone Remodeling in Osteomyelitis

    Directory of Open Access Journals (Sweden)

    Qianbo Chen

    2014-11-01

    Full Text Available Background and Aims: Osteomyelitis is a common manifestation of invasive Staphylococcus aureus infection characterized by bone loss and destruction. We investigated the role of toll-like receptor 2 (TLR2 in bacterial recognition and clearance in response to infection with an osteomyelitis isolate of S. aureus. Methods: Apoptosis was assessed in the osteoblastic cell line MC3T3-E1 by Annexin V-FITC/PI staining and flow cytometry. The expression of TLR2 and apoptosis-related and mitogen-activated protein kinase pathway proteins was assessed by qRT-PCR and western blotting. Alkaline phosphatase (ALP activity and calcium deposition were assessed by ALP activity assay and Alizarin red staining. Results: S. aureus induced apoptosis, upregulated TLR2 expression, and activated mitogen-activated protein kinase pathways in a time dependent manner. Inhibition of the c-Jun N-terminal kinase (JNK pathway downregulated TLR2 and suppressed the S. aureus induced activation of pro-apoptotic pathways. Short-hairpin RNA mediated silencing of TLR2 reversed S. aureus induced apoptosis and decrease in ALP activity and calcium deposition, and inhibition of JNK had a similar effect. Conclusion: We showed that osteoblast apoptosis and osteogenic differentiation in response to bacterial invasion are dependent on TLR2 expression and JNK activation, suggesting novel potential therapeutic targets for the treatment of osteomyelitis.

  3. Simulations of trabecular remodeling and fatigue: is remodeling helpful or harmful?

    Science.gov (United States)

    van Oers, René F M; van Rietbergen, Bert; Ito, Keita; Huiskes, Rik; Hilbers, Peter A J

    2011-05-01

    Microdamage-targeted resorption is paradoxal, because it entails the removal of bone from a region that was already overloaded. Under continued intense loading, resorption spaces could potentially cause more damage than they remove. To investigate this problem, we incorporated damage algorithms in a computer-simulation model for trabecular remodeling. We simulated damage accumulation and bone remodeling in a trabecular architecture, for two fatigue regimens, a 'moderate' regimen, and an 'intense' regimen with a higher number of loading cycles per day. Both simulations were also performed without bone remodeling to investigate if remodeling removed or exacerbated the damage. We found that remodeling tends to remove damage under the 'moderate' fatigue regimen, but it exacerbates damage under the 'intense' regimen. This harmful effect of remodeling may play a role in the development of stress fractures.

  4. Effects of implant surface coatings and composition on bone integration: a systematic review

    NARCIS (Netherlands)

    Junker, R.; Dimakis, A.; Thoneick, M.; Jansen, J.A.

    2009-01-01

    OBJECTIVE: The aim of the present review was to evaluate the bone integration efficacy of recently developed and marketed oral implants as well as experimental surface alterations. MATERIALS AND METHODS: A PubMed search was performed for animal studies, human reports and studies presenting bone-to-i

  5. In vivo bone remodeling rates determination and compressive stiffness variations before, during 60 days bed rest and two years follow up: A micro-FE-analysis from HR-pQCT measurements of the berlin Bed Rest Study-2

    Science.gov (United States)

    Ritter, Zully; Belavy, Daniel; Baumann, Wolfgang W.; Felsenberg, Dieter

    2017-03-01

    Bed rest studies are used for simulation and study of physiological changes as observed in unloading/non-gravity environments. Amongst others, bone mass reduction, similar as occurring due to aging osteoporosis, combined with bio-fluids redistribution and muscle atrophy have been observed and analyzed. Advanced radiological methods of high resolution such as HR-pQCT (XtremeCT) allow 3D-visualizing in vivo bone remodeling processes occurring during absence/reduction of mechanical stimuli (0 to <1 g) as simulated by bed rest. Induced bone micro-structure (e.g. trabecular number, cortical thickness, porosity) and density variations can be quantified. However, these parameters are average values of each sample and important information regarding bone mass distribution and within bone mechanical behaviour is lost. Finite element models with hexa-elements of identical size as the HR-pQCT measurements (0.082 mm×0.082 mm×0.082 mm, ca. 7E6 elements/sample) can be used for subject-specific in vivo stiffness calculation. This technique also allows quantifying if bone microstructural changes represent a risk of mechanical bone collapse (fracture).

  6. 正畸力作用下垂直型骨吸收牙周炎大鼠牙槽骨改建的实验研究%Periodontitis with vertical bone resorption under orthodontic force bone remodeling in rats

    Institute of Scientific and Technical Information of China (English)

    姚霜; 刘晓君; 周治; 杨鸘; 季娟娟; 沈勇

    2016-01-01

    目的:观察正畸力作用下牙周炎大鼠垂直吸收的牙槽骨改建,为牙周炎的临床正畸治疗提供依据。方法:将75只10周龄雄性SD大鼠,随机分为3组,正常加力对照组( A)、牙周炎垂直骨吸收对照组( B)、牙周炎垂直骨吸收加力实验组( C),每组各25只,各组动物分别于加力后8 h,1、7、14、21 d处死,取动物模型上颌左侧第一磨牙近中牙槽骨进行组织学及免疫学检测,所得结果进行对比研究。结果:正畸加力至7d时,实验组大鼠垂直吸收侧牙周膜纤维排列紊乱,出现无细胞结构,结缔组织可见少量炎症细胞,牙槽骨表面还可见功能活跃的多核破骨细胞,与对照组相比较无显著差异,实验组大鼠牙周组织中IGF⁃1表达达到峰值,光密度值最高,与对照组比较有显著差异( P<0.05);加力至14 d时,实验组大鼠垂直吸收侧牙周组织中RUNX2的表达达到峰值,其光密度值最高,明显高于正常加力对照组,其变化有统计学意义(P<0.05)。结论:控制牙周炎症和消除咬合创伤后,正畸力能刺激牙周炎大鼠垂直缺损牙槽骨区域的RUNX2和IGF⁃1的表达增强,合成骨胶原和骨基质的能力增强,从而促进牙槽骨的改建。%Objective:To observe the remodeling of alveolar bone in rats with the vertical absorption after loading orthodontic force, and to provide evidence for clinical orthodontic treatment. Methods:75 SD rats ( 10⁃week⁃old ,male) were randomly divided into three groups(25 in each group):loading force control group (A), control group of periodontitis with vertical bone absorption (B), loading force group to periodontitis with vertical bone absorption (C). With loading force on for 8 hours, 1d,7d, 14d and 21d,the alveolar bone of the first molar of left maxillary were taken to do the histological and immunological detection. Results:On the 7th day, the de

  7. 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...... of aged bones....

  8. 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

  9. Reperfusion Therapy in Integrative Medicine:the Most Basic Treatment for Preventing Ventricular Remodeling in Post-myocardial Infarction Patients

    Institute of Scientific and Technical Information of China (English)

    WANG Shuo-ren

    2007-01-01

    @@ Acute myocardial infarction (AMI) is the severest pathological basis of ventricular remodeling (VR) in coronary heart disease(CHD).VR is a process of ventricular changes in size,shape,and tissue structure caused by increasing of myocardial load or myocardial damage,including myocardial infarction,poisoning,inflammation,and metabolist abnormality.

  10. Androgens and bone.

    Science.gov (United States)

    Vanderschueren, Dirk; Vandenput, Liesbeth; Boonen, Steven; Lindberg, Marie K; Bouillon, Roger; Ohlsson, Claes

    2004-06-01

    Loss of estrogens or androgens increases the rate of bone remodeling by removing restraining effects on osteoblastogenesis and osteoclastogenesis, and also causes a focal imbalance between resorption and formation by prolonging the lifespan of osteoclasts and shortening the lifespan of osteoblasts. Conversely, androgens, as well as estrogens, maintain cancellous bone mass and integrity, regardless of age or sex. Although androgens, via the androgen receptor (AR), and estrogens, via the estrogen receptors (ERs), can exert these effects, their relative contribution remains uncertain. Recent studies suggest that androgen action on cancellous bone depends on (local) aromatization of androgens into estrogens. However, at least in rodents, androgen action on cancellous bone can be directly mediated via AR activation, even in the absence of ERs. Androgens also increase cortical bone size via stimulation of both longitudinal and radial growth. First, androgens, like estrogens, have a biphasic effect on endochondral bone formation: at the start of puberty, sex steroids stimulate endochondral bone formation, whereas they induce epiphyseal closure at the end of puberty. Androgen action on the growth plate is, however, clearly mediated via aromatization in estrogens and interaction with ERalpha. Androgens increase radial growth, whereas estrogens decrease periosteal bone formation. This effect of androgens may be important because bone strength in males seems to be determined by relatively higher periosteal bone formation and, therefore, greater bone dimensions, relative to muscle mass at older age. Experiments in mice again suggest that both the AR and ERalpha pathways are involved in androgen action on radial bone growth. ERbeta may mediate growth-limiting effects of estrogens in the female but does not seem to be involved in the regulation of bone size in males. In conclusion, androgens may protect men against osteoporosis via maintenance of cancellous bone mass and

  11. Mice lacking AMP-activated protein kinase α1 catalytic subunit have increased bone remodelling and modified skeletal responses to hormonal challenges induced by ovariectomy and intermittent PTH treatment

    Science.gov (United States)

    Jeyabalan, J; Shah, M; Viollet, B; Roux, J P; Chavassieux, P; Korbonits, M; Chenu, C

    2012-01-01

    AMP-activated protein kinase (AMPK) is a key regulator of cellular and body energy homeostasis. We previously demonstrated that AMPK activation in osteoblasts increases in vitro bone formation while deletion of the Ampkα1 (Prkaa1) subunit, the dominant catalytic subunit expressed in bone, leads to decreased bone mass in vivo. To investigate the cause of low bone mass in the Ampkα1−/− mice, we analysed bone formation and resorption in the tibia of these mice by dynamic histomorphometry and determined whether bone turnover can be stimulated in the absence of the Ampkα1 subunit. We subjected 12-week-old Ampkα1+/+ and Ampkα1−/− mice to ovariectomy (OVX), intermittent PTH (iPTH) administration (80 μg/kg per day, 5 days/week) or both OVX and iPTH hormonal challenges. Tibiae were harvested from these mice and bone micro-architecture was determined by micro-computed tomography. We show for the first time that Ampkα1−/− mice have a high bone turnover at the basal level in favour of bone resorption. While both Ampkα1+/+ and Ampkα1−/− mice lost bone mass after OVX, the bone loss in Ampkα1−/− mice was lower compared with controls. iPTH increased trabecular and cortical bone indexes in both ovariectomised Ampkα1+/+ and Ampkα1−/− mice. However, ovariectomised Ampkα1−/− mice showed a smaller increase in bone parameters in response to iPTH compared with Ampkα1+/+ mice. By contrast, non-ovariectomised Ampkα1−/− mice responded better to iPTH treatment than non-ovariectomised Ampkα1+/+ mice. Overall, these data demonstrate that Ampkα1−/− mice are less affected by changes in bone turnover induced by OVX but respond better to the anabolic challenge induced by iPTH. These results suggest that AMPKα1 activation may play a role in the hormonal regulation of bone remodelling. PMID:22700192

  12. Chromatin remodeling pathways in smooth muscle cell differentiation, and evidence for an integral role for p300.

    Directory of Open Access Journals (Sweden)

    Joshua M Spin

    Full Text Available BACKGROUND: Phenotypic alteration of vascular smooth muscle cells (SMC in response to injury or inflammation is an essential component of vascular disease. Evidence suggests that this process is dependent on epigenetic regulatory processes. P300, a histone acetyltransferase (HAT, activates crucial muscle-specific promoters in terminal (non-SMC myocyte differentiation, and may be essential to SMC modulation as well. RESULTS: We performed a subanalysis examining transcriptional time-course microarray data obtained using the A404 model of SMC differentiation. Numerous chromatin remodeling genes (up to 62% of such genes on our array platform showed significant regulation during differentiation. Members of several chromatin-remodeling families demonstrated involvement, including factors instrumental in histone modification, chromatin assembly-disassembly and DNA silencing, suggesting complex, multi-level systemic epigenetic regulation. Further, trichostatin A, a histone deacetylase inhibitor, accelerated expression of SMC differentiation markers in this model. Ontology analysis indicated a high degree of p300 involvement in SMC differentiation, with 60.7% of the known p300 interactome showing significant expression changes. Knockdown of p300 expression accelerated SMC differentiation in A404 cells and human SMCs, while inhibition of p300 HAT activity blunted SMC differentiation. The results suggest a central but complex role for p300 in SMC phenotypic modulation. CONCLUSIONS: Our results support the hypothesis that chromatin remodeling is important for SMC phenotypic switching, and detail wide-ranging involvement of several epigenetic modification families. Additionally, the transcriptional coactivator p300 may be partially degraded during SMC differentiation, leaving an activated subpopulation with increased HAT activity and SMC differentiation-gene specificity.

  13. Minimizing Surface Exposure to Climate Extremity in Coastal Megacities by Structure Remodelling using Integral Geographic Information System: Lessons from Greater Mumbai Metropolitan

    Science.gov (United States)

    Tiwari, A.

    2016-12-01

    Coastal metropolitans in South Asia represent the most densely populated and congested urban spaces ranking among the largest urban settlements of the planet. These megacities are characterized by inadequate infrastructure, lack of mitigation tools, and weak resilience of urban ecosystems. Additionally, climate change has increased vulnerability of poor and marginalized population living in rapidly growing coastal megacities to increased frequency, severity and intensity of extreme weather events. This has adversely affected local counter strategies and adaptation tools, transforming such events into hazards with the inability to respond and mitigate. Study aimed to develop a participatory framework for risk reduction in Greater Mumbai Metropolitan by Structure Remodeling (SR) in integral GIS. Research utilized terrain analysis tools and vulnerability mapping, and identified risk susceptible fabric and checked its scope for SR without: 1.adding to its (often) complex fragmentation, and 2.without interference with the ecosystem services accommodated by it. Surfaces available included paved ground, streetscapes commercial facades, rooftops,public spaces, open as well as dark spaces. Remodeling altered certain characteristics in the intrinsic or extrinsic cross-section profile or in both (if suitable) with infrastructure measures (grey, green, blue) that collectively involved ecosystem services and maintained natural hydrological connection. This method fairly reduced exposure of vulnerable surface and minimized risk to achieve extremity-neutral state. Harmonizing with public perception and incorporating priorities of local authorities, the method is significant as it rises above the fundamental challenges arising during management of (often) conflicting perspectives and interests of multiplicity of stakeholders involved at various levels in urban climate governance while ensuring inclusive solutions with reduced vulnerability and increased resilience. Additionally

  14. What causes bone loss?

    Science.gov (United States)

    ... bone biology. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology . 13th ed. Philadelphia, PA: Elsevier; 2016:chap 29. Maes C, Kronenberg HM. Bone development and remodeling. In: Jameson JL, ...

  15. 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.

  16. Metabolic remodeling in moderate synchronous versus dyssynchronous pacing-induced heart failure: integrated metabolomics and proteomics study.

    Directory of Open Access Journals (Sweden)

    Junko Shibayama

    Full Text Available Heart failure (HF is accompanied by complex alterations in myocardial energy metabolism. Up to 40% of HF patients have dyssynchronous ventricular contraction, which is an independent indicator of mortality. We hypothesized that electromechanical dyssynchrony significantly affects metabolic remodeling in the course of HF. We used a canine model of tachypacing-induced HF. Animals were paced at 200 bpm for 6 weeks either in the right atrium (synchronous HF, SHF or in the right ventricle (dyssynchronous HF, DHF. We collected biopsies from left ventricular apex and performed comprehensive metabolic pathway analysis using multi-platform metabolomics (GC/MS; MS/MS; HPLC and LC-MS/MS label-free proteomics. We found important differences in metabolic remodeling between SHF and DHF. As compared to Control, ATP, phosphocreatine (PCr, creatine, and PCr/ATP (prognostic indicator of mortality in HF patients were all significantly reduced in DHF, but not SHF. In addition, the myocardial levels of carnitine (mitochondrial fatty acid carrier and fatty acids (12:0, 14:0 were significantly reduced in DHF, but not SHF. Carnitine parmitoyltransferase I, a key regulatory enzyme of fatty acid ß-oxidation, was significantly upregulated in SHF but was not different in DHF, as compared to Control. Both SHF and DHF exhibited a reduction, but to a different degree, in creatine and the intermediates of glycolysis and the TCA cycle. In contrast to this, the enzymes of creatine kinase shuttle were upregulated, and the enzymes of glycolysis and the TCA cycle were predominantly upregulated or unchanged in both SHF and DHF. These data suggest a systemic mismatch between substrate supply and demand in pacing-induced HF. The energy deficit observed in DHF, but not in SHF, may be associated with a critical decrease in fatty acid delivery to the ß-oxidation pipeline, primarily due to a reduction in myocardial carnitine content.

  17. 雌激素对正畸骨改建相关细胞因子的影响%Effects of estrogen on cytokines related to bone remodeling in orthodontic treatment

    Institute of Scientific and Technical Information of China (English)

    朱倩; 蔡萍

    2014-01-01

    Decreased bone density and osteoporosis are not favorable to orthodontic treatment. Estrogen can promote alveolar bone formation and inhibit bone resorption. Estrogen regulates bone remodeling through various cytokines under orthodontic force. First, estrogen can inhibit bone resorption and promote bone restoration by upregulating the expression of osteoprotegerin and downregulating the receptor activator of nuclear factor-κB ligand. Second, estrogen can promote osteoblasts and osteocytes to secrete bone morphogenetic proteins, which accelerate alveolar bone remodeling. In addition, estrogen can control alveolar bone resorptionby significantly inhibiting tumor necrosis factor-α, interleukin-1, and interleukin-6. Estrogen can also inhibit bone resorption by suppressing the expression of interferon-γ. Estrogen deficiency caninduce osteoclastogenesis by increasing the expression of macrophage colony-stimulating factor. Therefore, administration of optimum dosagesof estrogen is necessary in patients with osteoporosis for effective and safe orthodontic treatments.%骨密度降低和骨质疏松不利于正畸治疗的进行,而雌激素可促进牙槽骨形成,抑制骨吸收。在正畸矫治力作用下,多种细胞因子参与雌激素对正畸骨的改建。首先,雌激素可以通过上调骨保护蛋白和下调核因子-κB受体活化因子配体的表达来抑制骨吸收,促进骨形成;其次,雌激素也可以通过促进成骨细胞和骨细胞分泌骨形态发生蛋白来加快牙槽骨的改建;另外,雌激素可以抑制肿瘤坏死因子α,白细胞介素-1和白细胞介素-6的表达,从而控制骨吸收;雌激素缺乏使巨噬细胞集落刺激因子基因的表达增加从而促进破骨细胞的形成,相反,雌激素可以通过抑制干扰素-γ的表达来抑制骨吸收。由此可见,对于某些骨质疏松患者,为达到有效安全的正畸治疗目的,补充适当剂量的雌激素不失为一种可靠的辅助治疗方法。

  18. Bone Cells Dynamics during Peri-Implantitis: a Theoretical Analysis

    Directory of Open Access Journals (Sweden)

    Maria Helena Fernandes

    2016-09-01

    Full Text Available Objectives: The present manuscript aims a detailed characterization of the bone cells dynamics during physiological bone remodelling and, subsequently, to address the cellular and molecular mechanisms that play a fundamental role in the immune-inflammatory-induced uncoupled bone remodelling observed in peri-implantitis. Results: An intimate relationship between the immune system and bone is acknowledged to be determinant for bone tissue remodelling and integrity. Due to the close interaction of immune and bone cells, the two systems share a number of surface receptors, cytokines, signalling pathways and transcription factors that are involved in mutual regulatory mechanisms. This physiological equilibrium is disturbed in pathological conditions, as verified in peri-implantitis establishment and development. Activation of the innate and adaptive immune response, challenged by the local bacterial infection, induces the synthesis of high levels of a variety of pro- and anti-inflammatory cytokines that disturb the normal functioning of the bone cells, by uncoupling bone resorption and formation, ending up with a net alveolar bone loss and subsequent implant failure. Most data points to an immune-inflammatory induced osteoclast differentiation and function, as the major underlying mechanism to the uncoupled bone resorption to bone formation. Further, the disturbed functioning of osteoblasts, reflected by the possible expression of a fibro-osteoblastic phenotype, may also play a role. Conclusions: Alveolar bone loss is a hallmark of peri-implantitis. A great deal of data is still needed on the cellular and humoral crosstalk in the context of an integrated view of the osteoimmunologic interplay occurring in the peri-implantitis environment subjacent to the bone loss outcome.

  19. 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 impac...

  20. 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.

  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. Role of the cell wall integrity and filamentous growth mitogen-activated protein kinase pathways in cell wall remodeling during filamentous growth.

    Science.gov (United States)

    Birkaya, Barbara; Maddi, Abhiram; Joshi, Jyoti; Free, Stephen J; Cullen, Paul J

    2009-08-01

    Many fungal species including pathogens exhibit filamentous growth (FG) as a means of foraging for nutrients. Genetic screens were performed to identify genes required for FG in the budding yeast Saccharomyces cerevisiae. Genes encoding proteins with established functions in transcriptional activation (MCM1, MATalpha2, PHD1, MSN2, SIR4, and HMS2), cell wall integrity (MPT5, WSC2, and MID2), and cell polarity (BUD5) were identified as potential regulators of FG. The transcription factors MCM1 and MATalpha2 induced invasive growth by promoting diploid-specific bipolar budding in haploid cells. Components of the cell wall integrity pathway including the cell surface proteins Slg1p/Wsc1p, Wsc2p, Mid2p, and the mitogen-activated protein kinase (MAPK) Slt2p/Mpk1p contributed to multiple aspects of the FG response including cell elongation, cell-cell adherence, and agar invasion. Mid2p and Wsc2p stimulated the FG MAPK pathway through the signaling mucin Msb2p and components of the MAPK cascade. The FG pathway contributed to cell wall integrity in parallel with the cell wall integrity pathway and in opposition with the high osmolarity glycerol response pathway. Mass spectrometry approaches identified components of the filamentous cell wall including the mucin-like proteins Msb2p, Flo11p, and subtelomeric (silenced) mucin Flo10p. Secretion of Msb2p, which occurs as part of the maturation of the protein, was inhibited by the ss-1,3-glucan layer of the cell wall, which highlights a new regulatory aspect to cell wall remodeling in this organism. Disruption of ss-1,3-glucan linkages induced mucin shedding and resulted in defects in cell-cell adhesion and invasion of cells into the agar matrix.

  3. Integration of a calcined bovine bone and BMSC-sheet 3D scaffold and the promotion of bone regeneration in large defects.

    Science.gov (United States)

    Liu, Yihan; Ming, Leiguo; Luo, Hailang; Liu, Wenjia; Zhang, Yongjie; Liu, Hongchen; Jin, Yan

    2013-12-01

    Reconstruction of large area bone defect with mechanical integrity to the skeleton is important for patient's rehabilitation. However with the limitation of scaffold material and suitable seed cell sources, the best treating strategy remains to be identified though various tissue engineering methods were reported. In this study, we investigated the feasibility of applying calcined bovine bone (CBB) which was coated by allograft bone marrow mesenchymal stem cells (BMSC)-sheet as a 3D scaffold material in bone repairing tissue engineering. The new scaffold material was implanted into osteoporosis rat cranial bone defects and repairing critical size bone defects (8 mm diameter). Data showed that CBB-BMSC-sheet combination had a stronger potential in osteogenic differentiation and mineralized formation both in vitro and in vivo than CBB-BMSC combination. In in vitro study BMSC-sheet had a more feasible characteristic upon bone repairing including richer ECM, larger mineralized area and stronger ALP activity in addition with a significant higher mRNA expression of osteogenic maker such as BMP-2, b-FGF, Col 1a1, OSX and Runx-2 than the control group. In in vivo study 3D reconstruction of micro CT, HE staining and bone strength results showed that newly formed bone in CBB-BMSC-sheet group was significant higher than that in CBB-BMSC group at 4, 8 and 12 weeks after transplantation in the aspect of area and volume. What was more, results indicated that allograft BMSC-sheet had survivaled in the scaffold material and participated in the newly formed bone which had the same thickness with surrounding autologous bone tissues after transplantation. Results of our study demonstrated that CBB-BMSC-sheet combination was a promising strategy in healing of large area bone defect in osteoporosis.

  4. 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

  5. Dual-energy X-ray absorptiometric densitometry in osteoarthritis of the hip. Influence of secondary bone remodeling of the femoral neck

    Energy Technology Data Exchange (ETDEWEB)

    Preidler, K.W. [Dept. of Radiology, Veterans Administration Medical Center and Univ. of California, San Diego, CA (United States); White, L.S. [Dept. of Radiology, Veterans Administration Medical Center and Univ. of California, San Diego, CA (United States); Tashkin, J. [Dept. of Radiology, Veterans Administration Medical Center and Univ. of California, San Diego, CA (United States); McDaniel, C.O. [Dept. of Radiology, Veterans Administration Medical Center and Univ. of California, San Diego, CA (United States); Brossmann, J. [Dept. of Radiology, Veterans Administration Medical Center and Univ. of California, San Diego, CA (United States); Andresen, R. [Dept. of Radiology, Veterans Administration Medical Center and Univ. of California, San Diego, CA (United States); Sartoris, D. [Dept. of Radiology, Veterans Administration Medical Center and Univ. of California, San Diego, CA (United States)

    1997-07-01

    Purpose: The aim of this study was to evaluate the influence of buttressing on bone densitometry measurements in the femoral neck, in Ward`s triangle, and in the greater trochanter. In addition, we attempted to establish the length of the femoral axis (FAL) and the true length of the femoral neck (FNL) as potential correlates with osteoarthritis (OA) or with buttressing. Material and Methods: Our study comprised 101 hips in 68 adult patients. Conventional radiographs of the hip joints were obtained in order to assess the presence and extent of OA by means of the 6-step grading system introduced in 1990 by CROFT et al., and in order to measure the cortical thickness at the medial aspect of the femoral neck. In addition, FAL and FNL were measured. All patients underwent dual energy X-ray absorptiometry so that bone density could be assessed in the femoral neck, in Ward`s triangle, and in the greater trochanter. The Spearman rank correlation was used to compare the measurements. Results: Statistical analysis showed a significant positive correlation between cortical thickness and bone density in the femoral neck and in Ward`s triangle. No correlation was found between cortical thickness and bone density in the greater trochanter, nor between cortical thickness and OA, FNL, and FAL, nor between OA and bone density, FNL, and FAL. (orig.).

  6. The skeletal subsystem as an integrative physiology paradigm.

    Science.gov (United States)

    Weiss, Aaron J; Iqbal, Jameel; Zaidi, Neeha; Mechanick, Jeffrey I

    2010-12-01

    Homeostatic bone remodeling depends on precise regulation of osteoblast-osteoclast coupling through intricate endocrine, immune, neuronal, and mechanical factors. The osteoblast-osteoclast model of bone physiology with layers of regulatory complexity can be investigated as a component of a local skeletal subsystem or as a part of a complete whole-body system. In this review, we flip the traditional investigative paradigm of scientific experimentation ("bottom-top research") to a "top-bottom" approach using systems biology. We first establish the intricacies of the two-cell model at the molecular signaling level. We then provide, on a systems level, an integrative physiologic approach involving many recognized organ-level subsystems having direct and/or indirect effects on bone remodeling. Lastly, a hypothetical model of bone remodeling based on frequency and amplitude regulatory mechanisms is presented. It is hoped that by providing a thorough model of skeletal homeostasis, future progress can be made in researching and treating skeletal morbidities.

  7. Bone metastasis versus bone marrow metastasis? Integration of diagnosis by 18F-fluorodeoxyglucose positron emission/computed tomography in advanced malignancy with super bone scan: Two case reports and literature review

    Directory of Open Access Journals (Sweden)

    Chia-Yang Lin

    2013-04-01

    Full Text Available Super scan pattern on technetium-99m methyldiphosphonate (Tc-99m MDP bone scintigraphy is a special condition of extremely high bone uptake relative to soft tissue with absent or faint renal radioactivity visualization, which is usually seen in diffuse bone metastases or discrete endocrine entities. Here, two cases with super bone scan are presented. One was a young man diagnosed with gastric cancer. The other was a middle-aged woman with a history of breast cancer with recent recurrence. Both cases had 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT diagnosis simultaneously. Based on imaging of 18F-FDG PET/CT, diffusely incremental 18F-FDG avidity in spine/pelvis on PET and subtle erosion of cortical bone on CT were seen. The cytological results of bone marrow biopsy showed evidence of malignant metastasis. However, there were several focal discrepant findings between the 18F-FDG PET/CT and Tc-99m MDP bone scan. According to integration of both imaging findings and the result of bone marrow biopsy, we believe that the disseminated malignant spread in bone marrow is a primitive alternation in the super bone scan and that it is also as a result of neoplasm-related endocrine factors.

  8. Development of an enzyme-linked immunosorbent assay for detection of chicken osteocalcin and its use in evaluation of perch effects on bone remodeling in caged White Leghorns

    Science.gov (United States)

    Osteocalcin (OC) is a sensitive biochemical marker for evaluating bone turnover in mammals. The role of avian OC is less clear because of a need for a chicken assay. Our objectives were to develop an assay using indirect competitive ELISA for detecting chicken serum OC and use the assay to examine t...

  9. Skeletal Complications in Neurofibromatosis Type 1: the Role of Neurofibromin Haploinsufficiency in Defective Skeletal Remodeling and Bone Healing in NF1

    Science.gov (United States)

    2009-01-01

    nutritional basis for congenital skeletal dysplasiae . Cell Metab 4:441-451. 3. Aliprantis, A.O., Walsh, N.C., McHugh, K.P., Gravallese, E., and Glimcher...proportion of patients with Neurofibromatosis Type 1 display skeletal abnormalities including scoliosis, pseudoarthrosis, and sphenoid bone dysplasia

  10. The Role of Osteocyte-related Factors in the Bone Remodeling%骨细胞相关因子在骨重建中的作用

    Institute of Scientific and Technical Information of China (English)

    安敏; 安荣泽; 王兆杰; 赵俊延

    2015-01-01

    骨细胞是一种动态的、具有复杂功能的细胞,也是骨组织中含量最丰富、分布最广泛的细胞。近几年研究发现,骨细胞在骨重建中的调节作用越来越明显,其分泌的骨硬化蛋白、RANKL及OPG是调节骨形成和骨吸收的重要调控因子。骨细胞特异性地分泌的骨硬化蛋白对骨形成具有特殊的抑制效果,主要机制是结合LRP5/LRP6,从而阻止经典Wnt信号通路。而骨硬化蛋白的单克隆抗体则通过拮抗其作用而保证Wnt信号通路的正常传导,引起骨形成、骨密度和骨强度增加。骨细胞同样会分泌RANKL及OPG,两者在生理和病理条件下直接或间接调节破骨细胞分化和功能,调控骨重吸收。该文就这一领域近年研究现状和发展方向作一综述。%As the most abundant and the most widely distributed in bone tissue, osteocytes are dynamic cells, with complex function. Recent studies have revealed that osteocytes play multiple important physiological roles, secreting many regulatory factors, such as osteosclerosis protein, receptor activator of the NF-kB ligand (RANKL) and osteoprotegerin (OPG). These factors play important roles in regulating bone formation and bone resorption. The sclerostin, is expressed at significant levels by osteocytes, interacts with Lrp5 and Lrp6 and inhibits the canonical Wnt signaling pathway. Sclerostin monoclonal antibody ensures Wnt pathway conducting normally by inhibiting sclerostin, increasing bone formation, bone mineral density and bone strength. Osteocytes also secretes RANKL and OPG, both of which regulating differentiation and function of osteoclasts directly or indirectly, in Physiological and pathological conditions, regulating bone reabsorption. In this paper, we make a review about the research status and development direction.

  11. The Bone Dysplasia Ontology: integrating genotype and phenotype information in the skeletal dysplasia domain.

    Science.gov (United States)

    Groza, Tudor; Hunter, Jane; Zankl, Andreas

    2012-03-26

    Skeletal dysplasias are a rare and heterogeneous group of genetic disorders affecting skeletal development. Patients with skeletal dysplasias suffer from many complex medical issues including degenerative joint disease and neurological complications. Because the data and expertise associated with this field is both sparse and disparate, significant benefits will potentially accrue from the availability of an ontology that provides a shared conceptualisation of the domain knowledge and enables data integration, cross-referencing and advanced reasoning across the relevant but distributed data sources. We introduce the design considerations and implementation details of the Bone Dysplasia Ontology. We also describe the different components of the ontology, including a comprehensive and formal representation of the skeletal dysplasia domain as well as the related genotypes and phenotypes. We then briefly describe SKELETOME, a community-driven knowledge curation platform that is underpinned by the Bone Dysplasia Ontology. SKELETOME enables domain experts to use, refine and extend and apply the ontology without any prior ontology engineering experience--to advance the body of knowledge in the skeletal dysplasia field. The Bone Dysplasia Ontology represents the most comprehensive structured knowledge source for the skeletal dysplasias domain. It provides the means for integrating and annotating clinical and research data, not only at the generic domain knowledge level, but also at the level of individual patient case studies. It enables links between individual cases and publicly available genotype and phenotype resources based on a community-driven curation process that ensures a shared conceptualisation of the domain knowledge and its continuous incremental evolution.

  12. The bone integration effects of platelet-rich fibrin by removal torque of titanium screw in rabbit tibia.

    Science.gov (United States)

    Cho, Sung-Am; Lee, Byung-Kil; Park, Sang-Hun; Ahn, Jae-Jin

    2014-01-01

    Platelet-rich fibrin (PRF) is nowadays often used in various fields, but no removal torque studies have yet been done to evaluate the effects of the platelet-rich fibrin on the bone integration at the initial healing period. An experimental study have been performed in rabbits to evaluate whether the complete PRF clots can accelerate the bone integration of implants at the initial healing period after creating bone defects in tibias. The effect of the complete PRF clots on bone integration was studied in two rabbit groups, 4-week group (group A) and 6-week group (group B) after preparing bony defects. Artificial bony defects were prepared in the tibias of rabbits. The complete PRF clots was applied to the defects in the experimental group, whereas the defects were unfilled in the control group. Four weeks later, machined implants were installed into the rabbit tibias (group A). Six weeks after installation, the removal torque from nine rabbits was measured to examine the bone healing effect of PRF. In another rabbits (group B), 6 weeks after preparing bony defects, installation was performed, and another 6 weeks after installation, the removal torque from nine rabbits was measured. The authors found a positive significant effect of the complete PRF clots on bone integration (higher bone density) in group A installed at 4 weeks after preparing bony defects (p = 0.008; t-test), but not in group B installed at 6 weeks after preparing bony defects (p = 0.677).

  13. Bone integration capability of nanopolymorphic crystalline hydroxyapatite coated on titanium implants

    Directory of Open Access Journals (Sweden)

    Suzuki T

    2012-02-01

    Full Text Available Masahiro Yamada*, Takeshi Ueno*, Naoki Tsukimura, Takayuki Ikeda, Kaori Nakagawa, Norio Hori, Takeo Suzuki, Takahiro OgawaLaboratory of Bone and Implant Sciences, The Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, UCLA School of Dentistry, Los Angeles, CA, USA *These authors contributed equally to this workAbstract: The mechanism by which hydroxyapatite (HA-coated titanium promotes bone–implant integration is largely unknown. Furthermore, refining the fabrication of nanostructured HA to the level applicable to the mass production process for titanium implants is challenging. This study reports successful creation of nanopolymorphic crystalline HA on microroughened titanium surfaces using a combination of flame spray and low-temperature calcination and tests its biological capability to enhance bone–implant integration. Sandblasted microroughened titanium implants and sandblasted + HA-coated titanium implants were subjected to biomechanical and histomorphometric analyses in a rat model. The HA was 55% crystallized and consisted of nanoscale needle-like architectures developed in various diameters, lengths, and orientations, which resulted in a 70% increase in surface area compared to noncoated microroughened surfaces. The HA was free from impurity contaminants, with a calcium/phosphorus ratio of 1.66 being equivalent to that of stoichiometric HA. As compared to microroughened implants, HA-coated implants increased the strength of bone–implant integration consistently at both early and late stages of healing. HA-coated implants showed an increased percentage of bone–implant contact and bone volume within 50 µm proximity of the implant surface, as well as a remarkably reduced percentage of soft tissue intervention between bone and the implant surface. In contrast, bone volume outside the 50 µm border was lower around HA-coated implants. Thus, this study

  14. Effect of Ovariectomy on Stimulating Intracortical Remodeling in Rats

    Directory of Open Access Journals (Sweden)

    Chun Lei Li

    2014-01-01

    Full Text Available Objective. Technically primates and dogs represent ideal models to investigate diseases characterized by abnormal intracortical remodeling. High expenses and ethical issues, however, restrict the use of those animals in research. Rodent models have been used as alternatives instead, but their value is limited, if none, because these animals lack intracortical bone remodeling. This study aimed at investigating the effect of ovariectomy onto the stimulation of intracortical remodeling in rat mandibles. Materials and Methods. Sixteen 12-week-old Spraque-Dawly (SD female rats were randomly assigned into two groups, receiving either ovariectomy or sham operation. All the rats were sacrificed 18 weeks postoperatively. The entire mandibles were harvested for microcomputed tomography (micro-CT and histomorphometric assessments. Results. Micro-CT examination showed significantly decreased bone mineral density (0.95 ± 0.01 versus 1.01 ± 0.02 g/cm3, P<0.001 and bone volume (65.78 ± 5.45 versus 87.41 ± 4.12%, P<0.001 in ovariectomy group. Histomorphometric assessment detected a sixfold increased intracortical bone remodeling as well as an increased bone modeling in mandibles of ovariectomized rats. Conclusion. For the first time, to the authors’ knowledge, it was detected that ovariectomy stimulates intracortical remodeling in rat mandibles. This animal model might be of use to study various bone diseases associated with an abnormal intracortical remodeling process.

  15. Paget’s Disease of Bone Presented as Normal Pressure Hydrocephalus: A Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Abbas Tafakhori

    2012-07-01

    Full Text Available Background: Paget’s disease is a focal bone disorder manifested as bone overgrowth and disrupted bone integrity as a result of accelerated bone remodelling rate. Rarely, Paget’s disease of the base of the skull results in hydrocephalic dementia, and the triad of normal pressure hydrocephalus syndrome is a much more scarce entity.Case Report: Herein, we report an elderly woman who presented in Imam Khomeini Hospital, Tehran, Iran, with normal pressure hydrocephalus syndrome due to Paget’s bone disease. Furthermore, we have reviewed relevant previous studiesConclusion: Paget’s disease can be presented as normal pressure hydrocephalus syndrome

  16. Growth Hormone Protects Against Ovariectomy-Induced Bone Loss in States of Low Circulating Insulin-like Growth Factor (IGF-1)*

    OpenAIRE

    Fritton, J. Christopher; Emerton, Kelly B; SUN, HUI; Kawashima, Yuki; Mejia, Wilson; Wu, Yingjie; Rosen, Clifford J.; Panus, David; Bouxsein, Mary; Majeska, Robert J.; Schaffler, Mitchell B.; Yakar, Shoshana

    2009-01-01

    Early after estrogen loss in postmenopausal women and ovariectomy (OVX) of animals, accelerated endosteal bone resorption leads to marrow expansion of long bone shafts that reduce mechanical integrity. Both growth hormone (GH) and insulin-like growth factor (IGF-1) are potent regulators of bone remodeling processes. To investigate the role of the GH/IGF-1 axis with estrogen deficiency, we used the liver IGF-1-deficient (LID) mouse. Contrary to deficits in controls, OVX of LID mice resulted in...

  17. Effects of zinc-substituted nano-hydroxyapatite coatings on bone integration with implant surfaces

    Institute of Scientific and Technical Information of China (English)

    Shi-fang ZHAO; Wen-jing DONG; Qiao-hong JIANG; Fu-ming HE; Xiao-xiang WANG; Guo-li YANG

    2013-01-01

    Objective:The purpose of this study was to investigate the effects of a zinc-substituted nano-hydroxyapatite (Zn-HA) coating,applied by an electrochemical process,on implant osseointegraton in a rabbit model.Methods:A Zn-HA coating or an HA coating was deposited using an electrochemical process.Surface morphology was examined using field-emission scanning electron microscopy.The crystal structure and chemical composition of the coatings were examined using an X-ray diffractometer (XRD) and Fourier transform infrared spectroscopy (FTIR).A total of 78 implants were inserted into femurs and tibias of rabbits.After two,four,and eight weeks,femurs and tibias were retrieved and prepared for histomorphometric evaluation and removal torque (RTQ) tests.Results:Rod-like HA crystals appeared on both implant surfaces.The dimensions of the Zn-HA crystals seemed to be smaller than those of HA.XRD patterns showed that the peaks of both coatings matched well with standard HA patterns.FTIR spectra showed that both coatings consisted of HA crystals.The Zn-HA coating significantly improved the bone area within all threads after four and eight weeks (P<0.05),the bone to implant contact (BIC) at four weeks (P<0.05),and RTQ values after four and eight weeks (P<0.05).Conclusions:The study showed that an electrochemically deposited Zn-HA coating has potential for improving bone integration with an implant surface.

  18. Mechanotransduction by bone cells in vitro: mechanobiology of bone tissue

    NARCIS (Netherlands)

    Mullender, M.; El Haj, A.J.; Yang, Y.; van Duin, M.A.; Burger, E.H.; Klein-Nulend, J.

    2004-01-01

    Mechanical force plays an important role in the regulation of bone remodelling in intact bone and bone repair. In vitro, bone cells demonstrate a high responsiveness to mechanical stimuli. Much debate exists regarding the critical components in the load profile and whether different components, such

  19. 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.

  20. Clinical study of thoracic bone remodeling with time length after minimal- invasive repair for pectus excavatum%微创矫治漏斗胸后时间延展胸廓骨重塑的临床研究

    Institute of Scientific and Technical Information of China (English)

    刘吉福; 叶金铎; 徐波; 王树寿; 武珊珊

    2011-01-01

    Objective To study the length of time and clinic effect of thoracic bone self remodeling after minimal-invasive correction for pectus excavatum(PE). Methods A total of 34 patients were enrolled, male 27 and female 7, aged 11 - 39 years old, mean age 18.1 years old. Patients were assigned into 2 groups. Group 1 was older children group which included 13 cases aged 11-17 years old, 9 with symmetry PE(type Ⅰ) and 4 with non-symmetry(type Ⅱ); the Haller index(Hl) were 3.2 - 4.6. Group 2 was adults group included 21 cases aged 18 - 39 years old, 10 with symmetry PE(type Ⅰ) and 11 with non-symmetry(type Ⅱ); HI were 3.2 - 5.7. Under general anesthesia, two incisions were made on both sides of the midaxillary line. Guided by the introducer and video-assistant thoracoscopic monitor, the substemal tunnel was then created and the depressed sternum was elevated, the thoracic bone remodeling was made by inserting the bar into retrosternumand rotated its convex forward. Single-bar was inserted for 10 and 12 patients in group 1 and 2, respectively; Double-bar was used for 3 and 9 patients in group 1 and 2, respectively. All patients were checked using chest CT scan and 3D reconstruction pre-operatively and on 7" and 90" day after operation. The sagittal view of the center line of thoracic vertebral body and the distance between sternum and frontal edge of thoracic vertebral body were measured. The position of heart and thorax shape were observed. Results Patients' results at pre- and 7-day of post-correction were compared. Among all patients treated with single-bar, the lower sternum moved forward, but manubrium and the upper sternum moved backwards from the central line. The results at 90-day post-correction showed that the manubrium and midsternum remained forward along the horary extension among patients who had double-bar treatment, the sternum moved forward persistently at 7-day and 90-day post-correction. The cardiac positions and chest shapes of 34 patients

  1. Engineering vascularized bone grafts by integrating a biomimetic periosteum and β-TCP scaffold.

    Science.gov (United States)

    Kang, Yunqing; Ren, Liling; Yang, Yunzhi

    2014-06-25

    Treatment of large bone defects using synthetic scaffolds remain a challenge mainly due to insufficient vascularization. This study is to engineer a vascularized bone graft by integrating a vascularized biomimetic cell-sheet-engineered periosteum (CSEP) and a biodegradable macroporous beta-tricalcium phosphate (β-TCP) scaffold. We first cultured human mesenchymal stem cells (hMSCs) to form cell sheet and human umbilical vascular endothelial cells (HUVECs) were then seeded on the undifferentiated hMSCs sheet to form vascularized cell sheet for mimicking the fibrous layer of native periosteum. A mineralized hMSCs sheet was cultured to mimic the cambium layer of native periosteum. This mineralized hMSCs sheet was first wrapped onto a cylindrical β-TCP scaffold followed by wrapping the vascularized HUVEC/hMSC sheet, thus generating a biomimetic CSEP on the β-TCP scaffold. A nonperiosteum structural cell sheets-covered β-TCP and plain β-TCP were used as controls. In vitro studies indicate that the undifferentiated hMSCs sheet facilitated HUVECs to form rich capillary-like networks. In vivo studies indicate that the biomimetic CSEP enhanced angiogenesis and functional anastomosis between the in vitro preformed human capillary networks and the mouse host vasculature. MicroCT analysis and osteocalcin staining show that the biomimetic CSEP/β-TCP graft formed more bone matrix compared to the other groups. These results suggest that the CSEP that mimics the cellular components and spatial configuration of periosteum plays a critical role in vascularization and osteogenesis. Our studies suggest that a biomimetic periosteum-covered β-TCP graft is a promising approach for bone regeneration.

  2. Effect of calcium citrate on bone integration in a rabbit femur defect model

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Peng-Fei Nie; Xiu-Cui Li; Ferdinand An Rompis; Hang Huang; Hua Zhang; Zhong-Lin Mu; Lei Peng; Wei Wang; Qing-Yu Chen; Zhong-Qin Lin; Shao-Wen Cheng; Dong-Quan Kou; Xiao-Zhou Ying; Yue Shen; Xiao-Jie Cheng

    2012-01-01

    ABSTRACT Objective:To explore effect of calcium citrate on bone integration in a rabbit femur defect model, and to compare the bone formation with different sizes by radiological and histological study. Methods:Twenty-four male Japanese white rabbits were randomly divided into three groups (GroupA, B, C) in this study. Under anesthesia, defects of four sizes (1.2, 1.5, 2.0 and2.5 mm) were created in each of the rabbits. Commercially pure calcium citrate powder was placed inside the medullary compartment of the femur (Experimental), while in the contralateral femur (Control) nothing was implanted. The defects were analyzed using radiography and histological analysis by using Imagepro-Plus6.0 software after animal was sacrificed at 4th(GroupA), 6th(GroupB) and8th(GroupC) weeks postoperatively. Four samples were analyzed for each size of defect and each healing period.Results:The histological and the radiologic evaluation were performed after sacrification of all rabbits on postoperative4th and6th weeks, It showed significant difference between the experimental group and the control group when these defects were less than or equal to2.0 mm. No statistical difference was observed when these defects were larger than2.0 mm at all healing periods except at the4th week.Conclusions: Calcium citrate affects the early periods of bone defects healing mechanism in Japanese white rabbits positively, especially when the defect is not too large. We suggest further studies on calcium citrate to determine the effects of various dosages, administration ways and the experimental time on the bone defects.

  3. Predictive value of [{sup 18}F]-fluoride PET for monitoring bone remodeling in patients with orthopedic conditions treated with a Taylor spatial frame

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    Sanchez-Crespo, Alejandro [Karolinska University Hospital, Department of Hospital Physics, Nuclear Medicine, Stockholm (Sweden); Karolinska University Hospital, Stockholm (Sweden); Christiansson, Frederik [Nykoepings Hospital, Department of Radiology, Nykoeping (Sweden); Karlsson Thur, Charlotte; Lundblad, Henrik [Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm (Sweden); Sundin, Anders [Uppsala University Hospital, Department of Radiology and Molecular Imaging, Uppsala (Sweden)

    2017-03-15

    The Taylor Spatial Frame (TSF) is used to correct orthopedic conditions such as correction osteotomies in delayed fracture healing and pseudarthrosis. Long-term TSF-treatments are common and may lead to complications. Current conventional radiological methods are often unsatisfactory for therapy monitoring. Hence, an imaging technique capable of quantifying bone healing progression would be advantageous. A cohort of 24 patients with different orthopedic conditions, pseudarthrosis (n = 10), deformities subjected to correction osteotomy (n = 9), and fracture (n = 5) underwent dynamic [{sup 18}F]-fluoride (Na{sup 18}F) PET/CT at 8 weeks and 4 months, respectively, after application of a TSF. Parametric images, corresponding to the net transport rate of [{sup 18}F]-fluoride from plasma to bone, K{sub i} were calculated. The ratio of the maximum K{sub i} at PET scan 2 and 1 (anti K{sub i,max}) as well as the ratio of the maximum Standard Uptake Value at PET scan 2 and 1 (SUV {sub max}) were calculated for each individual. Different treatment end-points were scored, and the overall treatment outcome score was compared with the osteoblastic activity progression as scored with anti K{sub i,max} or SUV {sub max}. anti K{sub i,max} and SUV {sub max} were not correlated within each orthopedic group (p > 0.1 for all groups), nor for the pooled population (p = 0.12). The distribution of anti K{sub i,max} was found significantly different among the different orthopedic groups (p = 0.0046) - also for SUV {sub max} (p = 0.022). The positive and negative treatment predictive values for anti K{sub i,max} were 66.7 % and 77.8 %, respectively. Corresponding values for SUV {sub max} were 25 % and 33.3 % The anti K{sub i,max} obtained from dynamic [{sup 18}F]-fluoride-PET imaging is a promising predictive factor to evaluate changes in bone healing in response to TSF treatment. (orig.)

  4. The Bone Dysplasia Ontology: integrating genotype and phenotype information in the skeletal dysplasia domain

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    Groza Tudor

    2012-03-01

    Full Text Available Abstract Background Skeletal dysplasias are a rare and heterogeneous group of genetic disorders affecting skeletal development. Patients with skeletal dysplasias suffer from many complex medical issues including degenerative joint disease and neurological complications. Because the data and expertise associated with this field is both sparse and disparate, significant benefits will potentially accrue from the availability of an ontology that provides a shared conceptualisation of the domain knowledge and enables data integration, cross-referencing and advanced reasoning across the relevant but distributed data sources. Results We introduce the design considerations and implementation details of the Bone Dysplasia Ontology. We also describe the different components of the ontology, including a comprehensive and formal representation of the skeletal dysplasia domain as well as the related genotypes and phenotypes. We then briefly describe SKELETOME, a community-driven knowledge curation platform that is underpinned by the Bone Dysplasia Ontology. SKELETOME enables domain experts to use, refine and extend and apply the ontology without any prior ontology engineering experience--to advance the body of knowledge in the skeletal dysplasia field. Conclusions The Bone Dysplasia Ontology represents the most comprehensive structured knowledge source for the skeletal dysplasias domain. It provides the means for integrating and annotating clinical and research data, not only at the generic domain knowledge level, but also at the level of individual patient case studies. It enables links between individual cases and publicly available genotype and phenotype resources based on a community-driven curation process that ensures a shared conceptualisation of the domain knowledge and its continuous incremental evolution.

  5. EFFECTS OF SHORT TERM PRACTICE OF BHASTRIKA PRANAYAMA ON METABOLIC FITNESS (METF AND BONE INTEGRITY (BI

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    Baljinder Singh Bal

    2015-07-01

    Full Text Available Purpose: The present study was conducted with the objective to determine the short term practice of bhastrika pranayama on Metabolic Fitness and Bone Integrity. Material: 30 university level females between the age group of 21-26 years were selected. The subjects were randomly matched and assigned into two groups: Group-A: Experimental (n 1=15; Group-B: Control (n 2=15. The subjects from Group-A: Experimental were provided to a 4-weeks bhastrika pranayama. Statistical Analysis: Student t test for paired samples was utilized to compare the means of the pre-test and the post-test. Results & Conclusions: Based on the analysis of the results obtained, we conclude that the significant differences were found in Metabolic Fitness (i.e., Maximal Oxygen Consumption (V O2max and blood pressure of University Level Girls. Insignificant between-group differences were noted in Blood Lipid, Blood Sugar and Bone Integrity of University Level Girls.

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

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    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.

  7. The effect of zoledronate on bone remodeling during the healing process Os efeitos do zoledronato na remodelação óssea durante o processo de reparação

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    Marcos Almeida Matos

    2007-04-01

    Full Text Available PURPOSE: To check the effect of zoledronate in bone remodeling during bone healing. METHODS: Thirty rabbits were divided into two groups of fifteen animals each (control and experimental group respectively. Shaft osteotomy was performed on the cranial portion of the fibula of each animal. In the experimental group, a single dose of 0.04mg/kg of zoledronate was administered. In the control group, the same volume of bi-distilled water was administered. After one, two and four weeks, animals of both groups were killed and histological sections of the fibular metaphyseal area were examined histomorphometrically. The parameters analyzed were tissue volume (TV, fractional trabecular bone volume (BV/TV and fractional medullary fibrous volume (FbV/TV. RESULTS: Tissue volume increased in the experimental group (237.2mm².10-2 compared to the control (166.62mm².10-2. Trabecular bone volume was significantly larger in the experimental (60.2% than in the control group (34.8%.The amount of fibrosis volume decreased in the experimental group (22% compared to the control (49.4%. CONCLUSION: The effect of zoledronate is characterized by accentuated stimulus of bone formation in the metaphyseal area, resulting in a larger amount of trabecular bone volume and little fibrosis volume.OBJETIVO: Verificar os efeitos do zoledronato na remodelação óssea durante a reparação óssea. MÉTODOS: Trinta coelhos foram divididos em dois grupos de quinze animais cada (grupos controle e experimento, respectivamente. Realizou-se osteotomia na diáfise proximal da fíbula de cada animal. No grupo experimento, aplicou-se dose única de 0,04mg/Kg de zoledronato. No grupo controle, a mesma quantidade de água bi-destilada foi administrada. Após uma, duas e quatro semanas, os animais de ambos os grupos foram sacrificados e cortes histológicos da metáfise fibular foram examinados histomorfometricamente. Os parâmetros analisados foram volume tecidual (TV, fração do volume

  8. 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

    目的 初步探讨护骨素OPG、核因子κB受体活化因子配体RANKL、核因子κB活化因子RANK在牙周炎牙槽骨吸收及骨重建过程中的作用.方法 对小鼠单核巨噬细胞白血病细胞株RAW264.7实验组进行体外诱导培养,对照组为完全培养基培养;小鼠成骨样细胞株MC3T3-E1实验组采用前期实验收集的骨吸收上清处理,对照组采用完全培养基培养;以免疫荧光等方法检测细胞OPG、RANKL、RANK的表达.30只8周龄雄性SD大鼠建立实验性牙槽骨吸收模型,研究其吸收重建规律.以免疫组化S-P法检测OPG、RANKL、RANK的表达情况.结果 实验组MC3T3-E细胞经骨吸收上清处理7d后,OPG蛋白平均荧光强度为(29.636±5.652),对照组为(15.568±1.229),表达显著上调(P<0.01);但实验组RANKL蛋白平均荧光强度为(6.806±1.738),对照组为(18.082±2.732),表达被显著抑制(P<0.01),OPG/RANKL比值在上清处理后高于对照组(P<0.05).采用大肠杆菌内毒素E-LPS注射法成功制备大鼠牙槽骨吸收模型.在牙槽骨吸收区域OPG水平较无骨吸收区域有所降低,RANKL的表达则相反.结论 OPG、RANKL、RANK参与了大鼠实验性骨吸收活动;破骨细胞骨吸收上清可能通过改变OPG与RANKL的比值,从而影响骨重建中骨形成与骨吸收的动态平衡.%Objective To investigate the potential role of a system containing osteoprotegerin (OPG) , receptor activator of NF-kB ligand ( RANKL) , and receptor activator of nuclear factor-kappa B ( RANK) , also as, OPG/RANKL/RANK system in the resorption and remodeling mechanisms of alveolar bone. Methods Mouse RAW264. 7 cell line was induced to osteoclasts in vitro, and mouse MC3T3-E1 cell line was treated with bone resorption supernatant. The control cells was cultured with regular medium. The expression levels of OPG, RANKL and RANK in the cells was detected by immunofluorescence assay. Thirty 8-week-old male SD rats were used to establish the

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

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    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.

  10. Vascular Remodeling in Experimental Hypertension

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    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.

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

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    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. 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.

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    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.

  13. Changes of trabecular bone under control of biologically mechanical mechanism

    Science.gov (United States)

    Wang, C.; Zhang, C. Q.; Dong, X.; Wu, H.

    2008-10-01

    In this study, a biological process of bone remodeling was considered as a closed loop feedback control system, which enables bone to optimize and renew itself over a lifetime. A novel idea of combining strain-adaptive and damage-induced remodeling algorithms at Basic Multicellular Unit (BMU) level was introduced. In order to make the outcomes get closer to clinical observation, the stochastic occurrence of microdamage was involved and a hypothesis that remodeling activation probability is related to the value of damage rate was assumed. Integrated with Finite Element Analysis (FEA), the changes of trabecular bone in morphology and material properties were simulated in the course of five years. The results suggest that deterioration and anisotropy of trabecluar bone are inevitable with natural aging, and that compression rather than tension can be applied to strengthen the ability of resistance to fracture. This investigation helps to gain more insight the mechanism of bone loss and identify improved treatment and prevention for osteoporosis or stress fracture.

  14. Advanced computational workflow for the multi-scale modeling of the bone metabolic processes.

    Science.gov (United States)

    Dao, Tien Tuan

    2017-06-01

    Multi-scale modeling of the musculoskeletal system plays an essential role in the deep understanding of complex mechanisms underlying the biological phenomena and processes such as bone metabolic processes. Current multi-scale models suffer from the isolation of sub-models at each anatomical scale. The objective of this present work was to develop a new fully integrated computational workflow for simulating bone metabolic processes at multi-scale levels. Organ-level model employs multi-body dynamics to estimate body boundary and loading conditions from body kinematics. Tissue-level model uses finite element method to estimate the tissue deformation and mechanical loading under body loading conditions. Finally, cell-level model includes bone remodeling mechanism through an agent-based simulation under tissue loading. A case study on the bone remodeling process located on the human jaw was performed and presented. The developed multi-scale model of the human jaw was validated using the literature-based data at each anatomical level. Simulation outcomes fall within the literature-based ranges of values for estimated muscle force, tissue loading and cell dynamics during bone remodeling process. This study opens perspectives for accurately simulating bone metabolic processes using a fully integrated computational workflow leading to a better understanding of the musculoskeletal system function from multiple length scales as well as to provide new informative data for clinical decision support and industrial applications.

  15. Mandibular bone resorption in patients treated with tissue-integrated prostheses and in complete-denture wearers

    Energy Technology Data Exchange (ETDEWEB)

    Sennerby, L.; Carlsson, G.E.; Bergman, B.; Warfvinge, J.

    1988-01-01

    Mandibular bone resorption was studied in patients treated with tissue-integrated prostheses (TIP) and in complete-denture wearers by distance and area measurements on cephalometric radiographs. The area measurements were performed by means of a computer. Two TIP groups with short and long periods (average chi=2.4 and 23.9 years) of edentulousness, and wearing complete dentures before fixture installtion, were followed up to over 7-8 years. Mandibular bone resorption was remarkably small behind the distally positioned fixtures in comparison with the correspondings region in complete-denture wearers. Patients with complete dentures showed a continous resorption of the mandibular alveolar ridge over 21 years, even though there were great individual variations. The bone loss was most pronounced anteriorly and during the first 2 years after extraction of the residual teeth. It is concluded that treatment with tissue-integrated prostheses seems to reduce bone resorption in the mandible, probably owing to favorable load conditions and adequate stimulation of the bone.

  16. Bioactive ceramic coating on orthopedic implants for enhanced bone tissue integration

    Science.gov (United States)

    Aniket

    Tissue integration between bone and orthopedic implant is essential for implant fixation and longevity. An immunological response leads to fibrous encapsulation of metallic implants leading to implant instability and failure. Bioactive ceramics have the ability to directly bond to bone; however, they have limited mechanical strength for load bearing applications. Coating bioactive ceramics on metallic implant offers the exciting opportunity to enhance bone formation without compromising the mechanical strength of the implant. In the present study, we have developed a novel bioactive silica-calcium phosphate nanocomposite (SCPC) coating on medical grade Ti-6Al-4V orthopedic implant using electrophoretic deposition (EPD) and evaluated bone tissue response to the coated implant at the cellular level. The effect of SCPC composition and suspending medium pH on the zeta potential of three different SCPC formulations; SCPC25, SCPC50 and SCPC75 were analyzed. The average zeta potential of SCPC50 in pure ethanol was more negative than that of SCPC25 or SCPC75; however the difference was not statistically significant. Ti-6Al-4V discs were passivated, coated with SCPC50 (200 nm - 10 mum) and thermally treated at 600 - 800 ºC to produce a coating thickness in the range of 43.1 +/- 5.7 to 30.1 +/- 4.6 μm. After treatment at 600, 700 and 800 ºC, the adhesion strength at the SCPC50/Ti-6Al-4V interface was 42.6 +/- 3.6, 44.7 +/- 8.7 and 47.2 +/- 4.3 MPa, respectively. XRD analyses of SCPC50 before and after EPD coating indicated no change in the crystallinity of the material. Fracture surface analyses showed that failure occurred within the ceramic layer or at the ceramic/polymer interface; however, the ceramic/metal interface was intact in all samples. The adhesion strength of SCPC50-coated substrates after immersion in PBS for 2 days (11.7 +/- 3.9 MPa) was higher than that measured on commercially available hydroxyapatite (HA) coated substrates (5.5 +/- 2.7 MPa), although the

  17. Quantitative analysis on orientation of human bone integrated with midpalatal implant by micro X-ray diffractometer

    Energy Technology Data Exchange (ETDEWEB)

    Murata, Masaru, E-mail: murata@hoku-iryo-u.ac.jp [Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho 061-0293 (Japan); Akazawa, Toshiyuki [Hokkaido Research Organization, Nishi-11, Kita-19, Kita-ku, Sapporo 060-0819 (Japan); Yuasa, Toshihiro; Okayama, Miki; Tazaki, Junichi [Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho 061-0293 (Japan); Hanawa, Takao [Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo 101-0062 (Japan); Arisue, Makoto; Mizoguchi, Itaru [Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho 061-0293 (Japan)

    2012-12-01

    Highlights: Black-Right-Pointing-Pointer A titanium fixture is implanted into palatal bone of an 18-year-old patient as the unmoved anchorage for the orthodontic treatment. Black-Right-Pointing-Pointer The fixture is integrated with compact bone with cortical bone-like osteon. Black-Right-Pointing-Pointer Microbeam X-ray diffraction denotes the crystallinity and orientation of HAp. Black-Right-Pointing-Pointer X-ray images of c-face in HAp reveal functionally graded distribution of bone quality. Black-Right-Pointing-Pointer The crystal growth of c-face is caused by propagation of the continuous lateral stress. - Abstract: A midpalatal implant system has been used as the unmoved anchorage for teeth movement. An 18-year-old male patient presented with reversed occlusion and was diagnosed as malocclusion. A pure titanium fixture (lengths: 4 mm, diameter: 3.3 mm, Orthosystem{sup Registered-Sign }, Institute Straumann, Switzerland) was implanted into the palatal bone of the patient as the orthodontic anchorage. The implant anchorage was connected with the upper left and right first molars, and had been used for 3 years. After dynamic treatments, the titanium fixture connected with bone was removed surgically, fixed in formalin solution, and embedded in resin. Specimens were cut along the frontal section of face and the direction of longitudinal axis of the implant, stained, and observed histologically. The titanium fixture was integrated directly with compact bone showing cortical bone-like structure such as lamella and osteon. In addition, to qualitatively characterize the implant-supported human bone, the crystallinity and orientation of hydroxyapatite (HAp) phase were evaluated by the microbeam X-ray diffraction analysis. Preferential alignment of c-axis of HAp crystals was represented by the relative intensity ratio of (0 0 2)-face diffraction peak to (3 1 0)-face one. The values decreased monotonously along the direction of the lateral stress from the site near the

  18. Improving Depiction of Temporal Bone Anatomy With Low-Radiation Dose CT by an Integrated Circuit Detector in Pediatric Patients

    Science.gov (United States)

    He, Jingzhen; Zu, Yuliang; Wang, Qing; Ma, Xiangxing

    2014-01-01

    Abstract The purpose of this study was to determine the performance of low-dose computed tomography (CT) scanning with integrated circuit (IC) detector in defining fine structures of temporal bone in children by comparing with the conventional detector. The study was performed with the approval of our institutional review board and the patients’ anonymity was maintained. A total of 86 children  0.05). The low-dose CT images acquired with the IC detector provide better depiction of fine osseous structures of temporal bone than that with the conventional DC detector. PMID:25526489

  19. Remodeling A School Shop?

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    Baker, G. E.

    1970-01-01

    Presents guidelines for remodeling a school shop combining major considerations of funds, program changes, class management, and flexibility, with the needs of wiring, painting, and placement of equipment. (Author)

  20. Role of Oxidative Damage in Radiation-Induced Bone Loss

    Science.gov (United States)

    Schreurs, Ann-Sofie; Alwood, Joshua S.; Limoli, Charles L.; Globus, Ruth K.

    2014-01-01

    During prolonged spaceflight, astronauts are exposed to both microgravity and space radiation, and are at risk for increased skeletal fragility due to bone loss. Evidence from rodent experiments demonstrates that both microgravity and ionizing radiation can cause bone loss due to increased bone-resorbing osteoclasts and decreased bone-forming osteoblasts, although the underlying molecular mechanisms for these changes are not fully understood. We hypothesized that excess reactive oxidative species (ROS), produced by conditions that simulate spaceflight, alter the tight balance between osteoclast and osteoblast activities, leading to accelerated skeletal remodeling and culminating in bone loss. To test this, we used the MCAT mouse model; these transgenic mice over-express the human catalase gene targeted to mitochondria, the major organelle contributing free radicals. Catalase is an anti-oxidant that converts reactive species, hydrogen peroxide into water and oxygen. This animal model was selected as it displays extended lifespan, reduced cardiovascular disease and reduced central nervous system radio-sensitivity, consistent with elevated anti-oxidant activity conferred by the transgene. We reasoned that mice overexpressing catalase in mitochondria of osteoblast and osteoclast lineage cells would be protected from the bone loss caused by simulated spaceflight. Over-expression of human catalase localized to mitochondria caused various skeletal phenotypic changes compared to WT mice; this includes greater bone length, decreased cortical bone area and moment of inertia, and indications of altered microarchitecture. These findings indicate mitochondrial ROS are important for normal bone-remodeling and skeletal integrity. Catalase over-expression did not fully protect skeletal tissue from structural decrements caused by simulated spaceflight; however there was significant protection in terms of cellular oxidative damage (MDA levels) to the skeletal tissue. Furthermore, we

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

    Science.gov (United States)

    Florencio-Silva, Rinaldo; Sasso, Gisela Rodrigues da Silva; Sasso-Cerri, Estela; Simões, Manuel Jesus; Cerri, Paulo Sérgio

    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 result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

  2. Differentiation and growth of bone ornamentation in vertebrates: a comparative histological study among the Crocodylomorpha.

    Science.gov (United States)

    de Buffrénil, V; Clarac, F; Fau, M; Martin, S; Martin, B; Pellé, E; Laurin, M

    2015-04-01

    Bone ornamentation, that is, hollow (pits and grooves) or protruding (ridges) repetitive reliefs on the surface of dermal bones, is a frequent, though poorly studied and understood, feature in vertebrates. One of the most typical examples of this characteristic is given by the Crurotarsi, a taxon formed by the crocodilians and their closest allies, which generally display deep ornamentation on skull roof and osteoderms. However, the ontogenetic process responsible for the differentiation and development of this character remains controversial. This study was conducted to settle the question on histological and microanatomical evidence in several crurotarsan taxa. Observational and experimental data in extant and extinct crocodyliforms show that bone ornamentation is initially created, and later maintained during somatic growth (that is indefinite in crocodilians), by a complex process of bone remodeling comprising local resorption of superficial bone cortices, followed by partial reconstruction. The superficial reliefs of crocodilian dermal bones are thus permanently modified through pit enlargement, drift, stretching, shrinking, or complete filling. Ridges are also remodeled in corresponding ways. These processes allow accommodation of unitary ornamental motifs to the overall dimensions of the bones during growth. A parsimony optimization based on the results of this study, but integrating also published data on bone histology in non-crocodyliform crurotarsans and some non-crurotarsan taxa, suggests that the peculiar mechanism described above for creating and maintaining bone ornamentation is a general feature of the Crurotarsi and is quite distinct from that attributed by previous authors to other vertebrates. © 2014 Wiley Periodicals, Inc.

  3. [The skeletal regulating mechanisms and concepts in growth and development of cranial-facial bones and orthodontic treatment].

    Science.gov (United States)

    Chen, Song; Chen, Yang-xi

    2009-10-01

    There are three kinds of mechanisms regulating the growth and development of skeletal tissue: Bone growth, bone modeling and bone remodeling. However, in the current orthodontics literature, there continues to be substantial confusion regarding the usage of the term "bone remodeling". This article reviews the historical causes for this semantics problem and explains the difference between bone modeling and remodeling, as well as the detailed skeletal regulating mechanisms in the growth and development of cranial-facial bones and orthodontic treatment. At last, this article suggests Chinese orthodontists use the terms "bone modeling" and "bone remodeling" more precisely to avoid scientific confusion and barriers to scientific exchange with other biomedical disciplines.

  4. Size does matter: an integrative in vivo-in silico approach for the treatment of critical size bone defects.

    Directory of Open Access Journals (Sweden)

    Aurélie Carlier

    2014-11-01

    Full Text Available Although bone has a unique restorative capacity, i.e., it has the potential to heal scarlessly, the conditions for spontaneous bone healing are not always present, leading to a delayed union or a non-union. In this work, we use an integrative in vivo-in silico approach to investigate the occurrence of non-unions, as well as to design possible treatment strategies thereof. The gap size of the domain geometry of a previously published mathematical model was enlarged in order to study the complex interplay of blood vessel formation, oxygen supply, growth factors and cell proliferation on the final healing outcome in large bone defects. The multiscale oxygen model was not only able to capture the essential aspects of in vivo non-unions, it also assisted in understanding the underlying mechanisms of action, i.e., the delayed vascularization of the central callus region resulted in harsh hypoxic conditions, cell death and finally disrupted bone healing. Inspired by the importance of a timely vascularization, as well as by the limited biological potential of the fracture hematoma, the influence of the host environment on the bone healing process in critical size defects was explored further. Moreover, dependent on the host environment, several treatment strategies were designed and tested for effectiveness. A qualitative correspondence between the predicted outcomes of certain treatment strategies and experimental observations was obtained, clearly illustrating the model's potential. In conclusion, the results of this study demonstrate that due to the complex non-linear dynamics of blood vessel formation, oxygen supply, growth factor production and cell proliferation and the interactions thereof with the host environment, an integrative in silico-in vivo approach is a crucial tool to further unravel the occurrence and treatments of challenging critical sized bone defects.

  5. Chitosan-glycerol phosphate/blood implants elicit hyaline cartilage repair integrated with porous subchondral bone in microdrilled rabbit defects.

    Science.gov (United States)

    Hoemann, C D; Sun, J; McKee, M D; Chevrier, A; Rossomacha, E; Rivard, G-E; Hurtig, M; Buschmann, M D

    2007-01-01

    We have previously shown that microfractured ovine defects are repaired with more hyaline cartilage when the defect is treated with in situ-solidified implants of chitosan-glycerol phosphate (chitosan-GP) mixed with autologous whole blood. The objectives of this study were (1) to characterize chitosan-GP/blood clots in vitro, and (2) to develop a rabbit marrow stimulation model in order to determine the effects of the chitosan-GP/blood implant and of debridement on the formation of incipient cartilage repair tissue. Blood clots were characterized by histology and in vitro clot retraction tests. Bilateral 3.5 x 4 mm trochlear defects debrided into the calcified layer were pierced with four microdrill holes and filled with a chitosan-GP/blood implant or allowed to bleed freely as a control. At 1 day post-surgery, initial defects were characterized by histomorphometry (n=3). After 8 weeks of repair, osteochondral repair tissues between or through the drill holes were evaluated by histology, histomorphometry, collagen type II expression, and stereology (n=16). Chitosan-GP solutions structurally stabilized the blood clots by inhibiting clot retraction. Treatment of drilled defects with chitosan-GP/blood clots led to the formation of a more integrated and hyaline repair tissue above a more porous and vascularized subchondral bone plate compared to drilling alone. Correlation analysis of repair tissue between the drill holes revealed that the absence of calcified cartilage and the presence of a porous subchondral bone plate were predictors of greater repair tissue integration with subchondral bone (Phyaline and integrated repair tissue associated with a porous subchondral bone replete with blood vessels. Concomitant regeneration of a vascularized bone plate during cartilage repair could provide progenitors, anabolic factors and nutrients that aid in the formation of hyaline cartilage.

  6. 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

  7. Cabozantinib Resolves Bone Scans in Tumor-Naïve Mice Harboring Skeletal Injuries

    Directory of Open Access Journals (Sweden)

    Michael G. Doran

    2014-10-01

    Full Text Available The receptor tyrosine kinase inhibitor cabozantinib (XL184, BMS-907351 Cometriq has displayed impressive clinical activity against several indications, culminating in its recent approval for medullary thyroid cancer. Among malignancies with tropism for the bone (prostate, breast, one striking feature of early clinical reports about this drug has been the rapid and complete resolution of bone scans, a phenomenon almost never observed even among therapies already shown to confer survival benefit. In castration-resistant prostate cancer, not all conventional response indicators change as dramatically posttreatment, raising the possibility that cabozantinib may impair the ability of bone-seeking radionuclides to integrate within the remodeling bone. To test this hypothesis, we surgically induced bone remodeling via physical insult in non–tumor-bearing mice and performed 18F-sodium fluoride (18F-NaF positron emission tomographic (PET and technetium 99m–methylene diphosphonate (99mTc-MDP single-photon emission computed tomographic (SPECT scans pre- and posttreatment with cabozantinib and related inhibitors. A consistent reduction in the accumulation of either radiotracer at the site of bone remodeling was observed in animals treated with cabozantinib. Given that cabozantinib is known to inhibit several receptor tyrosine kinases, we drugged animals with various permutations of more selective inhibitors to attempt to refine the molecular basis of bone scan resolution. Neither the vascular endothelial growth factor receptor (VEGFR inhibitor axitinib, the MET inhibitor crizotinib, nor the combination was capable of inhibiting 18F-NaF accumulation at known bioactive doses. In summary, although the mechanism by which cabozantinib suppresses radionuclide incorporation into foci undergoing bone remodeling remains unknown, that this phenomenon occurs in tumor-naïve models indicates that caution should be exercised in interpreting the clinical significance

  8. Thoracic Bone Remodeling and Clinical Therapeutic Effect after Minimally Invasive Repair for Pectus Excavatum in Children%微创手术矫治儿童漏斗胸后胸廓骨重塑与临床疗效

    Institute of Scientific and Technical Information of China (English)

    刘吉福; 徐波; 武珊珊

    2012-01-01

    Objective To study thoracic bone remodeling and clinical effects after minimally invasive correction for pectus excavatum (PE) in children. Methods A retrospective review was conducted of a prospectively gathered database of 74 child patients who underwent minimally invasive repair of PE at General Hospital of Beijing Military District between Apr. 2009 and Sept. 2010. Of the patients, 63 were males and 11 females; the age was (11. 90±8. 50) years, 11 patients < 10-year-old among them. Under general anesthesia, two incisions were made at the side midaxillary line, and the introducer created a tunnel at the trans-substernum and shaped the thoracic cavity. The bar was then inserted into the retrosternum by video-assistant thoracoscopic monitoring. All patients were checked by chest computerized tomography (CT) scan preoperatively and one week after operation, with three-dimensional reconstruction. The sagittal view was by means of the center line of the body of thoracic vertebrae. The distance between the sternum and the frontal edge of the body of thoracic vertebrae was measured and the return of displacement of the heart was observed. Results All 74 operations were successful; there were no deaths. One bar was used for 66 patients (89. 19%), while two bars were used for the other 8 patients (10. 81%). Comparing the results of pre- with post-correction, for patients younger than 10 years (n=11) who had one bar placed, the inferior extremity of the manubrium and midsternum displaced forward to 3. 76-22. 92 mm. For 11-17 year-old patients (n=55), anterior displacement of only the middle and lower part of the midsternum was 2. 08-10.42 mm. There was a significant difference between the two groups in the inferior extremity of the midsternum displaced (t=14. 24, P < 0. 05). For those patients with two bars, the inferior extremity of the manubrium and the midstemum were each displaced forward 4. 19-15. 03 mm at 7 d after operation. At 7 d after operation, the cardiac

  9. Three-Dimensional Bone Adaptation of the Proximal Femur

    DEFF Research Database (Denmark)

    Bagge, Mette

    1998-01-01

    The bone remodeling of a three-dimensional model of the proximal femur is considered. The bone adaptation is numerically described as an evolution in time formulated such that the structural change goes in an optimal direction within each time step for the optimal boundary conditions. In the bone...... remodeling scheme is included the memory of past loadings to account for the delay in the bone response to the load changes. In order to get a realistic bone adaptation process, the bone structure at the onset of the remodeling needs to be realistic too. A start design is obtained by structural optimization...

  10. Adipose tissue remodeling in pathophysiology of obesity.

    Science.gov (United States)

    Lee, Mi-Jeong; Wu, Yuanyuan; Fried, Susan K

    2010-07-01

    Recent studies demonstrate that adipose tissue undergoes a continuous process of remodeling that is pathologically accelerated in the obese state. Contrary to earlier dogma, adipocytes die and are replaced by newly differentiated ones. This review will summarize recent advances of our knowledge of the mechanisms that regulate adipose tissue remodeling and highlight the influences of obesity, depot, and sex, as well as the relevance of rodent models to humans. A substantial literature now points to the importance of dynamic changes in adipocyte and immune cell turnover, angiogenesis, and extracellular matrix remodeling in regulating the expandability and functional integrity of this tissue. In obesity, the macrophages are recruited, surrounding dead adipocytes and polarized toward an inflammatory phenotype. The number of dead adipocytes is closely associated with the pathophysiological consequences of obesity, including insulin resistance and hepatic steatosis. Further, there are substantial depot, sex and species differences in the extent of remodeling. Adipose tissue undergoes a continuous remodeling process that normally maintains tissue health, but may spin out of control and lead to adipocyte death in association with the recruitment and activation of macrophages, and systemic insulin resistance.

  11. Impairment of osteoclastic bone resorption in rapidly growing female p47phox knockout mice

    Science.gov (United States)

    Bone formation is dependent on the activity and differentiation of osteoblasts; whereas resorption of preexisting mineralized bone matrix by osteoclasts is necessary not only for bone development but also for regeneration and remodeling. Bone remodeling is a process in which osteoblasts and osteocla...

  12. 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.

  13. Animal Models of Bone Loss in Inflammatory Arthritis: from Cytokines in the Bench to Novel Treatments for Bone Loss in the Bedside—a Comprehensive Review

    NARCIS (Netherlands)

    C.H. Alves (Celso Henrique); E. Farrell (Eric); M. Vis (M.); E.M. Colin (Edgar); E.W. Lubberts (Erik)

    2016-01-01

    textabstractThroughout life, bone is continuously remodelled. Bone is formed by osteoblasts, from mesenchymal origin, while osteoclasts induce bone resorption. This process is tightly regulated. During inflammation, several growth factors and cytokines are increased inducing osteoclast differentiati

  14. 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

  15. Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes.

    Science.gov (United States)

    Li, Guangyi; Yin, Jimin; Gao, Junjie; Cheng, Tak S; Pavlos, Nathan J; Zhang, Changqing; Zheng, Ming H

    2013-01-01

    Osteoarthritis (OA) is a major cause of disability in the adult population. As a progressive degenerative joint disorder, OA is characterized by cartilage damage, changes in the subchondral bone, osteophyte formation, muscle weakness, and inflammation of the synovium tissue and tendon. Although OA has long been viewed as a primary disorder of articular cartilage, subchondral bone is attracting increasing attention. It is commonly reported to play a vital role in the pathogenesis of OA. Subchondral bone sclerosis, together with progressive cartilage degradation, is widely considered as a hallmark of OA. Despite the increase in bone volume fraction, subchondral bone is hypomineralized, due to abnormal bone remodeling. Some histopathological changes in the subchondral bone have also been detected, including microdamage, bone marrow edema-like lesions and bone cysts. This review summarizes basic features of the osteochondral junction, which comprises subchondral bone and articular cartilage. Importantly, we discuss risk factors influencing subchondral bone integrity. We also focus on the microarchitectural and histopathological changes of subchondral bone in OA, and provide an overview of their potential contribution to the progression of OA. A hypothetical model for the pathogenesis of OA is proposed.

  16. Microsphere-integrated gelatin-siloxane hybrid scaffolds for bone tissue engineering :in vitro bioactivity & antibacterial activity

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Microsphere integrated gelatin-siloxane hybrid scaffolds were successfully synthesized by using a combined sol-gel processing,post-gelation soaking and freeze-drying process.A bone-like apatite layer was able to form in the Ca2+-containing porous hybrids upon soaking in a simulated body fluid (SBF) up to 1 day.The rate of gentamicin sulfate (GS) release from the GS-loaded gelatin-siloxane hybrid microsphere became constant after a 4 h burst.The antibacterial activity was assessed by the agar diffusion test (ADT) and the bactericidal effect test.It is evident that the as-synthesized porous scaffolds have excellent bioactivity and antibacterial activity,and may be favorable in bone tissue engineering.

  17. Correlating the nanoscale mechanical and chemical properties of knockout mice bones

    Science.gov (United States)

    Kavukcuoglu, Nadire Beril

    Bone is a mineral-organic composite where the organic matrix is mainly type I collagen plus small amounts of non-collagenous proteins including osteopontin (OPN), osteocalcin (OC) and fibrillin 2 (Fbn2). Mature bone undergoes remodeling continually so new bone is formed and old bone resorbed. Uncoupling between the bone resorption and bone formation causes an overall loss of bone mass and leads to diseases like osteoporosis and osteopenia. These are characterized by structural deterioration of the bone tissue and an increased risk of fracture. The non-collagenous bone proteins are known to have a role in regulating bone turnover and to affect the structural integrity of bone. OPN and OC play a key role in bone resorption and formation, while absence of Fbn-2 causes a connective tissue disorder (congenital contractural arachnodactyly) and has been associated with decreased bone mass. In this thesis nanoindentation and Raman-microspectroscopy techniques were used to investigate and correlate the mechanical and chemical properties of cortical femoral bones from OPN deficient (OPN-/-), OC deficient (OC-/-) and Fbn-2 deficient (Fbn2-/-) mice and their age, sex and background matched wild-type controls (OPN+/+, OC+/+ and Fbn2+/+). For OPN the hardness (H) and elastic modulus (E) of under 12 week OPN-/- bones were significantly lower than for OPN+/+ bones, but Raman showed no significant difference. Mechanical properties of bones from mice older than 12 weeks were not significantly different with genotype. However, mineralization and crystallinity from >50 week OPN-/- bones were significantly higher than for OPN+/+ bones. Mechanical properties of OPN-/- bones showed no variation with age, but mineralization, crystallinity and type-B carbonate substitution increased for both genotypes. For OC-/- intra-bone analyses showed that the hardness and crystallinity of the bones were significantly higher, especially in the mid-cortical sections, compared to OC+/+ bones. Fbn2

  18. Treatment of Bone Marrow Failure Syndrome with Integrated Traditional and Western Medicine

    Institute of Scientific and Technical Information of China (English)

    MA Rou

    2007-01-01

    @@ Aplastic anemia (AA) and myelodysplastic syndrome (MDS) are both included in the bone marrow failure syndromes (BMFS). AA is a group of diseases characterized by hematopoietic stem/progenitor cell damage,peripheral blood cytopenia, and clinical manifestations including anemia, bleeding and infection, which eventually lead to bone marrow failure.The incidence rate of AA in China is 7.4/106, higher than that in Western countries, among which the morbidity of acute AA and chronic AA (CAA) is 1.4/106 and 6.0/106,respectively.

  19. Analysis of bone protein and mineral composition in bone disease using synchrotron infrared microspectroscopy

    Science.gov (United States)

    Miller, Lisa M.; Hamerman, David; Chance, Mark R.; Carlson, Cathy S.

    1999-10-01

    Infrared (IR) microspectroscopy is an analytical technique that is highly sensitive to the chemical components in bone. The brightness of a synchrotron source permits the examination of individual regions of bone in situ at a spatial resolution superior to that of a conventional infrared source. At Beamlines U10B and U2B at the National Synchrotron Light Source, we are examining the role of bone chemical composition in bone disease. In osteoarthritis (OA), it has been demonstrated that the bone underlying the joint cartilage (subchondral bone) becomes thickened prior to cartilage breakdown. Using synchrotron infrared microspectroscopy, we have examined the chemical composition of the subchondral bone in histologically normal and OA monkeys. Results demonstrate that the subchondral bone of OA monkeys is significantly more mineralized than the normal bone, primarily due to an increase in carbonate concentration in the OA bone. High resolution analysis indicates that differences in carbonate content are uniform throughout the subchondral bone region, suggesting that high subchondral bone carbonate may be a marker for OA. Conversely, increases in phosphate content are more pronounced in the region near the marrow space, suggesting that, as the subchondral bone thickens, the bone also becomes more mineralized. Osteoporosis is a disease characterized by a reduction in bone mass and a skeleton that is more susceptible to fracture. To date, it is unclear whether bone remodeled after the onset of osteoporosis differs in chemical composition from older bone. Using fluorescence-assisted infrared microspectroscopy, we are comparing the composition of monkey bone remodeled at various time points after the onset of osteoporosis (induced by ovariectomy). We find that the chemical composition of bone remodeled one year after ovariectomy and one year prior to necropsy is similar to normal bone. On the other hand, bone remodeled two years after ovariectomy is less mature, indicated

  20. Oxidized alginate hydrogels for bone morphogenetic protein-2 delivery in long bone defects.

    Science.gov (United States)

    Priddy, Lauren B; Chaudhuri, Ovijit; Stevens, Hazel Y; Krishnan, Laxminarayanan; Uhrig, Brent A; Willett, Nick J; Guldberg, Robert E

    2014-10-01

    Autograft treatment of large bone defects and fracture non-unions is complicated by limited tissue availability and donor site morbidity. Polymeric biomaterials such as alginate hydrogels provide an attractive tissue engineering alternative due to their biocompatibility, injectability, and tunable degradation rates. Irradiated RGD-alginate hydrogels have been used to deliver proteins such as bone morphogenetic protein-2 (BMP-2), to promote bone regeneration and restoration of function in a critically sized rat femoral defect model. However, slow degradation of irradiated alginate hydrogels may impede integration and remodeling of the regenerated bone to its native architecture. Oxidation of alginate has been used to promote degradation of alginate matrices. The objective of this study was to evaluate the effects of alginate oxidation on BMP-2 release and bone regeneration. We hypothesized that oxidized-irradiated alginate hydrogels would elicit an accelerated release of BMP-2, but degrade faster in vivo, facilitating the formation of higher quality, more mature bone compared to irradiated alginate. Indeed, oxidation of irradiated alginate did accelerate in vitro BMP-2 release. Notably, the BMP-2 retained within both constructs was bioactive at 26days, as observed by induction of alkaline phosphatase activity and positive Alizarin Red S staining of MC3T3-E1 cells. From the in vivo study, robust bone regeneration was observed in both groups through 12weeks by radiography, micro-computed tomography analyses, and biomechanical testing. Bone mineral density was significantly greater for the oxidized-irradiated alginate group at 8weeks. Histological analyses of bone defects revealed enhanced degradation of oxidized-irradiated alginate and suggested the presence of more mature bone after 12weeks of healing.

  1. Comparing and visualizing titanium implant integration in rat bone using 2D and 3D techniques.

    Science.gov (United States)

    Arvidsson, Anna; Sarve, Hamid; Johansson, Carina B

    2015-01-01

    The aim was to compare the osseointegration of grit-blasted implants with and without a hydrogen fluoride treatment in rat tibia and femur, and to visualize bone formation using state-of-the-art 3D visualization techniques. Grit-blasted implants were inserted in femur and tibia of 10 Sprague-Dawley rats (4 implants/rat). Four weeks after insertion, bone implant samples were retrieved. Selected samples were imaged in 3D using Synchrotron Radiation-based μCT (SRμCT). The 3D data was quantified and visualized using two novel visualization techniques, thread fly-through and 2D unfolding. All samples were processed to cut and ground sections and 2D histomorphometrical comparisons of bone implant contact (BIC), bone area (BA), and mirror image area (MI) were performed. BA values were statistically significantly higher for test implants than controls (p 3D analysis was a valuable complement to 2D analysis, facilitating improved visualization. However, further studies are required to evaluate aspects of 3D quantitative techniques, with relation to light microscopy that traditionally is used for osseointegration studies.

  2. Dietary acid load, trabecular bone integrity, and mineral density in an ageing population: the Rotterdam study

    NARCIS (Netherlands)

    E.A.L. de Jonge (Ester); F. Koromani (Fjorda); A. Hofman (Albert); A.G. Uitterlinden (André); O.H. Franco (Oscar); F. Rivadeneira Ramirez (Fernando); J.C. Kiefte-de Jong (Jessica)

    2017-01-01

    textabstractSummary: We studied the relation between a diet that is high in acid-forming nutrients (e.g. proteins) and low in base-forming nutrients (e.g. potassium) and bone structure. We showed a negative relation, which was more prominent if proteins were of animal rather than of vegetable origin

  3. 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

  4. Workshop Report on the European Bone Sarcoma Networking Meeting: Integration of Clinical Trials with Tumor Biology.

    Science.gov (United States)

    Thomas, David M; Wilhelm, Miriam; Cleton-Jansen, Anne-Marie; Dirksen, Uta; Entz-Werlé, Natacha; Gelderblom, Hans; Hassan, Bass; Jürgens, Heribert; Koster, Jan; Kovar, Heinrich; Lankester, Arjan C; Lewis, Ian J; Myklebost, Ola; Nathrath, Michaela H M; Picci, Piero; Whelan, Jeremy S; Hogendoorn, Pancras C W; Bielack, Stefan S

    2011-09-01

    A key workshop was held in The Netherlands in June 2011, hosted by several European bone sarcoma networks and with a broad range of stakeholders from Europe and Australia. The purpose of the meeting was to identify the strengths and weaknesses in current clinical trials for bone sarcomas and to make recommendations as to how to accelerate progress in this field. Two areas of particular interest were discussed. First, all participants agreed upon the importance of tumor biology to understanding clinical responses for all types of bone sarcoma. Various barriers to biobanking tumor and germline specimens were canvassed and are outlined in this paper. Second, there was consideration of the particular challenges of dealing with adolescent and young adult cancers, exemplified by bone sarcomas. Participants recommended greater engagement of both pediatric and adult sarcoma trial organizations to address this issue. Specific opportunities were identified to develop biological sub-studies within osteosarcoma, focused on understanding germ line risk and pharmacogenomics defining toxicity and biological responses. In Ewing sarcoma, it was harder to define opportunities for biological insights. There was agreement that the results for insulin-like growth factor pathway inhibition in Ewing family tumors were disappointing, but represented a clear indication of the need for companion biologic studies to develop predictive biomarkers. The meeting ended with broad commitment to working together to make progress in this rare but important subgroup of cancers.

  5. Computer-aided bone age assessment for ethnically diverse older children using integrated fuzzy logic system

    Science.gov (United States)

    Ma, Kevin; Moin, Paymann; Zhang, Aifeng; Liu, Brent

    2010-03-01

    Bone Age Assessment (BAA) of children is a clinical procedure frequently performed in pediatric radiology to evaluate the stage of skeletal maturation based on the left hand x-ray radiograph. The current BAA standard in the US is using the Greulich & Pyle (G&P) Hand Atlas, which was developed fifty years ago and was only based on Caucasian population from the Midwest US. To bring the BAA procedure up-to-date with today's population, a Digital Hand Atlas (DHA) consisting of 1400 hand images of normal children of different ethnicities, age, and gender. Based on the DHA and to solve inter- and intra-observer reading discrepancies, an automatic computer-aided bone age assessment system has been developed and tested in clinical environments. The algorithm utilizes features extracted from three regions of interests: phalanges, carpal, and radius. The features are aggregated into a fuzzy logic system, which outputs the calculated bone age. The previous BAA system only uses features from phalanges and carpal, thus BAA result for children over age of 15 is less accurate. In this project, the new radius features are incorporated into the overall BAA system. The bone age results, calculated from the new fuzzy logic system, are compared against radiologists' readings based on G&P atlas, and exhibits an improvement in reading accuracy for older children.

  6. The role of osteoclasts in breast cancer bone metastasis

    Directory of Open Access Journals (Sweden)

    François Le Pape

    2016-09-01

    Full Text Available Breast cancer frequently metastasises to the skeleton, interfering with the normal bone remodelling process and inducing bone degradation. Bone degradation is caused by osteoclasts, the normal bone-resorbing cells. Osteoclast-mediated bone degradation subsequently leads to the release of bone-derived factors that promote skeletal tumour growth. Osteoclasts themselves stimulate tumour growth. This Review describes the molecular mechanisms through which osteoclasts and breast cancer cells collaborate with each other, triggering the formation of osteolytic bone metastasis.

  7. [Hydroxyapatite bone substitute (Ostim) in sinus floor elevation. Maxillary sinus floor augmentation: bone regeneration by means of a nanocrystalline in-phase hydroxyapatite (Ostim)].

    Science.gov (United States)

    Smeets, Ralf; Grosjean, Maurice B; Jelitte, Gerd; Heiland, Max; Kasaj, Adrian; Riediger, Dieter; Yildirim, Murat; Spiekermann, Hubertus; Maciejewski, Oliver

    2008-01-01

    The range of bone regeneration materials suitable for maxillar bone augmentation has increased steadily in the past few years and there is now a wide variety of materials being used. In the present case report, we analyzed the state of bone regeneration after sinus floor augmentation using a nanocrystalline in-phase synthetic anorganic hydroxyapatite bone grafting material (Ostim). A 60-year-old female patient underwent maxillary sinus floor elevation and the cavity was filled with Ostim three years before. Actually, she presented herself with loosening of the dental implant at position 17, as a result of parafunction. At the time of the insertion of a second implant at position 17, bone samples were taken by using a trepan drilling device from the previously augmented area. These samples were analyzed histologically to determine the extent of bone remodeling around the deposits of Ostim. We found that the Ostim deposits were surrounded largely by woven bone and, in parts, by lamellar bone and had facilitated osteoconductive bone regeneration. The adjacent implant, at position 16, which beared a crown exposed to proper biting forces without parafunction, showed proper clinical and radiological characteristics of complete and firm integration into the area which was also filled with Ostim three years ago. We conclude that the use of the nanocrystalline hydroxyapatite Ostim with its stable volume properties appears to be suitable for maxillary sinus floor augmentation. Furthermore, we even found osteoconductive bone regeneration under Ostim near the site of the loosened implant.

  8. Analysis of bone ingrowth on a tantalum cup

    Directory of Open Access Journals (Sweden)

    D′Angelo F

    2008-01-01

    Full Text Available Background: Trabecular Metal (TM is a new highly porous material made of tantalum (Zimmer, Warsaw, Indiana, USA. Its three-dimensional structure is composed of a series of interconnected dodecahedron pores that are on average 550 μm in diameter. This size is considered optimal for bone ingrowth and is similar to trabecular bone. The elastic modulus of TM (3 GPa is more similar to that of cancellous (0,1-1,5 GPa or cortical (112-18 GPa bone and is significantly less similar to that of Titanium (110 GPa and Co-Cr alloys (220 GPa. These features enable bone apposition and remodeling. The purpose of the present study was to evaluate the histology of the bone-implant interface in a human specimen. Materials and Methods: A highly porous tantalum cup (Zimmer, Warsaw, Indiana, USA was removed for recurrent dislocations three years after implantation. In order to obtain a slice of the cup, two cuts were made on the centre using an Exakt cutting machine. Then the slice was embedded in a Technovit resin and a Hematoxylin-eosin stain was used to study the bone tissue. Bone ingrowth was calculated using a method based on simple calculations of planar geometry. Results: The histological evaluation of the periprosthetic tissues revealed a typical chronic inflammation with few particles of polyethylene that were birefringent using polarized light. The quantitative evaluation of bone ingrowth revealed that more than 95% of voids were filled with bone. Discussion: In the literature, a lot of studies focused on tantalum were carried on animal model. Up to now little information is available about the histology of the bone-tantalum interface in a human artificial joint. We had an opportunity to remove a well integrated cup hence this study. The histology confirmed the strong relationship between the structure of this material and bone. The morphometric analysis revealed a high percentage of bone ingrowth.

  9. Chromatin Remodeling and Plant Immunity.

    Science.gov (United States)

    Chen, W; Zhu, Q; Liu, Y; Zhang, Q

    2017-01-01

    Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance?

  10. Effect of Zirconia Dental Implant Surfaces on Bone Integration: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    2017-01-01

    Background. The information available about osseointegration and the bone to implant interaction of zirconia implants with various surface modifications is still far from sufficient. Objective. The purpose of this systematic review and meta-analysis was to evaluate and compare zirconia dental implants with different surface topographies, with a focus on bone to implant contact and removal torque. Methods. The systematic review of the extracted publications was performed to compare the bone to implant contact (BIC) with removal torque (RT) values of titanium dental implants and machined and surfaced modified zirconia implants. Results. A total of fifteen articles on BIC and RT values were included in the quantitative analysis. No significant difference in the BIC values was observed between titanium and machined zirconia implants (p = 0.373; 95% CI: −0.166 to 0.443). However, a significantly better BIC values were observed for acid etched zirconia implants compared with those of titanium implants (p = 0.032; 95% CI: 0.068 to 1.461). Unmodified zirconia implants showed favorable BIC values compared to modified-surface zirconia implants (p = 0.021; 95% CI: −0.973 to −0.080). Conclusion. Acid etched zirconia implants may serve as a possible substitute for successful osseointegration. PMID:28299337

  11. Remodeling with the sun

    Energy Technology Data Exchange (ETDEWEB)

    Bodzin, S. [ed.

    1997-05-01

    Remodeling is the perfect time to improve daylighting, direct gain heating and shading with passive solar techniques. It can also provide the best opportunity to add solar water heating or even photoboltaics to a home. This article describes addition of such energy efficient plans to a home in terms of what is needed and what the benefits are: adding windows, North glass, east and west glass, south glass, daylighting, the roof, shingles and roofing tiles, walls and floors, solar hot water, photovoltaics. Two side bars discuss the sunplace: a passive solar room and angles and overhangs.

  12. 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...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  14. 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

  15. Analyzing the cellular contribution of bone marrow to fracture healing using bone marrow transplantation in mice.

    Science.gov (United States)

    Colnot, C; Huang, S; Helms, J

    2006-11-24

    The bone marrow is believed to play important roles during fracture healing such as providing progenitor cells for inflammation, matrix remodeling, and cartilage and bone formation. Given the complex nature of bone repair, it remains difficult to distinguish the contributions of various cell types. Here we describe a mouse model based on bone marrow transplantation and genetic labeling to track cells originating from bone marrow during fracture healing. Following lethal irradiation and engraftment of bone marrow expressing the LacZ transgene constitutively, wild type mice underwent tibial fracture. Donor bone marrow-derived cells, which originated from the hematopoietic compartment, did not participate in the chondrogenic and osteogenic lineages during fracture healing. Instead, the donor bone marrow contributed to inflammatory and bone resorbing cells. This model can be exploited in the future to investigate the role of inflammation and matrix remodeling during bone repair, independent from osteogenesis and chondrogenesis.

  16. Sex steroids and bone.

    Science.gov (United States)

    Manolagas, S C; Kousteni, S; Jilka, R L

    2002-01-01

    The adult skeleton is periodically remodeled by temporary anatomic structures that comprise juxtaposed osteoclast and osteoblast teams and replace old bone with new. Estrogens and androgens slow the rate of bone remodeling and protect against bone loss. Conversely, loss of estrogen leads to increased rate of remodeling and tilts the balance between bone resorption and formation in favor of the former. Studies from our group during the last 10 years have elucidated that estrogens and androgens decrease the number of remodeling cycles by attenuating the birth rate of osteoclasts and osteoblasts from their respective progenitors. These effects result, in part, from the transcriptional regulation of genes responsible for osteoclastogenesis and mesenchymal cell replication and/or differentiation and are exerted through interactions of the ligand-activated receptors with other transcription factors. However, increased remodeling alone cannot explain why loss of sex steroids tilts the balance of resorption and formation in favor of the former. Estrogens and androgens also exert effects on the lifespan of mature bone cells: pro-apoptotic effects on osteoclasts but anti-apoptotic effects on osteoblasts and osteocytes. These latter effects stem from a heretofore unexpected function of the classical "nuclear" sex steroid receptors outside the nucleus and result from activation of a Src/Shc/extracellular signal-regulated kinase signal transduction pathway probably within preassembled scaffolds called caveolae. Strikingly, estrogen receptor (ER) alpha or beta or the androgen receptor can transmit anti-apoptotic signals with similar efficiency, irrespective of whether the ligand is an estrogen or an androgen. More importantly, these nongenotropic, sex-nonspecific actions are mediated by the ligand-binding domain of the receptor and can be functionally dissociated from transcriptional activity with synthetic ligands. Taken together, these lines of evidence strongly suggest that

  17. Adverse Remodeling and Reverse Remodeling After Myocardial Infarction.

    Science.gov (United States)

    Bhatt, Ankeet S; Ambrosy, Andrew P; Velazquez, Eric J

    2017-08-01

    The purpose of this review it to summarize the current literature on remodeling after myocardial infarction, inclusive of pathophysiological considerations, imaging modalities, treatment strategies, and future directions. As patients continue to live longer after myocardial infarction (MI), the prevalence of post-MI heart failure continues to rise. Changes in the left ventricle (LV) after MI involve complex interactions between cellular and extracellular components, under neurohormonal regulation. Treatments to prevent adverse LV remodeling and promote reverse remodeling in the post-MI setting include early revascularization, pharmacotherapy aimed at neurohormonal blockade, and device-based therapies that address ventricular dyssynchrony. Despite varying definitions of adverse LV remodeling examined across multiple imaging modalities, the presence of an enlarged LV cavity and/or reduced ejection fraction is consistently associated with poor clinical outcomes. Advances in our knowledge of the neurohormonal regulation of adverse cardiac remodeling have been instrumental in generating therapies aimed at arresting adverse remodeling and promoting reserve remodeling. Further investigation into other specific mechanisms of adverse LV remodeling and pathways to disrupt these mechanisms is ongoing and may provide incremental benefit to current evidence-based therapies.

  18. Biomarkers of bone and mineral metabolism following bone marrow transplantation.

    Science.gov (United States)

    Baek, Ki Hyun; Kang, Moo Il

    2009-01-01

    The loss of bone mass often occurs after patients undergo bone marrow transplantation (BMT). The rapid impairment of bone formation and the increase in bone resorption, as mirrored by the biochemical markers of bone turnover, might play a role in this bone loss, and especially during the immediate post-BMT period. The possible direct causes for this paradoxical uncoupling are exposure to immunosuppressants, hypogonadism, the changes of cytokines, the changes of the bone growth factors, and the damage to the osteoprogenitor cells because of myeloablative therapy. In this chapter, we discuss the general aspects of post-BMT bone loss with a peculiar focus on the remodeling imbalance of bone and its relation to the use of immunosuppressants and the changes of sex hormones, growth factors, and cytokines.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Sara Tavella

    Full Text Available 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.

  2. 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.

  3. 猪急性心肌梗死后骨髓干细胞自体移植对左心室重构的影响%Effects of bone marrow stem cells autologous transplantation on ventricular remodeling after acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    曾建平; 彭忮柳; 刘颖; 刘原; 黄浩波; 周胜华; 刘平; 黄河; 孙智山; 吴名星; 刘利华; 孙建平; 吴礼源

    2008-01-01

    Objective To investigate the effects of bone marrow stem cells autologous transplantation on left ventricular remodeling after acute myocardial infarction. Methods Acute myocardial infarction models were successfully established in 10 swines, which were ran-dom divided into two groups, placebo group and trasplantation group. One week after operation, bone marrow stem cells autologous transplan-tation was performed, and control group was administrated with placebo. B-ultrasound and emission computed tomography aexaminations were performed to assess the left ventrieular end diastolic dimension, left ventricular tip wall thickness, left ventricular end diastolic volume and left ventricula ejection fraction before operation, one week, three months after acute myocardial infarction. Results Compared with that of control group, three months after acute myocardial infarction, transplantation group witnessed smaller left ventricular end diastolic dimension, thicker left ventricular tip wall, smaller left ventricular end diastolic volume and higher left ventricular ejection fraction. Conclusions Bone marrow autologous transplantation after acute myocardial infarction can alleviate left ventricular remodeling.%目的 观察猪心肌梗死(心梗)后冠脉内注射移植骨髓干细胞时心室重_构的影响.方法 前降支球囊封堵法成功建立10头猪急性心肌梗死动物模型,随机均分为安慰刺组和移植组.造模1周后,移植组冠脉内注自体骨髓干细胞,安慰剂组注射1640培养基作为对照.造模前、造模后1周、造模后3月分别行心脏超声和SPECT检查,对比观察骨髓干细胞自体移植对急性心梗后左室重构的影响.结果与安慰剂组相比,移植组造模后3月时左室舒张内径更小,心尖室壁厚度更大,左室舒张末期容积更小,射血分数更高.结论 骨髓干细胞自体移植能有效减轻急性心肌梗死后左室重构.

  4. Myostatin deficiency partially rescues the bone phenotype of osteogenesis imperfecta model mice.

    Science.gov (United States)

    Oestreich, A K; Carleton, S M; Yao, X; Gentry, B A; Raw, C E; Brown, M; Pfeiffer, F M; Wang, Y; Phillips, C L

    2016-01-01

    Mice with osteogenesis imperfecta (+/oim), a disorder of bone fragility, were bred to mice with muscle over growth to test whether increasing muscle mass genetically would improve bone quality and strength. The results demonstrate that femora from mice carrying both mutations have greater mechanical integrity than their +/oim littermates. Osteogenesis imperfecta is a heritable connective tissue disorder due primarily to mutations in the type I collagen genes resulting in skeletal deformity and fragility. Currently, there is no cure, and therapeutic strategies encompass the use of antiresorptive pharmaceuticals and surgical bracing, with limited success and significant potential for adverse effects. Bone, a mechanosensing organ, can respond to high mechanical loads by increasing new bone formation and altering bone geometry to withstand increased forces. Skeletal muscle is a major source of physiological loading on bone, and bone strength is proportional to muscle mass. To test the hypothesis that congenic increases in muscle mass in the osteogenesis imperfecta murine model mouse (oim) will improve their compromised bone quality and strength, heterozygous (+/oim) mice were bred to mice deficient in myostatin (+/mstn), a negative regulator of muscle growth. The resulting adult offspring were evaluated for hindlimb muscle mass, and bone microarchitecture, physiochemistry, and biomechanical integrity. +/oim mice deficient in myostatin (+/mstn +/oim) were generated and demonstrated that myostatin deficiency increased body weight, muscle mass, and biomechanical strength in +/mstn +/oim mice as compared to +/oim mice. Additionally, myostatin deficiency altered the physiochemical properties of the +/oim bone but did not alter bone remodeling. Myostatin deficiency partially improved the reduced femoral bone biomechanical strength of adult +/oim mice by increasing muscle mass with concomitant improvements in bone microarchitecture and physiochemical properties.

  5. The use of brushite calcium phosphate cement for enhancement of bone-tendon integration in an anterior cruciate ligament reconstruction rabbit model.

    Science.gov (United States)

    Wen, Chun-Yi; Qin, Ling; Lee, Kwong-Man; Chan, Kai-Ming

    2009-05-01

    This study was designed to investigate the osteoconductivity and bioresorption of brushite calcium phosphate cement (CPC) in bone-tendon interface healing after anterior cruciate ligament (ACL) reconstruction. Surgical reconstruction using grafted tendon in bone tunnel was performed bilaterally in 28 skeletal mature rabbits. Brushite CPC was implanted between grafted tendon and bone tunnel of one limb with the contralateral one as the control. A batch of 14 rabbits was sacrificed at 6 and 12 weeks, respectively, after surgery. At each time point, six rabbits were used for micro-CT and subsequent histological examinations, whereas the remaining eight rabbits were used for pull-out testing. The components of brushite CPC-dicalcium phosphate dihydrate matrix degraded rapidly with beta-tricalcium phosphate granules left for guiding new bone formation. Brushite CPC augmented the peri-tendon bone volume and promoted bone growth into the healing interface. The ultimate strength and stiffness of the graft-tunnel complexes on experimental side was higher than that of the control by 117% and 102%, respectively, at 6 weeks postoperatively (p brushite CPC caused a paradigm shift in failure mode from intra-tunnel to intra-articular portion at 12 weeks postoperatively (p = 0.013). Brushite CPC significantly enhanced the bone-tendon integration after ACL reconstruction, which provided a scientific basis for clinical application.

  6. Understanding coupling between bone resorption and formation

    DEFF Research Database (Denmark)

    Andersen, Thomas Levin; Abdelgawad, Mohamed Essameldim; Kristensen, Helene Bjørg

    2013-01-01

    . Collectively, our observations suggest that arrested reversal cells reflect aborted remodeling cycles that did not progress to the bone formation step. We, therefore, propose that bone loss in postmenopausal osteoporosis does not only result from a failure of the bone formation step, as commonly believed......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...

  7. Melatonin improves bone mineral density at the femoral neck in postmenopausal women with osteopenia

    DEFF Research Database (Denmark)

    Amstrup, Anne Kristine; Sikjaer, Tanja; Heickendorff, Lene

    2015-01-01

    Melatonin is known for its regulation of circadian rhythm. Recently, studies have shown that melatonin may have a positive effect on the skeleton. By increasing age, the melatonin levels decrease, which may lead to a further imbalanced bone remodeling. We aimed to investigate whether treatment...... with melatonin could improve bone mass and integrity in humans. In a double-blind RCT, we randomized 81 postmenopausal osteopenic women to 1-yr nightly treatment with melatonin 1 mg (N = 20), 3 mg (N = 20), or placebo (N = 41). At baseline and after 1-yr treatment, we measured bone mineral density (BMD) by dual...... X-ray absorptiometry, quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) and determined calciotropic hormones and bone markers. Mean age of the study subjects was 63 (range 56-73) yr. Compared to placebo, femoral neck BMD increased by 1.4% in response to melatonin...

  8. 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...

  9. 牙弓/牙槽骨弓的塑形矫治——基于牙弓形态发育不良的儿童错(拾)畸形诊断与阻断治疗%Dental alveolar bone and dental arch remodeling in children: orthodontic diagnosis and treatments based on individual child arch development

    Institute of Scientific and Technical Information of China (English)

    李小兵

    2016-01-01

    The etiology of malocclusions basically involves both congenital and environmental factors. Malocclusion is the result of the abnormal development of the orofacial complex (including tooth, dental alveolar bone, upper and lower jaws). Early orthodontic interceptive treatments involve the elimination of all congenital and environmental factors that contribute to the malformation of the orofacial complex, as well as interrupt the deviated development of the orofacial complex and the occlusion. Early orthodontic interceptive treatments mainly aim to use children's growth potential to correct abnormal develop-ments of occlusions and orthodontically treat malocclusions more efficiently. The early orthodontic interceptive treatments include correcting the child's bad oral habits, training the abnormal functioned para-oral muscles, maintaining the normal eruptions of succeeding permanent teeth, applying interceptive treatments to the mal-developed teeth, and employing functional orthopedic treatments for abnormal growths of the upper and lower jaws. In orthodontics, correcting mal-positioned teeth is called orthodontic treatment, while rectifying the abnormal relationships of the upper and lower jaws is called functional orthopedic treatment. However, no clear definition is available as regards to the early orthodontic interceptive treatment of malocclusions caused by the deviated development of the dental alveolar bone. This new theory of "early dental alveolar bone and dental arch remodeling technique" was proposed by Professor Li Xiaobing of the Department of Pediatric Dentistry, Faculty of Pediatric Dentistry and Orthodontics in West China Hospital of Stomatology through his clinical analyses and investigation of his early orthodontic interceptive treatments. He defined the early orthodontic corrections of abnormal growth of dental alveolar bone as "remodel". The "early dental alveolar bone and dental arch remodeling theory and technique" is proved useful in

  10. Effects of mechanical stimuli on adaptive remodeling of condylar cartilage.

    Science.gov (United States)

    Sriram, D; Jones, A; Alatli-Burt, I; Darendeliler, M A

    2009-05-01

    Trabecular bone has been shown to be responsive to low-magnitude, high-frequency mechanical stimuli. This study aimed to assess the effects of these stimuli on condylar cartilage and its endochondral bone. Forty female 12-week-old C3H mice were divided into 3 groups: baseline control (killed at day 0), sham (killed at day 28 without exposure to mechanical stimuli), and experimental (killed following 28 days of exposure to mechanical stimuli). The experimental group was subjected to mechanical vibration of 30 Hz, for 20 minutes per day, 5 days per week, for 28 days. The specimens were analyzed by micro-computed tomography. The experimental group demonstrated a significant decrease in the volume of condylar cartilage and also a significant increase in bone histomorphometric parameters. The results suggest that the low-magnitude, high-frequency mechanical stimuli enhance adaptive remodeling of condylar cartilage, evidenced by the advent of endochondral bone replacing the hypertrophic cartilage.

  11. Digital radiographic evaluation of alveolar bone loss, density and lamina dura integrity on post splinting mandibular anterior with chronic periodontitis

    Science.gov (United States)

    Rafini, F.; Priaminiarti, M.; Sukardi, I.; Lessang, R.

    2017-08-01

    The healing of periodontal splinting can be detected both with clinical and radiographic examination. In this study, the alveolar bone was evaluated by radiographic digital periapical analysis. Periodontal tooth splinting is periodontal support therapy used to prevent periodontal injury during repair and regeneration of periodontal therapy. Radiographic digital periapical analysis of alveolar bone in the mandibular anterior region with chronic periodontitis and 2/3 cervical bone loss after three months of periodontal splinting. Eighty four proximal site (43 mesial and 41 distal) from 16 patients with chronic periodontitis and treated with spinting were examined by taking periapical digital radiographic at day 1 and 91. The bone loss, bone density and utility of lamina dura were evaluated. The statistical analysis after three months evaluation using T-test for bone loss, Wilcoxon sign rank test for bone density and utility lamina dura showed no significantly differences (pperiodontitis with 2/3 alveolar bone loss after three months splinting.

  12. Subchondral chitosan/blood implant-guided bone plate resorption and woven bone repair is coupled to hyaline cartilage regeneration from microdrill holes in aged rabbit knees.

    Science.gov (United States)

    Guzmán-Morales, J; Lafantaisie-Favreau, C-H; Chen, G; Hoemann, C D

    2014-02-01

    Little is known of how to routinely elicit hyaline cartilage repair tissue in middle-aged patients. We tested the hypothesis that in skeletally aged rabbit knees, microdrill holes can be stimulated to remodel the bone plate and induce a more integrated, voluminous and hyaline cartilage repair tissue when treated by subchondral chitosan/blood implants. New Zealand White rabbits (13 or 32 months old, N = 7) received two 1.5 mm diameter, 2 mm depth drill holes in each knee, either left to bleed as surgical controls or press-fit with a 10 kDa (distal hole: 10K) or 40 kDa (proximal hole: 40K) chitosan/blood implant with fluorescent chitosan tracer. Post-operative knee effusion was documented. Repair tissues at day 0 (N = 1) and day 70 post-surgery (N = 6) were analyzed by micro-computed tomography, and by histological scoring and histomorphometry (SafO, Col-2, and Col-1) at day 70. All chitosan implants were completely cleared after 70 days, without increasing transient post-operative knee effusion compared to controls. Proximal control holes had worse osteochondral repair than distal holes. Both implant formulations induced bone remodeling and improved lateral integration of the bone plate at the hole edge. The 40K implant inhibited further bone repair inside 50% of the proximal holes, while the 10K implant specifically induced a "wound bloom" reaction, characterized by decreased bone plate density in a limited zone beyond the initial hole edge, and increased woven bone (WB) plate repair inside the initial hole (P = 0.016), which was accompanied by a more voluminous and hyaline cartilage repair (P hyaline cartilage repair can be promoted by treating acute drill holes with a biodegradable subchondral implant that elicits bone plate resorption followed by anabolic WB repair within a 70-day repair period. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  13. 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.

  14. Understanding the chromatin remodeling code.

    Science.gov (United States)

    Ha, Misook

    2013-10-01

    Remodeling a chromatin structure enables the genetic elements stored in a genome to function in a condition-specific manner and predisposes the interactions between cis-regulatory elements and trans-acting factors. A chromatin signature can be an indicator of the activity of the underlying genetic elements. This paper reviews recent studies showing that the combination and arrangements of chromatin remodeling marks play roles as chromatin code affecting the activity of genetic elements. This paper also reviews recent studies inferring the primary DNA sequence contexts associated with chromatin remodeling that suggest interactions between genetic and epigenetic factors. We conclude that chromatin remodeling, which provides accurate models of gene expression and morphological variations, may help to find the biological marks that cannot be detected by genome-wide association study or genetic study. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Bone tumor

    Science.gov (United States)

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

  16. Evolutionary patterns of bone histology and bone compactness in xenarthran mammal long bones.

    Science.gov (United States)

    Straehl, Fiona R; Scheyer, Torsten M; Forasiepi, Analía M; MacPhee, Ross D; Sánchez-Villagra, Marcelo R

    2013-01-01

    Bone microstructure reflects physiological characteristics and has been shown to contain phylogenetic and ecological signals. Although mammalian long bone histology is receiving increasing attention, systematic examination of the main clades has not yet been performed. Here we describe the long bone microstructure of Xenarthra based on thin sections representing twenty-two species. Additionally, patterns in bone compactness of humeri and femora are investigated. The primary bone tissue of xenarthran long bones is composed of a mixture of woven, parallel-fibered and lamellar bone. The vascular canals have a longitudinal, reticular or radial orientation and are mostly arranged in an irregular manner. Concentric rows of vascular canals and laminar organization of the tissue are only found in anteater bones. The long bones of adult specimens are marked by dense Haversian bone, a feature that has been noted for most groups of mammals. In the long bones of armadillos, secondary osteons have an oblique orientation within the three-dimensional bone tissue, thus resulting in their irregular shape when the bones are sectioned transversely. Secondary remodeling is generally more extensive in large taxa than in small taxa, and this could be caused by increased loading. Lines of arrested growth are assumed to be present in all specimens, but they are restricted to the outermost layer in bones of armadillos and are often masked by secondary remodeling in large taxa. Parameters of bone compactness show a pattern in the femur that separates Cingulata and Pilosa (Folivora and Vermilingua), with cingulates having a lower compactness than pilosans. In addition, cingulates show an allometric relationship between humeral and femoral bone compactness.

  17. Monitoring of Postoperative Bone Healing Using Smart Trauma-Fixation Device With Integrated Self-Powered Piezo-Floating-Gate Sensors.

    Science.gov (United States)

    Borchani, Wassim; Aono, Kenji; Lajnef, Nizar; Chakrabartty, Shantanu

    2016-07-01

    Achieving better surgical outcomes in cases of traumatic bone fractures requires postoperative monitoring of changes in the growth and mechanical properties of the tissue and bones during the healing process. While current in-vivo imaging techniques can provide a snapshot of the extent of bone growth, it is unable to provide a history of the healing process, which is important if any corrective surgery is required. Monitoring the time evolution of in-vivo mechanical loads using existing technology is a challenge due to the need for continuous power while maintaining patient mobility and comfort. This paper investigates the feasibility of self-powered monitoring of the bone-healing process using our previously reported piezo-floating-gate (PFG) sensors. The sensors are directly integrated with a fixation device and operate by harvesting energy from microscale strain variations in the fixation structure. We show that the sensors can record and store the statistics of the strain evolution during the healing process for offline retrieval and analysis. Additionally, we present measurement results using a biomechanical phantom comprising of a femur fracture fixation plate; bone healing is emulated by inserting different materials, with gradually increasing elastic moduli, inside a fracture gap. The PFG sensor can effectively sense, compute, and record continuously evolving statistics of mechanical loading over a typical healing period of a bone, and the statistics could be used to differentiate between different bone-healing conditions. The proposed sensor presents a reliable objective technique to assess bone-healing progress and help decide on the removal time of the fixation device.

  18. 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.

  19. 不同矫治正畸作用下牙周骨改建过程中压力侧相关因子的变化%Changes of related factors on the pressure side under different appliance orthodontic during periodontal bone remodeling

    Institute of Scientific and Technical Information of China (English)

    马永平; 葛长青; 高琳青

    2013-01-01

    BACKGROUND: Recent studies have shown that receptor activator of nuclear factor-κB ligand is closely related to osteoclast differentiation, formation and function in bone remodeling during orthodontic tooth movement. OBJECTIVE: To observe the changes in receptor activator of nuclear factor-κB ligand expression in the pressure side during periodontal tissue remodeling under different appliance orthodontics, and to explore the effect of different orthodontic appliances. METHODS: Sixty-four healthy rabbits were divided into four groups: control group, MBT appliance group, Begg appliance group, Damon Ⅲ appliance group, 16 rabbits in each group. In the MBT appliance group, Begg appliance group and Damon Ⅲ appliance group, corresponding appliances were used to correct the maxil ary incisors and first molars respectively, and the mesial movement traction force was 80 g; the control group did not receive correction. Four rabbits were selected from each group for testing at 3, 7, 14 and 21 days after correction. RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that the periodontal ligament cavity in the pressure side was narrow and the edge of the alveolar bone exhibited resorption pits. Tartrate-resistant acid phosphatase staining showed bone remodeling was active and the number of osteoclasts reached peak at 7 days after correction. Real-time quantitative PCR showed that the mRNA expression of receptor activator of nuclear factor-κB ligand on the pressure side of the alveolar bone tissue was significantly increased after force loading, and reached peak at 7 days after forcing, then gradual y decreased. At 7 days after forcing, the number of osteoclasts and the mRNA expression of receptor activator of nuclear factor-κB ligand in the Damon Ⅲ appliance group were higher than those in the MBT appliance group and Begg appliance group (P < 0.05). In bone remodeling process, mRNA expression of receptor activator of nuclear factor-κB ligand was positively

  20. Improving depiction of temporal bone anatomy with low-radiation dose CT by an integrated circuit detector in pediatric patients: a preliminary study.

    Science.gov (United States)

    He, Jingzhen; Zu, Yuliang; Wang, Qing; Ma, Xiangxing

    2014-12-01

    The purpose of this study was to determine the performance of low-dose computed tomography (CT) scanning with integrated circuit (IC) detector in defining fine structures of temporal bone in children by comparing with the conventional detector. The study was performed with the approval of our institutional review board and the patients' anonymity was maintained. A total of 86 children0.05). The low-dose CT images acquired with the IC detector provide better depiction of fine osseous structures of temporal bone than that with the conventional DC detector.

  1. A calcitonin receptor (CALCR) single nucleotide polymorphism is associated with growth performance and bone integrity in response to dietary phosphorus deficiency.

    Science.gov (United States)

    Alexander, L S; Qu, A; Cutler, S A; Mahajan, A; Rothschild, M F; Cai, W; Dekkers, J C; Stahl, C H

    2010-03-01

    Although concerns over the environmental impact of excess P in the excreta from pig production and governmental regulations have driven research toward reducing dietary supplementation of P to swine diets for over a decade, recent dramatic increases in feed costs have further motivated researchers to identify means to further reduce dietary P supplementation. We have demonstrated that genetic background impacts P utilization in young pigs and have identified genetic polymorphisms in several target genes related to mineral utilization. In this study, we examined the impact of a SNP in the calcitonin receptor gene (CALCR) on P utilization in growing pigs. In Exp. 1, 36 gilts representing the 3 genotypes identified by this CALCR SNP (11, 12, and 22) were fed a P-adequate (PA) or a marginally P-deficient (approximately 20% less available P; PD) diet for 14 wk. As expected, P deficiency reduced plasma P concentration, bone strength, and mineral content (P < 0.05). However, the dietary P deficiency was mild enough to not affect the growth performance of these pigs. A genotype x dietary P interaction (P < 0.05) was observed in measures of bone integrity and mineral content, with the greatest reduction in bone strength and mineral content due to dietary P deficiency being associated with the allele 1. In Exp. 2, 168 pigs from a control line and low residual feed intake (RFI) line were genotyped for the CALCR SNP and fed a PA diet. As expected, pigs from the low RFI line consumed less feed but also gained less BW when compared with the control line (P < 0.05). Although ADFI did not differ between genotypes, pigs having the 11 genotype gained less BW (P < 0.05) than pigs having the 12 or 22 genotypes. Pigs of the 11 and 12 genotypes had bones that tolerated greater load when compared with animals having the 22 genotype (P < 0.05). A similar trend was observed in bone modulus and ash % (P < 0.10). These data are supportive of the association of this CALCR SNP with bone

  2. Estrogen effects on interleukin-1 expression in alveolar bone remodeling of osteoporotic rats%雌激素干预骨质疏松大鼠牙槽骨改建过程中白细胞介素1的表达

    Institute of Scientific and Technical Information of China (English)

    王袖和; 王长庆; 朱玉平; 张晓东

    2013-01-01

    BACKGROUND:Currently rats are the most frequently used animal for the models of osteoporosis and ovariectomized rat models have been widely applied due to ovariectomized female rats are similar to human body in bone mineral density changes and response after estrogen administration. OBJECTIVE:To establish rat models of osteoporotic tooth extraction wound healing, and to investigate the effect of estrogen on the interleukin-1 expression and distribution in the remodeling of osteoporotic alveolar bone. METHODS:Sixty-five purebred female rats, 3 months old, were randomly divided into two groups:osteoporosis model group (n=40;ovariectomy under general anesthesia) and sham operation group (n=25;fat tissue around ovary was removed). After 8-week feeding, osteoporosis models were established and the left upper molar was pul ed out under general anesthesia. Histomorphomeric parameters test was performed on the jaw bone. In osteoporosis model group, 15 rats were randomly selected to give subcutaneous injection of estradiol benzoate, as the estrogen treatment group. Immunohistochemical method was applied to observe the interleukin-1 expression in the remodeling of osteoporotic alveolar bone. RESULTS AND CONCLUSION:After ovariotomy, the amount of trabecula decreased and the medul ary cavity of the bone became larger, the jaw bone intensity decreased. After administration of estrogen, the positive expression of interleukin-1 was reduced as compared with osteoporosis model group. Experimental findings indicate that, osteoporosis can be detected in Sprague-Dawley female rats aged 3 months at 8 weeks after ovariotomy, and administration of estrogen can obviously decrease interleukin-1 positive expression in the remodeling of osteoporotic alveolar bone.%背景:目前大鼠是骨质疏松研究中使用最多的模型动物,其中大鼠去卵巢动物模型应用最广泛,雌性大鼠在卵巢切除后,其骨质变化和给予雌激素后的反应与人相似。

  3. Total water, phosphorus relaxation and inter-atomic organic to inorganic interface are new determinants of trabecular bone integrity.

    Science.gov (United States)

    Rai, Ratan Kumar; Barbhuyan, Tarun; Singh, Chandan; Mittal, Monika; Khan, Mohd Parvez; Sinha, Neeraj; Chattopadhyay, Naibedya

    2013-01-01

    Bone is the living composite biomaterial having unique structural property. Presently, there is a considerable gap in our understanding of bone structure and composition in the native state, particularly with respect to the trabecular bone, which is metabolically more active than cortical bones, and is readily lost in post-menopausal osteoporosis. We used solid-state nuclear magnetic resonance (NMR) to compare trabecular bone structure and composition in the native state between normal, bone loss and bone restoration conditions in rat. Trabecular osteopenia was induced by lactation as well as prolonged estrogen deficiency (bilateral ovariectomy, Ovx). Ovx rats with established osteopenia were administered with PTH (parathyroid hormone, trabecular restoration group), and restoration was allowed to become comparable to sham Ovx (control) group using bone mineral density (BMD) and µCT determinants. We used a technique combining (1)H NMR spectroscopy with (31)P and (13)C to measure various NMR parameters described below. Our results revealed that trabecular bones had diminished total water content, inorganic phosphorus NMR relaxation time (T1) and space between the collagen and inorganic phosphorus in the osteopenic groups compared to control, and these changes were significantly reversed in the bone restoration group. Remarkably, bound water was decreased in both osteopenic and bone restoration groups compared to control. Total water and T1 correlated strongly with trabecular bone density, volume, thickness, connectivity, spacing and resistance to compression. Bound water did not correlate with any of the microarchitectural and compression parameters. We conclude that total water, T1 and atomic space between the crystal and organic surface are altered in the trabecular bones of osteopenic rats, and PTH reverses these parameters. Furthermore, from these data, it appears that total water and T1 could serve as trabecular surrogates of micro-architecture and compression

  4. Total water, phosphorus relaxation and inter-atomic organic to inorganic interface are new determinants of trabecular bone integrity.

    Directory of Open Access Journals (Sweden)

    Ratan Kumar Rai

    Full Text Available Bone is the living composite biomaterial having unique structural property. Presently, there is a considerable gap in our understanding of bone structure and composition in the native state, particularly with respect to the trabecular bone, which is metabolically more active than cortical bones, and is readily lost in post-menopausal osteoporosis. We used solid-state nuclear magnetic resonance (NMR to compare trabecular bone structure and composition in the native state between normal, bone loss and bone restoration conditions in rat. Trabecular osteopenia was induced by lactation as well as prolonged estrogen deficiency (bilateral ovariectomy, Ovx. Ovx rats with established osteopenia were administered with PTH (parathyroid hormone, trabecular restoration group, and restoration was allowed to become comparable to sham Ovx (control group using bone mineral density (BMD and µCT determinants. We used a technique combining (1H NMR spectroscopy with (31P and (13C to measure various NMR parameters described below. Our results revealed that trabecular bones had diminished total water content, inorganic phosphorus NMR relaxation time (T1 and space between the collagen and inorganic phosphorus in the osteopenic groups compared to control, and these changes were significantly reversed in the bone restoration group. Remarkably, bound water was decreased in both osteopenic and bone restoration groups compared to control. Total water and T1 correlated strongly with trabecular bone density, volume, thickness, connectivity, spacing and resistance to compression. Bound water did not correlate with any of the microarchitectural and compression parameters. We conclude that total water, T1 and atomic space between the crystal and organic surface are altered in the trabecular bones of osteopenic rats, and PTH reverses these parameters. Furthermore, from these data, it appears that total water and T1 could serve as trabecular surrogates of micro-architecture and

  5. The effect of a fibrin glue on the integration of Bio-Oss with bone tissue. A experimental study in labrador dogs.

    Science.gov (United States)

    Carmagnola, Daniela; Berglundh, Tord; Lindhe, Jan

    2002-05-01

    Bio-Oss is a deproteinized bovine mineral used in bone augmentation procedures. The particles are often mixed with a protein product (Tisseel) to form a mouldable graft material. The aim of the present experiment was to study the healing of self-contained bone defects after the placement of Bio-Oss particles alone or mixed with Tisseel in cylindrical defects in the edentulous mandibular ridge of dogs. In 4 labrador dogs, the 2nd, 3rd and 4th mandibular premolars were extracted bilaterally. 3 months later, 3 cylindrical bone defects, 4 mm in diameter and 8 mm in depth, were produced in the right side of the mandible. Following a crestal incision, full thickness flaps were raised and the bone defects were prepared with a trephine drill. The defects were filled with Bio-Oss (Geistlich Biomaterials, Wolhuser, Switzerland) particles alone or mixed with Tisseel (Immuno AG, Vienna, Austria), or left "untreated". A collagen membrane (Bio-Gide, Geistlich Biomaterials, Wolhuser, Switzerland) was placed to cover all defects and the flaps were sutured. 2 months later, the defect preparation and grafting procedures were repeated in the left side of the mandible. After another month, the animals were sacrificed and biopsies obtained from the defect sites. Bio-Oss-treated defects revealed a higher percentage of contact between graft particles and bone tissue than defects treated with Bio-Oss+ Tisseel (15% and 30% at 1 and 3 months versus 0.4% and 8%, respectively). Further, the volume of connective tissue in the Bio-Oss treated defects decreased from the 1 to the 3 month interval (from 44% to 30%). This soft tissue was replaced with newly formed bone. In the Bio-Oss+ Tisseel treated defects, however, the proportion of connective tissue remained unchanged between 1 and 3 months. The adjunct of Tisseel may jeopardize the integration of Bio-Oss particles with bone tissue.

  6. 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.

  7. 犬牙槽骨种植实验及种植体-骨结合评价方法%The evaluation methods of dental implant in canine alveolar bone and bone integration

    Institute of Scientific and Technical Information of China (English)

    冯丽芳(综述); 吴琳(审校)

    2013-01-01

    种植体与骨形成良好的骨结合界面是种植义齿修复成功的重要标志之一,而动物实验是评价种植体与骨结合界面的重要手段,其中犬牙槽骨是研究牙种植体植入的理想部位之一。本文就犬牙槽骨内植入种植体的实验方法及种植体与骨结合情况的评价方法做一综述。%Good osseointegration interface of implant and bone form is one of important signs of the success of implant denture restoration. Animal experiment is one important means to evaluate dental implant and osseointegration interface. One of ideal sites for dental implant implanted is canine alveolar bone . In this paper the experiment method of dental im-plant implanted in canine alveolar bone and the evaluation methods of dental implant and bone integration will be re-viewed.

  8. Remodeling dynamics in the alveolar process in skeletally mature dogs.

    Science.gov (United States)

    Huja, Sarandeep S; Fernandez, Soledad A; Hill, Kara J; Li, Yan

    2006-12-01

    Bone turnover rates can be altered by metabolic and mechanical demands. Due to the difference in the pattern of loading, we hypothesized that there are differences in bone remodeling rates between the maxillary and mandibular alveolar processes. Furthermore, in a canine model, the alveolar process of teeth that lack contact (e.g., second premolars) would have a different turnover rate than bone supporting teeth with functional contact (e.g., first molars). Six skeletally mature male dogs were given a pair of calcein labels. After sacrifice, specimens representing the anterior and posterior locations of both jaws were prepared for examination by histomorphometric methods to evaluate the bone volume/total volume (BV/TV; %), bone volume (mm2), mineral apposition rate (MAR; microm/day), and bone formation rate (BFR; %/year) in the alveolar process. There were no significant differences (P>0.05) in the BV/TV within the jaws. The bone volume within the alveolar process of the mandible was 2.8-fold greater than in the maxilla. The MAR was not significantly different between the jaws and anteroposterior locations. However, the BFR was significantly (Parchitecture.

  9. The effect of polystyrene sodium sulfonate grafting on polyethylene terephthalate artificial ligaments on in vitro mineralisation and in vivo bone tissue integration

    Science.gov (United States)

    Vaquette, Cédryck; Viateau, Véronique; Guérard, Sandra; Anagnostou, Fani; Manassero, Mathieu; Castner, David G.; Migonney, Véronique

    2013-01-01

    This study investigates the impact of polystyrene sodium sulfonate (PolyNaSS) grafting onto the osseointegration of a polyethylene terephthalate artificial ligament (Ligament Advanced Reinforcement System, LARS™) used for Anterior Cruciate Ligament (ACL). The performance of grafted and non-grafted ligaments was assessed in vitro by culturing human osteoblasts under osteogenic induction and this demonstrated that the surface modification was capable of up-regulating the secretion of ALP and induced higher level of mineralisation as measured 6 weeks post-seeding by Micro-Computed Tomography. Grafted and non-grafted LARS™ were subsequently implanted in an ovine model for ACL reconstruction and the ligament-to-bone interface was evaluated by histology and biomechanical testing 3 and 12 months post-implantation. The grafted ligaments exhibited more frequent direct ligament-to-bone contact and bone formation in the core of the ligament at the later time point than the nongrafted specimens, the grafting also significantly reduced the fibrous encapsulation of the ligament 12 months post-implantation. However, this improved osseo-integration was not translated into a significant increase in the biomechanical pull-out loads. These results provide evidences that PolyNaSS grafting improved the osseo-integration of the artificial ligament within the bone tunnels. This might positively influence the outcome of the surgical reconstructions, as higher ligament stability is believed to limit micro-movement and therefore permits earlier and enhanced healing. PMID:23790438

  10. Three-Dimensional Bone Adaptation of the Proximal Femur

    DEFF Research Database (Denmark)

    Bagge, Mette

    1998-01-01

    The bone remodeling of a three-dimensional model of the proximal femur is considered. The bone adaptation is numerically described as an evolution in time formulated such that the structural change goes in an optimal direction within each time step for the optimal boundary conditions. In the bone...

  11. Modeling and remodeling of human extraction sockets.

    Science.gov (United States)

    Trombelli, Leonardo; Farina, Roberto; Marzola, Andrea; Bozzi, Leopoldo; Liljenberg, Birgitta; Lindhe, Jan

    2008-07-01

    The available studies on extraction wound repair in humans are affected by significant limitations and have failed to evaluate tissue alterations occurring in all compartments of the hard tissue defect. To monitor during a 6-month period the healing of human extraction sockets and include a semi-quantitative analysis of tissues and cell populations involved in various stages of the processes of modeling/remodeling. Twenty-seven biopsies, representative of the early (2-4 weeks, n=10), intermediate (6-8 weeks, n=6), and late phase (12-24 weeks, n=11) of healing, were collected and analysed. Granulation tissue that was present in comparatively large amounts in the early healing phase of socket healing, was in the interval between the early and intermediate observation phase replaced with provisional matrix and woven bone. The density of vascular structures and macrophages slowly decreased from 2 to 4 weeks over time. The presence of osteoblasts peaked at 6-8 weeks and remained almost stable thereafter; a small number of osteoclasts were present in a few specimens at each observation interval. The present findings demonstrated that great variability exists in man with respect to hard tissue formation within extraction sockets. Thus, whereas a provisional connective tissue consistently forms within the first weeks of healing, the interval during which mineralized bone is laid down is much less predictable.

  12. Osteocyte-viability-based simulations of trabecular bone loss and recovery in disuse and reloading

    NARCIS (Netherlands)

    Wang, H.; Ji, B.; Liu, X.S.; van Oers, R.F.M.; Guo, X.E.; Huang, Y.; Hwang, K.C.

    2014-01-01

    Osteocyte apoptosis is known to trigger targeted bone resorption. In the present study, we developed an osteocyte-viability-based trabecular bone remodeling (OVBR) model. This novel remodeling model, combined with recent advanced simulation methods and analysis techniques, such as the element-by-ele

  13. Evaluation of bone remodeling with (18)F-fluoride and correlation with the glucose metabolism measured by (18)F-FDG in lumbar spine with time in an experimental nude rat model with osteoporosis using dynamic PET-CT.

    Science.gov (United States)

    Cheng, Caixia; Heiss, Christian; Dimitrakopoulou-Strauss, Antonia; Govindarajan, P; Schlewitz, G; Pan, Leyun; Schnettler, Reinhard; Weber, Klaus; Strauss, Ludwig G

    2013-01-01

    Rats with osteoporosis were involved by combining ovariectomy (OVX) either with calcium and Vitamin D deficiency diet (Group D), or with glucocorticoid (dexamethasone) treatment (Group C). In the period of 1-12 months, dynamic PET-CT studies were performed in three groups of rats including Group D, Group C and the control Group K (sham-operated). Standardized uptake values (SUVs) were calculated, and a 2-tissue compartmental learning-machine model (calculation of K1-k4, VB and the plasma clearance of tracer to bone mineral (Ki) as well as a non-compartmental model based on the fractal dimension (FD) was used for quantitative analysis of both groups. The evaluation of PET data was performed over the lumbar spine. The correlation analysis revealed a significant linear correlation for certain dPET quantitative parameters and time up to 12 months after induction of osteoporosis. Based on the (18)F-Fluoride data, we noted a significant negative correlation for K1 (the fluoride/hydroxyl exchange) in the Group C and a significant positive correlation for k3, SUV (bone metabolism) and FD in the Group K. The evaluation of the (18)F-FDG data revealed a significant positive correlation for SUV (glucose metabolism) only in Group C. The correlation between the two tracers revealed significant results between K1 of (18)F-Fluoride and SUV of FDG in Group K as well as between FD of (18)F-Fluoride and FDG in Group D and C and between k3 of (18)F-Fluoride and SUV of FDG in Group C.

  14. Evaluation of bone remodeling with 18F-fluoride and correlation with the glucose metabolism measured by 18F-FDG in lumbar spine with time in an experimental nude rat model with osteoporosis using dynamic PET-CT

    Science.gov (United States)

    Cheng, Caixia; Heiss, Christian; Dimitrakopoulou-Strauss, Antonia; Govindarajan, P; Schlewitz, G; Pan, Leyun; Schnettler, Reinhard; Weber, Klaus; Strauss, Ludwig G

    2013-01-01

    Rats with osteoporosis were involved by combining ovariectomy (OVX) either with calcium and Vitamin D deficiency diet (Group D), or with glucocorticoid (dexamethasone) treatment (Group C). In the period of 1-12 months, dynamic PET-CT studies were performed in three groups of rats including Group D, Group C and the control Group K (sham-operated). Standardized uptake values (SUVs) were calculated, and a 2-tissue compartmental learning-machine model (calculation of K1-k4, VB and the plasma clearance of tracer to bone mineral (Ki) as well as a non-compartmental model based on the fractal dimension (FD) was used for quantitative analysis of both groups. The evaluation of PET data was performed over the lumbar spine. The correlation analysis revealed a significant linear correlation for certain dPET quantitative parameters and time up to 12 months after induction of osteoporosis. Based on the 18F-Fluoride data, we noted a significant negative correlation for K1 (the fluoride/hydroxyl exchange) in the Group C and a significant positive correlation for k3, SUV (bone metabolism) and FD in the Group K. The evaluation of the 18F-FDG data revealed a significant positive correlation for SUV (glucose metabolism) only in Group C. The correlation between the two tracers revealed significant results between K1 of 18F-Fluoride and SUV of FDG in Group K as well as between FD of 18F-Fluoride and FDG in Group D and C and between k3 of 18F-Fluoride and SUV of FDG in Group C. PMID:23526138

  15. Remodeling Science Education

    Science.gov (United States)

    Hestenes, David

    2013-01-01

    Radical reform in science and mathematics education is needed to prepare citizens for challenges of the emerging knowledge-based global economy. We consider definite proposals to establish: (1) "Standards of science and math literacy" for all students. (2) "Integration of the science curriculum" with structure of matter,…

  16. Chromatin dynamics: interplay between remodeling enzymes and histone modifications.

    Science.gov (United States)

    Swygert, Sarah G; Peterson, Craig L

    2014-08-01

    Chromatin dynamics play an essential role in regulating the accessibility of genomic DNA for a variety of nuclear processes, including gene transcription and DNA repair. The posttranslational modification of the core histones and the action of ATP-dependent chromatin remodeling enzymes represent two primary mechanisms by which chromatin dynamics are controlled and linked to nuclear events. Although there are examples in which a histone modification or a remodeling enzyme may be sufficient to drive a chromatin transition, these mechanisms typically work in concert to integrate regulatory inputs, leading to a coordinated alteration in chromatin structure and function. Indeed, site-specific histone modifications can facilitate the recruitment of chromatin remodeling enzymes to particular genomic regions, or they can regulate the efficiency or the outcome of a chromatin remodeling reaction. Conversely, chromatin remodeling enzymes can also influence, and sometimes directly modulate, the modification state of histones. These functional interactions are generally complex, frequently transient, and often require the association of myriad additional factors. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Characterizing the inorganic/organic interface in cancer bone metastasis

    Science.gov (United States)

    Wu, Fei

    Bone metastasis frequently occurs in patients with advanced breast cancer and remains a major source of mortality. At the molecular level, bone is a nanocomposite composed of inorganic bone mineral deposited within an organic extracellular matrix (ECM). Although the exact mechanisms of bone metastasis remain unclear, the nanoscale materials properties of bone mineral have been implicated in this process. Bone apatite is closely related to synthetic hydroxyapatite (HAP, Ca10(PO4)6(OH)2) in terms of structural and mechanical properties. Additionally, although the primary protein content of bone is collagen I, the glycoprotein fibronectin (Fn) is essential in maintaining the overall integrity of the bone matrix. Importantly, in vivo, neither breast cancer cells nor normal bone cells interact directly with the bone mineral but rather with the protein film adsorbed onto the mineral surface. Therefore, we hypothesized that breast cancer cell functions were regulated by differential fibronectin adsorption onto hydroxyapatite, which led to pathological remodeling of the bone matrix and sustained bone metastasis. Three model systems containing HAP and Fn were developed for this thesis. In model system I, a library of synthetic HAP nanoparticles were utilized to investigate the effect of mineral size, shape, and crystallinity on Fn conformation, using Forster resonance energy transfer (FRET) spectroscopy. In model system II, Fn-functionalized large geologic HAP crystals were used instead of HAP nanoparticles to avoid cellular uptake when investigating subsequent cell functions. Overall our FRET analysis (models I and II) revealed that Fn conformation depended on size, surface chemistry, and roughness of underlying HAP. When breast cancer cells were seeded on the Fn-coated HAP crystal facets (model II), our data indicated high secretion levels of proangiogenic and proinflammatory factors associated with the presence of unfolded Fn conformations, likely caused by differential

  18. 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...

  19. Bioceramics of apatites: an option for bone regeneration; Bioceramica de apatitas: uma opcao para regeneracao ossea

    Energy Technology Data Exchange (ETDEWEB)

    Arxer, Eliana Alves; Almeida Filho, Edson de; Guastaldi, Antonio Carlos, E-mail: iarxer@iq.unesp.br [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Araraquara, SP (Brazil). Instituto de Quimica

    2011-07-01

    The bioceramics of calcium phosphate called apatite, are widely used as material for bone replacement and regeneration, due to its similarity to the mineral component of bones and teeth. The apatites are biocompatible, bioactive and integrate with living tissue by the same active process of physiological bone remodeling. These bioceramics may be used in medical, dental and orthopedic applications. In this research, it was used the wet method for the synthesis of the powder and biomimetic method for coating the surface. The Solubility study was performed in the layer deposited, apatite, for possible application as a platform for inorganic drug delivery. The bioceramics were characterized by MEV, DRX, and EDS. The curves of solubility of apatite in coatings showed that the OCP phase had a higher rate of release in the short term (4 days) while the HA phase showed a gradual release throughout the experiment (16 days). (author)

  20. Multiple myeloma: Changes in serum C-terminal telopeptide of collagen type I and bone-specific alkaline phosphatase can be used in daily practice to detect imminent osteolysis

    DEFF Research Database (Denmark)

    Lund, Thomas; Abildgaard, Niels; Andersen, Thomas L;

    2010-01-01

    Abstract Objective: Monitoring of bone disease in multiple myeloma is becoming increasingly important since bone protecting treatment with bisphosphonate is becoming restricted after the awareness of osteonecrosis of the jaw. Despite the potential of biochemical markers of bone remodeling...

  1. Human dental pulp cells exhibit bone cell-like responsiveness to fluid shear stress

    NARCIS (Netherlands)

    Kraft, D.C.E.; Bindslev, D.A.; Melsen, B.; Klein-Nulend, J.

    2011-01-01

    Background aims. For engineering bone tissue to restore, for example, maxillofacial defects, mechanosensitive cells are needed that are able to conduct bone cell-specific functions, such as bone remodelling. Mechanical loading affects local bone mass and architecture in vivo by initiating a cellular

  2. Bone Adaptation Around Orthopaedic Implants of Varying Materials

    DEFF Research Database (Denmark)

    Bagge, Mette

    1998-01-01

    The bone adaptation around orthopaedic implants is simulated using a three-dimensional finite element model. The remodeling scheme has its origin in optimization methods, and includes anisotropy and time-dependent loading......The bone adaptation around orthopaedic implants is simulated using a three-dimensional finite element model. The remodeling scheme has its origin in optimization methods, and includes anisotropy and time-dependent loading...

  3. Bone Adaptation Around Orthopaedic Implants of Varying Materials

    DEFF Research Database (Denmark)

    Bagge, Mette

    1998-01-01

    The bone adaptation around orthopaedic implants is simulated using a three-dimensional finite element model. The remodeling scheme has its origin in optimization methods, and includes anisotropy and time-dependent loading......The bone adaptation around orthopaedic implants is simulated using a three-dimensional finite element model. The remodeling scheme has its origin in optimization methods, and includes anisotropy and time-dependent loading...

  4. The mammalian lectin galectin-8 induces RANKL expression, osteoclastogenesis, and bone mass reduction in mice

    Science.gov (United States)

    Vinik, Yaron; Shatz-Azoulay, Hadas; Vivanti, Alessia; Hever, Navit; Levy, Yifat; Karmona, Rotem; Brumfeld, Vlad; Baraghithy, Saja; Attar-Lamdar, Malka; Boura-Halfon, Sigalit; Bab, Itai; Zick, Yehiel

    2015-01-01

    Skeletal integrity is maintained by the co-ordinated activity of osteoblasts, the bone-forming cells, and osteoclasts, the bone-resorbing cells. In this study, we show that mice overexpressing galectin-8, a secreted mammalian lectin of the galectins family, exhibit accelerated osteoclasts activity and bone turnover, which culminates in reduced bone mass, similar to cases of postmenopausal osteoporosis and cancerous osteolysis. This phenotype can be attributed to a direct action of galectin-8 on primary cultures of osteoblasts that secrete the osteoclastogenic factor RANKL upon binding of galectin-8. This results in enhanced differentiation into osteoclasts of the bone marrow cells co-cultured with galectin-8-treated osteoblasts. Secretion of RANKL by galectin-8-treated osteoblasts can be attributed to binding of galectin-8 to receptor complexes that positively (uPAR and MRC2) and negatively (LRP1) regulate galectin-8 function. Our findings identify galectins as new players in osteoclastogenesis and bone remodeling, and highlight a potential regulation of bone mass by animal lectins. DOI: http://dx.doi.org/10.7554/eLife.05914.001 PMID:25955862

  5. Micronutrients-incorporated calcium phosphate particles with protective effect on osteoporotic bone tissue.

    Science.gov (United States)

    Chen, X; Zhang, L; Yang, X; Li, Z; Sun, X; Lin, M; Yang, G; Gou, Z

    2013-01-01

    Supplementation of individual micronutrient is inadequate for maintaining bone function because single micronutrient can not contribute significantly a positive remodeling balance. We developed the highly integrated, stably dietary multi-micronutrients with good bioavailability and low adverse effect on the improvement of bone consolidation in osteoporosis. The trace element-codoped calcium phosphate (teCaP) particles were prepared in the modified body fluid and carefully evaluated. Rats, aged 3 months, were ovariectomized and when 6 month intervened with the conditioned, low, moderate, and high teCaP diets. The teCaP particles showed highly dissolvable in stomach juice-mimicing acidic solutions. Three months after intervention, the body weight increase showed remarkable differences among the low teCaP diet (~52 g), moderate teCaP diet (~34 g) and high teCaP diet (~23 g) group. In particular, the intake of moderate teCaP greatly improved the retention of trace elements in femural bone for better protection against the skeletal weakening, and resulted in a significant increase of bone mineral density (104.06%) in comparison with the conventional high calcium plus vitamin D3 diet (Control group). These investigations improve our understanding of micronutrient retention on bone consolidation in osteoporotic bone tissue, and also provide new mild wet-chemical approach to prepare potent nutritionally effective edible complements to synergistically relieve bone degeneration and prevent osteoporosis.

  6. 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.

  7. Integration of comprehensive 3D microCT and signaling analysis reveals differential regulatory mechanisms of craniofacial bone development.

    Science.gov (United States)

    Ho, Thach-Vu; Iwata, Junichi; Ho, Hoang Anh; Grimes, Weston C; Park, Shery; Sanchez-Lara, Pedro A; Chai, Yang

    2015-04-15

    Growth factor signaling regulates tissue-tissue interactions to control organogenesis and tissue homeostasis. Specifically, transforming growth factor beta (TGFβ) signaling plays a crucial role in the development of cranial neural crest (CNC) cell-derived bone, and loss of Tgfbr2 in CNC cells results in craniofacial skeletal malformations. Our recent studies indicate that non-canonical TGFβ signaling is activated whereas canonical TGFβ signaling is compromised in the absence of Tgfbr2 (in Tgfbr2(fl/fl);Wnt1-Cre mice). A haploinsufficiency of Tgfbr1 (aka Alk5) (Tgfbr2(fl/fl);Wnt1-Cre;Alk5(fl/+)) largely rescues craniofacial deformities in Tgfbr2 mutant mice by reducing ectopic non-canonical TGFβ signaling. However, the relative involvement of canonical and non-canonical TGFβ signaling in regulating specific craniofacial bone formation remains unclear. We compared the size and volume of CNC-derived craniofacial bones (frontal bone, premaxilla, maxilla, palatine bone, and mandible) from E18.5 control, Tgfbr2(fl/fl);Wnt1-Cre, and Tgfbr2(fl/fl);Wnt1-Cre;Alk5(fl/+)mice. By analyzing three dimensional (3D) micro-computed tomography (microCT) images, we found that different craniofacial bones were restored to different degrees in Tgfbr2(fl/fl);Wnt1-Cre;Alk5(fl/+) mice. Our study provides comprehensive information on anatomical landmarks and the size and volume of each craniofacial bone, as well as insights into the extent that canonical and non-canonical TGFβ signaling cascades contribute to the formation of each CNC-derived bone. Our data will serve as an important resource for developmental biologists who are interested in craniofacial morphogenesis.

  8. Hierarchical Fabrication of Engineered Vascularized Bone Biphasic Constructs via Dual 3D Bioprinting: Integrating Regional Bioactive Factors into Architectural Design.

    Science.gov (United States)

    Cui, Haitao; Zhu, Wei; Nowicki, Margaret; Zhou, Xuan; Khademhosseini, Ali; Zhang, Lijie Grace

    2016-09-01

    A biphasic artificial vascularized bone construct with regional bioactive factors is presented using dual 3D bioprinting platform technique, thereby forming a large functional bone grafts with organized vascular networks. Biocompatible mussel-inspired chemistry and "thiol-ene" click reaction are used to regionally immobilize bioactive factors during construct fabrication for modulating or improving cellular events. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. 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.

  10. Bone Biopsy

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Bone Biopsy Bone biopsy uses a needle and imaging ... the limitations of Bone Biopsy? What is a Bone Biopsy? A bone biopsy is an image-guided ...

  11. Effect of Kidney-tonifying, Dampness-dispelling and Blood-activating Chinese Medicine on Bone Remodeling of Cell Model in Vitro%补肾祛湿活血中药对模拟体外骨重塑作用的细胞特征的影响

    Institute of Scientific and Technical Information of China (English)

    宁显明; 艾志鹏; 张继虹; 王海彬; 刘红; 朱洪民

    2014-01-01

    目的探讨补肾活血中药(珍骨丸)与祛湿活血中药(骨刺风湿丸)对体外骨重塑作用的影响。方法将MC3T3-E1细胞、 RAW264.7细胞分别诱导为成骨细胞(osteoblasts, OB)与破骨细胞(osteoclasts, OC),并将两者共培养。通过免疫细胞化学染色鉴定该共培养体系构建成功与否;以灌胃的方法分别将双醋瑞因、珍骨丸及骨刺风湿丸制备成含药血清;运用含药血清处理共培养细胞并进行Western blotting和Real-time PCR分析。结果珍骨丸与骨刺风湿丸处理共培养细胞后骨保护素(osteoprotegerin, OPG)表达显著上升(P<0.05),糖蛋白130(glycoprotein 130, gp 130)表达显著下降(P<0.05)。结论珍骨丸、骨刺风湿丸通过抑制gp130来抑制OC的骨吸收,并通过RANKL-RANK-OPG系统促进骨形成,增加骨密度达到治疗骨关节炎的作用。%Objective To explore the effect of Zhengu Pills ( a kidney-tonifying and blood-activating Chinese medicine) and Guci Fengshi Pills ( a dampness-dispelling and blood-activating Chinese medicine) on bone remodeling of cell model in vitro. Methods MC3T3-E1 and RAW264.7 cells were differentiated into osteoblasts ( OB) and osteoclasts ( OC) after stimulated by different inductive agents respectively, and then OB and OC were co-cultured. Immunocytochemical staining was applied to identify the construction of co-cultured OB and OC system. The serum containing corresponding medicine was prepared after the rats were given intragastric administration of Diacerein, Zhengu Pills and Guci Fengshi Pills. And then the obtained serum was used for treatment of co-cultured cells separately. At the end of experiment, Western blotting and real-time polymerase chain reaction (PCR) tests were carried out. Results The osteoprotegerin (OPG) expression was increased and gene expression of glycoprotein 130 (gp130) was decreased in co-cultured cells after treatment with the

  12. 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.

  13. Diabetes mellitus related bone metabolism and periodontal disease.

    Science.gov (United States)

    Wu, Ying-Ying; Xiao, E; Graves, Dana T

    2015-06-26

    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.

  14. Diabetes mellitus related bone metabolism and periodontal disease

    Science.gov (United States)

    Wu, Ying-Ying; Xiao, E; Graves, Dana T

    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. PMID:25857702

  15. 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.

  16. The Rho-GEF Kalirin regulates bone mass and the function of osteoblasts and osteoclasts

    OpenAIRE

    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...

  17. Erythropoietin in bone - Controversies and consensus.

    Science.gov (United States)

    Hiram-Bab, Sahar; Neumann, Drorit; Gabet, Yankel

    2017-01-01

    Erythropoietin (Epo) is the main hormone that regulates the production of red blood cells (hematopoiesis), by stimulating their progenitors. Beyond this vital function, several emerging roles have been noted for Epo in other tissues, including neurons, heart and retina. The skeletal system is also affected by Epo, however, its actions on bone are, as yet, controversial. Here, we review the seemingly contradicting evidence regarding Epo effects on bone remodeling. We also discuss the evidence pointing to a direct versus indirect effect of Epo on the osteoblastic and osteoclastic cell lineages. The current controversy may derive from a context-dependent mode of action of Epo, namely opposite skeletal actions during bone regeneration and steady-state bone remodeling. Differences in conclusions from the published in-vitro studies may thus relate to the different experimental conditions. Taken together, these studies indicate a complexity of Epo functions in bone cells.

  18. 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.

  19. 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.

  20. In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone Formation.

    Science.gov (United States)

    Wittkowske, Claudia; Reilly, Gwendolen C; Lacroix, Damien; Perrault, Cecile M

    2016-01-01

    This review describes the role of bone cells and their surrounding matrix in maintaining bone strength through the process of bone remodeling. Subsequently, this work focusses on how bone formation is guided by mechanical forces and fluid shear stress in particular. It has been demonstrated that mechanical stimulation is an important regulator of bone metabolism. Shear stress generated by interstitial fluid flow in the lacunar-canalicular network influences maintenance and healing of bone tissue. Fluid flow is primarily caused by compressive loading of bone as a result of physical activity. Changes in loading, e.g., due to extended periods of bed rest or microgravity in space are associated with altered bone remodeling and formation in vivo. In vitro, it has been reported that bone cells respond to fluid shear stress by releasing osteogenic signaling factors, such as nitric oxide, and prostaglandins. This work focusses on the application of in vitro models to study the effects of fluid flow on bone cell signaling, collagen deposition, and matrix mineralization. Particular attention is given to in vitro set-ups, which allow long-term cell culture and the application of low fluid shear stress. In addition, this review explores what mechanisms influence the orientation of collagen fibers, which determine the anisotropic properties of bone. A better understanding of these mechanisms could facilitate the design of improved tissue-engineered bone implants or more effective bone disease models.

  1. In vitro bone cell models: Impact of fluid shear stress on bone formation

    Directory of Open Access Journals (Sweden)

    Claudia Wittkowske

    2016-11-01

    Full Text Available This review describes the role of bone cells and their surrounding matrix in maintaining bone strength through the process of bone remodelling. Subsequently, this work focusses on how bone formation is guided by mechanical forces and fluid shear stress in particular. It has been demonstrated that mechanical stimulation is an important regulator of bone metabolism. Shear stress generated by interstitial fluid flow in the lacunar-canalicular network influences maintenance and healing of bone tissue. Fluid flow is primarily caused by compressive loading of bone as a result of physical activity. Changes in loading, e.g. due to extended periods of bed rest or microgravity in space are associated with altered bone remodelling and formation in vivo. In vitro, it has been reported that bone cells respond to fluid shear stress by releasing osteogenic signalling factors such as nitric oxide and prostaglandins. This work focusses on the application of in vitro models to study the effects of fluid flow on bone cell signalling, collagen deposition and matrix mineralization. Particular attention is given to in vitro set-ups which allow long-term cell culture and the application of low fluid shear stress. In addition, this review explores what mechanisms influence the orientation of collagen fibres which determine the anisotropic properties of bone. A better understanding of these mechanisms could facilitate the design of improved tissue-engineered bone implants or more effective bone disease models.

  2. 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

  3. Bone Densitometry (Bone Density Scan)

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Bone Densitometry (DEXA) Bone densitometry, also called dual-energy ... limitations of DEXA Bone Densitometry? What is a Bone Density Scan (DEXA)? Bone density scanning, also called ...

  4. 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

  5. Continuum remodeling revisited : deformation rate driven functional adaptation using a hypoelastic constitutive law.

    Science.gov (United States)

    Negus, Charles H; Impelluso, Thomas J

    2007-07-01

    Recent research effort in bone remodeling has been directed toward describing interstitial fluid flow in the lacuno-canalicular system and its potential as a cellular stimulus. Regardless of the precise contents of the mechanotransduction "black box", it seems clear that the fluid flow on which the remodeling is predicated cannot occur under static loading conditions. In an attempt to help continuum remodeling simulations catch up with cellular and subcellular research, this paper presents a simple, strain rate driven remodeling algorithm for density allocation and principal material direction rotations. An explicit finite element code was written and deployed on a supercomputer which discretizes the remodeling process and uses an objective hypoelastic constitutive law to simulate trabecular realignment. Results indicate that a target strain rate for this dynamic approach is |D ( I )| = 1.7% per second which seems reasonable when compared to observed strain rates. Simulations indicate that a morpho-mechanically realistic three-dimensional bone can be synthesized by applying a few dynamic loads at the envelope of common daily physiological rates, even with no static loading component.

  6. Integrin-extracellular matrix interactions in connective tissue remodeling and osteoblast differentiation

    Science.gov (United States)

    Globus, R. K.; Moursi, A.; Zimmerman, D.; Lull, J.; Damsky, C.

    1995-01-01

    The differentiaton of bone cells is a complex multistep process. Bone is somewhat unusual in that it is very actively and continually remodeled in the adult and that maintenance of its mass in the mature organism is exquisitely sensitive to mechanical as well as chemical signals. Bone is also unique because it consists of a very large amount of extracellular matrix (ECM) that is mineralized. The integrin family of ECM receptors has been shown to play an important role in tissue morphogenesis in several systems. Our studies on the regulation of matrix remodeling enzymes by integrins in rabbit synovial fibroblasts show that two b1 integrin fibronectin (FN) receptor complexes (alpha 5 beta 1 and alpha 4 beta 1) cooperate in detecting subtle changes in the composition of the ECM. As a result of signal transduction by these integrins, the levels of mRNA and protein for several members of the metalloproteinase family are regulated in these cells. We have also used antibody and RGD peptide perturbation studies to determine the significance of cell/ECM interactions to normal osteogenesis. We found that interactions between the cell binding domain of FN and integrins are required for both normal morphogenesis and gene expression in cultured osteoblasts that differentiate to form bone-like tissue in culture. These data lead us to propose that beta 1 integrins play an important role in osteoblast differentiation as well as in bone remodeling.

  7. 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.

  8. Oxidized alginate hydrogels for BMP-2 delivery in long bone defects

    Science.gov (United States)

    Priddy, Lauren B; Chaudhuri, Ovijit; Stevens, Hazel Y; Krishnan, Laxminarayanan; Uhrig, Brent A; Willett, Nick J; Guldberg, Robert E

    2014-01-01

    Autograft treatment of large bone defects and fracture non-unions is complicated by limited tissue availability and donor site morbidity. Polymeric biomaterials such as alginate hydrogels provide an attractive tissue engineering alternative due to their biocompatibility, injectability, and tunable degradation rates. Irradiated RGD-alginate hydrogels have been used to deliver proteins such as bone morphogenetic protein-2 (BMP-2), to promote bone regeneration and restoration of function in a critically sized rat femoral defect model. However, slow degradation of irradiated alginate hydrogels may impede integration and remodeling of the regenerated bone to its native architecture. Oxidation of alginate has been used to promote degradation of alginate matrices. The objective of this study was to evaluate the effects of alginate oxidation on BMP-2 release and bone regeneration. We hypothesized that oxidized-irradiated alginate hydrogels would elicit an accelerated release of BMP-2, but degrade faster in vivo, facilitating the formation of higher quality, more mature bone compared to irradiated alginate. Indeed, oxidation of irradiated alginate did accelerate in vitro BMP-2 release. Notably, the BMP-2 retained within both constructs was bioactive at 26 days, as observed by induction of alkaline phosphatase activity and positive Alizarin Red S staining of MC3T3-E1 cells. From the in vivo study, robust bone regeneration was observed in both groups through 12 weeks by radiography, micro-CT analyses, and biomechanical testing. Bone mineral density (BMD) was significantly greater for the oxidized-irradiated alginate group at 8 weeks. Histological analyses of bone defects revealed enhanced degradation of oxidized-irradiated alginate and suggested the presence of more mature bone after 12 weeks of healing. PMID:24954001

  9. Calcium remodeling in colorectal cancer.

    Science.gov (United States)

    Villalobos, Carlos; Sobradillo, Diego; Hernández-Morales, Miriam; Núñez, Lucía

    2017-06-01

    Colorectal cancer (CRC) is the third most frequent form of cancer and the fourth leading cause of cancer-related death in the world. Basic and clinical data indicate that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may prevent colon cancer but mechanisms remain unknown. Aspirin metabolite salicylate and other NSAIDs may inhibit tumor cell growth acting on store-operated Ca(2+) entry (SOCE), suggesting an important role for this pathway in CRC. Consistently, SOCE is emerging as a novel player in different forms of cancer, including CRC. SOCE and store-operated currents (SOCs) are dramatically enhanced in CRC while Ca(2+) stores are partially empty in CRC cells. These features may contribute to CRC hallmarks including enhanced cell proliferation, migration, invasion and survival. At the molecular level, enhanced SOCE and depleted stores are mediated by overexpression of Orai1, Stromal interaction protein 1 (STIM1) and Transient receptor protein channel 1 (TRPC1) and downregulation of STIM2. In normal colonic cells, SOCE is mediated by Ca(2+)-release activated Ca(2+) channels made of STIM1, STIM2 and Orai1. In CRC cells, SOCE is mediated by different store-operated currents (SOCs) driven by STIM1, Orai1 and TRPC1. Loss of STIM2 contributes to depletion of Ca(2+) stores and enhanced resistance to cell death in CRC cells. Thus, SOCE is a novel key player in CRC and inhibition by salicylate and other NSAIDs may contribute to explain chemoprevention activity. Colorectal cancer (CRC) is the third most frequent form of cancer worldwide. Recent evidence suggests that intracellular Ca(2+) remodeling may contribute to cancer hallmarks. In addition, aspirin and other NSAIDs might prevent CRC acting on remodeled Ca(2+) entry pathways. In this review, we will briefly describe 1) the players involved in intracellular Ca(2+) homeostasis with a particular emphasis on the mechanisms involved in SOCE activation and inactivation, 2) the evidence that aspirin

  10. Immunohistochemical characterization of wound healing at two different bone graft substitutes.

    Science.gov (United States)

    Sager, M; Ferrari, D; Wieland, M; Dard, M; Becker, J; Schwarz, F

    2012-05-01

    The immunohistochemical characteristics of wound healing following application of a biphasic calcium phosphate or a collagen coated natural bone combined with a native collagen membrane in a dog model was assessed. Standardized buccal dehiscence-type defects were surgically created following implant bed preparation in 6 dogs. Following implant placement, defects were randomly filled with a collagen coated natural bone mineral (GBO), or a biphasic hydroxyapatite/beta tricalcium phosphate (SBC), and covered with a native collagen membrane. After 1, 4, and 9 weeks' submerged healing, dissected blocks were processed for immunohistochemical (collagen type I (CI), osteocalcin (OC), angiogenesis (TG)) analysis. At 1 week, GBO and SBC granules were homogeneously surrounded by a well vascularized, non-mineralized tissue (NMT). CI and OC antigen reactivity was commonly observed adjacent to both bone graft substitutes. At 4 and 9 weeks, SBC and GBO granules were completely integrated into a secondly formed network of spongiosa. At 9 weeks, dissolution of some granules was observed in the SBC group. Adjacent to these granules, NMT was significantly increased and revealed a pronounced CI, OC and TG antigen reactivity. The initial pattern of bone regeneration and graft integration was comparable in both groups; bone remodelling was more pronounced with SBC.

  11. An integrative approach for comparing microcirculation between normal and alveolar cleft gingiva in children scheduled for secondary bone grafting procedures

    NARCIS (Netherlands)

    D.M.J. Milstein; Y.W. Cheung; L. Ziukaite; C. Ince; H.P. van den Akker; J.A.H. Lindeboom

    2013-01-01

    Objective The aim of this study was to compare microcirculatory parameters in normal versus alveolar cleft gingiva in children selected for secondary bone grafting procedures. Study Design This study included 11 consecutive patients with complete unilateral alveolar clefts who required secondary bon

  12. Titanium implants induce expression of matrix metalloproteinases in bone during osseointegration.

    Science.gov (United States)

    Shubayev, Veronica I; Brånemark, Rickard; Steinauer, Joanne; Myers, Robert R

    2004-01-01

    Implanted pure titanium fixtures are able to completely integrate with bone, in part because of the formation of a strong extracellular matrix (ECM) bond at the titanium-bone interface. In this study, we used a rodent femur model of intramedullary osseointegration to analyze the changes in immunoreactivity of ECM-controlling matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinase-3 (TIMP-3), and tumor necrosis factor alpha (TNF-alpha) during osseointegration. We observed dramatic increases in MMP-2, MMP-9, MMP-7, TIMP-3, and TNF-alpha in osteocytes, osteoclasts, haversian canals, and the interface matrix in bone ipsilateral to the titanium implant. An increase in TIMP-3, MMP-9, and MMP-7 in hypertrophied chondrocytes and the vascular component of the epiphysial growth plate was also observed in experimental bone. These findings were not seen in contralateral or sham-operated bone, where the titanium fixtures were threaded into the femur and immediately removed. Our data link titanium-induced bone remodeling to changes in expression and distribution of MMPs.

  13. 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.

  14. A transcriptome-proteome integrated network identifies endoplasmic reticulum thiol oxidoreductase (ERp57) as a hub that mediates bone metastasis.

    Science.gov (United States)

    Santana-Codina, Naiara; Carretero, Rafael; Sanz-Pamplona, Rebeca; Cabrera, Teresa; Guney, Emre; Oliva, Baldo; Clezardin, Philippe; Olarte, Omar E; Loza-Alvarez, Pablo; Méndez-Lucas, Andrés; Perales, Jose Carlos; Sierra, Angels

    2013-08-01

    Bone metastasis is the most common distant relapse in breast cancer. The identification of key proteins involved in the osteotropic phenotype would represent a major step toward the development of new prognostic markers and therapeutic improvements. The aim of this study was to characterize functional phenotypes that favor bone metastasis in human breast cancer. We used the human breast cancer cell line MDA-MB-231 and its osteotropic BO2 subclone to identify crucial proteins in bone metastatic growth. We identified 31 proteins, 15 underexpressed and 16 overexpressed, in BO2 cells compared with parental cells. We employed a network-modeling approach in which these 31 candidate proteins were prioritized with respect to their potential in metastasis formation, based on the topology of the protein-protein interaction network and differential expression. The protein-protein interaction network provided a framework to study the functional relationships between biological molecules by attributing functions to genes whose functions had not been characterized. The combination of expression profiles and protein interactions revealed an endoplasmic reticulum-thiol oxidoreductase, ERp57, functioning as a hub that retained four down-regulated nodes involved in antigen presentation associated with the human major histocompatibility complex class I molecules, including HLA-A, HLA-B, HLA-E, and HLA-F. Further analysis of the interaction network revealed an inverse correlation between ERp57 and vimentin, which influences cytoskeleton reorganization. Moreover, knockdown of ERp57 in BO2 cells confirmed its bone organ-specific prometastatic role. Altogether, ERp57 appears as a multifunctional chaperone that can regulate diverse biological processes to maintain the homeostasis of breast cancer cells and promote the development of bone metastasis.

  15. 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

  16. How does joint remodeling work?: new insights in the molecular regulation of the architecture of joints.

    Science.gov (United States)

    Schett, Georg

    2007-01-01

    Remodeling of joints is a key feature of inflammatory and degenerative joint disease. Bone erosion, cartilage degeneration and growth of bony spurs termed osteophytes are key features of structural joint pathology in the course of arthritis, which lead to impairment of joint function. Understanding their molecular mechanisms is essential to tailor targeted therapeutic approaches to protect joint architecture from inflammatory and mechanical stress. This addendum summarizes the new insights in the molecular regulation of bone formation in the joint and its relation to bone resorption. It describes how inflammatory cytokines impair bone formation and block the repair response of joints towards inflammatory stimuli. It particularly points out the key role of Dickkopf-1 protein, a regulator of the Wingless signaling and inhibitor of bone formation. This new link between inflammation and bone formation is also crucial for explaining the generation of osteophytes, bony spurs along joints, which are characterized by new bone and cartilage formation. This mechanism is largely dependent on an activation of wingless protein signaling and can lead to complete joint fusion. This addendum summarized the current concepts of joint remodeling in the limelight of these new findings.

  17. 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.

  18. 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

  19. Residual stress in bone structure and tissue of rabbit's tibiofibula.

    Science.gov (United States)

    Tadano, Shigeru; Okoshi, Taro

    2006-01-01

    This paper presents an X-ray diffraction method of measuring the residual stress/strain in bone tissue of rabbit's tibia. To derive the residual stress, bone powder of the diameter less than 40 micrometers was used as a control specimen at non-stressed state. From the X-ray measurements, it was clear that the distribution of residual stress existed in the bone tissue. The tensile residual stress at bone axial direction occurred in the proximal-medial region of rabbit's tibia. The compressive stress occurred in the other regions. In addition, the mechanism to generate the residual stress was investigated by sequential cutting of the tibiofibula system from bone structure scale to bone tissue scale. The remodeling is a phenomenon that the bone structure adapts functionally to mechanical environment. The residual stress will become a mechanical trigger to induce the remodeling.

  20. 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.

  1. BONES WITH BIOCERAMICS

    Directory of Open Access Journals (Sweden)

    Wijianto Wijianto

    2017-01-01

    Full Text Available This paper discuss about ceramics in application as bone implant. Bioceramics for instance Hydroxyapatite, usually is abbreviated with HA or HAp, is a mineral that is very good physical properties as bone replacement in human body. To produce Hydroxyapatite, coating process is used which have good potential as they can exploit the biocompatible and bone bonding properties of the ceramic. There are many advantages and disadvantages of bioceramics as bone implant. Advantages of hydroxyapatite as bone implant are rapidly integrated into the human body, and is most interesting property that will bond to bone forming indistinguishable unions. On contrary, disadvantages of hydroxyapatite as bone implant are poor mechanical properties (in particular fatigue properties mean that hydroxyapatite cannot be used in bulk form for load bearing applications such as orthopaedics and poor adhesion between the calcium phosphate coating and the material implant will occur.

  2. 比较早期和晚期骨髓单个核细胞移植对猪急性心肌梗死后左室重构的影响%Comparison of effects of early and late bone marrow mononuclear cells transplantation on left ventricular remodeling after acute myocardial infarction in swines

    Institute of Scientific and Technical Information of China (English)

    曾建平; 刘颖; 易文艳; 黄河; 孙智山; 康松涛; 彭湘洪; 吴名星; 吴澧源; 孙建平; 彭枝柳

    2011-01-01

    目的 对比观察猪急性心肌梗死后早期(1周)和延期(3个月)进行的骨髓单个核细胞移植对心肌梗死后左室重构的影响.方法 前降支球囊封堵法成功建立15头猪急性心肌梗死模型,随机均分为对照组、早期移植组和延期移植组.造模1周后急性移植组行自体骨髓单个核细胞移植,对照组注射1640培养基10 ml作为对照;造模3个月后延期移植组行自体骨髓单个核细胞移植,造模后1周、造模后3个月、造模后6个月各组分别行心脏超声和SPECT检测,超声检查分析左室舒张末期内径,SPECT分析左室舒张末期容积、射血分数.结果 造模6个月后延期移植组的LVd值[(54.20±3.70) mm]低于对照组[(63.20±5.63) mm],但高于早期移植组[(47.40±1.14)mm];EDV值[(163.00 ±6.96) ml]低于对照组[(209.40±18.69)ml],但高于早期移植组[135.40±4.93)ml];EF值(0.25±0.02)高于对照组(0.19±0.02),但低于早期移植组(0.37±:0.02).结论 猪急性心梗3月后骨髓干细胞移植能有效抑制左室重构的进一步恶化,但其疗效不如早期移植组.%Objective To compare the effects on left ventricular remodeling of bone marrow mononuclear cells transplantation one week and three months after acute myocardial infarction.Methods Acute myocardial infarction models were successfully established in 15 swine,which were randomly divided into three groups:placebo group,early transplantation group and late trasplantation group.One week after model had been established,early transplantation group underwent bone marrow mononuclear cells transplantation,and then so did the late trasplantation group three months after acute myocardial infarction.B-ultrasound and single photon emission computed tomography (SPECT) examinations were performed to assess the left ventricular end diastolic dimension( LVd),left ventricular end diastolic volume(EDV) and left ventricular ejection fraction(EF) before and one week,three months,six months

  3. 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.

  4. 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.

  5. Three-dimensional Microarchitecture of Adolescent Cancellous Bone

    DEFF Research Database (Denmark)

    Ding, Ming; Hvid, I; Overgaard, Søren

    INTRODUCTION: The human skeleton optimizes its microarchitecture by elaborate adaptations to mechanical loading during development, growth and modeling. The mechanisms for adaptation involve a multistep process of cellular mechanotransduction stimulating bone modeling and remodeling resulting...... during development and growth. We hypothesized that adolescent cancellous bone differed significantly from adult cancellous bone in their microarchitecture and mechanical properties. METHODS: Twenty-three human proximal tibiae were harvested and divided into 3 groups according to their ages: adolescence...... on cancellous bone collagen, mineralization and nanostructure. The results provide valuable information on bone development and growth, and are important for fracture repair, defect healing, biomaterial application, and pathogenesis of bone diseases in adolescence....

  6. Numerical analysis of an osseointegrated prosthesis fixation with reduced bone failure risk and periprosthetic bone loss.

    Science.gov (United States)

    Tomaszewski, P K; van Diest, M; Bulstra, S K; Verdonschot, N; Verkerke, G J

    2012-07-26

    Currently available implants for direct attachment of prosthesis to the skeletal system after transfemoral amputation (OPRA system, Integrum AB, Sweden and ISP Endo/Exo prosthesis, ESKA Implants AG, Germany) show many advantages over the conventional socket fixation. However, restraining biomechanical issues such as considerable bone loss around the stem and peri-prosthetic bone fractures are present. To overcome these limiting issues a new concept of the direct intramedullary fixation was developed. We hypothesize that the new design will reduce the peri-prosthetic bone failure risk and adverse bone remodeling by restoring the natural load transfer in the femur. Generic CT-based finite element models of an intact femur and amputated bones implanted with 3 analyzed implants were created and loaded with a normal walking and a forward fall load. The strain adaptive bone remodeling theory was used to predict long-term bone changes around the implants and the periprosthetic bone failure risk was evaluated by the von Mises stress criterion. The results show that the new design provides close to physiological distribution of stresses in the bone and lower bone failure risk for the normal walking as compared to the OPRA and the ISP implants. The bone remodeling simulations did not reveal any overall bone loss around the new design, as opposed to the OPRA and the ISP implants, which induce considerable bone loss in the distal end of the femur. This positive outcome shows that the presented concept has a potential to considerably improve safety of the rehabilitation with the direct fixation implants.

  7. Optimizing texture measures quantifying bone structures as well as MR-sequences at 3 Tesla: an integrative statistical approach

    Science.gov (United States)

    Raeth, Christoph W.; Mueller, Dirk; Rummeny, Ernst J.; Link, Thomas M.; Vogel, Mika; Koenig, Hartmut; Boehm, Holger; Monetti, Roberto

    2006-03-01

    High resolution MR-scanners working with magnetic field strengths of 3 Tesla are clinically available nowadays. They offer the possibility to obtain 3D images with unprecedented spatial resolution and/or signal-to-noise-ratio (SNR) allowing for an accurate visualization of the trabecular bone structure. It has been demonstrated that scaling indices are well suited to quantify these structures, especially to discriminate between plate-like and rod-like structural elements, which is crucial for the diagnosis of osteoporosis. Until now image quality has mainly been assessed by visual impression or by measures based on the SNR. In this work we present a methodology to assess different MR-sequences with respect to the texture measure that is used later in the image analysis. We acquired for a bone specimen HR-MR-sequences with different spatial resolution and signal to noise ratio. For these data sets we selected two volumes of interest (VOI) of same size located in the trabecular bone and in the background of the image. For both VOIs the scaling indices are calculated for different scale parameters. Subsequently the 'texture contrast' between structure and background is calculated by comparing the probability distributions of the scaling indices using a quadratic distance measure. By means of the contrast the optimal set of scale parameters is determined. By comparing the contrast for the different MR sequences the best suited ones are determined. It turns out that sequences with slightly lower spatial resolution but better signal to noise ration yield a better texture contrast than sequences with the best spatial resolution. The presented methodology offers the possibility to optimize simultaneously texture measures and MR-sequences, which will allow for an adapted and thus optimized analysis of image structures, e.g. trabecular bone, in the HR-MR data.

  8. 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.

  9. Mechanisms of multiple myeloma bone disease

    Science.gov (United States)

    Galson, Deborah L; Silbermann, Rebecca; Roodman, G David

    2012-01-01

    Multiple myeloma is the second most common hematological malignancy and the most frequent cancer to involve the skeleton. Multiple myeloma bone disease (MMBD) is characterized by abnormal bone remodeling with dysfunction of both bone resorption and bone formation, and thus can be used as a paradigm for other inflammatory bone diseases, and the regulation of osteoclasts and osteoblasts in malignancy. Studies of MMBD have identified novel regulators that increase osteoclastogenesis and osteoclast function, repress osteoblast differentiation, increase angiogenesis, or permanently alter stromal cells. This review will discuss the current understanding of mechanisms of osteoclast and osteoblast regulation in MMBD, and therapeutic approaches currently in use and under development that target mediators of bone destruction and blockade of bone formation for myeloma patients, including new anabolic therapies. PMID:23951515

  10. Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

    Science.gov (United States)

    Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

    2016-01-01

    Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone-fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues - subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT - is differently associated with bone mineral density (BMD) variations. However, compared with the other fat depots, BMAT displays striking features that makes it a substantial actor in bone alterations. BMAT quantity is well associated with BMD loss in aging, menopause, and other metabolic conditions, such as anorexia nervosa. Consequently, BMAT is sensed as a relevant marker of a compromised bone integrity. However, analyses of BMAT development in metabolic diseases (obesity and diabetes) are scarce and should be, thus, more systematically addressed to better apprehend the bone modifications in that pathophysiological contexts. Moreover, bone marrow (BM) adipogenesis occurs throughout the whole life at different rates. Following an ordered spatiotemporal expansion, BMAT has turned to be a heterogeneous fat depot whose adipocytes diverge in their phenotype and their response to stimuli according to their location in bone and BM. In vitro, in vivo, and clinical studies point to a detrimental role of BM adipocytes (BMAs) throughout the release of paracrine factors that modulate osteoblast and/or osteoclast formation and function. However, the anatomical dissemination and the difficulties to access BMAs still hamper our understanding of the relative contribution of BMAT secretions compared with those of peripheral adipose tissues. A further characterization of the phenotype and the functional regulation of BMAs are ever more required. Based on currently available data and comparison with other fat tissues

  11. Pressure Bearing Device Affects Extraction Socket Remodeling of Maxillary Anterior Tooth. A Prospective Clinical Trial.

    Science.gov (United States)

    Jiang, Xi; Zhang, Yu; Chen, Bo; Lin, Ye

    2017-04-01

    Extraction socket remodeling and ridge preservation strategies have been extensively explored. To evaluate the efficacy of applying a micro-titanium stent as a pressure bearing device on extraction socket remodeling of maxillary anterior tooth. Twenty-four patients with a extraction socket of maxillary incisor were treated with spontaneous healing (control group) or by applying a micro-titanium stent as a facial pressure bearing device over the facial bone wall (test group). Two virtual models obtained from cone beam computed tomography data before extraction and 4 months after healing were 3-dimenionally superimposed. Facial bone wall resorption, extraction socket remodeling features and ridge width preservation rate were determined and compared between the groups. Thin facial bone wall resulted in marked resorption in both groups. The greatest palatal shifting distance of facial bone located at the coronal level in the control group, but middle level in the test group. Compared with the original extraction socket, 87.61 ± 5.88% ridge width was preserved in the test group and 55.09 ± 14.46% in the control group. Due to the facial pressure bearing property, the rigid micro-titanium stent might preserve the ridge width and alter the resorption features of extraction socket. © 2016 Wiley Periodicals, Inc.

  12. Osteopontin: Relation between Adipose Tissue and Bone Homeostasis

    Science.gov (United States)

    Messina, Antonietta; Monda, Vincenzo; Viggiano, Emanuela; Valenzano, Anna; Esposito, Teresa; Cibelli, Giuseppe

    2017-01-01

    Osteopontin (OPN) is a multifunctional protein mainly associated with bone metabolism and remodeling. Besides its physiological functions, OPN is implicated in the pathogenesis of a variety of disease states, such as obesity and osteoporosis. Importantly, during the last decades obesity and osteoporosis have become among the main threats to health worldwide. Because OPN is a protein principally expressed in cells with multifaceted effects on bone morphogenesis and remodeling and because it seems to be one of the m