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Sample records for integrate bone remodelling

  1. Cellular and Molecular Mechanisms of Bone Remodeling*

    OpenAIRE

    Raggatt, Liza J.; Partridge, Nicola C.

    2010-01-01

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

  2. [Three-dimensional finite element analysis on mechanical behavior of the bone remodeling and bone integration between the bone-implant interface after hip replacement].

    Science.gov (United States)

    Li, Yong-Jiang; Zhang, Li-Cheng; Zhang, Mei-Chao; Yang, Guo-Jing; Lin, Rui-Xin; Cai, Chun-Yuan; Zhong, Shi-Zhen

    2014-04-01

    To discuss the primary stability of the fixed interface between the cementless prosthesis and femur, and its influence on bone ingrowth and secondary stability under the roughened surface and press fit of different prostheses by finite element analysis. :A three-dimensional finite element module of total hip arthroplasty (THA) was developed with Mimics software. There was a collection of data when simulating hip arthroplasty. The frictional coefficient between the fixed interface was 0,0.15,0.40 and 1.00 representing the roughness of prosthesis surface. The press fit was 0, 0.01,0.05 and 0.10 mm according to the operation. The Vion Mises stress distribution and the contact pressure,friction stress and relative sliding displacement between the interface were analysed and compared when simulating the maneuver of climbing stairs. At a fixed press fit of 0.05 mm,the contact pressure between the interface was 230 , 231, 222 and 275 MN under four different frictional coefficient (0,0. 15,0.40 and 1.00) with little change; the relative sliding displacement was 0.529, 0.129, 0.107 and 0.087 mm with a consistent and obvious decline. As the fixed frictional coefficient was 0.40,the contact pressure between the interface were 56.0,67.7 ,60.4 and 49.6 MN under four different press fit (0, 0.01, 0.05 and 0.10 mm) with a reduction; the relative sliding displacement was 0.064,0.062,0.043 and 0.042 mm with an obvious decline, and there was a maximal friction stress when press fit of 0.01 mm. There is a dynamic process of the bone remodeling and bone integration between the interface after hip replacement, determining the long-term outcome. The interface clearance and the frictional coefficient are the key factors of the bone integration.

  3. 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

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

    International Nuclear Information System (INIS)

    Sharma, Gulshan B.; Robertson, Douglas D.

    2013-01-01

    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

  5. [Bone remodeling and modeling/mini-modeling.

    Science.gov (United States)

    Hasegawa, Tomoka; Amizuka, Norio

    Modeling, adapting structures to loading by changing bone size and shapes, often takes place in bone of the fetal and developmental stages, while bone remodeling-replacement of old bone into new bone-is predominant in the adult stage. Modeling can be divided into macro-modeling(macroscopic modeling)and mini-modeling(microscopic modeling). In the cellular process of mini-modeling, unlike bone remodeling, bone lining cells, i.e., resting flattened osteoblasts covering bone surfaces will become active form of osteoblasts, and then, deposit new bone onto the old bone without mediating osteoclastic bone resorption. Among the drugs for osteoporotic treatment, eldecalcitol(a vitamin D3 analog)and teriparatide(human PTH[1-34])could show mini-modeling based bone formation. Histologically, mature, active form of osteoblasts are localized on the new bone induced by mini-modeling, however, only a few cell layer of preosteoblasts are formed over the newly-formed bone, and accordingly, few osteoclasts are present in the region of mini-modeling. In this review, histological characteristics of bone remodeling and modeling including mini-modeling will be introduced.

  6. New predictive model for monitoring bone remodeling

    Czech Academy of Sciences Publication Activity Database

    Bougherara, H.; Klika, Václav; Maršík, František; Mařík, I.; Yahia, L.H.

    95A, č. 1 (2010), s. 9-24 ISSN 1549-3296 R&D Projects: GA ČR GA106/03/1073; GA ČR(CZ) GA106/03/0958 Institutional research plan: CEZ:AV0Z20760514 Keywords : bone remodeling * open system thermodynamics * bone biochemistry Subject RIV: BJ - Thermodynamics Impact factor: 3.044, year: 2010

  7. Application of Petri Nets in Bone Remodeling

    Directory of Open Access Journals (Sweden)

    Lingxi Li

    2009-07-01

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

  8. Digital Astronaut: Bone Remodeling Model

    Data.gov (United States)

    National Aeronautics and Space Administration — Significant progress has been made with regard to the plan outlined in the 2014 report for building in the effects of exercise induced loading on preserving bone...

  9. [Bone Cell Biology Assessed by Microscopic Approach. Bone histomorphometry of remodeling, modeling and minimodeling].

    Science.gov (United States)

    Yamamoto, Noriaki; Shimakura, Taketoshi; Takahashi, Hideaki

    2015-10-01

    Bone histomorphometry is defined as a quantitative evaluation of bone remodeling. In bone remodeling, bone resorption and bone formation are coupled with scalloped cement lines. Another mechanism of bone formation is minimodeling which bone formation and resorption are independent. The finding of minimodeling appeared in special condition with metabolic bone disease or anabolic agents. We need further study for minimodeling feature and mechanism.

  10. Remodelling of Living Bone - Numerical Simulation

    Czech Academy of Sciences Publication Activity Database

    Klika, V.; Maršík, František; Barsa, P.

    2007-01-01

    Roč. 14, 1+2 (2007), s. 112-117 ISSN 1212-4575. [Lublin-Prague-Sydney Symposium /8./. Lublin, 20.04.2007-21.04.2007] R&D Projects: GA ČR GA106/03/1073; GA MŠk(CZ) 1M06031 Institutional research plan: CEZ:AV0Z20760514 Keywords : bone remodelling * dynamic loading * biochemical model Subject RIV: BO - Biophysics

  11. 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.

  12. Osteoblast recruitment routes in human cancellous bone remodeling

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  13. 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...

  14. [Hormones and osteoporosis update. Regulation of bone remodeling by neuropeptides and neurotransmitters].

    Science.gov (United States)

    Takeda, Shu

    2009-07-01

    From the discovery of the regulation of bone remodelling by leptin, much attention has been focused on neurogenic control of bone remodelling. Various hypothalamic neuropeptides, which are involved in appetite regulation, are now revealed to be important regulators of bone remodelling. More recently, neurotransmitters, such as serotonin or catecholamines, are proven to be bone remodelling regulators.

  15. Bone remodelling: its local regulation and the emergence of bone fragility.

    Science.gov (United States)

    Martin, T John; Seeman, Ego

    2008-10-01

    Bone modelling prevents the occurrence of damage by adapting bone structure - and hence bone strength - to its loading circumstances. Bone remodelling removes damage, when it inevitably occurs, in order to maintain bone strength. This cellular machinery is successful during growth, but fails during advancing age because of the development of a negative balance between the volumes of bone resorbed and formed during remodelling by the basic multicellular unit (BMU), high rates of remodelling during midlife in women and late in life in both sexes, and a decline in periosteal bone formation. together resulting in bone loss and structural decay each time a remodelling event occurs. The two steps in remodelling - resorption of a volume of bone by osteoclasts and formation of a comparable volume by osteoblasts - are sequential, but the regulatory events leading to these two fully differentiated functions are not. Reparative remodelling is initiated by damage producing osteocyte apoptosis, which signals the location of damage via the osteocyte canalicular system to endosteal lining cells which forms the canopy of a bone-remodelling compartment (BRC). Within the BRC, local recruitment of osteoblast precursors from the lining cells, the marrow and circulation, direct contact with osteoclast precursors, osteoclastogenesis and molecular cross-talk between precursors, mature cells, cells of the immune system, and products of the resorbed matrix, titrate the birth, work and lifespan of the cells of this multicellular remodelling machinery to either remove or form a net volume of bone appropriate to the mechanical requirements.

  16. Regulation of bone remodeling by vitamin K2.

    Science.gov (United States)

    Myneni, V D; Mezey, E

    2017-11-01

    All living tissues require essential nutrients such as amino acids, fatty acids, carbohydrates, minerals, vitamins, and water. The skeleton requires nutrients for development, maintaining bone mass and density. If the skeletal nutritional requirements are not met, the consequences can be quite severe. In recent years, there has been growing interest in promotion of bone health and inhibition of vascular calcification by vitamin K2. This vitamin regulates bone remodeling, an important process necessary to maintain adult bone. Bone remodeling involves removal of old or damaged bone by osteoclasts and its replacement by new bone formed by osteoblasts. The remodeling process is tightly regulated, when the balance between bone resorption and bone formation shifts to a net bone loss results in the development of osteoporosis in both men and women. In this review, we focus on our current understanding of the effects of vitamin K2 on bone cells and its role in prevention and treatment of osteoporosis. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  17. 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

    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....... 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...

  18. The reversal phase of the bone-remodeling cycle

    DEFF Research Database (Denmark)

    Delaisse, Jean-Marie

    2014-01-01

    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......The reversal phase couples bone resorption to bone formation by generating an osteogenic environment at remodeling sites. The coupling mechanism remains poorly understood, despite the identification of a number of 'coupling' osteogenic molecules. A possible reason is the poor attention...

  19. 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).

  20. Computational bone remodelling simulations and comparisons with DEXA results.

    Science.gov (United States)

    Turner, A W L; Gillies, R M; Sekel, R; Morris, P; Bruce, W; Walsh, W R

    2005-07-01

    Femoral periprosthetic bone loss following total hip replacement is often associated with stress shielding. Extensive bone resorption may lead to implant or bone failure and complicate revision surgery. In this study, an existing strain-adaptive bone remodelling theory was modified and combined with anatomic three-dimensional finite element models to predict alterations in periprosthetic apparent density. The theory incorporated an equivalent strain stimulus and joint and muscle forces from 45% of the gait cycle. Remodelling was simulated for three femoral components with different design philosophies: cobalt-chrome alloy, two-thirds proximally coated; titanium alloy, one-third proximally coated; and a composite of cobalt-chrome surrounded by polyaryletherketone, fully coated. Theoretical bone density changes correlated significantly with clinical densitometry measurements (DEXA) after 2 years across the Gruen zones (R2>0.67, p<0.02), with average differences of less than 5.4%. The results suggest that a large proportion of adaptive bone remodelling changes seen clinically with these implants may be explained by a consistent theory incorporating a purely mechanical stimulus. This theory could be applied to pre-clinical testing of new implants, investigation of design modifications, and patient-specific implant selection.

  1. 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

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

    International Nuclear Information System (INIS)

    Tanaka, H.; Mine, T.; Ogasa, H.; Taguchi, T.; Liang, C.T.

    2011-01-01

    Highlights: → This is the first study to determine the relationship between osteogenic differentiation and RANKL/OPG expression during bone remodeling in vivo. → The OPG expression peak occurred during the bone formation phase, whereas the marked elevation of RANKL expression was observed during the bone resorption phase. → Histological analysis showed that RANKL/OPG immunoreactivity was predominantly associated with bone marrow cells in the marrow cavity. → 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 κB 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 α1 (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 expression of bone formation

  3. Altered thermogenesis and impaired bone remodeling in Misty mice.

    Science.gov (United States)

    Motyl, Katherine J; Bishop, Kathleen A; DeMambro, Victoria E; Bornstein, Sheila A; Le, Phuong; Kawai, Masanobu; Lotinun, Sutada; Horowitz, Mark C; Baron, Roland; Bouxsein, Mary L; Rosen, Clifford J

    2013-09-01

    Fat mass may be modulated by the number of brown-like adipocytes in white adipose tissue (WAT) in humans and rodents. Bone remodeling is dependent on systemic energy metabolism and, with age, bone remodeling becomes uncoupled and brown adipose tissue (BAT) function declines. To test the interaction between BAT and bone, we employed Misty (m/m) mice, which were reported be deficient in BAT. We found that Misty mice have accelerated age-related trabecular bone loss and impaired brown fat function (including reduced temperature, lower expression of Pgc1a, and less sympathetic innervation compared to wild-type (+/ +)). Despite reduced BAT function, Misty mice had normal core body temperature, suggesting heat is produced from other sources. Indeed, upon acute cold exposure (4°C for 6 hours), inguinal WAT from Misty mice compensated for BAT dysfunction by increasing expression of Acadl, Pgc1a, Dio2, and other thermogenic genes. Interestingly, acute cold exposure also decreased Runx2 and increased Rankl expression in Misty bone, but only Runx2 was decreased in wild-type. Browning of WAT is under the control of the sympathetic nervous system (SNS) and, if present at room temperature, could impact bone metabolism. To test whether SNS activity could be responsible for accelerated trabecular bone loss, we treated wild-type and Misty mice with the β-blocker, propranolol. As predicted, propranolol slowed trabecular bone volume/total volume (BV/TV) loss in the distal femur of Misty mice without affecting wild-type. Finally, the Misty mutation (a truncation of DOCK7) also has a significant cell-autonomous role. We found DOCK7 expression in whole bone and osteoblasts. Primary osteoblast differentiation from Misty calvaria was impaired, demonstrating a novel role for DOCK7 in bone remodeling. Despite the multifaceted effects of the Misty mutation, we have shown that impaired brown fat function leads to altered SNS activity and bone loss, and for the first time that cold

  4. PTH treatment activates intracortical bone remodeling in patients with hypoparathyroidism

    DEFF Research Database (Denmark)

    Sikjær, Tanja Tvistholm; Rejnmark, Lars; Thomsen, Jesper Skovhus

    2017-01-01

    Hypoparathyroidism (hypoPT) is characterized by a state of low bone turnover and high BMD. We have previously shown that hypoPT patients treated with PTH(1-84) for six months have highly increased bone turnover markers and a decrease in aBMD at the hip and spine(1). The present study aims...... to investigate the effect of PTH(1-84) on cortical bone and intracortical bone remodeling in hypoPT. The study was conducted on 20 transiliac bone biopsies from hypoPT patients after six months of treatment with either PTH(1-84) 100 µg s.c./day N=10 or placebo N=10. The groups were age- (±6 years) and gender...... and diameter were measured. Cortical porosity and pore density did not differ between groups, but PTH treatment had a marked effect on the remodeling status of the pores. The percentage of pores undergoing remodeling was higher in the PTH-group than in placebo-group reported as median values (IQR[25-75%]) (52...

  5. 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

  6. Oxidative stress in bone remodeling: role of antioxidants.

    Science.gov (United States)

    Domazetovic, Vladana; Marcucci, Gemma; Iantomasi, Teresa; Brandi, Maria Luisa; Vincenzini, Maria Teresa

    2017-01-01

    ROS are highly reactive molecules which consist of a number of diverse chemical species, including radical and non-radical oxygen species. Oxidative stress occurs as a result of an overproduction of ROS not balanced by an adequate level of antioxidants. The natural antioxidants are: thiol compounds among which GSH is the most representative, and non-thiol compounds such as polyphenols, vitamins and also various enzymes. Many diseases have been linked to oxidative stress including bone diseases among which one of the most important is the osteoporosis. The redox state changes are also related to the bone remodeling process which allows the continuous bone regeneration through the coordinated action of bone cells: osteoclasts, osteoblasts and osteocytes. Changes in ROS and/or antioxidant systems seem to be involved in the pathogenesis of bone loss. ROS induce the apoptosis of osteoblasts and osteocytes, and this favours osteoclastogenesis and inhibits the mineralization and osteogenesis. Excessive osteocyte apoptosis correlates with oxidative stress causing an imbalance in favor of osteoclastogenesis which leads to increased turnover of bone remodeling and bone loss. Antioxidants either directly or by counteracting the action of oxidants contribute to activate the differentiation of osteoblasts, mineralization process and the reduction of osteoclast activity. In fact, a marked decrease in plasma antioxidants was found in aged or osteoporotic women. Some evidence shows a link among nutrients, antioxidant intake and bone health. Recent data demonstrate the antioxidant properties of various nutrients and their influence on bone metabolism. Polyphenols and anthocyanins are the most abundant antioxidants in the diet, and nutritional approaches to antioxidant strategies, in animals or selected groups of patients with osteoporosis or inflammatory bone diseases, suggest the antioxidant use in anti-resorptive therapies for the treatment and prevention of bone loss.

  7. 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

  8. Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation.

    Science.gov (United States)

    McGee-Lawrence, Meghan; Buckendahl, Patricia; Carpenter, Caren; Henriksen, Kim; Vaughan, Michael; Donahue, Seth

    2015-07-01

    Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losing cortical or trabecular bone mass. Bears have been shown to preserve trabecular bone volume and architectural parameters and cortical bone strength, porosity and geometrical properties during hibernation. The mechanisms that prevent disuse osteoporosis in bears are unclear as previous studies using histological and serum markers of bone remodeling show conflicting results. However, previous studies used serum markers of bone remodeling that are known to accumulate with decreased renal function, which bears have during hibernation. Therefore, we measured serum bone remodeling markers (BSALP and TRACP) that do not accumulate with decreased renal function, in addition to the concentrations of serum calcium and hormones involved in regulating bone remodeling in hibernating and active bears. Bone resorption and formation markers were decreased during hibernation compared with when bears were physically active, and these findings were supported by histomorphometric analyses of bone biopsies. The serum concentration of cocaine and amphetamine regulated transcript (CART), a hormone known to reduce bone resorption, was 15-fold higher during hibernation. Serum calcium concentration was unchanged between hibernation and non-hibernation seasons. Suppressed and balanced bone resorption and formation in hibernating bears contributes to energy conservation, eucalcemia and the preservation of bone mass and strength, allowing bears to survive prolonged periods of extreme environmental conditions, nutritional deprivation and anuria. © 2015. Published by The Company of Biologists Ltd.

  9. Correlation between pre-operative periprosthetic bone density and post-operative bone loss in THA can be explained by strain-adaptive remodelling

    NARCIS (Netherlands)

    Kerner, J.; Huiskes, H.W.J.; Lenthe, van G.H.; Weinans, H.; Rietbergen, van B.; Engh, C.A.; Amis, A.A.

    1999-01-01

    Periprosthetic adaptive bone remodelling after total hip arthroplasty can be simulated in computer models, combining bone remodelling theory with finite element analysis. Patient specific three-dimensional finite element models of retrieved bone specimens from an earlier bone densitometry (DEXA)

  10. 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...... operated on with pedicle screws between L4 and L5. The stress shielding effect was also examined. The bone remodeling results were compared with prospective bone mineral content measurements of 4 patients. They were measured after surgery, 3-, 6- and 12-months postoperatively. RESULTS: After 1 year...

  11. Mechanisms of bone remodeling: implications for clinical practice.

    Science.gov (United States)

    Kenny, Anne M; Raisz, Lawrence G

    2002-01-01

    The adult skeleton undergoes continuous remodeling. The remodeling cycle involves the interaction of cells of osteoblastic and osteoclastic lineage and is regulated by both systemic hormones and local factors. In addition to the systemic calcium-regulating hormones, parathyroid hormone, 1,25-dihydroxy vitamin D and calcitonin, sex hormones play an important role. Estrogen has been identified as the major inhibitor of bone resorption in both men and women. Androgen is important not only as a source of estrogen, through the action of aromatase, but also for its direct effect in stimulating bone formation. The effects of sex hormones may be mediated by their ability to alter the secretion of local cytokines, prostaglandins and growth factors. Sex hormone action is also modulated by the level of sex hormone-binding globulin in the circulation. A more precise analysis of these effects has been made possible by the development of new methods of measuring not only bone mineral density, but also relative rates of bone formation and resorption using biochemical markers. These new approaches have allowed us to define more precisely the specific roles of androgens, estrogens and other regulatory hormones in human skeletal physiology and pathophysiology.

  12. In silico biology of bone modelling and remodelling: adaptation.

    Science.gov (United States)

    Gerhard, Friederike A; Webster, Duncan J; van Lenthe, G Harry; Müller, Ralph

    2009-05-28

    Modelling and remodelling are the processes by which bone adapts its shape and internal structure to external influences. However, the cellular mechanisms triggering osteoclastic resorption and osteoblastic formation are still unknown. In order to investigate current biological theories, in silico models can be applied. In the past, most of these models were based on the continuum assumption, but some questions related to bone adaptation can be addressed better by models incorporating the trabecular microstructure. In this paper, existing simulation models are reviewed and one of the microstructural models is extended to test the hypothesis that bone adaptation can be simulated without particular knowledge of the local strain distribution in the bone. Validation using an experimental murine loading model showed that this is possible. Furthermore, the experimental model revealed that bone formation cannot be attributed only to an increase in trabecular thickness but also to structural reorganization including the growth of new trabeculae. How these new trabeculae arise is still an unresolved issue and might be better addressed by incorporating other levels of hierarchy, especially the cellular level. The cellular level sheds light on the activity and interplay between the different cell types, leading to the effective change in the whole bone. For this reason, hierarchical multi-scale simulations might help in the future to better understand the biomathematical laws behind bone adaptation.

  13. [Bone Cell Biology Assessed by Microscopic Approach. A mathematical approach to understand bone remodeling].

    Science.gov (United States)

    Kameo, Yoshitaka; Adachi, Taiji

    2015-10-01

    It is well known that bone tissue can change its outer shape and internal structure by remodeling according to a changing mechanical environment. However, the mechanism of bone functional adaptation induced by the collaborative metabolic activities of bone cells in response to mechanical stimuli remains elusive. In this article, we focus on the hierarchy of bone structure and function from the microscopic cellular level to the macroscopic tissue level. We provide an overview of a mathematical approach to understand the adaptive changes in trabecular morphology under the application of mechanical stress.

  14. 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.

  15. Revisiting the links between bone remodelling and osteocytes: insights from across phyla.

    Science.gov (United States)

    Currey, John D; Dean, Mason N; Shahar, Ron

    2017-08-01

    We question two major tenets of bone biology: that the primary role of remodelling is to remove damage in the bone (so-called damage-driven remodelling) and that osteocytes are the only strain-sensing orchestrators of this process. These concepts are distilled largely from research on model mammal species, but in fact, there are a number of features of various bones, from mammalian and non-mammalian species, that do not accord with these 'rules'. Here, we assemble a variety of examples, ranging from species that lack osteocytes but that still seem capable of remodelling their bones, to species with osteocytic bones that do not remodel, and to instances of inter-species, inter-bone and/or intra-bone variation in bone remodelling that show that this purported repair process is not always where the 'rules' tell us it should be. This collection of points argues that our understanding of the advantages, roles and primary drivers of remodelling are inadequate and biased to quite a small phylogenetic cross section of the species that possess bone. We suggest a variety of new directions for bone research that would provide us with a better understanding of bone remodelling, tying together the interests of comparative biologists, palaeontologists and medical researchers. © 2016 Cambridge Philosophical Society.

  16. 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

    matrix molecules, collagen's potency was superior and only equaled by fibronectin. Next, the majority of the newly recruited osteoblast lineage cells positioned immediately next to the osteoclasts exhibit uPARAP/Endo180, an endocytic collagen receptor reported to be involved in collagen internalization......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...

  17. 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.

  18. Genetic and environmental variances of bone microarchitecture and bone remodeling markers: a twin study.

    Science.gov (United States)

    Bjørnerem, Åshild; Bui, Minh; Wang, Xiaofang; Ghasem-Zadeh, Ali; Hopper, John L; Zebaze, Roger; Seeman, Ego

    2015-03-01

    All genetic and environmental factors contributing to differences in bone structure between individuals mediate their effects through the final common cellular pathway of bone modeling and remodeling. We hypothesized that genetic factors account for most of the population variance of cortical and trabecular microstructure, in particular intracortical porosity and medullary size - void volumes (porosity), which establish the internal bone surface areas or interfaces upon which modeling and remodeling deposit or remove bone to configure bone microarchitecture. Microarchitecture of the distal tibia and distal radius and remodeling markers were measured for 95 monozygotic (MZ) and 66 dizygotic (DZ) white female twin pairs aged 40 to 61 years. Images obtained using high-resolution peripheral quantitative computed tomography were analyzed using StrAx1.0, a nonthreshold-based software that quantifies cortical matrix and porosity. Genetic and environmental components of variance were estimated under the assumptions of the classic twin model. The data were consistent with the proportion of variance accounted for by genetic factors being: 72% to 81% (standard errors ∼18%) for the distal tibial total, cortical, and medullary cross-sectional area (CSA); 67% and 61% for total cortical porosity, before and after adjusting for total CSA, respectively; 51% for trabecular volumetric bone mineral density (vBMD; all p accounted for 47% to 68% of the variance (all p ≤ 0.001). Cross-twin cross-trait correlations between tibial cortical porosity and medullary CSA were higher for MZ (rMZ  = 0.49) than DZ (rDZ  = 0.27) pairs before (p = 0.024), but not after (p = 0.258), adjusting for total CSA. For the remodeling markers, the data were consistent with genetic factors accounting for 55% to 62% of the variance. We infer that middle-aged women differ in their bone microarchitecture and remodeling markers more because of differences in their genetic factors than

  19. Capturing microscopic features of bone remodeling into a macroscopic model based on biological rationales of bone adaptation.

    Science.gov (United States)

    Kim, Young Kwan; Kameo, Yoshitaka; Tanaka, Sakae; Adachi, Taiji

    2017-10-01

    To understand Wolff's law, bone adaptation by remodeling at the cellular and tissue levels has been discussed extensively through experimental and simulation studies. For the clinical application of a bone remodeling simulation, it is significant to establish a macroscopic model that incorporates clarified microscopic mechanisms. In this study, we proposed novel macroscopic models based on the microscopic mechanism of osteocytic mechanosensing, in which the flow of fluid in the lacuno-canalicular porosity generated by fluid pressure gradients plays an important role, and theoretically evaluated the proposed models, taking biological rationales of bone adaptation into account. The proposed models were categorized into two groups according to whether the remodeling equilibrium state was defined globally or locally, i.e., the global or local uniformity models. Each remodeling stimulus in the proposed models was quantitatively evaluated through image-based finite element analyses of a swine cancellous bone, according to two introduced criteria associated with the trabecular volume and orientation at remodeling equilibrium based on biological rationales. The evaluation suggested that nonuniformity of the mean stress gradient in the local uniformity model, one of the proposed stimuli, has high validity. Furthermore, the adaptive potential of each stimulus was discussed based on spatial distribution of a remodeling stimulus on the trabecular surface. The theoretical consideration of a remodeling stimulus based on biological rationales of bone adaptation would contribute to the establishment of a clinically applicable and reliable simulation model of bone remodeling.

  20. Effects of occlusal inclination and loading on mandibular bone remodeling: a finite element study.

    Science.gov (United States)

    Rungsiyakull, Chaiy; Rungsiyakull, Pimdeun; Li, Qing; Li, Wei; Swain, Michael

    2011-01-01

    To provide a preliminary understanding of the biomechanics with respect to the effect of cusp inclination and occlusal loading on the mandibular bone remodeling. Three different cusp inclinations (0, 10, and 30 degrees) of a ceramic crown and different occlusal loading locations (central fossa and 1- and 2-mm offsets horizontally) were taken into account to explore the stresses and strains transferred from the crown to the surrounding dental bone through the implant. A strain energy density obtained from two-dimensional plane-strain finite element analysis was used as the mechanical stimulus to drive cancellous and cortical bone remodeling in a buccolingual mandibular section. Different ceramic cusp inclinations had a significant effect on bone remodeling responses in terms of the change in the average peri-implant bone density and overall stability. The remodeling rate was relatively high in the first few months of loading and gradually decreased until reaching its equilibrium. A larger cusp inclination and horizontal offset (eg, 30 degrees and 2-mm offset) led to a higher bone remodeling rate and greater interfacial stress. The dental implant superstructure design (in terms of cusp inclination and loading location) determines the load transmission pattern and thus largely affects bone remodeling activities. Although the design with a lower cusp inclination recommended in previous studies may reduce damage and fracture failure, it could, to a certain extent, compromise bone engagement and long-term stability.

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

    Science.gov (United States)

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

    2016-05-01

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

  2. 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

    The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released by the ost......The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released...... by the osteoclasts. However, the osteoclasts are separated from the mature bone forming osteoblasts in time and space. Therefore the target cell of these osteoclastic factors has remained unknown. Recent explorations of the physical microenvironment of osteoclasts revealed a cell layer lining the bone marrow...... and forming a canopy over the whole remodeling surface, spanning from the osteoclasts to the bone forming osteoblasts. Several observations show that these canopy cells are a source of osteoblast progenitors, and we hypothesized therefore that they are the likely cells targeted by the osteogenic factors...

  3. Periprosthetic bone remodelling of short-stem total hip arthroplasty: a systematic review.

    Science.gov (United States)

    Yan, Shuang G; Weber, Patrick; Steinbrück, Arnd; Hua, Xingyi; Jansson, Volkmar; Schmidutz, Florian

    2017-11-27

    Short-stem hip arthroplasty (SHA) was designed to preserve bone stock and provide an improved load transfer. To gain more evidence regarding the load transfer, this review analysed the periprosthetic bone remodelling of SHA in comparison to standard hip arthroplasty (THA). PubMed and ScienceDirect were screened to extract dual-energy X-ray absorptiometry (DXA) studies evaluating the periprosthetic bone remodelling of SHA and two proven THA designs. From the studies included, the postoperative change in periprosthetic bone mineral density (BMD) after one year and the trend over two years was determined. Fifteen studies with four SHAs (CFP, Metha, Nanos, Fitmore) and two THAs (CLS and Bicontact) designs were included. All SHA and THA stems revealed an initial decrease at the calcar and major trochanter (Gruen 1 and 7) with the Metha, Nanos and Fitmore showing a smaller and more balanced remodelling compared to THA. The pattern after one year and the trend over two years argue for a methaphyseal anchorage of the Metha and Nanos, whereas the Fitmore and CFP seem to anchor metha-diaphyseal. Clearly different pattern of bone remodelling were observed between all four SHAs. Periprosthetic bone remodelling is also present in SHA, with the main bone reduction observed proximally. However, certain SHA stems show a more balanced remodelling compared to THA, arguing for a favourable load transfer. Also, the femoral length where bone remodelling occurs is clearly shorter in SHA. As distinctively different pattern between the SHA designs were observed, they should not be judged as a single implant group.

  4. 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

  5. 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.

  6. Application of VEGFA and FGF-9 enhances angiogenesis, osteogenesis and bone remodeling in type 2 diabetic long bone regeneration.

    Directory of Open Access Journals (Sweden)

    Christoph Wallner

    Full Text Available Although bone regeneration is typically a reliable process, type 2 diabetes is associated with impaired or delayed healing processes. In addition, angiogenesis, a crucial step in bone regeneration, is often altered in the diabetic state. In this study, different stages of bone regeneration were characterized in an unicortical bone defect model comparing transgenic type 2 diabetic (db-/db- and wild type (WT mice in vivo. We investigated angiogenesis, callus formation and bone remodeling at early, intermediate and late time points by means of histomorphometry as well as protein level analyses. In order to enhance bone regeneration, defects were locally treated with recombinant FGF-9 or VEGFA. Histomorphometry of aniline blue stained sections indicated that bone regeneration is significantly decreased in db-/db- as opposed to WT mice at intermediate (5 days post operation and late stages (7 days post operation of bone regeneration. Moreover, immunohistochemical analysis revealed significantly decreased levels of RUNX-2, PCNA, Osteocalcin and PECAM-1 in db-/db- defects. In addition, osteoclastogenesis is impaired in db-/db- indicating altered bone remodeling. These results indicate significant impairments in angiogenesis and osteogenesis in type 2 diabetic bones. Importantly, angiogenesis, osteogenesis and bone remodeling could be reconstituted by application of recombinant FGF-9 and, in part, by VEGFA application. In conclusion, our study demonstrates that type 2 diabetes affects angiogenesis, osteogenesis and subsequently bone remodeling, which in turn leads to decreased bone regeneration. These effects could be reversed by local application of FGF-9 and to a lesser degree VEGFA. These data could serve as a basis for future therapeutic applications aiming at improving bone regeneration in the type 2 diabetic patient population.

  7. 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.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

    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.

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

    NARCIS (Netherlands)

    Colloca, M.; Blanchard, R.; Hellmich, C.; Ito, K.; Rietbergen, van B.

    2014-01-01

    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

  10. Parametric study of control mechanism of cortical bone remodeling under mechanical stimulus

    Science.gov (United States)

    Wang, Yanan; Qin, Qing-Hua

    2010-03-01

    The control mechanism of mechanical bone remodeling at cellular level was investigated by means of an extensive parametric study on a theoretical model described in this paper. From a perspective of control mechanism, it was found that there are several control mechanisms working simultaneously in bone remodeling which is a complex process. Typically, an extensive parametric study was carried out for investigating model parameter space related to cell differentiation and apoptosis which can describe the fundamental cell lineage behaviors. After analyzing all the combinations of 728 permutations in six model parameters, we have identified a small number of parameter combinations that can lead to physiologically realistic responses which are similar to theoretically idealized physiological responses. The results presented in the work enhanced our understanding on mechanical bone remodeling and the identified control mechanisms can help researchers to develop combined pharmacological-mechanical therapies to treat bone loss diseases such as osteoporosis.

  11. Effect of occlusal (mechanical) stimulus on bone remodelling in rat mandibular condyle.

    Science.gov (United States)

    Gazit, D; Ehrlich, J; Kohen, Y; Bab, I

    1987-09-01

    Mechanical load influences the remodelling of skeletal tissues. In the mandibular condyle, occlusal alterations and the consequent mechanical stimulus induce changes in chondrocytes and cartilage mineralization. In the present study we quantified in the mandibular condyle the effect of occlusal interference on remodelling of the subchondral bone. Computerized histomorphometry after 5-21-day exposure to the influence of a unilateral occlusal splint revealed an increased rate of trabecular remodelling, consisting of enhancement in osteoblast and osteoclast numbers and activities. The bone formation parameters reached their high values on Days 5 or 9 and remained stable thereafter. Bone resorption showed a gradual increase throughout the experimental period. These results further characterize the temporomandibular joint reaction to occlusal alterations. It is suggested that the present increase in bone turnover together with the known enhancement in chondrogenesis are part of a process of functional adaptation in response to mechanical stimulus.

  12. 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.

  13. 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.

    2016-01-01

    -fluted 125-mm uncemented press-fit titanium alloy stem with hydroxyapatite coating of the proximal part of the stem. Measurements of bone mineral density (BMD; g/cm2) were done postoperatively and after 3, 6, and 12 mo in the part of the femur bone containing the Global Modular Replacement System stem using...... of 8%-9% during the first postoperative year was seen along the femoral stem, but in the bone containing the hydroxyapatite-coated part of the stem, the decrease in BMD was 14%, thus indicating that stress shielding of this part of the bone may play a role for the adaptive bone remodeling....

  14. Numerical evaluation of bone remodelling and adaptation considering different hip prosthesis designs.

    Science.gov (United States)

    Levadnyi, Ievgen; Awrejcewicz, Jan; Gubaua, José Eduardo; Pereira, Jucélio Tomás

    2017-12-01

    The change in mechanical properties of femoral cortical bone tissue surrounding the stem of the hip endoprosthesis is one of the causes of implant instability. We present an analysis used to determine the best conditions for long-term functioning of the bone-implant system, which will lead to improvement of treatment results. In the present paper, a finite element method coupled with a bone remodelling model is used to evaluate how different three-dimensional prosthesis models influence distribution of the density of bone tissue. The remodelling process begins after the density field is obtained from a computed tomography scan. Then, an isotropic Stanford model is employed to solve the bone remodelling process and verify bone tissue adaptation in relation to different prosthesis models. The study results show that the long-stem models tend not to transmit loads to proximal regions of bone, which causes the stress-shielding effect. Short stems or application in the calcar region provide a favourable environment for transfer of loads to the proximal region, which allows for maintenance of bone density and, in some cases, for a positive variation, which causes absence of the aseptic loosening of an implant. In the case of hip resurfacing, bone mineral density changes slightly and is closest to an intact femur. Installation of an implant modifies density distribution and stress field in the bone. Thus, bone tissue is stimulated in a different way than before total hip replacement, which evidences Wolff's law, according to which bone tissue adapts itself to the loads imposed on it. The results suggest that potential stress shielding in the proximal femur and cortical hypertrophy in the distal femur may, in part, be reduced through the use of shorter stems, instead of long ones, provided stem fixation is adequate. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Bone status in patients with epilepsy: relationship to markers of bone remodeling

    Directory of Open Access Journals (Sweden)

    Sherifa Ahmed Hamed

    2014-08-01

    Full Text Available Patients with epilepsy and treated with antiepileptic drugs (AEDs may develop metabolic bone disease, however, the exact pathogenesis of bone loss with AEDs is still unclear. Included were 75 adults with epilepsy (mean age: 31.90±5.62years; duration of treatment with AEDs: 10.57±3.55years and 40 matched healthy controls. Bone mineral content (BMC and densities (BMD of the femoral neck and lumbar spine were measured using dual energy X-ray absorptiometry (DEXA. Blood samples were analyzed for calcium, magnesium, phosphate, alkaline phosphatase (ALP, 25-hydroxy vitamin D (25OHD, soluble receptor activator of nuclear factor kB ligand (sRANKL, osteoprotegerin (OPG and OPG/RANKL ratio (markers of bone remodeling. Compared to controls, patients had lower BMD, BMC, Z-score and T-score at the femoral neck and lumbar spine (all p<0.001. 72% and 29.33% of patients had osteoporosis of the lumbar spine and femoral neck. Patients had significantly lower serum calcium, 25(OHD and OPG and higher ALP, sRANKL levels and sRANKL/OPG (all p<0.001. 52% of patients had hypocalcemia, 93% had hypovitaminosis D, 31% had high levels of sRANKL and 49% had low levels of OPG. No differences were identified between DEXA and laboratory results in relation to the type, dose or serum levels of AEDs. BMD at the femoral neck and lumbar spine were found to be correlated with the duration of illness (p=0.043; p=0.010, duration of treatment with AEDs (p<0.001; p=0.012 and serum levels of 25(OHD (p<0.042; p=0.010, sRANKLs (p=0.005; p=0.01 and OPG (p<0.006; p<0.01. In linear regression analysis and after adjusting for gender, age, weight, duration and number of AEDs, we observed an association between BMD, 25(OHD (p=0.04 and sRANKL (p=0.03 concentrations. We conclude that AEDs may compromise bone health through disturbance of mineral metabolism and acceleration of bone turnover mechanisms.

  16. Hydrogels That Allow and Facilitate Bone Repair, Remodeling, and Regeneration.

    Science.gov (United States)

    Short, Aaron R; Koralla, Deepthi; Deshmukh, Ameya; Wissel, Benjamin; Stocker, Benjamin; Calhoun, Mark; Dean, David; Winter, Jessica O

    2015-10-28

    Bone defects can originate from a variety of causes, including trauma, cancer, congenital deformity, and surgical reconstruction. Success of the current "gold standard" treatment (i.e., autologous bone grafts) is greatly influenced by insufficient or inappropriate bone stock. There is thus a critical need for the development of new, engineered materials for bone repair. This review describes the use of natural and synthetic hydrogels as scaffolds for bone tissue engineering. We discuss many of the advantages that hydrogels offer as bone repair materials, including their potential for osteoconductivity, biodegradability, controlled growth factor release, and cell encapsulation. We also discuss the use of hydrogels in composite devices with metals, ceramics, or polymers. These composites are useful because of the low mechanical moduli of hydrogels. Finally, the potential for thermosetting and photo-cross-linked hydrogels as three-dimensionally (3D) printed, patient-specific devices is highlighted. Three-dimensional printing enables controlled spatial distribution of scaffold materials, cells, and growth factors. Hydrogels, especially natural hydrogels present in bone matrix, have great potential to augment existing bone tissue engineering devices for the treatment of critical size bone defects.

  17. Fragility fractures and bone remodeling in type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Tatiana O. Yalochkina

    2017-11-01

    Full Text Available Fracture risk is significantly increased in both type 1 and type 2 diabetes and individuals with diabetes experience worse fracture outcomes compared to normoglycemic individuals. Patients with T1DM have decreased bone mineral density (BMD, whereas patients with T2DM demonstrate increased BMD compared to healthy control. The latest studies show increased incidence of low-traumatic fractures in patients with T2DM instead of high bone mineral density (BMD. The risk of osteoporotic fractures in patients with T2DM can be explained by disease complications and increased risk of falls and consequent trauma. However, the most important cause of bone fragility in T2DM is the deterioration in bone microarchitecture, the mechanism of which is not completely understood. High BMD in patients with T2DM does not allow us to use dual-energy X-ray-absorptiometry as a “gold standard” test for diagnosticsof osteoporosis. Consequently,new risk factors and diagnostic algorithm as well as treatment strategy should be developed for patients with T2DM. In addition to this, some researchers considered that the group of T2DM is geterogenous and physicians might face patients with osteoporosis and mild diabetes that add very little to bone fragility; patients with osteoporosis and moderate or severe diabetes which also affects bone tissue –diabetoosteoporosis; and patients without osteoporosis but severe diabetes which cause bone tissue deterioration with the development of diabetic bone disease. New diagnostic tools and algorithm and new experimental research are needed for better understanding bone deterioration in patients with T2DM. This review summarizes our current knowledge on fracture rate, risk factors for fractures and causes of bone deterioration in subjects with T2DM.

  18. Bone remodeling after hip joint replacement. Numerical Modeling and Comparism with Clinical Observation

    Czech Academy of Sciences Publication Activity Database

    Klika, Václav; Maršík, František; Landor, I.

    2007-01-01

    Roč. 14, 3-4 (2007), s. 340-343 ISSN 1212-4575. [Prague-Sydney-Lublin Symposium /9./, Kubát's Podiatric Day /12./. Prague, 19.10.2007-20.10.2007] Institutional research plan: CEZ:AV0Z20760514 Keywords : bone remodeling * prosthesis * RANKL/RANK/OPG pathway Subject RIV: BO - Biophysics

  19. The law of adaptive bone remodeling : a case for crying Newton?

    NARCIS (Netherlands)

    Huiskes, R.; Odgaard, A.; Weinans, H.

    1995-01-01

    The biological mechanisms of strain-adaptive bone remodeling are largely unknown. Yet, several authors published algorithms to mimic this process, without prior validation of its premises. Biologists are sometimes confused by this seemingly irresponsible behavior. However, this kind of inductive

  20. 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. Copyright © 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  1. Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling

    Directory of Open Access Journals (Sweden)

    Neha S. Dole

    2017-11-01

    Full Text Available Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR. Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRIIocy−/−, we show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility.

  2. Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling.

    Science.gov (United States)

    Dole, Neha S; Mazur, Courtney M; Acevedo, Claire; Lopez, Justin P; Monteiro, David A; Fowler, Tristan W; Gludovatz, Bernd; Walsh, Flynn; Regan, Jenna N; Messina, Sara; Evans, Daniel S; Lang, Thomas F; Zhang, Bin; Ritchie, Robert O; Mohammad, Khalid S; Alliston, Tamara

    2017-11-28

    Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR). Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRII ocy-/- ), we show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility. Published by Elsevier Inc.

  3. Trabecular bone structure and strength - remodelling and repair

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  4. 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....... 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...

  5. Load-adaptive bone remodeling simulations reveal osteoporotic microstructural and mechanical changes in whole human vertebrae.

    Science.gov (United States)

    Badilatti, Sandro D; Christen, Patrik; Parkinson, Ian; Müller, Ralph

    2016-12-08

    Osteoporosis is a major medical burden and its impact is expected to increase in our aging society. It is associated with low bone density and microstructural deterioration. Treatments are available, but the critical factor is to define individuals at risk from osteoporotic fractures. Computational simulations investigating not only changes in net bone tissue volume, but also changes in its microstructure where osteoporotic deterioration occur might help to better predict the risk of fractures. In this study, bone remodeling simulations with a mechanical feedback loop were used to predict microstructural changes due to osteoporosis and their impact on bone fragility from 50 to 80 years of age. Starting from homeostatic bone remodeling of a group of seven, mixed sex whole vertebrae, five mechanostat models mimicking different biological alterations associated with osteoporosis were developed, leading to imbalanced bone formation and resorption with a total net loss of bone tissue. A model with reduced bone formation rate and cell sensitivity led to the best match of morphometric indices compared to literature data and was chosen to predict postmenopausal osteoporotic bone loss in the whole group. Thirty years of osteoporotic bone loss were predicted with changes in morphometric indices in agreement with experimental measurements, and only showing major deviations in trabecular number and trabecular separation. In particular, although being optimized to match to the morphometric indices alone, the predicted bone loss revealed realistic changes on the organ level and on biomechanical competence. While the osteoporotic bone was able to maintain the mechanical stability to a great extent, higher fragility towards error loads was found for the osteoporotic bones. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    on the bone surface from the marrow cavity. The present study on human iliac crest biopsy specimens reveals that BRC canopies appear frequently absent above both eroded and formative surfaces in post-menopausal osteoporosis patients, and that this absence was associated with bone loss in these patients...... surfaces was associated with a shift in the osteoblast morphological characteristics, from cuboidal to flattened. Collectively, this study shows that the BRCs are unique anatomical structures implicated in bone remodeling in a widespread disease, such as post-menopausal osteoporosis. Furthermore...

  7. Modic (endplate) changes in the lumbar spine: bone micro-architecture and remodelling.

    Science.gov (United States)

    Perilli, Egon; Parkinson, Ian H; Truong, Le-Hoa; Chong, Kuan C; Fazzalari, Nicola L; Osti, Orso L

    2015-09-01

    In the literature, inter-vertebral MRI signal intensity changes (Modic changes) were associated with corresponding histological observations on endplate biopsies. However, tissue-level studies were limited. No quantitative histomorphometric study on bone biopsies has yet been conducted for Modic changes. The aim of this study was to characterise the bone micro-architectural parameters and bone remodelling indices associated with Modic changes. Forty patients suffering from disabling low back pain, undergoing elective spinal surgery, and exhibiting Modic changes on MRI (Modic 1, n = 9; Modic 2, n = 25; Modic 3, n = 6), had a transpedicular vertebral body biopsy taken of subchondral bone. Biopsies were first examined by micro-CT, for 3D morphometric analysis of bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular separation, trabecular number, and structure model index. Then, samples underwent histological analysis, for determination of bone remodelling indices: osteoid surface to bone surface ratio (OS/BS), eroded surface to bone surface (ES/BS) and osteoid surface to eroded surface ratio (OS/ES). Micro-CT analysis revealed significantly higher BV/TV (up to 70% increase, p < 0.01) and Tb.Th (up to +57%, p < 0.01) in Modic 3 biopsies, compared to Modic 1 and 2. Histological analysis showed significantly lower OS/BS in Modic 2 biopsies (more than 28% decrease, p < 0.05) compared to 1 and 3. ES/BS progressively decreased from Modic 1 to 2 to 3, whereas OS/ES progressively increased with significantly higher values in Modic 3 (up to 159% increase, p < 0.05) than in Modic 1 and 2. Significant differences were found in bone micro-architectural parameters and remodelling indices among Modic types. Modic 1 biopsies had evidence of highest bone turnover, possibly due to an inflammatory process; Modic 2 biopsies were consistent with a reduced bone formation/remodelling stage; Modic 3 biopsies suggested a more stable sclerotic phase, with significantly

  8. Trabecular bone structure and strength - remodelling and repair

    DEFF Research Database (Denmark)

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

    2000-01-01

    vertical and horizontal struts reaching a certain magnitude and thereby inducing buckling under compression. 4) Microdamage and microfractures will occur - mainly in these very loaded vertical struts. The microfractures will be repaired by microcallus formation, and these calluses will later be removed...... 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...

  9. Bone remodelling biomarkers after whole body cryotherapy (WBC) in elite rugby players.

    Science.gov (United States)

    Galliera, Emanuela; Dogliotti, Giada; Melegati, Gianluca; Corsi Romanelli, Massimiliano M; Cabitza, Paolo; Banfi, Giuseppe

    2013-08-01

    Whole body cryotherapy (WBC) consists of a brief exposure to extreme cold air (-110°C) in a controlled chamber and it is applied in sports medicine to improve recovery from musculoskeletal trauma. The aim of this study is to better define the beneficial effect of WCB on the musculoskeletal system of athletes, in particular on bone remodelling. Remodelling osteoimmunological biomarkers OPG, RANKL and RANK were measured after WBC treatment in 10 male rugby players randomly selected from the Italian National team. OPG levels were increased significantly, supporting the view that WBC induces an osteogenic effect. Further studies evaluating the effect of WBC on bone metabolism are desirable. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Modulation of cognition and anxiety-like behavior by bone remodeling

    Directory of Open Access Journals (Sweden)

    Lori Khrimian

    2017-12-01

    Full Text Available Objective: That the bone-derived hormone osteocalcin is necessary to promote normal brain development and function, along with its recently described sufficiency in reversing cognitive manifestations of aging, raises novel questions. One of these is to assess whether bone health, which deteriorates rapidly with aging, is a significant determinant of cognition and anxiety-like behavior. Methods: To begin addressing this question, we used mice haploinsufficient for Runx2, the master gene of osteoblast differentiation and the main regulator of Osteocalcin expression. Control and Runx2+/− mice were evaluated for the expression of osteocalcin's target genes in the brain and for behavioral parameters, using two assays each for cognition and anxiety-like behavior. Results: We found that adult Runx2+/− mice had defects in bone resorption, reduced circulating levels of bioactive osteocalcin, and reduced expression of osteocalcin's target genes in the brain. Consequently, they had significant impairment in cognitive function and increased anxiety-like behavior. Conclusions: These results indicate that bone remodeling is a determinant of brain function. Keywords: Runx2, Osteocalcin, Bone remodeling, Cognition

  11. Bone remodeling and regulating biomarkers in women at the time of breast cancer diagnosis.

    Science.gov (United States)

    Yao, Song; Zhang, Yali; Tang, Li; Roh, Janise M; Laurent, Cecile A; Hong, Chi-Chen; Hahn, Theresa; Lo, Joan C; Ambrosone, Christine B; Kushi, Lawrence H; Kwan, Marilyn L

    2017-02-01

    The majority of breast cancer patients receive endocrine therapy, including aromatase inhibitors known to cause increased bone resorption. Bone-related biomarkers at the time of breast cancer diagnosis may predict future risk of osteoporosis and fracture after endocrine therapy. In a large population of 2,401 female breast cancer patients who later underwent endocrine therapy, we measured two bone remodeling biomarkers, TRAP5b and BAP, and two bone regulating biomarkers, RANKL and OPG, in serum samples collected at the time of breast cancer diagnosis. We analyzed these biomarkers and their ratios with patients' demographic, lifestyle, clinical tumor characteristics, as well as bone health history. The presence of bone metastases, prior bisphosphonate (BP) treatment, and blood collection after chemotherapy had a significant impact on biomarker levels. After excluding these cases and controlling for blood collection time, several factors, including age, race/ethnicity, body mass index, physical activity, alcohol consumption, smoking, and hormonal replacement therapy, were significantly associated with bone biomarkers, while vitamin D or calcium supplements and tumor characteristics were not. When prior BP users were included in, recent history of osteoporosis and fracture was also associated. Our findings support further investigation of these biomarkers with bone health outcomes after endocrine therapy initiation in women with breast cancer.

  12. 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.

  13. [Osteoclasts and early bone remodeling after orthodontic micro-implant placement].

    Science.gov (United States)

    Zhang, Wei; Guo, Jia-jia; Zhu, Wen-qian; Tang, Guo-hua

    2013-08-01

    To observe the incidence of osteoclasts during early bone remodeling after orthodontic micro-implant placement. 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. 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's lacunae. New bone formation and mineralization were apparent on day 14. Meanwhile, large amounts of osteoclasts were found in the latticed woven bone. On day 28, woven trabeculae with lamellate structures connected to lamellar bone and fewer osteoclasts were identified. Semi-quantitative analysis showed that the number of the osteoclasts was at peak on day 14. There were significant differences among each time point (Pmicro-implant insertion.

  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. The course of some bone remodelling plasma metabolites in healthy horses and in horses offered a calcium-deficient diet.

    Science.gov (United States)

    de Behr, V; Daron, D; Gabriel, A; Remy, B; Dufrasne, I; Serteyn, D; Istasse, L

    2003-04-01

    An inquiry was carried out to assess the concentrations of plasma metabolites related to bone remodelling in 21 saddle horses of Warmblood breed aged 4-26 years, five draught horses of Ardennes breed aged 4-10 years, and 10 Ardennes foals aged 9-11 months. They were fed according to normal feeding practice in Belgium. The changes in some bone remodelling plasma metabolite concentrations were studied when an unbalanced diet was offered and later corrected for four Warmblood horses. Bone formation was evaluated by bone alkaline phosphatase (BALP), total alkaline phosphatase (TALP) and osteocalcin (bone gla-protein, OC). Bone resorption was assessed by hydroxyproline (HYP). Total calcium, ionized calcium, phosphorus (P) and 25-hydroxyvitamin D3 [25-(OH)D] concentrations were more or less constant. The comparison of four bone remodelling factors between the Ardennes and Warmblood horses showed higher concentrations in the Ardennes breed. Bone marker concentrations decreased according to age. The correction of the unbalanced Ca : P diet induced inconsistent effects at plasma level. The interpretation of the different bone parameters appeared to be difficult if not associated with other parameters such as a complete anamnesis and clinical examination of the animal in addition to dietary evaluation.

  16. Various effects of antidepressant drugs on bone microarchitectecture, mechanical properties and bone remodeling

    International Nuclear Information System (INIS)

    Bonnet, N.; Bernard, P.; Beaupied, H; Bizot, J.C.; Trovero, F.; Courteix, D.; Benhamou, C.L.

    2007-01-01

    The aim of this study was to evaluate the effects of various drugs which present antidepressant properties: selective serotonin-reuptake inhibitors (SSRIs, fluoxetine), serotonin and noradrenaline-reuptake inhibitors (Desipramine) and phosphodiesterase inhibitors (PDE, rolipram and tofisopam) on bone microarchitecture and biomechanical properties. Twelve female mice were studied per group starting at an age of 10 weeks. During 4 weeks, they received subcutaneously either placebo or 20 mg kg -1 day -1 of desipramine, fluoxetine or 10 mg kg -1 day -1 of rolipram or tofisopam. Serum Osteocalcin and CTx were evaluated by ELISA. Bone microarchitecture of the distal femur was characterized by X-ray microCT (Skyscan1072). Mechanical properties were assessed by three-point bending test (Instron 4501) and antidepressant efficacy by forced swimming and open field tests. Fluoxetine displayed lower TbTh (- 6.1%, p -1 , 6431 ± 1182 MPa) than in placebo (101 ± 9 N mm -1 , 8441 ± 1180 MPa). Bone markers indicated a significantly higher bone formation in tofisopam (+ 8.6%) and a lower in fluoxetine (- 56.1%) compared to placebo. These data suggest deleterious effects for SSRIs, both on trabecular and cortical bone and a positive effect of PDE inhibitors on trabecular bone. Furthermore tofisopam anabolic effect in terms of bone markers, suggests a potential therapeutic effect of the PDE inhibitors on bone

  17. Role of the small integrin-binding ligand N-linked glycoprotein (SIBLING), bone sialoprotein (BSP) in bone development and remodeling.

    OpenAIRE

    Malaval, L.; Aubin, J.; Vico, L.

    2009-01-01

    14 pages; International audience; Members of the “small, integrin binding ligand, N-linked glycoprotein” (SIBLING) family, which have both mineral binding and cell binding (integrins) abilities, appear as potent regulators of bone mineralisation and remodeling. Among these, osteopontin (OPN) and bone sialoprotein (BSP) are highly expressed in early bone. Gene knockout of OPN results in increased mineralisation and a resorption defect making mutant mice unable to respond to such challenges as ...

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Radiation dose to trabecular bone marrow stem cells from 3H, 14C and selected α-emitters incorporated in a bone remodeling compartment

    International Nuclear Information System (INIS)

    Nie Huiling; Richardson, Richard B

    2009-01-01

    A Monte Carlo simulation of repeated cubic units representing trabecular bone cavities in adult bone was employed to determine absorbed dose fractions evaluated for 3 H, 14 C and a set of α-emitters incorporated within a bone remodeling compartment (BRC). The BRC consists of a well-oxygenated vascular microenvironment located within a canopy of bone-lining cells. The International Commission on Radiological Protection (ICRP) considers that an important target for radiation-induced bone cancer is the endosteum marrow layer adjacent to bone surface where quiescent bone stem cells reside. It is proposed that the active stem cells and progenitor cells located above the BRC canopy, the 'BRC stem cell niche', is a more important radiation-induced cancer target volume. Simulation results from a static model, where no remodeling occurs, indicate that the mean dose from bone and bone surface to the 50 μm quiescent bone stem cell niche, the current ICRP target, was substantially lower (two to three times lower) than that to the narrower and hypoxic 10 μm endosteum for 3 H, 14 C and α-particles with energy range 0.5-10 MeV. The results from a dynamic model indicate that the temporal α-radiation dose to active stem/progenitor cells located in the BRC stem cell niche from the material incorporated in and buried by forming bone was 9- to 111-fold greater than the dose to the quiescent bone stem cell niche. This work indicates that the remodeling portion of the bone surface, rather than the quiescent (endosteal) surface, has the greatest risk of radiation-induced bone cancer, particularly from short-range radiation, due to the elevated dose and the radiosensitizing oxygen effect.

  20. Biological effects of drinking-water mineral composition on calcium balance and bone remodeling markers.

    Science.gov (United States)

    Roux, S; Baudoin, C; Boute, D; Brazier, M; De La Guéronniere, V; De Vernejoul, M C

    2004-01-01

    To compare the effects of 2 drinking waters containing similar calcium (Ca) concentration in order to analyze the role of ions other than Ca on bone metabolism. These mineral drinking-waters differed by their mineral composition primarily concerning the concentration of bicarbonate (HCO3-), high in the HB, and sulfate, high in HS water. Of 60 included women, 39 completed the study. Patients were randomly assigned to an intake of 1 liter per day of mineral water HB or HS for 28 d, followed by cross-over to the alternative drinking-water for a further 28 d. At baseline and after each period of one month, Ca metabolism parameters, acid-base status, and bone remodeling markers were measured. Changes in Ca metabolism were significant in the HB group where the ionized Ca increased and the PTH decreased. Serum pH showed a similar increase whatever the used drinking water compared to baseline. In the HB group, significant increase in urine pH, and significant decrease in AT-HCO3- and NH4+ were observed. Bone resorption markers, urinary CTx/Cr, Pyr/Cr, and D-Pyr/Cr, significantly decreased in the HB group compared to baseline, and were not significantly modified in the HS group. These results showed a beneficial effect of the bicarbonaterich HB water on bone metabolism. This may account for a better bioavailability of the Ca, a greater alkalinization, and a larger decrease in PTH level secondary to a higher ionized Ca level. The higher content of silica in HB water may have also participated to the positive action on bone balance that was observed. In this short term study, these data underlined the potential role of the mineral drinking water composition on bone metabolism.

  1. Impact of marked weight loss induced by bariatric surgery on bone mineral density and remodeling

    Directory of Open Access Journals (Sweden)

    F.A. Pereira

    2007-04-01

    Full Text Available Data about the impact of bariatric surgery (BS and subsequent weight loss on bone are limited. The objective of the present study was to determine bone mineral density (BMD, bone remodeling metabolites and hormones that influence bone trophism in premenopausal women submitted to BS 9.8 months, on average, before the study (OGg, N = 16. The data were compared to those obtained for women of normal weight (CG, N = 11 and for obese women (OG, N = 12. Eight patients in each group were monitored for one year, with the determination of BMD, of serum calcium, phosphorus, magnesium, parathyroid hormone, 25-hydroxyvitamin D, insulin-like growth factor-I (IGF-I and osteocalcin, and of urinary calcium and deoxypyridinoline. The biochemical determinations were repeated every three months in the longitudinal study and BMD was measured at the end of the study. Parathyroid hormone levels were similar in the three groups. IGF-I levels (CG = 332 ± 62 vs OG = 230 ± 37 vs OGg = 128 ± 19 ng/mL were significantly lower in the operated patients compared to the non-operated obese women. Only OGg patients presented a significant fall in BMD of 6.2% at L1-L4, of 10.2% in the femoral neck, and of 5.1% in the forearm. These results suggest that the weight loss induced by BS is associated with a significant loss of bone mass even at sites that are not influenced by weight overload, with hormonal factors such as IGF-I being associated with this process.

  2. The influence of Young's modulus of loaded implants on bone remodeling: an experimental and numerical study in the goat knee.

    NARCIS (Netherlands)

    Stoppie, N.; Oosterwyck, H. Van; Jansen, J.A.; Wolke, J.G.C.; Wevers, M.; Naert, I.

    2009-01-01

    The aim of this study was to examine the influence of the Young's modulus of the implant material on the bone remodeling in a loaded condition. A combined animal experimental and computational study was set up. The animal experimental group comprised of 16 Saanen goats, each receiving one titanium

  3. Expression of microRNA related to bone remodeling regulation in plasma in patients with acromegaly

    Directory of Open Access Journals (Sweden)

    Tatiana A. Grebennikova

    2017-11-01

    Full Text Available Backgraund. MiсroRNA are small regulatory factors that regulate gene expression by post-transcriptional regulation of mRNA, playing an important role in numerous cellular processes including organogenesis, apoptosis, cell proliferation and differentiation. Acromegaly causes bone fragility, but the pathogenetic mechanism is generally unknown. Aim. To evaluate levels of microRNA related to bone remodeling regulation in plasma samples from patients with acromegaly Materials and methods. Fasting plasma samples were taken and stored in aliquot at ≤ -80°C from consecutive subjects with clinically evident and biochemically confirmed active acromegaly and healthy volunteers matched by age, sex and body mass index (BMI. miRNeasy Serum/Plasma Kit, TaqMan Advanced miRNA cDNA Synthesis Kit, TaqMan Advanced miRNA Assays were used to assay plasma miRNA expression. Insulin-like growth factor 1 (IGF1 was measured by immunochemiluminescence assay (Liaison. Results. We enrolled 40 subjects 22 patients suffered from acromegaly and 18 matched healthy controls matched by sex, age and BMI. The median age of patients with acromegaly was 42 years (Q25;Q75 – 37;43 with no difference among the groups, p=0.205; BMI – 28 (24;32 kg/m2, p=0.253. The median IGF1 in subjects with acromegaly – 622 (514;1000 ng/ml was significantly higher as compared to the control group (p<0.001. Patients with acromegaly had significantly higher expression of microRNA-100-5р (p=0.051, microRNA-550а-5р (p=0.048, microRNA-7b-5р (p=0.005 and microRNA-96-5р (p=0.042 among 27 bone-specific microRNA tested in plasma Conclusions. This study reveals that several microRNAs, known to regulate bone remodeling can be detected in plasma samples of patients with acromegaly and may be suggested as biomarkers for skeletal involvement in patients with acromegaly.

  4. Bone-remodeling transcript levels are independent of perching in end-of-lay white leghorn chickens.

    Science.gov (United States)

    Dale, Maurice D; Mortimer, Erin M; Kolli, Santharam; Achramowicz, Erik; Borchert, Glenn; Juliano, Steven A; Halkyard, Scott; Sietz, Nick; Gatto, Craig; Hester, Patricia Y; Rubin, David A

    2015-01-23

    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.

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

    Directory of Open Access Journals (Sweden)

    Maurice D. Dale

    2015-01-01

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

  6. 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

    in all Gruen zones with the largest declines in group D. BMD changes in Gruen zones 1, 2, 3, 6, and 7 correlated with height, and body weight. Advanced age was associated with an increase in bone loss in Gruen zones 1, 2, 3, 6, and 7. A large stem size was associated with a decline in BMD in Gruen zones......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....

  7. Analysing the effect of multiple sclerosis on vitamin D related biochemical markers of bone remodelling.

    Science.gov (United States)

    McKenna, Malachi J; Murray, Barbara; Lonergan, Roisin; Segurado, Ricardo; Tubridy, Niall; Kilbane, Mark T

    2018-03-01

    The Irish population is at risk of vitamin D deficiency during the winter months, but the secular trend over the past 40 years is for marked improvement. Multiple sclerosis (MS) is common in Ireland with a latitudinal pattern favouring highest incidence in northern regions; MS is linked strongly with vitamin D status as a causal factor. We sought firstly to study the relationship between vitamin D status and vitamin D-related bone biochemistry, and secondly to evaluate if MS had an independent effect on vitamin D related markers of bone remodelling. Using a case-control design of 165 pairs (MS patient and matched control) residing in three different geographic regions during winter months, we measured serum 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), C-terminal telopeptide of type I collagen (CTX) and total procollagen type I amino-terminal propeptide (PINP). Given the paired case-control design, associations were explored using mixed-effects linear regression analysis with the patient-control pair as a random effect and after log transformation of 25OHD. A two-way interaction effect was tested for vitamin D status (25OHD <30nmol/L) and the presence of MS on PTH, CTX, and PINP. In the total group, just over one-third (34.5%) had 25OHD <30nmol/L. PTH was elevated in 7.6%. CTX was not elevated in any case, and PINP was elevated in 4.5%. On mixed-effects linear regression analysis after adjusting for confounders (age, sex, renal function, and serum albumin), we demonstrated the principal determinant of 25OHD was geographical location (p<0.001), of PTH was 25OHD (p<0.001), of CTX was PTH (p<0.001), and of PINP was PTH (p<0.001). MS did not have an independent effect on PTH (p=0.921), CTX (p=0.912), or PINP (p=0.495). As regards an interaction effect, the presence of MS and 25OHD <30nmol/L was not significant but tended towards having lower PTH (p=0.207). In conclusion, in Ireland in winter only a minority had any abnormality in the secondary indices of

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

    Directory of Open Access Journals (Sweden)

    Alice M. C. Lee

    2014-12-01

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

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

    Science.gov (United States)

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

    2015-11-01

    Established clinical approaches to treat bone voids include the implantation of autograft or allograft bone, ceramics, and other bone void fillers (BVFs). Composites prepared from lysine-derived polyurethanes and allograft bone can be injected as a reactive liquid and set to yield BVFs with mechanical strength comparable to trabecular bone. In this study, we investigated the effects of porosity, allograft particle size, and matrix mineralization on remodeling of injectable and settable allograft/polymer composites in a rabbit femoral condyle plug defect model. Both low viscosity and high viscosity grafts incorporating small (<105 μm) particles only partially healed at 12 weeks, and the addition of 10% demineralized bone matrix did not enhance healing. In contrast, composite grafts with large (105-500 μm) allograft particles healed at 12 weeks postimplantation, as evidenced by radial μCT and histomorphometric analysis. This study highlights particle size and surface connectivity as influential parameters regulating the remodeling of composite bone scaffolds. © 2015 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Omar Akil

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

  12. [Influence of preoperative bone mass density in periprosthetic bone remodeling after implantation of ABG-II prosthesis: A 10-year follow-up].

    Science.gov (United States)

    Aguilar Ezquerra, A; Panisello Sebastiá, J J; Mateo Agudo, J

    2016-01-01

    Preoperative bone mass index has shown to be an important factor in peri-prosthetic bone remodelling in short follow-up studies. Bone density scans (DXA) were used to perform a 10-year follow-up study of 39 patients with a unilateral, uncemented hip replacement. Bone mass index measurements were made at 6 months, one year, 3 years, 5 years, and 10 years after surgery. Pearson coefficient was used to quantify correlations between preoperative bone mass density (BMD) and peri-prosthetic BMD in the 7 Gruen zones at 6 months, one year, 3 years, 5 years, and 10 years. Pre-operative BMD was a good predictor of peri-prosthetic BMD one year after surgery in zones 1, 2, 4, 5 and 6 (Pearson index from 0.61 to 0.75). Three years after surgery it has good predictive power in zones 1, 4 and 5 (0.71-0.61), although in zones 3 and 7 low correlation was observed one year after surgery (0.51 and 0.57, respectively). At the end of the follow-up low correlation was observed in the 7 Gruen zones. Sex and BMI were found to not have a statistically significant influence on peri-prosthetic bone remodelling. Although preoperative BMD seems to be an important factor in peri-prosthetic remodelling one year after hip replacement, it loses its predictive power progressively, until not being a major factor in peri-prosthetic remodelling ten years after surgery. Copyright © 2015 SECOT. Published by Elsevier Espana. All rights reserved.

  13. Numerical analysis of the biomechanical complications accompanying the total hip replacement with NANOS-Prosthetic: bone remodelling and prosthesis migration

    Directory of Open Access Journals (Sweden)

    Almohallami A.

    2015-09-01

    Full Text Available Aseptic loosening of the prosthesis is still a problem in artificial joint implants. The ýloosening can be caused by the resorption of the bone surrounding ýthe prosthesis according to stress shielding. A numerical model was developed and validated by means of DEXA-studies in order to ýanalyse the bone remodelling process in the periprosthetic bone. A total loss of about 3.7% of the bone density in the periprosthetic Femur with NANOS is computed. The bone remodelling calculation was validated by means of a DEXA-study with a 3-years-follow-up. The model was further developed in order to be able to calculate and consider the migration of the implants. This method was applied on the ýNANOS-implant with a computed total migration of about 0.43 mm. These calculations showed good results in comparison with a 2-year-follow-up clinical study, whereby a RSA-method was used to determine the stem migration in the bone. In order to ýstudy the mutual influence between the implant migration and the hip contact forces ý, a software is developed by our scientific group to couple a multi body simulation (MBS of human lower limps with the FEA of the periprosthetic Femur.

  14. 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

    inserted bilaterally into the femoral condyles of 10 skeletally mature mongrel dogs. The implants were initially surrounded by a 2 mm gap. Implants with 0.3 microg rhTGF-beta1 were compared with implants without growth factor. The dogs were sacrificed after six weeks. Bone remodeling was evaluated...... by histomorphometry on Goldner-stained undecalcified sections. The bone volume in the gap was increased significantly from 17.6% in the control group to 25.6% in the rhTGF-beta1 group (p = 0.03). Also bone surface was increased in the rhTGF-beta1 group. The osteoclast covered surfaces were increased from 3.......6% in the control group to 5.9% in the rhTGF-beta1 group (p = 0.02). In the surrounding trabecular bone no significant changes in bone remodeling parameters was demonstrated. This study suggests that rhTGF-beta1 adsorbed onto TCP-ceramic coated implants accelerates repair activity in the newly formed bone close...

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

    Directory of Open Access Journals (Sweden)

    Fabrizio Accardi

    2015-01-01

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

  16. Identification of a constitutive law for trabecular bone samples under remodeling in the framework of irreversible thermodynamics

    Science.gov (United States)

    Louna, Zineeddine; Goda, Ibrahim; Ganghoffer, Jean-François

    2018-01-01

    We construct in the present paper constitutive models for bone remodeling based on micromechanical analyses at the scale of a representative unit cell (RUC) including a porous trabecular microstructure. The time evolution of the microstructure is simulated as a surface remodeling process by relating the surface growth remodeling velocity to a surface driving force incorporating a (surface) Eshelby tensor. Adopting the framework of irreversible thermodynamics, a 2D constitutive model based on the setting up of the free energy density and a dissipation potential is identified from FE simulations performed over a unit cell representative of the trabecular architecture obtained from real bone microstructures. The static and evolutive effective properties of bone at the scale of the RUC are obtained by combining a methodology for the evaluation of the average kinematic and static variables over a prototype unit cell and numerical simulations with controlled imposed first gradient rates. The formulated effective growth constitutive law at the scale of the homogenized set of trabeculae within the RUC is of viscoplastic type and relates the average growth strain rate to the homogenized stress tensor. The postulated model includes a power law function of an effective stress chosen to depend on the first and second stress invariants. The model coefficients are calibrated from a set of virtual testing performed over the RUC subjected to a sequence of loadings. Numerical simulations show that overall bone growth does not show any growth kinematic hardening. The obtained results quantify the strength and importance of different types of external loads (uniaxial tension, simple shear, and biaxial loading) on the overall remodeling process and the development of elastic deformations within the RUC.

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

    Science.gov (United States)

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

    2016-06-01

    3D-manufactured hydrogels with precise contours and biological adhesion motifs are interesting candidates in the regenerative medicine field for the culture and differentiation of human bone-marrow-derived mesenchymal stem cells (MSCs). 3D-bioprinting is a powerful technique to approach one step closer the native organization of cells. This study investigates the effect of the incorporation of collagen type I in 3D-bioprinted polysaccharide-based hydrogels to the modulation of cell morphology, osteogenic remodeling potential, and mineralization. By combining thermo-responsive agarose hydrogels with collagen type I, the mechanical stiffness and printing contours of printed constructs can be improved compared to pure collagen hydrogels which are typically used as standard materials for MSC osteogenic differentiation. The results presented here show that MSC not only survive the 3D-bioprinting process but also maintain the mesenchymal phenotype, as proved by live/dead staining and immunocytochemistry (vimentin positive, CD34 negative). Increased solids concentrations of collagen in the hydrogel blend induce changes in cell morphology, namely, by enhancing cell spreading, that ultimately contribute to enhanced and directed MSC osteogenic differentiation. 3D-bioprinted agarose-collagen hydrogels with high-collagen ratio are therefore feasible for MSC osteogenic differentiation, contrarily to low-collagen blends, as proved by two-photon microscopy, Alizarin Red staining, and real-time polymerase chain reaction. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

    Giorgio, Ivan; Andreaus, Ugo; Madeo, Angela

    2016-03-01

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

  19. Omics analysis of human bone to identify genes and molecular networks regulating skeletal remodeling in health and disease.

    Science.gov (United States)

    Reppe, Sjur; Datta, Harish K; Gautvik, Kaare M

    2017-08-01

    The skeleton is a metabolically active organ throughout life where specific bone cell activity and paracrine/endocrine factors regulate its morphogenesis and remodeling. In recent years, an increasing number of reports have used multi-omics technologies to characterize subsets of bone biological molecular networks. The skeleton is affected by primary and secondary disease, lifestyle and many drugs. Therefore, to obtain relevant and reliable data from well characterized patient and control cohorts are vital. Here we provide a brief overview of omics studies performed on human bone, of which our own studies performed on trans-iliacal bone biopsies from postmenopausal women with osteoporosis (OP) and healthy controls are among the first and largest. Most other studies have been performed on smaller groups of patients, undergoing hip replacement for osteoarthritis (OA) or fracture, and without healthy controls. The major findings emerging from the combined studies are: 1. Unstressed and stressed bone show profoundly different gene expression reflecting differences in bone turnover and remodeling and 2. Omics analyses comparing healthy/OP and control/OA cohorts reveal characteristic changes in transcriptomics, epigenomics (DNA methylation), proteomics and metabolomics. These studies, together with genome-wide association studies, in vitro observations and transgenic animal models have identified a number of genes and gene products that act via Wnt and other signaling systems and are highly associated to bone density and fracture. Future challenge is to understand the functional interactions between bone-related molecular networks and their significance in OP and OA pathogenesis, and also how the genomic architecture is affected in health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Integration of concepts: cardiac extracellular matrix remodeling after myocardial infarction

    NARCIS (Netherlands)

    Cleutjens, Jack P. M.; Creemers, Esther E. J. M.

    2002-01-01

    The cardiac extracellular matrix consists of a three-dimensional structural network of interstitial collagens to which other matrix components are attached. The main physiological functions of this network are to retain tissue integrity and cardiac pump function. Collagen deposition is controlled

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

    Directory of Open Access Journals (Sweden)

    Jinhu Xiong

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

  2. Bone marrow adipocytes resist lipolysis and remodeling in response to β-adrenergic stimulation.

    Science.gov (United States)

    Scheller, Erica L; Khandaker, Shaima; Learman, Brian S; Cawthorn, William P; Anderson, Lindsay M; Pham, H A; Robles, Hero; Wang, Zhaohua; Li, Ziru; Parlee, Sebastian D; Simon, Becky R; Mori, Hiroyuki; Bree, Adam J; Craft, Clarissa S; MacDougald, Ormond A

    2018-01-26

    Bone marrow adipose tissue (BMAT) is preserved or increased in states of caloric restriction. Similarly, we found that BMAT in the tail vertebrae, but not the red marrow in the tibia, resists loss of neutral lipid with acute, 48-hour fasting in rats. The mechanisms underlying this phenomenon and its seemingly distinct regulation from peripheral white adipose tissue (WAT) remain unknown. To test the role of β-adrenergic stimulation, a major regulator of adipose tissue lipolysis, we examined the responses of BMAT to β-adrenergic agonists. Relative to inguinal WAT, BMAT had reduced phosphorylation of hormone sensitive lipase (HSL) after treatment with pan-β-adrenergic agonist isoproterenol. Phosphorylation of HSL in response to β3-adrenergic agonist CL316,243 was decreased by an additional ~90% (distal tibia BMAT) or could not be detected (tail vertebrae). Ex vivo, adrenergic stimulation of lipolysis in purified BMAT adipocytes was also substantially less than iWAT adipocytes and had site-specific properties. Specifically, regulated bone marrow adipocytes (rBMAs) from proximal tibia and femur underwent lipolysis in response to both CL316,243 and forskolin, while constitutive BMAs from the tail responded only to forskolin. This occurred independently of changes in gene expression of β-adrenergic receptors, which were similar between adipocytes from iWAT and BMAT, and could not be explained by defective coupling of β-adrenergic receptors to lipolytic machinery through caveolin 1. Specifically, we found that whereas caveolin 1 was necessary to mediate maximal stimulation of lipolysis in iWAT, overexpression of caveolin 1 was insufficient to rescue impaired BMAT signaling. Lastly, we tested the ability of BMAT to respond to 72-hour treatment with CL316,243 in vivo. This was sufficient to cause beiging of iWAT adipocytes and a decrease in iWAT adipocyte cell size. By contrast, adipocyte size in the tail BMAT and distal tibia remained unchanged. However, within the

  3. Strontium-Doped Calcium Phosphate and Hydroxyapatite Granules Promote Different Inflammatory and Bone Remodelling Responses in Normal and Ovariectomised Rats

    Science.gov (United States)

    Xia, Wei; Emanuelsson, Lena; Norlindh, Birgitta; Omar, Omar; Thomsen, Peter

    2013-01-01

    The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone. PMID:24376855

  4. Postnatal mandible growth in wild and laboratory mice: Differences revealed from bone remodeling patterns and geometric morphometrics.

    Science.gov (United States)

    Martínez-Vargas, Jessica; Muñoz-Muñoz, Francesc; Martinez-Maza, Cayetana; Molinero, Amalia; Ventura, Jacint

    2017-08-01

    Comparative information on the variation in the temporospatial patterning of mandible growth in wild and laboratory mice during early postnatal ontogeny is scarce but important to understand variation among wild rodent populations. Here, we compare mandible growth between two ontogenetic series from the second to the eighth week of postnatal life, corresponding to two different groups of mice reared under the same conditions: the classical inbred strain C57BL/6J, and Mus musculus domesticus. We characterize the ontogenetic patterns of bone remodeling of the mandibles belonging to these laboratory and wild mice by analyzing bone surface, as well as examine their ontogenetic form changes and bimodular organization using geometric morphometrics. Through ontogeny, the two mouse groups display similar directions of mandible growth, according to the temporospatial distribution of bone remodeling fields. The allometric shape variation of the mandibles of these mice entails the relative enlargement of the ascending ramus. The organization of the mandible into two modules is confirmed in both groups during the last postnatal weeks. However, especially after weaning, the mandibles of wild and laboratory mice differ in the timing and localization of several remodeling fields, in addition to exhibiting different patterns of shape variation and differences in size. The stimulation of dentary bone growth derived from the harder post-weaning diet might account for some features of postnatal mandible growth common to both groups. Nonetheless, a large component of the postnatal growth of the mouse mandible appears to be driven by the inherent genetic programs, which might explain between-group differences. © 2017 Wiley Periodicals, Inc.

  5. 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

  6. Influence of Bone Remodeling Inhibition on the Development of Experimental Stress Fractures

    National Research Council Canada - National Science Library

    Schaffler, Mitchell B

    2005-01-01

    .... Using a bisphosphonate (BIS) to suppress remodeling in the rabbit tibial stress fracture model, we found that antiresorptive therapy reduced the intensity of the stress fracture response in this model...

  7. Comparison of different hip prosthesis shapes considering micro-level bone remodeling and stress-shielding criteria using three-dimensional design space topology optimization.

    Science.gov (United States)

    Boyle, Christopher; Kim, Il Yong

    2011-06-03

    Since the late 1980s, computational analysis of total hip arthroplasty (THA) prosthesis components has been completed using macro-level bone remodeling algorithms. The utilization of macro-sized elements requires apparent bone densities to predict cancellous bone strength, thereby, preventing visualization and analysis of realistic trabecular architecture. In this study, we utilized a recently developed structural optimization algorithm, design space optimization (DSO), to perform a micro-level three-dimensional finite element bone remodeling simulation on the human proximal femur pre- and post-THA. The computational simulation facilitated direct performance comparison between two commercially available prosthetic implant stems from Zimmer Inc.: the Alloclassic and the Mayo conservative. The novel micro-level approach allowed the unique ability to visualize the trabecular bone adaption post-operation and to quantify the changes in bone mineral content by region. Stress-shielding and strain energy distribution were also quantified for the immediate post-operation and the stably fixated, post-remodeling conditions. Stress-shielding was highest in the proximal region and remained unchanged post-remodeling; conversely, the mid and distal portions show large increases in stress, suggesting a distal shift in the loadpath. The Mayo design conserves bone mass, while simultaneously reducing the incidence of stress-shielding compared to the Alloclassic, revealing a key benefit of the distinctive geometry. Several important factors for stable fixation, determined in clinical evaluations from the literature, were evident in both designs: high levels of proximal bone loss and distal bone densification. The results suggest this novel computational framework can be utilized for comparative hip prosthesis shape, uniquely considering the post-operation bone remodeling as a design criterion. Copyright © 2011 Elsevier Ltd. All rights reserved.

  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...

  9. 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 postpr......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...

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

    DEFF Research Database (Denmark)

    Ito, H; Koefoed, M; Tiyapatanaputi, P

    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 ...

  11. Bariatric Roux-En-Y Gastric Bypass Surgery: Adipocyte Proteins Involved in Increased Bone Remodeling in Humans.

    Science.gov (United States)

    Biagioni, Maria Fernanda G; Mendes, Adriana L; Nogueira, Célia Regina; Leite, Celso V; Gollino, Loraine; Mazeto, Gláucia Mfs

    2017-07-01

    Bariatric surgery has been associated with bone remodeling changes. The action of adipokines on the expression of receptor activator of nuclear factor kappa β ligand (RANKL) and osteoprotegerin (OPG) and on an increase in sclerostin could be related to these changes. This study aimed to assess the repercussions of weight loss, fat mass (FM), and fat-free mass (FFM) loss and biochemical and hormonal changes on bone remodeling markers after Roux-en-Y gastric bypass (RYGB). Anthropometric data, parathyroid hormone (PTH), bone-specific alkaline phosphatase (BSAP), collagen type 1 C-telopeptide (CTX), 25-hydroxy vitamin D (25-OH-VitD), leptin, adiponectin, RANKL, OPG, and sclerostin of 30 menstruating women were measured preoperatively (Pre), and 3, 12, and 24 months (m) after RYGB. Leptin (34.4 (14.7; 51.9) vs. 22.5 (1.9; 52.7) ng/mL) and OPG (3.6 (1.1; 11.5) vs. 3.4 (1.5; 6) pmol/L) decreased, and adiponectin (7.4 (1.7; 18.4) vs. 13.8 (3.0; 34.6) μg/mL), CTX (0.2 (0.1; 2.2) vs. 0.6 (0.4; 6.0) ng/mL), RANKL (0.1 (0.0; 0.5) vs. 0.3 (0.0; 2.0) pmol/L), and sclerostin (21.7 (3.2; 75.1) vs. 34.8 (6.4; 80.5) pmol/L) increased after 3 m. BSAP increased after 12 m (10.1 (5.4; 18.9) vs. 13.9 (6.9; 30.2) μg/mL) (p < 0.005). CTX correlated positively with adiponectin at 24 m and inversely with leptin Pre; OPG at 3 m; weight, FM, FFM, and leptin at 24 m. RANKL correlated directly with weight at 3 m. Sclerostin correlated inversely with weight Pre and FM at 3 m. BSAP correlated negatively with 25-OH-VitD at 12 m, and positively with PTH at 24 m. RYGB induced weight loss, and biochemical, hormonal, and body composition changes are associated with higher bone remodeling.

  12. Piezoelectricity could predict sites of formation/resorption in bone remodelling and modelling.

    Science.gov (United States)

    Fernández, J R; García-Aznar, J M; Martínez, R

    2012-01-07

    We have developed a mathematical approach for modelling the piezoelectric behaviour of bone tissue in order to evaluate the electrical surface charges in bone under different mechanical conditions. This model is able to explain how bones change their curvature, where osteoblasts or osteoclasts could detect in the periosteal/endosteal surfaces the different electrical charges promoting bone formation or resorption. This mechanism also allows to understand the BMU progression in function of the electro-mechanical bone behaviour. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. 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.

  14. 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. 

  15. Effects of different loading patterns on the trabecular bone morphology of the proximal femur using adaptive bone remodeling.

    Science.gov (United States)

    Banijamali, S Mohammad Ali; Oftadeh, Ramin; Nazarian, Ara; Goebel, Ruben; Vaziri, Ashkan; Nayeb-Hashemi, Hamid

    2015-01-01

    In this study, the changes in the bone density of human femur model as a result of different loadings were investigated. The model initially consisted of a solid shell representing cortical bone encompassing a cubical network of interconnected rods representing trabecular bone. A computationally efficient program was developed that iteratively changed the structure of trabecular bone by keeping the local stress in the structure within a defined stress range. The stress was controlled by either enhancing existing beam elements or removing beams from the initial trabecular frame structure. Analyses were performed for two cases of homogenous isotropic and transversely isotropic beams.Trabecular bone structure was obtained for three load cases: walking, stair climbing and stumbling without falling. The results indicate that trabecular bone tissue material properties do not have a significant effect on the converged structure of trabecular bone. In addition, as the magnitude of the loads increase, the internal structure becomes denser in critical zones. Loading associated with the stumbling results in the highest density;whereas walking, considered as a routine daily activity, results in the least internal density in different regions. Furthermore, bone volume fraction at the critical regions of the converged structure is in good agreement with previously measured data obtained from combinations of dual X-ray absorptiometry (DXA) and computed tomography (CT). The results indicate that the converged bone architecture consisting of rods and plates are consistent with the natural bone morphology of the femur. The proposed model shows a promising means to understand the effects of different individual loading patterns on the bone density.

  16. Radiographic healing and remodelling of cortical and cancellous bone grafts after rigid plate fixation

    International Nuclear Information System (INIS)

    Waris, P.; Karaharju, E.; Slaetis, P.; Paavolainen, P.

    1980-01-01

    Cortical and cancellous interposition grafts, with rigid plate fixation, in the tibiofibular bones of 130 rabbits were followed radiographically for one year. The cancellous grafts healed earlier, but by 12 weeks both graft types had been incorporated, the distal host-graft interface being the last to heal. Progressive cancellous transformation in both the graft and host bone led to an increased over-all bone diameter, a widened medullary canal and a thinned porotic wall. (Auth.)

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

    Directory of Open Access Journals (Sweden)

    Lihui Li

    Full Text Available 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.

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

    Science.gov (United States)

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

    2014-05-01

    New therapeutic strategies are needed in the treatment of asthma besides vaccines and pharmacotherapies. For the development of novel therapies, the use of mesenchymal stem cells (MSCs) is a promising approach in regenerative medicine. Delivery of compact bone (CB) derived MSCs to the injured lungs is an alternative treatment strategy for chronic asthma. In this study, we aimed to isolate highly enriched population of MSCs from mouse CB with regenerative capacity, and to investigate the impact of these cells in airway remodeling and inflammation in experimental ovalbumin-induced mouse model of chronic asthma. mCB-MSCs were isolated, characterized, labeled with GFP and then transferred into mice with chronic asthma developed by ovalbumin (OVA) provocation. Histopathological changes including basement membrane, epithelium, subepithelial smooth thickness and goblet cell hyperplasia, and MSCs migration to lung tissues were evaluated. These histopathological alterations were increased in ovalbumin-treated mice compared to PBS group (Pasthma. The results reported here provided evidence that mCB-MSCs may be an alternative strategy for the treatment of remodeling and inflammation associated with chronic asthma. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Impact of Platform Switching on Peri-Implant Bone Remodeling around Short Implants in the Posterior Region, 1-Year Results from a Split-Mouth Clinical Trial

    NARCIS (Netherlands)

    Telleman, Gerdien; Raghoebar, Gerry M.; Vissink, Arjan; Meijer, Henny J. A.

    Aim: To assess the effect of platform switching on peri-implant bone remodeling around short implants (8.5mm) placed in the resorbed posterior mandibular and maxillary region of partially edentulous patients. Materials and Methods: Seventeen patients with one or more missing teeth at both sides in

  20. Remodelling of living bone induced by dynamic loading and drug delivery—Numerical modelling and clinical treatment

    Czech Academy of Sciences Publication Activity Database

    Maršík, František; Klika, Václav; Chlup, Hynek

    2010-01-01

    Roč. 80, č. 6 (2010), s. 1278-1288 ISSN 0378-4754 R&D Projects: GA ČR GA106/03/1073; GA ČR(CZ) GA106/08/0557 Grant - others:GA ČR(CZ) GA201/06/0352 Institutional research plan: CEZ:AV0Z20760514 Keywords : bone remodelling * chemical kinetics * biochemical model Subject RIV: BJ - Thermodynamics Impact factor: 0.812, year: 2010 http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6V0T-4VT1FYX-1-1&_cdi=5655&_user=640952&_pii=S0378475409000664&_origin=search&_coverDate=02%2F28%2F2010&_sk=999199993&view=c&wchp=dGLzVlz-zSkzV&md5=efaf801defe31154a1c6c44a9c5edef0&ie=/sdarticle.pdf

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

    International Nuclear Information System (INIS)

    Liu, Hongrui; Cui, Jian; Feng, Wei; Lv, Shengyu; Du, Juan; Sun, Jing; Han, Xiuchun; Wang, Zhenming; Lu, Xiong; Yimin; Oda, Kimimitsu; Amizuka, Norio; Li, Minqi

    2015-01-01

    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

  2. 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.

  3. [Influence of hormonal contraceptives on indices of zinc homeostasis and bone remodeling in young adult women].

    Science.gov (United States)

    Simões, Tania Mara Rodrigues; Zapata, Carmiña Lucía Vargas; Donangelo, Carmen Marino

    2015-09-01

    To investigate the influence of the use of oral hormonal contraceptive agents (OCA) on the biochemical indices related to metabolic zinc utilization and distribution, and to bone turnover in young adult women. Cross-sectional study. Blood and urine samples from non-users (-OCA; control; n=69) and users of hormonal contraceptives for at least 3 months (+OCA; n=62) were collected under controlled conditions. Indices of zinc homeostasis and of bone turnover were analyzed in serum or plasma (total, albumin-bound and α2-macroglobulin-bound zinc, albumin and total and bone alkaline phosphatase activity), in erythrocytes (zinc and metallothionein) and in urine (zinc, calcium and hydroxyproline). The habitual zinc and calcium intakes were evaluated by a food frequency questionnaire. Dietary zinc intake was similar in both groups and on average above recommended values, whereas calcium intake was similarly sub-adequate in +OCA and -OCA. Compared to controls, +OCA had lower concentrations of total and α2-macroglobulin-bound zinc (11 and 28.5%, respectively, puse decreases serum zinc, alters zinc distribution in major serum fractions with possible effects on tissue uptake, enhances zinc retention in the body and decreases bone turnover. Prolonged OCA use may lead to lower peak bone mass and/or to impaired bone mass maintenance in young women, particularly in those with marginal calcium intake. The observed OCA effects were more evident in women younger than 25 years and in nulliparous women, deserving special attention in future studies.

  4. Thoroughbred horses in race training have lower levels of subchondral bone remodelling in highly loaded regions of the distal metacarpus compared to horses resting from training.

    Science.gov (United States)

    Holmes, J M; Mirams, M; Mackie, E J; Whitton, R C

    2014-12-01

    Bone is repaired by remodelling, a process influenced by its loading environment. The aim of this study was to investigate the effect of a change in loading environment on bone remodelling by quantifying bone resorption and formation activity in the metacarpal subchondral bone in Thoroughbred racehorses. Sections of the palmar metacarpal condyles of horses in race training (n = 24) or resting from training (n = 24) were examined with light microscopy and back scattered scanning electron microscopy (BSEM). Bone area fraction, osteoid perimeter and eroded bone surface were measured within two regions of interest: (1) the lateral parasagittal groove (PS); (2) the lateral condylar subchondral bone (LC). BSEM variables were analysed for the effect of group, region and interaction with time since change in work status. The means ± SE are reported. For both regions of interest in the training compared to the resting group, eroded bone surface was lower (PS: 0.39 ± 0.06 vs. 0.65 ± 0.07 per mm, P = 0.010; LC: 0.24 ± 0.04 vs. 0.85 ± 0.10 per mm, P Thoroughbred racehorses. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. 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.

  6. In vivo structural and cellular remodeling of engineered bone-ligament-bone constructs used for anterior cruciate ligament reconstruction in sheep.

    Science.gov (United States)

    Florida, Shelby E; VanDusen, Keith W; Mahalingam, Vasudevan D; Schlientz, Aleesa J; Wojtys, Edward M; Wellik, Deneen M; Larkin, Lisa M

    2016-11-01

    Anterior cruciate ligament (ACL) ruptures rank among the most prevalent and costly sports-related injuries. Current tendon grafts used for ACL reconstruction are limited by suboptimal biomechanical properties. We have addressed these issues by engineering multiphasic bone-ligament-bone (BLB) constructs that develop structural and mechanical properties similar to native ACL. The purpose of this study was to examine the acute remodeling process that occurs as the BLB grafts advance toward the adult ligament phenotype in vivo. Thus, we implanted BLB constructs fabricated from male cells into female host sheep and allowed 3, 7, 14, or 28 days (n = 4 at each time point) for recovery. To address whether or not graft-derived cells were even necessary, a subset of BLB constructs (n = 3) were acellularized, implanted, and allowed 28 days for recovery. At each recovery time point, the following histological analyses were performed: picrosirius red staining to assess collagen alignment and immunohistochemistry to assess both graft development and host immune response. Polymerase chain reaction (PCR) analysis, performed on every explanted BLB, was used to detect the presence of graft-derived male cells remaining in the constructs and/or migration into surrounding host tissue. The analysis of the PCR and histology samples revealed a rapid migration of host-derived macrophages and neutrophils into the graft at 3 days, followed by increased collagen density and alignment, vascularization, innervation, and near complete repopulation of the graft with host cells within 28 days. This study provides a greater understanding of the processes of ligament regeneration in our BLB constructs as they remodel toward the adult ligament phenotype.

  7. In vivo micro-CT analysis of bone remodeling in a rat calvarial defect model

    Energy Technology Data Exchange (ETDEWEB)

    Umoh, Joseph U; Holdsworth, David W [Pre-Clinical Imaging Research Centre, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, PO Box 5015, 100 Perth Drive, London, ON N6A 5K8 (Canada); Sampaio, Arthur V; Underhill, T Michael [Laboratory of Molecular Skeletogenesis, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC (Canada); Welch, Ian [Animal Care and Veterinary Services, University of Western Ontario, London, ON (Canada); Pitelka, Vasek; Goldberg, Harvey A [CIHR Group in Skeletal Development and Remodelling, University of Western Ontario, London, ON (Canada)], E-mail: jumoh@imaging.robarts.ca, E-mail: asampaio@interchange.ubc.ca, E-mail: tunderhi@interchange.ubc.ca, E-mail: iwelch@uwo.ca, E-mail: vasek.pitelka@schulich.uwo.ca, E-mail: hagoldbe@uwo.ca, E-mail: david.holdsworth@imaging.robarts.ca

    2009-04-07

    The rodent calvarial defect model is commonly used to investigate bone regeneration and wound healing. This study presents a micro-computed tomography (micro-CT) methodology for measuring the bone mineral content (BMC) in a rat calvarial defect and validates it by estimating its precision error. Two defect models were implemented. A single 6 mm diameter defect was created in 20 rats, which were imaged in vivo for longitudinal experiments. Three 5 mm diameter defects were created in three additional rats, which were repeatedly imaged ex vivo to determine precision. Four control rats and four rats treated with bone morphogenetic protein were imaged at 3, 6, 9 and 12 weeks post-surgery. Scan parameters were 80 kVp, 0.45 mA and 180 mAs. Images were reconstructed with an isotropic resolution of 45 {mu}m. At 6 weeks, the BMC in control animals (4.37 {+-} 0.66 mg) was significantly lower (p < 0.05) than that in treated rats (11.29 {+-} 1.01 mg). Linear regression between the BMC and bone fractional area, from 20 rats, showed a strong correlation (r{sup 2} = 0.70, p < 0.0001), indicating that the BMC can be used, in place of previous destructive analysis techniques, to characterize bone growth. The high precision (2.5%) of the micro-CT methodology indicates its utility in detecting small BMC changes in animals.

  8. 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

  9. Periprosthetic bone densitometry of the hip: Influence of design and hydroxyapatite coating on regional bone remodeling; 5 year follow-up

    International Nuclear Information System (INIS)

    Rosenthall

    2002-01-01

    Aim: To determine bone mineral density changes surrounding two differently designed titanium alloy porous-coated femoral hip prostheses (S-ROM and Multilock) as a function of time. Materials and Methods: The periprosthetic bone regions were defined by the seven Gruen zones. Measurements were obtained by DXA utilizing a dedicated software program (LUNAR ORTH). Inclusion criteria required that the patients were asymptomatic with Harris hip scores >95, showed no radiographic evidence of loosening and that they had primary implants. The protocol specified that bone measurements be obtained within one week after implantation as a baseline reference and at 6 months, 12 months and yearly thereafter. 111 consecutive S-ROM and 65 consecutive Multilock patients were enrolled in this ongoing prospective study. Of the 65 patients with Multilock implants, 25 had a 50 micron thick coating of hydroxyapatite-tricalcium phosphate (HA) sprayed over the porous surface and 40 were without coating. Results: At 6 months the mean BMD of all zones showed a significant decrease relative to the baseline measurement, varying from 6% to 17%. Gruen zones 2 to 6 exhibited variable degrees of recovery by 60 months. The maximum mineral losses were registered proximally in zone 1 (greater trochanter) and zone 7 (calcar and lesser trochanter), which are recognized sites of prosthetic stress shielding. The detailed results at 60 months are presented. In Gruen zone 1 the mineral loss in the S-ROM implant is significantly less the than either Multilock type. Also, mineral loss with Multilock-HA is about 55% less than the Multilock-uncoated. In Gruen zone 7 there is no difference between S-ROM and Multilock-uncoated, but Multilock-HA lost 44% less density than Multilock-uncoated. Conclusion: Regional bone remodeling appears to be related to prosthesis design. HA coating substantially and significantly reduces mineral loss in the proximal porous area; the mechanism is speculative

  10. 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

    and at the level of the light-microscopically assessed contact of these three entities with the bone or canopy surfaces. Between 51 and 100 microm, their densities leveled to that found above quiescent surfaces. Electron microscopy asserted the close proximity between BRC canopies and capillaries lined...

  11. Bone remodelling of the proximal femur after total hip arthroplasty with 2 different hip implant designs

    DEFF Research Database (Denmark)

    Christiansen, Janus D.; Laursen, Mogens B; Ejaz, Ashir

    2018-01-01

    INTRODUCTION: The thrust plate prosthesis (TPP) was introduced to preserve bone in patients undergoing total hip arthroplasty. We assessed the long-term results of hip arthroplasty in patients who received the TPP compared to a traditional intramedullary stem (Bi-Metric). METHODS......: In this prospective observational cohort study, we evaluated bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA), radiological imaging and clinical outcome using Harris Hip Score (HHS). Twenty patients received the TPP (group A) and 18 patients received the Bi-Metric stem (group B). Baseline......% (95% confidence interval [CI], 4-16; p = 0.003) and 8% (95% CI, 1-15; p = 0.03) at 8 years. Regarding ROI4, group A had a lesser decrease in general compared to group B. The radiological findings did not reveal any subsidence or detectable implant migration. HHS improved from 53 (23-69) to 93 (55...

  12. 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.

  13. In vivo micro-CT analysis of bone remodeling in a rat calvarial defect model

    Science.gov (United States)

    Umoh, Joseph U.; Sampaio, Arthur V.; Welch, Ian; Pitelka, Vasek; Goldberg, Harvey A.; Underhill, T. Michael; Holdsworth, David W.

    2009-04-01

    The rodent calvarial defect model is commonly used to investigate bone regeneration and wound healing. This study presents a micro-computed tomography (micro-CT) methodology for measuring the bone mineral content (BMC) in a rat calvarial defect and validates it by estimating its precision error. Two defect models were implemented. A single 6 mm diameter defect was created in 20 rats, which were imaged in vivo for longitudinal experiments. Three 5 mm diameter defects were created in three additional rats, which were repeatedly imaged ex vivo to determine precision. Four control rats and four rats treated with bone morphogenetic protein were imaged at 3, 6, 9 and 12 weeks post-surgery. Scan parameters were 80 kVp, 0.45 mA and 180 mAs. Images were reconstructed with an isotropic resolution of 45 µm. At 6 weeks, the BMC in control animals (4.37 ± 0.66 mg) was significantly lower (p small BMC changes in animals.

  14. 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

    International Nuclear Information System (INIS)

    Manrique, Alain; Lemarchand, Patricia; Delasalle, Beatrice; Lamirault, Guillaume; Trochu, Jean-Noel; Le Tourneau, Thierry; Lairez, Olivier; Roncalli, Jerome; Sportouch-Duckan, Catherine; Piot, Christophe; Le Corvoisier, Philippe; Neuder, Yannick; Richardson, Marjorie; Lebon, Alain; Teiger, Emmanuel; Hossein-Foucher, Claude

    2016-01-01

    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.)

  15. 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.)

  16. Effects of clodronate on early alveolar bone remodeling and root resorption related to orthodontic forces: a histomorphometric analysis.

    Science.gov (United States)

    Choi, Josefina; Baek, Seung-Hak; Lee, Jae-Il; Chang, Young-Il

    2010-11-01

    The objective of this study was to evaluate the short-term effects of clodronate, a first-generation bisphosphonate, on early alveolar bone remodeling and root resorption related to orthodontic tooth movement. The samples consisted of 54 sex-matched Wistar rats (weight, 180-230 g) allocated to the 2.5 mmol/L clodronate, 10 mmol/L clodronate, and control groups (n = 18 for each group). After application of a nickel-titanium closed-coil spring (force, 60 g) between the maxillary central incisor and first molar, 2.5 mmol/L of clodronate, 10 mmol/L of clodronate, or saline solution was injected into the subperiosteum adjacent to the maxillary first molar every third day. All animals received tetracycline, calcein, and alizarin red by intraperitoneal injection at 1, 6, and 14 days, respectively. The amounts of tooth movement were measured at 3, 6, 9, 12, and 15 days. The animals were killed at 4, 7, and 17 days. Histomorphometric analyses of bone mineral appositional rate, labeled surface, percentage of root resorption area, and number of root resorption lacunae of the mesiobuccal root of the maxillary first molar at 4, 7, and 17 days were done. One-way analysis of variance (ANOVA) with the post-hoc test were done for statistical analyses. Rats in the 10 mmol/L clodronate group had significant decreases of tooth movement (12 and 15 days, P root resorption area and numbers of root resorption lacunae (7 day, P root resorption related to orthodontic tooth movement, patients should be informed about a possible decrease in the amount of tooth movement and a prolonged period of orthodontic treatment. Copyright © 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  17. The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model.

    Science.gov (United States)

    Hayami, Tadashi; Pickarski, Maureen; Wesolowski, Gregg A; McLane, Julia; Bone, Ashleigh; Destefano, James; Rodan, Gideon A; Duong, Le T

    2004-04-01

    It has been suggested that subchondral bone remodeling plays a role in the progression of osteoarthritis (OA). To test this hypothesis, we characterized the changes in the rat anterior cruciate ligament transection (ACLT) model of OA and evaluated the effects of alendronate (ALN), a potent inhibitor of bone resorption, on cartilage degradation and on osteophyte formation. Male Sprague-Dawley rats underwent ACLT or sham operation of the right knee. Animals were then treated with ALN (0.03 and 0.24 microg/kg/week subcutaneously) and necropsied at 2 or 10 weeks postsurgery. OA changes were evaluated. Subchondral bone volume and osteophyte area were measured by histomorphometric analysis. Coimmunostaining for transforming growth factor beta (TGF beta), matrix metalloproteinase 9 (MMP-9), and MMP-13 was performed to investigate the effect of ALN on local activation of TGF beta. ALN was chondroprotective at both dosages, as determined by histologic criteria and collagen degradation markers. ALN suppressed subchondral bone resorption, which was markedly increased 2 weeks postsurgery, and prevented the subsequent increase in bone formation 10 weeks postsurgery, in the untreated tibial plateau of ACLT joints. Furthermore, ALN reduced the incidence and area of osteophytes in a dose-dependent manner. ALN also inhibited vascular invasion into the calcified cartilage in rats with OA and blocked osteoclast recruitment to subchondral bone and osteophytes. ALN treatment reduced the local release of active TGF beta, possibly via inhibition of MMP-13 expression in articular cartilage and MMP-9 expression in subchondral bone. Subchondral bone remodeling plays an important role in the pathogenesis of OA. ALN or other inhibitors of bone resorption could potentially be used as disease-modifying agents in the treatment of OA.

  18. Callus remodelling model

    Science.gov (United States)

    Miodowska, Justyna; Bielski, Jan; Kromka-Szydek, Magdalena

    2018-01-01

    The objective of this paper is to investigate the healing process of the callus using bone remodelling approach. A new mathematical model of bone remodelling is proposed including both underload and overload resorption, as well as equilibrium and bone growth states. The created model is used to predict the stress-stimulated change in the callus density. The permanent and intermittent loading programs are considered. The analyses indicate that obtaining a sufficiently high values of the callus density (and hence the elasticity) modulus is only possible using time-varying load parameters. The model predictions also show that intermittent loading program causes delayed callus healing. Understanding how mechanical conditions influence callus remodelling process may be relevant in the bone fracture treatment and initial bone loading during rehabilitation.

  19. The effect of cinacalcet on bone remodeling and renal function in transplant patients with persistent hyperparathyroidism.

    Science.gov (United States)

    Schwarz, Anke; Merkel, Saskia; Leitolf, Holger; Haller, Hermann

    2011-03-15

    Parathyroidectomy is associated with renal functional losses in transplant patients; cinacalcet offers an attractive alternative. We performed a prospective observational study in 58 patients with persisting hyperparathyroidism after renal transplantation (Ca≥2.6 mmol/L) and impaired renal transplant function (estimated glomerular filtration rate [eGFR] bone-specific alkaline phosphatase, osteocalcin, and telopeptide at 0, 1, 2, 3, 6, 9, and 12 months of cinacalcet treatment. Fractional excretion of calcium and phosphorus (n=24) were monitored at 0 and 1 month. At inclusion, creatinine was 181±70 μmol/L, eGFR 43±19 mL/min, PTH 371±279 pg/mL, and Ca 2.73±0.22 mmol/L. We observed nephrocalcinosis in 58% of biopsied patients at enrollment. After cinacalcet, Ca decreased significantly and normalized at nearly any measurement. Phosphorus increased significantly at months 1, 9, and 12. PTH decreased significantly, but only at months 9 and 12 and did not normalize. Bone-specific alkaline phosphatase increased significantly (>normal) by month 12. eGFR decreased and serum creatinine increased at all time points. The Δ(creatinine) % increase correlated significantly with the Δ(PTH) % decrease at month 1 and 12. Telopeptide and alkaline phosphatase correlated with PTH and telopeptide also correlated with serum creatinine. Calcium-phosphorus homeostasis in hypercalcemic renal transplant patients normalizes under cinacalcet and PTH decreases, albeit not to normal. The renal functional decline could be PTH mediated, analogous to the effects observed after parathyroidectomy.

  20. 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

  1. 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.

  2. Bone fragment union and remodeling after arthroscopic bony bankart repair for traumatic anterior shoulder instability with a glenoid defect: influence on postoperative recurrence of instability.

    Science.gov (United States)

    Nakagawa, Shigeto; Ozaki, Ritsuro; Take, Yasuhiro; Mae, Tatsuo; Hayashida, Kenji

    2015-06-01

    Although good clinical outcomes have been reported after arthroscopic bony Bankart repair, the extent of bone union is still unclear. To investigate bone union after arthroscopic bony Bankart repair and its influence on postoperative recurrence of instability. Cohort study; Level of evidence, 3. Among 113 consecutive shoulders that underwent arthroscopic bony Bankart repair, postoperative evaluation of bone union by computed tomography (CT) was performed at various times in 81 shoulders. Bone union was investigated during 3 periods: 3 to 6 months postoperatively (first period), 7 to 12 months postoperatively (second period), and 13 months or more postoperatively (third period). The influence of the size of the preoperative glenoid defect and the size of the bone fragment on bone union was investigated, as well as the influence of bone union on postoperative recurrence of instability. In shoulders with bone union, bone fragment remodeling and changes in the glenoid defect size were also investigated. The bone union rate was 30.5% in the first period, 55.3% in the second period, and 84.6% in the third period. Among 53 shoulders with CT evaluation in the second period or later and follow-up for a minimum of 1 year, there was complete union in 33 shoulders (62.3%), partial union in 3 (5.7%), nonunion in 8 (15.1%), and no fragment on CT in 9 (17.0%). The complete union rate was 50% for 22 shoulders with small bone fragments (fragments (5%-10%), and 86.7% for 15 shoulders with large fragments (>10%). The recurrence rate for postoperative instability was only 6.1% for shoulders with complete union, while it was 50% for shoulders with partial union, nonunion, no fragment, and no fragment on CT. The recurrence rate was significantly higher (36.4%) in shoulders with small fragments, but it was significantly lower in shoulders with bone union. In shoulders with bone union, the bone fragment frequently became larger over time, while the size of the glenoid defect decreased

  3. Uranium's effects on bone integrity

    International Nuclear Information System (INIS)

    Souidi, Maamar; Wade-Gueye, Ndeye Marieme; Manens, Line; Blanchardon, Eric; Aigueperse, Jocelyne

    2018-01-01

    Uranium is a radioactive heavy metal naturally present in the environment. Its recent use in various civilian and military applications sometimes result in its release into the environment. After chronic ingestion, uranium accumulates in various organs, preferentially in bones. Several studies have shown that exposure to high concentrations of uranium affects bone growth. Little is known, however, about the effects of chronic exposure to low doses of uranium on bone, especially when ingested via drinking water, the main route by which the public is exposed to this radionuclide. This study examined the effects of chronic exposure to natural uranium through drinking water on bone integrity and bone turnover. Rats were contaminated with different concentrations of natural uranium (15, 10, and 40 mg / l) for 9 months. A high-resolution three-dimensional microtomography scanner was used for the first time to study uranium's impact on bone metabolism and thus on bone tissue integrity. After nine months of uranium exposure, micro-architecture analysis revealed that the cortical bone diameter of the femoral diaphysis of rats contaminated at a concentration of 40 mg/L of uranium had decreased significantly. In conclusion, our findings that chronic ingestion of uranium at low concentrations affects growth of cortical bone width suggests that it may affect bone strength. These results thus suggest the need to pay special attention to children during chronic low-dose exposure to this radionuclide. (authors)

  4. The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group

    DEFF Research Database (Denmark)

    Terpos, E; Dimopoulos, M A; Sezer, O

    2010-01-01

    progression and overall survival. Bone markers have also been used for the early diagnosis of bone lesions. This International Myeloma Working Group report summarizes the existing data for the role of bone markers in assessing the extent of MM bone disease and in monitoring bone turnover during anti...

  5. Early effects of zoledronic acid and teriparatide on bone microarchitecture, remodeling and collagen crosslinks: comparison between iliac crest and lumbar vertebra in ewes.

    Science.gov (United States)

    Portero-Muzy, N R; Chavassieux, P M; Bouxsein, M L; Gineyts, E; Garnero, P; Chapurlat, R D

    2012-10-01

    Iliac crest bone biopsies are used to assess the mechanism of action of drug treatments, yet there are little data comparing this site to sites prone to fracture. The purpose of this study was to compare the delay and the amplitude of responses to treatment in two different bone sites. The short-term effects of zoledronic acid and teriparatide on microarchitecture, collagen crosslinks and bone remodeling were evaluated in iliac crest and lumbar vertebrae. Aged ewes (n=8/gr) received either vehicle (CTRL) or a single injection of zoledronic acid (ZOL, 10mg) or daily injections of teriparatide (TPTD, 20 μg/d) for 3 months. Blood samples were collected monthly for assessing bone turnover markers. At the end of the study, a transiliac bone biopsy (IC) and L1 lumbar vertebrae (LV1) were collected to assess bone microarchitecture; pyridinoline (PYD), deoxypyridinoline (DPD), pentosidine (PEN) content, static and dynamic parameters of bone remodeling. In CTRL, Tb-BV/TV was significantly higher in LV1 than IC (psALP (p<0.001) and sCTX (p<0.001) were observed in the ZOL-group whereas in TPTD-group, after transient increases, they returned to baseline values. When compared to their respective CTRL, ZOL induced significant increases in Tb.BV/TV, Conn.D, Tb.N and Tb.Sp, in IC but not in LV1. Regardless of the site, ZOL markedly depressed the bone turnover: The static parameters of bone formation significantly decreased and the diminution of MS/BS, BFR/BS and Ac.f varied from -94 to -98% vs CTRL (p<0.01 to 0.001). It was associated with a diminution of the DPD content and the PYD/DPD ratio mainly in IC cortices. In contrast, after 3 months, TPTD did not modify the 3D structure and microarchitecture in IC and LV1, except a trend of higher Conn.D in IC, compared to IC-CTRL. TPTD treatment induced a significant increase in cortical porosity in LV1 (p<0.05) when compared to LV1-CTRL. Static parameters of bone formation and resorption were augmented in both sites, significantly

  6. Stable fixation of an osseointegated implant system for above-the-knee amputees: titel RSA and radiographic evaluation of migration and bone remodeling in 55 cases.

    Science.gov (United States)

    Nebergall, Audrey; Bragdon, Charles; Antonellis, Anne; Kärrholm, Johan; Brånemark, Rickard; Malchau, Henrik

    2012-04-01

    Rehabilitation of patients with transfemoral amputations is particularly difficult due to problems in using standard socket prostheses. We wanted to assess long-term fixation of the osseointegrated implant system (OPRA) using radiostereometric analysis (RSA) and periprosthetic bone remodeling. 51 patients with transfemoral amputations (55 implants) were enrolled in an RSA study. RSA and plain radiographs were scheduled at 6 months and at 1, 2, 5, 7, and 10 years after surgery. RSA films were analyzed using UmRSA software. Plain radiographs were graded for bone resorption, cancellization, cortical thinning, and trabecular streaming or buttressing in specifically defined zones around the implant. At 5 years, the median (SE) migration of the implant was -0.02 (0.06) mm distally. The rotational movement was 0.42 (0.32) degrees around the longitudinal axis. There was no statistically significant difference in median rotation or migration at any follow-up time. Cancellization of the cortex (plain radiographic grading) appeared in at least 1 zone in over half of the patients at 2 years. However, the prevalence of cancellization had decreased by the 5-year follow-up. The RSA analysis for the OPRA system indicated stable fixation of the implant. The periprosthetic bone remodeling showed similarities with changes seen around uncemented hip stems. The OPRA system is a new and promising approach for addressing the challenges faced by patients with transfemoral amputations.

  7. 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

  8. 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.

  9. 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 housed in conventional cages with or without perches. Serum samples were collected from 71-wk-old White Leghorn hens subjected to 4 treatments. Treatment 1 was control 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 < 0.0001). Levels of serum OC using the developed chicken ELISA were higher than that detected using the Rat-Mid ELISA (P < 0.0001). Results from the 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.

  10. Marginal Bone Remodeling around healing Abutment vs Final Abutment Placement at Second Stage Implant Surgery: A 12-month Randomized Clinical Trial.

    Science.gov (United States)

    Nader, Nabih; Aboulhosn, Maissa; Berberi, Antoine; Manal, Cordahi; Younes, Ronald

    2016-01-01

    control condition than the test condition. The results of this prospective study demonstrated the benefit of placing a prosthetic component with a stable connection at second-stage surgery, in terms of reduced marginal bone remodeling when compared with conventional procedure. The use of a stable connection in a healing component during try-in stages prior to final restoration placement leads to less periimplant marginal bone loss.

  11. Simulation of 239Pu location in trabecular bone: a computerized model of adult endosteal bone remodeling and its interaction with injected 239Pu

    International Nuclear Information System (INIS)

    Kimmel, D.B.; Jee, W.S.S.

    1979-01-01

    A computer simulation of the relationship of bone microanatomic metabolic activity to the microscopic location of 239 Pu in bone has been attempted. The model incorporates the rate of bone turnover, cell location and density, bone resorptive activity (as it removes 239 Pu from bone), bone formation activity (as it buries 239 Pu in bone), recycling of 239 Pu, and liver translocation of 239 Pu to bone, such that the skeletal retention curve for 239 Pu injected in monomeric form into the young adult beagle is matched. The eventual aim of this work is to calculate the radiation dose to bone cells, knowing the relative location of 239 Pu deposited in bone and the cells that reside at bone surfaces as it changes throughout the lifespan of an animal. Early results indicate that osteosarcoma incidence may be proportional to the number of alpha hits which occur to osteoprogenitor cells and osteoblasts, the dividing cell population found near surfaces where bone turnover is in progress

  12. 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.

  13. Design of bone-integrating organic-inorganic composite suitable for bone repair.

    Science.gov (United States)

    Miyazaki, Toshiki

    2013-01-01

    Several ceramics exhibit specific biological affinity, i.e. direct bone integration, when implanted in bony defects. They are called bioactive ceramics and utilized as important bone substitutes. However, there is limitation on clinical application, because of their inappropriate mechanical properties such as high Young's modulus and low fracture toughness. Novel bioactive materials exhibiting high machinability and flexibility have been desired in medical fields. Mixing bioactive ceramic powders and organic polymers have developed various organic-inorganic composites. Their mechanical property and bioactivity are mainly governed by the ceramics content. It is known that bioactive ceramics integrate with the bone through bone-like hydroxyapatite layer formed on their surfaces by chemical reaction with body fluid. This is triggered by a catalytic effect of various functional groups. On the basis of these facts, novel bioactive organic-inorganic nanocomposites have been developed. In these composites, inorganic components effective for triggering the hydroxyapatite nucleation are dispersed in polymer matrix at molecular level. Concept of the organic-inorganic composite is also applicable for providing polymethyl methacrylate (PMMA) bone cement with the bioactivity.

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

    Science.gov (United States)

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

    2000-01-01

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

  15. 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...

  16. 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 (FTV 50% ). 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%, FTV 50% 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.

  17. 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...

  18. Ultrasonic characterization of cancellous bone using apparent integrated backscatter

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmeister, B K [Department of Physics, Rhodes College, 2000 North Parkway, Memphis, TN 38112 (United States); III, C I Jones [Department of Physics, Rhodes College, 2000 North Parkway, Memphis, TN 38112 (United States); Caldwell, G J [Department of Physics, Rhodes College, 2000 North Parkway, Memphis, TN 38112 (United States); Kaste, S C [Department of Diagnostic Imaging, St Jude Children' s Research Hospital, Memphis, TN 38105 (United States)

    2006-06-07

    Apparent integrated backscatter (AIB) is a measure of the frequency-averaged (integrated) backscattered power contained in some portion of a backscattered ultrasonic signal. AIB has been used extensively to study soft tissues, but its usefulness as a tissue characterization technique for cancellous bone has not been demonstrated. To address this, we performed measurements on 17 specimens of cancellous bone over two different frequency ranges using a 1 MHz and 5 MHz broadband ultrasonic transducer. Specimens were obtained from bovine tibiae and prepared in the shape of cubes (15 mm side length) with faces oriented along transverse (anterior, posterior, medial and lateral) and longitudinal (superior and inferior) principal anatomic directions. A mechanical scanning system was used to acquire multiple backscatter signals from each direction for each cube. AIB demonstrated highly significant linear correlations with bone mineral density (BMD) for both the transverse (R{sup 2} = 0.817) and longitudinal (R{sup 2} = 0.488) directions using the 5 MHz transducer. In contrast, the correlations with density were much weaker for the 1 MHz transducer (R{sup 2} = 0.007 transverse, R{sup 2} = 0.228 longitudinal). In all cases where a significant correlation was observed, AIB was found to decrease with increasing BMD.

  19. Comparative Analysis of Bone Structural Parameters Reveals Subchondral Cortical Plate Resorption and Increased Trabecular Bone Remodeling in Human Facet Joint Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Cordula Netzer

    2018-03-01

    Full Text Available Facet joint osteoarthritis is a prominent feature of degenerative spine disorders, highly prevalent in ageing populations, and considered a major cause for chronic lower back pain. Since there is no targeted pharmacological therapy, clinical management of disease includes analgesic or surgical treatment. The specific cellular, molecular, and structural changes underpinning facet joint osteoarthritis remain largely elusive. The aim of this study was to determine osteoarthritis-related structural alterations in cortical and trabecular subchondral bone compartments. To this end, we conducted comparative micro computed tomography analysis in healthy (n = 15 and osteoarthritic (n = 22 lumbar facet joints. In osteoarthritic joints, subchondral cortical plate thickness and porosity were significantly reduced. The trabecular compartment displayed a 42 percent increase in bone volume fraction due to an increase in trabecular number, but not trabecular thickness. Bone structural alterations were associated with radiological osteoarthritis severity, mildly age-dependent but not gender-dependent. There was a lack of association between structural parameters of cortical and trabecular compartments in healthy and osteoarthritic specimens. The specific structural alterations suggest elevated subchondral bone resorption and turnover as a potential treatment target in facet joint osteoarthritis.

  20. 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...

  1. 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...

  2. A prospective dual-energy X-ray absorptiometry study of bone remodeling after implantation of the Nanos short-stemmed prosthesis.

    Science.gov (United States)

    Zeh, Alexander; Pankow, Franziska; Röllinhoff, Marc; Delank, Stefan; Wohlrab, David

    2013-04-01

    The aim of this study was to analyze the bone remodeling around the Nanos stem (Smith & Nephew, Marl, Germany) after primary total hip arthroplasty for coxarthrosis. In 25 patients (15 male, 10 female, mean age 59.9 years) with the diagnosis of coxarthrosis, a DEXA scan was performed immediately after surgery, 97 days (SD 6.1 days) and 368 days (SD 6.2 days) after implantation of a Nanos prosthesis. Plain radiographs were analyzed digitally for radiolucent lines, varus-valgus femoral stem alignment, measurement of stem migration and changes in varus-valgus femoral stem alignment. The position of the center of rotation (COR) and the offset were assessed pre- and postoperatively. Harris Hip Score was used to evaluate the clinical outcome. The DEXA scan showed a significant and relevant increase in BMD (Bone Mineral Density) in Gruen-Zone 6 (12%) and a decrease in Zone 1 (15%), 2 (5%) and 7 (12%), which was interpreted as reflecting a distal load transfer in the metaphysis of the femur. There was no clinically relevant migration or tilting of the Nanos stem. Radiolucent lines were noted in 12 cases, mainly at the polished tip area of the prosthesis; this was not regarded as a sign of impaired osseointegration. There was no significant difference between the position of the COR and the pre- and postoperative offset. The absence of stem migration, angulation, or relevant radiolucent lines is seen as evidence for an unimpaired osseointegration of the Nanos stem approximately 12 months after implantation. It is concluded that the Nanos prosthesis can reduce loss of BMD of the proximal femur composed with conventional stems or other short-stemmed implants.

  3. 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.

  4. New application of 18F-fluoride PET for the detection of bone remodeling in early-stage osteoarthritis of the hip.

    Science.gov (United States)

    Kobayashi, Naomi; Inaba, Yutaka; Tateishi, Ukihide; Yukizawa, Yohei; Ike, Hiroyuki; Inoue, Tomio; Saito, Tomoyuki

    2013-10-01

    Recent studies have reported the acceleration of subchondral bone remodeling during the development of osteoarthritis (OA). However, it is not possible to evaluate such molecular abnormalities using conventional radiographic techniques. We have applied 18F-fluoride PET to the analysis of painful or dysplastic hips at various stages of OA and then compared this with radiographic findings and clinical findings. A consecutive series of 65 joints from 48 patients (average age, 40 years; range, 19-72 years) with a hip joint complaint or radiographic dysplastic hip were enrolled in this study. Twenty-five contralateral joints without any evidence of OA or clinical symptoms were assigned as a normal control group. Radiographic evaluations were performed on the basis of Kellgren and Lawrence grade and the minimum joint space. Clinical evaluations were performed using the grading scale for pain severity and the SUVmax was measured for each joint. The association between SUVmax and the radiographic or clinical findings was evaluated. 18F-fluoride PET shows a significantly higher uptake value for progressive-stage OA cases than for early-stage cases and also shows a significantly higher uptake value in cases with severe pain. Even in early-OA-stage patients who do not show joint space narrowing on a plain x-ray, cases with severe pain show a significantly higher uptake value. 18F-fluoride PET has great potential as an imaging method for diagnosing early-stage OA without any marked radiographic changes.

  5. Impaired bone formation in ovariectomized mice reduces implant integration as indicated by longitudinal in vivo micro-computed tomography.

    Science.gov (United States)

    Li, Zihui; Kuhn, Gisela; Schirmer, Michael; Müller, Ralph; Ruffoni, Davide

    2017-01-01

    Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on the impact of osteoporosis on peri-implant bone (re)modeling, which is ultimately responsible for the long term stability of the bone-implant system. Here, we inserted an implant in a mouse model mimicking estrogen deficiency-induced bone loss and we monitored with longitudinal in vivo micro-computed tomography the spatio-temporal changes in bone (re)modeling and architecture, considering the separate contributions of trabecular, endocortical and periosteal surfaces. Specifically, 12 week-old C57BL/6J mice underwent OVX/SHM surgery; 9 weeks after we inserted special metal-ceramics implants into the 6th caudal vertebra and we measured bone response with in vivo micro-CT weekly for the following 6 weeks. Our results indicated that ovariectomized mice showed a reduced ability to increase the thickness of the cortical shell close to the implant because of impaired peri-implant bone formation, especially at the periosteal surface. Moreover, we observed that healthy mice had a significantly higher loss of trabecular bone far from the implant than estrogen depleted animals. Such behavior suggests that, in healthy mice, the substantial increase in peri-implant bone formation which rapidly thickened the cortex to secure the implant may raise bone resorption elsewhere and, specifically, in the trabecular network of the same bone but far from the implant. Considering the already deteriorated bone structure of estrogen depleted mice, further bone loss seemed to be hindered. The obtained knowledge on the dynamic response of diseased bone following implant insertion should provide useful guidelines to develop advanced treatments for osteoporotic fracture fixation based on local and selective manipulation of bone turnover in the peri-implant region.

  6. Impaired bone formation in ovariectomized mice reduces implant integration as indicated by longitudinal in vivo micro-computed tomography.

    Directory of Open Access Journals (Sweden)

    Zihui Li

    Full Text Available Although osteoporotic bone, with low bone mass and deteriorated bone architecture, provides a less favorable mechanical environment than healthy bone for implant fixation, there is no general agreement on the impact of osteoporosis on peri-implant bone (remodeling, which is ultimately responsible for the long term stability of the bone-implant system. Here, we inserted an implant in a mouse model mimicking estrogen deficiency-induced bone loss and we monitored with longitudinal in vivo micro-computed tomography the spatio-temporal changes in bone (remodeling and architecture, considering the separate contributions of trabecular, endocortical and periosteal surfaces. Specifically, 12 week-old C57BL/6J mice underwent OVX/SHM surgery; 9 weeks after we inserted special metal-ceramics implants into the 6th caudal vertebra and we measured bone response with in vivo micro-CT weekly for the following 6 weeks. Our results indicated that ovariectomized mice showed a reduced ability to increase the thickness of the cortical shell close to the implant because of impaired peri-implant bone formation, especially at the periosteal surface. Moreover, we observed that healthy mice had a significantly higher loss of trabecular bone far from the implant than estrogen depleted animals. Such behavior suggests that, in healthy mice, the substantial increase in peri-implant bone formation which rapidly thickened the cortex to secure the implant may raise bone resorption elsewhere and, specifically, in the trabecular network of the same bone but far from the implant. Considering the already deteriorated bone structure of estrogen depleted mice, further bone loss seemed to be hindered. The obtained knowledge on the dynamic response of diseased bone following implant insertion should provide useful guidelines to develop advanced treatments for osteoporotic fracture fixation based on local and selective manipulation of bone turnover in the peri-implant region.

  7. 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.

  8. 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.

  9. Is cortical bone hip? What determines cortical bone properties?

    Science.gov (United States)

    Epstein, Sol

    2007-07-01

    Increased bone turnover may produce a disturbance in bone structure which may result in fracture. In cortical bone, both reduction in turnover and increase in hip bone mineral density (BMD) may be necessary to decrease hip fracture risk and may require relatively greater proportionate changes than for trabecular bone. It should also be noted that increased porosity produces disproportionate reduction in bone strength, and studies have shown that increased cortical porosity and decreased cortical thickness are associated with hip fracture. Continued studies for determining the causes of bone strength and deterioration show distinct promise. Osteocyte viability has been observed to be an indicator of bone strength, with viability as the result of maintaining physiological levels of loading and osteocyte apoptosis as the result of a decrease in loading. Osteocyte apoptosis and decrease are major factors in the bone loss and fracture associated with aging. Both the osteocyte and periosteal cell layer are assuming greater importance in the process of maintaining skeletal integrity as our knowledge of these cells expand, as well being a target for pharmacological agents to reduce fracture especially in cortical bone. The bisphosphonate alendronate has been seen to have a positive effect on cortical bone by allowing customary periosteal growth, while reducing the rate of endocortical bone remodeling and slowing bone loss from the endocortical surface. Risedronate treatment effects were attributed to decrease in bone resorption and thus a decrease in fracture risk. Ibandronate has been seen to increase BMD as the spine and femur as well as a reduced incidence of new vertebral fractures and non vertebral on subset post hoc analysis. And treatment with the anabolic agent PTH(1-34) documented modeling and remodelling of quiescent and active bone surfaces. Receptor activator of nuclear factor kappa B ligand (RANKL) plays a key role in bone destruction, and the human monoclonal

  10. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Osteoclasts prefer aged bone

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  12. Bone graft revascularization strategies

    NARCIS (Netherlands)

    Willems, W.F.

    2014-01-01

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

  13. Integration of the Residual Limb with Prostheses via Direct Skin-Bone-Peripheral Nerve Interface

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0791 TITLE: Integration of the Residual Limb with Prostheses via Direct Skin- Bone-Peripheral Nerve Interface...ABOVE ADDRESS. 1. REPORT DATE October 2017 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2016 - 29 Sep 2017 4. TITLE AND SUBTITLE Integration of the...translational study to develop Skin and Bone Integrated Pylon with Peripheral Neural Interface (SBIP-PNI) directly attached to the residuum and the

  14. [Bone homeostasis and Mechano biology.

    Science.gov (United States)

    Nakashima, Tomoki

    The weight-bearing exercises help to build bones and to maintain them strength. Bone is constantly renewed by the balanced action of osteoblastic bone formation and osteoclastic bone resorption both of which mainly occur at the bone surface. This restructuring process called "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. During bone remodeling, resorption by osteoclasts precedes bone formation by osteoblasts. Based on the osteocyte location within the bone matrix and the cellular morphology, it is proposed that osteocytes potentially contribute to the regulation of bone remodeling in response to mechanical and endocrine stimuli.

  15. Ultrasonic longitudinal waves to monitor the integration of titanium rods with host bone

    Science.gov (United States)

    Wang, Wentao; Lynch, Jerome P.

    2017-04-01

    Osseointegrated prostheses which integrate the prosthesis directly to the limb bone are being developed for patients that are unable to wear traditional socket prostheses. While osseointegration of the prosthesis offers amputees improvement in their quality of life, there remains a need to better understand the integration process that occurs between the bone and the prosthesis. Quantification of the degree of integration is important to track the recuperation process of the amputee, guide physical therapy regimes, and to identify when the state of integration may change (due to damage to the bone). This study explores the development of an assessment strategy for quantitatively assessing the degree of integration between an osseointegrated prosthesis and host bone. Specifically, the strategy utilizes a titanium rod prosthesis as a waveguide with guided waves used to assess the degree of integration. By controlling waveforms launched by piezoelectric wafers bonded on the percutaneous tip of the prosthesis, body waves are introduced into the waveguide with wave reflections at the boneprosthesis interface recorded by the same array. Changes in wave energy are correlated to changes at the contact interface between the titanium rod and the bone material. Both simulation and experimental tests are presented in this paper. Experimental testing is performed using a high-density polyethylene (HDPE) host because the elastic modulus and density of HDPE are close to that of human and animal bone. Results indicate high sensitivity of the longitudinal wave energy to rod penetration depth and confinement stress issued by the host bone.

  16. 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

  17. Progesterone as a bone-trophic hormone.

    Science.gov (United States)

    Prior, J C

    1990-05-01

    Experimental, epidemiological, and clinical data indicate that progesterone is active in bone metabolism. Progesterone appears to act directly on bone by engaging an osteoblast receptor or indirectly through competition for a glucocorticoid osteoblast receptor. Progesterone seems to promote bone formation and/or increase bone turnover. It is possible, through estrogen-stimulated increased progesterone binding to the osteoblast receptor, that progesterone plays a role in the coupling of bone resorption with bone formation. A model of the interdependent actions of progesterone and estrogen on appropriately-"ready" cells in each bone multicellular unit can be tied into the integrated secretions of these hormones within the ovulatory cycle. Figure 5 is an illustration of this concept. It shows the phases of the bone remodeling cycle in parallel with temporal changes in gonadal steroids across a stylized ovulatory cycle. Increasing estrogen production before ovulation may reverse the resorption occurring in a "sensitive" bone multicellular unit while gonadal steroid levels are low at the time of menstrual flow. The bone remodeling unit would then be ready to begin a phase of formation as progesterone levels peaked in the midluteal phase. From this perspective, the normal ovulatory cycle looks like a natural bone-activating, coherence cycle. Critical analysis of the reviewed data indicate that progesterone meets the necessary criteria to play a causal role in mineral metabolism. This review provides the preliminary basis for further molecular, genetic, experimental, and clinical investigation of the role(s) of progesterone in bone remodeling. Much further data are needed about the interrelationships between gonadal steroids and the "life cycle" of bone. Feldman et al., however, may have been prophetic when he commented; "If this anti-glucocorticoid effect of progesterone also holds true in bone, then postmenopausal osteoporosis may be, in part, a progesterone deficiency

  18. What causes bone loss?

    Science.gov (United States)

    ... Paula FJA, Black DM, Rosen CJ. Osteoporosis and bone biology. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology . 13th ed. Philadelphia, PA: ... HM. Bone development and remodeling. In: Jameson JL, De Groot ...

  19. Microarchitecture of the Augmented Bone Following Sinus Elevation with an Albumin Impregnated Demineralized Freeze-Dried Bone Allograft (BoneAlbumin versus Anorganic Bovine Bone Mineral: A Randomized Prospective Clinical, Histomorphometric, and Micro-Computed Tomography Study

    Directory of Open Access Journals (Sweden)

    Kivovics Márton

    2018-01-01

    Full Text Available Serum albumin has been identified as an endogenous protein that is integral to early bone regeneration. We hypothesized that albumin addition to allografts may result in better bone remodeling than what can be achieved with anorganic xenografts. Sinus elevations were performed at 32 sites of 18 patients with the lateral window technique. Sites either received filling with an anorganic bovine bone mineral (ABBM, BioOss, Geistlich, CH or albumin impregnated allograft (BoneAlbumin, OrthoSera, AT. After 6-months patients received dental implants and 16 bone core biopsy samples were obtained from the ABBM filled, and 16 from the BoneAlbumin augmented sites. The biopsies were examined by histomorphometry and µCT. Percentage of the residual graft in the BoneAlbumin group was 0–12.7%, median 5.4% vs. ABBM 6.3–35.9%, median 16.9%, p < 0.05. Results of the µCT analysis showed that the microarchitecture of the augmented bone in the BoneAlbumin group resembles that of the native maxilla in morphometric parameters Trabecular Pattern Factor and Connectivity. Our data show that while ABBM successfully integrates into the newly formed bone tissue as persisting particles, BoneAlbumin is underway towards complete remodeling with new bone closely resembling that of the intact maxilla.

  20. Effect of Hydroxyapatite on Bone Integration in a Rabbit Tibial Defect Model

    Science.gov (United States)

    Sohn, Sung-Keun; Kim, Kyung-Taek; Kim, Chul-Hong; Ahn, Hee-Bae; Rho, Mee-Sook; Jeong, Min-Ho; Sun, Sang-Kyu

    2010-01-01

    Background The aim of the present study was to prepare hydroxyapatite (HA) and then characterize its effect on bone integration in a rabbit tibial defect model. The bone formation with different designs of HA was compared and the bony integration of several graft materials was investigated qualitatively by radiologic and histologic study. Methods Ten rabbits were included in this study; two holes were drilled bilaterally across the near cortex and the four holes in each rabbit were divided into four treatment groups (HAP, hydroxyapatite powder; HAC, hydroxyapatite cylinder; HA/TCP, hydroxyapatite/tri-calcium phosphate cylinder, and titanium cylinder). The volume of bone ingrowth and the change of bone mineral density were statistically calculated by computed tomography five times for each treatment group at 0, 2, 4, 6, and 8 weeks after grafting. Histologic analysis was performed at 8 weeks after grafting. Results The HAP group showed the most pronounced effect on the bone ingrowth surface area, which seen at 4, 6, and 8 weeks after graft (p 0.05). On histological examination, the HAP group revealed well-recovered cortical bone, but the bone was irregularly thickened and haphazardly admixed with powder. The HAC group showed similar histological features to those of the HA/TCP group; the cortical surface of the newly developed bone was smooth and the bone matrix on the surface of the cylinder was regularly arranged. Conclusions We concluded that both the hydroxyapatite powder and cylinder models investigated in our study may be suitable as a bone substitute in the rabbit tibial defect model, but their characteristic properties are quite different. In contrast to hydroxyapatite powder, which showed better results for the bone ingrowth surface, the hydroxyapatite cylinder showed better results for the sustained morphology. PMID:20514266

  1. 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

    on the physical organisation of the myeloma cell microenvironment. The proximity between myeloma cells and osteoclasts or osteoblasts was shown to be conditioned by the recently discovered layer of flat cells that separates the osteoclasts and osteoblasts from the bone marrow, by forming a canopy over bone...

  2. Effect of Integration Patterns Around Implant Neck on Stress Distribution in Peri-Implant Bone: A Finite Element Analysis.

    Science.gov (United States)

    Han, Jingyun; Sun, Yuchun; Wang, Chao

    2017-08-01

    To investigate the biomechanical performance of different osseointegration patterns between cortical bone and implants using finite element analysis. Fifteen finite element models were constructed of the mandibular fixed prosthesis supported by implants. Masticatory loads (200 N axial, 100 N oblique, 40 N horizontal) were applied. The cortical bone/implant interface was divided equally into four layers: upper, upper-middle, lower-middle, and lower. The bone stress and implant displacement were calculated for 5 degrees of uniform integration (0, 20%, 40%, 60%, and 100%) and 10 integration patterns. The stress was concentrated in the bone margin and gradually decreased as osseointegration progressed, when the integrated and nonintegrated areas were alternated on the bone-implant surface. Compared with full integration, the integration of only the lower-middle layer or lower half layers significantly decreased von Mises, tensile, and compressive stresses in cortical bone under oblique and horizontal loads, and these patterns did not induce higher stress in the cancellous bone. For the integration of only the upper or upper-middle layer, stress in the cortical and cancellous bones significantly increased and was considerably higher than in the case of nonintegration. In addition, the maximum stress in the cortical bone was sensitive to the quantity of integrated nodes at the bone margin; lower quantity was associated with higher stress. There was no significant difference in the displacement of implants among 15 models. Integration patterns of cortical bone significantly affect stress distribution in peri-implant bone. The integration of only the lower-middle or lower half layers helps to increase the load-bearing capacity of peri-implant bone and decrease the risk of overloading, while upper integration may further increase the risk of bone resorption. © 2016 by the American College of Prosthodontists.

  3. 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.

  4. Vitamin D, muscle and bone: Integrating effects in development, aging and injury.

    Science.gov (United States)

    Girgis, Christian M; Baldock, Paul A; Downes, Michael

    2015-07-15

    Beyond the established effects of muscle loading on bone, a complex network of hormones and growth factors integrates these adjacent tissues. One such hormone, vitamin D, exerts broad-ranging effects in muscle and bone calcium handling, differentiation and development. Vitamin D also modulates muscle and bone-derived hormones, potentially facilitating cross-talk between these tissues. In the clinical setting, vitamin D deficiency or mutations of the vitamin D receptor result in generalized atrophy of muscle and bone, suggesting coordinated effects of vitamin D at these sites. In this review, we discuss emerging evidence that vitamin D exerts specific effects throughout the life of the musculoskeletal system - in development, aging and injury. From this holistic viewpoint, we offer new insights into an old debate: whether vitamin D's effects in the musculoskeletal system are direct via local VDR signals or indirect via its systemic effects in calcium and phosphate homeostasis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Effects of Autogenous Bone Marrow Aspirate Concentrate on Radiographic Integration of Femoral Condylar Osteochondral Allografts.

    Science.gov (United States)

    Oladeji, Lasun O; Stannard, James P; Cook, Cristi R; Kfuri, Mauricio; Crist, Brett D; Smith, Matthew J; Cook, James L

    2017-10-01

    Transplantation of fresh osteochondral allografts (OCAs) is an attractive treatment option for symptomatic articular cartilage lesions in young, healthy patients. Because the lack of OCA bone integration can be a cause of treatment failure, methods for speeding and enhancing OCA bone integration to mitigate this potential complication are highly desirable. To determine if autogenous bone marrow aspirate concentrate (BMC) treatment of large femoral condylar OCAs would be associated with superior radiographic OCA bone integration compared with nontreated allografts during the critical first 6 months after surgery. Cohort study; Level of evidence, 3. A review of patients enrolled in a prospective registry who were treated with transplantation of large OCAs to one or both femoral condyles at our institution from March 12, 2013 to March 14, 2016 was performed. Patients were stratified into 2 groups based on BMC treatment versus no BMC treatment; the treatment was nonrandomized and was rooted in a shift in practice and a continuing effort to optimize OCA transplantation at our institution. Patients were excluded if they did not have orthogonal view radiographs performed at 6 weeks, 3 months, and 6 months postoperatively. Each condyle undergoing OCA transplantation was assessed individually by an independent musculoskeletal radiologist, who was blinded to the treatment group and time point. OCAs were assessed with respect to graft integration (0%-100%; 0 = no integration, 100 = complete integration) and degree of sclerosis (0-3; 0 = normal, 1 = mild sclerosis, 2 = moderate sclerosis, and 3 = severe sclerosis) of the graft at each time point. This study identified 17 condyles in 15 patients who underwent OCA transplantation without BMC and 29 condyles in 22 patients who underwent OCA transplantation with BMC. The BMC group had significantly ( P = .033) higher graft integration scores at 6 weeks, 3 months, and 6 months after surgery. Graft sclerosis was significantly ( P

  6. Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-α.

    Science.gov (United States)

    Brunetti, G; Papadia, F; Tummolo, A; Fischetto, R; Nicastro, F; Piacente, L; Ventura, A; Mori, G; Oranger, A; Gigante, I; Colucci, S; Ciccarelli, M; Grano, M; Cavallo, L; Delvecchio, M; Faienza, M F

    2016-07-01

    In this study, we investigated the bone cell activity in patients with osteogenesis imperfecta (OI) treated and untreated with neridronate. We demonstrated the key role of Dickkopf-1 (DKK1), receptor activator of nuclear factor-κB ligand (RANKL), and tumor necrosis factor alpha (TNF-α) in regulating bone cell of untreated and treated OI subjects. These cytokines could represent new pharmacological targets for OI. Bisphosphonates are widely used in the treatment of children with osteogenesis imperfecta (OI) with the objective of reducing the risk of fractures. Although bisphosphonates increase bone mineral density in OI subjects, the effects on fracture incidence are conflicting. The aim of this study was to investigate the mechanisms underlying bone cell activity in subjects with mild untreated forms of OI and in a group of subjects with severe OI treated with cycles of intravenous neridronate. Sclerostin, DKK1, TNF-α, RANKL, osteoprotegerin (OPG), and bone turnover markers were quantified in serum of 18 OI patients (12 females, mean age 8.86 ± 3.90), 8 of which were receiving cyclic intravenous neridronate, and 21 sex- and age-matched controls. The effects on osteoblastogenesis and OPG expression of media conditioned by the serum of OI patients and anti-DKK1 neutralizing antibody were evaluated. Osteoclastogenesis was assessed in cultures from patients and controls. DKK1 and RANKL levels were significantly increased both in untreated and in treated OI subjects with respect to controls. The serum from patients with high DKK1 levels inhibited both osteoblast differentiation and OPG expression in vitro. High RANKL and low OPG messenger RNA (mRNA) levels were found in lymphomonocytes from patients. High amounts of TNF-α were expressed by monocytes, and an elevated percentage of circulating CD11b-CD51/CD61+ osteoclast precursors was observed in patients. Our study demonstrated the key role of DKK1, RANKL, and TNF-α in regulating bone cell activity of subjects

  7. α-Xylosidase plays essential roles in xyloglucan remodelling, maintenance of cell wall integrity, and seed germination in Arabidopsis thaliana.

    Science.gov (United States)

    Shigeyama, Takuma; Watanabe, Asuka; Tokuchi, Konatsu; Toh, Shigeo; Sakurai, Naoki; Shibuya, Naoto; Kawakami, Naoto

    2016-10-01

    Regulation and maintenance of cell wall physical properties are crucial for plant growth and environmental response. In the germination process, hypocotyl cell expansion and endosperm weakening are prerequisites for dicot seeds to complete germination. We have identified the Arabidopsis mutant thermoinhibition-resistant germination 1 (trg1), which has reduced seed dormancy and insensitivity to unfavourable conditions for germination owing to a loss-of-function mutation of TRG1/XYL1, which encodes an α-xylosidase. Compared to those of wild type, the elongating stem of trg1 showed significantly lower viscoelasticity, and the fruit epidermal cells were longitudinally shorter and horizontally enlarged. Actively growing tissues of trg1 over-accumulated free xyloglucan oligosaccharides (XGOs), and the seed cell wall had xyloglucan with a greatly reduced molecular weight. These observations suggest that XGOs reduce xyloglucan size by serving as an acceptor in transglycosylation and eventually enhancing cell wall loosening. TRG1/XYL1 gene expression was abundant in growing wild-type organs and tissues but relatively low in cells at most actively elongating part of the tissues, suggesting that α-xylosidase contributes to maintaining the mechanical integrity of the primary cell wall in the growing and pre-growing tissues. In germinating seeds of trg1, expression of genes encoding specific abscisic acid and gibberellin metabolism enzymes was altered in accordance with the aberrant germination phenotype. Thus, cell wall integrity could affect seed germination not only directly through the physical properties of the cell wall but also indirectly through the regulation of hormone gene expression. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  8. Hard tissue regeneration using bone substitutes: an update on innovations in materials.

    Science.gov (United States)

    Sarkar, Swapan Kumar; Lee, Byong Taek

    2015-05-01

    Bone is a unique organ composed of mineralized hard tissue, unlike any other body part. The unique manner in which bone can constantly undergo self-remodeling has created interesting clinical approaches to the healing of damaged bone. Healing of large bone defects is achieved using implant materials that gradually integrate with the body after healing is completed. Such strategies require a multidisciplinary approach by material scientists, biological scientists, and clinicians. Development of materials for bone healing and exploration of the interactions thereof with the body are active research areas. In this review, we explore ongoing developments in the creation of materials for regenerating hard tissues.

  9. Effects of titanium surface topography on bone integration: a systematic review.

    Science.gov (United States)

    Wennerberg, Ann; Albrektsson, Tomas

    2009-09-01

    To analyse possible effects of titanium surface topography on bone integration. Our analyses were centred on a PubMed search that identified 1184 publications of assumed relevance; of those, 1064 had to be disregarded because they did not accurately present in vivo data on bone response to surface topography. The remaining 120 papers were read and analysed, after removal of an additional 20 papers that mainly dealt with CaP-coated and Zr implants; 100 papers remained and formed the basis for this paper. The bone response to differently configurated surfaces was mainly evaluated by histomorphometry (bone-to-implant contact), removal torque and pushout/pullout tests. A huge number of the experimental investigations have demonstrated that the bone response was influenced by the implant surface topography; smooth (S(a)1-2 microm) surfaces showed stronger bone responses than rough (S(a)>2 microm) in some studies. One limitation was that it was difficult to compare many studies because of the varying quality of surface evaluations; a surface termed 'rough' in one study was not uncommonly referred to as 'smooth' in another; many investigators falsely assumed that surface preparation per se identified the roughness of the implant; and many other studies used only qualitative techniques such as SEM. Furthermore, filtering techniques differed or only height parameters (S(a), R(a)) were reported. * Surface topography influences bone response at the micrometre level. * Some indications exist that surface topography influences bone response at the nanometre level. * The majority of published papers present an inadequate surface characterization. * Measurement and evaluation techniques need to be standardized. * Not only height descriptive parameters but also spatial and hybrid ones should be used.

  10. Osseointegration of hydroxyapatite and remodeling-resorption of tricalciumphosphate ceramics.

    Science.gov (United States)

    Draenert, Miriam; Draenert, Alice; Draenert, Klaus

    2013-04-01

    Cancellous bone defects surrounded by still intact bone structures never heal. Ceramics offer a solution providing osteoconductive scaffolds. The purpose of the study is to evaluate whether structured β-TCP and HA implants can reconstruct cancellous bone defects, which role micro- and macro-porosity, stiffness and surface area play; finally the indication for both materials based on its resorbability. 10 German Shepard dogs were operated on both tibial heads implanting shell-like fully interconnected ceramic cylinders, using a wet grinding hollow drill coated with diamonds. β-TCP was compared with HA. A polychromatic sequential labelling with 4 different fluorochromes controlled bone formation dynamics. Non-decalcifying histology after perfusion fixation and vessel casting was performed. μ-CT was combined with high resolution microradiography and histology on thin ground crossections. The stages after 6 weeks, 2, 3, 4 months and 15 months were evaluated. In spite of osseointegration of HA and β-TCP, the osseointegration of both materials was completely different. Both shell-like bone void fillers were osseointegrated in a sandwich-like manner. HA yielded primarily a reinforcement of the recipient's cancellous-bone bed and full osseointegration after 4 months, whereas β-TCP-implants were fully osseointegrated after 6 weeks. HA did not show signs of resorption. The resorption of the β-TCP resulted during remodelling. The final stage showed restitution "ad integrum" of the β-TCP defects with a physiological architecture, whereas HA was integrated in the cancellous bone construction providing 600 μm measuring macropores showing osteoinductive properties. Copyright © 2013 Wiley Periodicals, Inc.

  11. Relevance of fiber integrated gelatin-nanohydroxyapatite composite scaffold for bone tissue regeneration

    Science.gov (United States)

    Halima Shamaz, Bibi; Anitha, A.; Vijayamohan, Manju; Kuttappan, Shruthy; Nair, Shantikumar; Nair, Manitha B.

    2015-10-01

    Porous nanohydroxyapatite (nanoHA) is a promising bone substitute, but it is brittle, which limits its utility for load bearing applications. To address this issue, herein, biodegradable electrospun microfibrous sheets of poly(L-lactic acid)-(PLLA)-polyvinyl alcohol (PVA) were incorporated into a gelatin-nanoHA matrix which was investigated for its mechanical properties, the physical integration of the fibers with the matrix, cell infiltration, osteogenic differentiation and bone regeneration. The inclusion of sacrificial fibers like PVA along with PLLA and leaching resulted in improved cellular infiltration towards the center of the scaffold. Furthermore, the treatment of PLLA fibers with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide enhanced their hydrophilicity, ensuring firm anchorage between the fibers and the gelatin-HA matrix. The incorporation of PLLA microfibers within the gelatin-nanoHA matrix reduced the brittleness of the scaffolds, the effect being proportional to the number of layers of fibrous sheets in the matrix. The proliferation and osteogenic differentiation of human adipose-derived mesenchymal stem cells was augmented on the fibrous scaffolds in comparison to those scaffolds devoid of fibers. Finally, the scaffold could promote cell infiltration, together with bone regeneration, upon implantation in a rabbit femoral cortical defect within 4 weeks. The bone regeneration potential was significantly higher when compared to commercially available HA (Surgiwear™). Thus, this biomimetic, porous, 3D composite scaffold could be offered as a promising candidate for bone regeneration in orthopedics.

  12. Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging

    International Nuclear Information System (INIS)

    Wagner, A; Sachse, A; Keller, M; Aurich, M; Wetzel, W-D; Hortschansky, P; Schmuck, K; Lohmann, M; Reime, B; Metge, J; Arfelli, F; Menk, R; Rigon, L; Muehleman, C; Bravin, A; Coan, P; Mollenhauer, J

    2006-01-01

    Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening

  13. Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging

    Science.gov (United States)

    Wagner, A.; Sachse, A.; Keller, M.; Aurich, M.; Wetzel, W.-D.; Hortschansky, P.; Schmuck, K.; Lohmann, M.; Reime, B.; Metge, J.; Arfelli, F.; Menk, R.; Rigon, L.; Muehleman, C.; Bravin, A.; Coan, P.; Mollenhauer, J.

    2006-03-01

    Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

  14. Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging.

    Science.gov (United States)

    Wagner, A; Sachse, A; Keller, M; Aurich, M; Wetzel, W-D; Hortschansky, P; Schmuck, K; Lohmann, M; Reime, B; Metge, J; Arfelli, F; Menk, R; Rigon, L; Muehleman, C; Bravin, A; Coan, P; Mollenhauer, J

    2006-03-07

    Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

  15. Qualitative evaluation of titanium implant integration into bone by diffraction enhanced imaging

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, A [Department of Orthopaedics of the University of Jena at the Waldkrankenhaus ' Rudolf Elle' , Jena (Germany); Sachse, A [Department of Orthopaedics of the University of Jena at the Waldkrankenhaus ' Rudolf Elle' , Jena (Germany); Keller, M [Department of Orthopaedics of the University of Jena at the Waldkrankenhaus ' Rudolf Elle' , Jena (Germany); Aurich, M [Department of Orthopaedics of the University of Jena at the Waldkrankenhaus ' Rudolf Elle' , Jena (Germany); Wetzel, W-D [Department of Orthopaedics of the University of Jena at the Waldkrankenhaus ' Rudolf Elle' , Jena (Germany); Hortschansky, P [Hans-Knoell-Institut fuer Naturstoffforschung, Jena (Germany); Schmuck, K [DePuy Biotech GmbH, Jena (Germany); Lohmann, M [Hasylab at DESY, Hamburg (Germany); Reime, B [Hasylab at DESY, Hamburg (Germany); Metge, J [CELLS-ALBA, Universitat Autonoma de Barcelona (Spain); Arfelli, F [Department of Physics, University of Trieste, Trieste (Italy); Menk, R [ELETTRA, Trieste (Italy); Rigon, L [ELETTRA, Trieste (Italy); Muehleman, C [Department of Biochemistry, Rush Medical College, Chicago, IL (United States); Bravin, A [European Synchrotron Radiation Facility, BP220 38043, Grenoble (France); Coan, P [European Synchrotron Radiation Facility, BP220 38043, Grenoble (France); Mollenhauer, J [Department of Orthopaedics of the University of Jena at the Waldkrankenhaus ' Rudolf Elle' , Jena (Germany)

    2006-03-07

    Diffraction enhanced imaging (DEI) uses refraction of x-rays at edges, which allows pronounced visualization of material borders and rejects scattering which often obscures edges and blurs images. Here, the first evidence is presented that, using DEI, a destruction-free evaluation of the quality of integration of metal implants into bone is possible. Experiments were performed in rabbits and sheep with model implants to investigate the option for DEI as a tool in implant research. The results obtained from DEI were compared to conventional histology obtained from the specimens. DE images allow the identification of the quality of ingrowth of bone into the hydroxyapatite layer of the implant. Incomplete integration of the implant with a remaining gap of less than 0.3 mm caused the presence of a highly refractive edge at the implant/bone border. In contrast, implants with bone fully grown onto the surface did not display a refractive signal. Therefore, the refractive signal could be utilized to diagnose implant healing and/or loosening.

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

    Science.gov (United States)

    Sanchez-Crespo, Alejandro; Christiansson, Frederik; Thur, Charlotte Karlsson; Lundblad, Henrik; Sundin, Anders

    2017-03-01

    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 [ 18 F]-fluoride (Na 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 [ 18 F]-fluoride from plasma to bone, K i were calculated. The ratio of the maximum K i at PET scan 2 and 1 ([Formula: see text]) as well as the ratio of the maximum Standard Uptake Value at PET scan 2 and 1 ([Formula: see text]) 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 [Formula: see text] or [Formula: see text]. [Formula: see text] and [Formula: see text] were not correlated within each orthopedic group (p > 0.1 for all groups), nor for the pooled population (p = 0.12). The distribution of [Formula: see text] was found significantly different among the different orthopedic groups (p = 0.0046) -also for [Formula: see text] (p = 0.022). The positive and negative treatment predictive values for [Formula: see text] were 66.7 % and 77.8 %, respectively. Corresponding values for [Formula: see text] were 25 % and 33.3 % CONCLUSIONS: The [Formula: see text] obtained from dynamic [ 18 F]-fluoride-PET imaging is a promising predictive factor to evaluate changes in bone healing in response to TSF treatment.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  18. Three-dimensional analysis of bone remodeling following ridge augmentation of compromised extraction sockets in periodontitis patients: A randomized controlled study.

    Science.gov (United States)

    Aimetti, Mario; Manavella, Valeria; Corano, Lisa; Ercoli, Elena; Bignardi, Cristina; Romano, Federica

    2018-02-01

    The aim of this study was to analyze linear and volumetric hard tissue changes in severely resorbed alveolar sockets after ridge augmentation procedure and to compare them with spontaneous healing using three-dimensional cone beam computed tomography (CBCT). Thirty patients (mean age 53.2 ± 6.3 years) requiring tooth extraction for advanced periodontitis were randomly allocated to test and control groups. The test sites were grafted using a collagenated bovine-derived bone (DBBM-C) covered with a collagen membrane, while control sites had spontaneous healing. Both groups healed by secondary intention. Linear and volumetric measurements were taken on superimposed CBCT images obtained after tooth extraction and 12 months later. Greater horizontal shrinkage, localized mainly in the crestal zone, was observed in the control group (4.92 ± 2.45 mm) compared to the test group (2.60 ± 1.24 mm). While both groups presented a rebuilding of the buccal wall, it was most pronounced in the grafted sockets (2.50 ± 2.12 mm vs. 0.51 ± 1.02 mm). A significant difference was also registered in the percentage of volume loss between grafted and non-grafted sites (9.14% vs. 35.16%, p-value sockets with extensive buccal bone deficiencies undergo significant three-dimensional volumetric alterations following natural healing. The immediate application of a slow-resorbing xenograft with a covering collagen membrane seems to be effective in improving alveolar ridge shape and dimensions, thus potentially reducing the need for adjunctive regenerative procedures at the time of implant placement. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Mehdi Rafiei

    2015-01-01

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

  20. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

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

  1. Statistics of hits to bone cell nuclei

    International Nuclear Information System (INIS)

    Kruglikov, I.L.; Polig, E.; Jee, W.S.S.

    1993-01-01

    The statistics of hits to the nuclei of bone cells irradiated from alpha sources labeling bone tissue is described. It is shown that the law of remodeling of a bone structural unit (BSU), which describes the distribution of quiescence periodes of this unit, affects the statistics of hits. It the irradiation of bone cells occurs during the whole cell cycle, the mean number of hits is independent of the law of remodeling. In this case the variance of hits has the minimum value for constant quiescence periods of BSUs (deterministic remodeling) and the maximum value for exponentially distributed quiescence periods (random remodeling). For the first generation of bone cells, i.e. for the cells which existed at the moment of the uptake of the nuclide, the mean number of hits depends on the law of remodeling. For random remodeling the mean number is equal to the mean value for the complete remodeling cycle. For deterministic remodeling the mean is only half this value. For the first generation of bone cells, changing the law of remodeling from random to deterministic increases the probability of no hits to the nuclei of bone cells. For the same mean value of hits, the difference does not exceed 13.3% of the total number of cells. For the subsequent generations of bone cells, such a change of the law of remodeling decreases the probability of no hits up to 20.4% of the total number of cells. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Vinken Mathieu

    2007-04-01

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

  3. 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

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

    Directory of Open Access Journals (Sweden)

    Danna Ye

    2016-01-01

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

  5. In vivo evaluation of the bone integration of coated poly(vinyl-alcohol) hydrogel fiber implants.

    Science.gov (United States)

    Moreau, David; Villain, Arthur; Bachy, Manon; Proudhon, Henry; Ku, David N; Hannouche, Didier; Petite, Hervé; Corté, Laurent

    2017-08-01

    Recently, it has been shown that constructs of poly(vinyl alcohol) (PVA) hydrogel fibers reproduce closely the tensile behavior of ligaments. However, the biological response to these systems has not been explored yet. Here, we report the first in vivo evaluation of these implants and focus on the integration in bone, using a rabbit model of bone tunnel healing. Implants consisted in bundles of PVA hydrogel fibers embedded in a PVA hydrogel matrix. Half of the samples were coated with a composite coating of hydroxyapatite (HA) particles embedded in PVA hydrogel. The biological integration was evaluated at 6 weeks using histology and micro-CT imaging. For all implants, a good biological tolerance and growth of new bone tissue are reported. All the implants were surrounded by a fibrous layer comparable to what was previously observed for poly(ethylene terephthalate) (PET) fibers currently used in humans for ligament reconstruction. An image analysis method is proposed to quantify the thickness of this fibrous capsule. Implants coated with HA were not significantly osteoconductive, which can be attributed to the slow dissolution of the selected hydroxyapatite. Overall, these results confirm the relevance of PVA hydrogel fibers for ligament reconstruction and adjustments are proposed to enhance its osseointegration.

  6. Early integration of a bone plug in the femoral tunnel in rectangular tunnel ACL reconstruction with a bone-patellar tendon-bone graft: a prospective computed tomography analysis.

    Science.gov (United States)

    Suzuki, Tomoyuki; Shino, Konsei; Nakagawa, Shigeto; Nakata, Ken; Iwahashi, Takehiko; Kinugasa, Kazutaka; Otsubo, Hidenori; Yamashita, Toshihiko

    2011-12-01

    The purpose of this prospective study was to evaluate how early the bone plug was integrated into the rectangular femoral tunnel after anatomical ACL reconstruction using a bone-patellar tendon-bone (BTB) graft via a rectangular tunnel (RT BTB ACL-R). Twenty consecutive patients who had undergone the reconstruction procedure were evaluated by CT scans at 4 and 8 weeks postoperatively. In each scan, 30 slices for multiplanar reconstruction were collected parallel to the long axis of the parallelepiped femoral tunnel and perpendicular to the tendinous plane of the bone plug. Each slice was classified as "complete," indicating no visible gap between the plug and the tunnel wall or trabecular continuity or "incomplete," showing a visible gap. Bone plug-tunnel integration was evaluated as "excellent," "good," "fair," or "poor" for >20, 11-20, 5-10, and values at the anterior interface between the bone plug and the tunnel wall were also measured on both scans. The mean changes in CT value at 8 weeks were significantly lower than those at 4 weeks. This study shows that bone plug-femoral tunnel integration was almost complete by 8 weeks after surgery using RT BTB ACL-R.

  7. Progesterone and Bone: Actions Promoting Bone Health in Women

    Directory of Open Access Journals (Sweden)

    Vanadin Seifert-Klauss

    2010-01-01

    Full Text Available Estradiol (E2 and progesterone (P4 collaborate within bone remodelling on resorption (E2 and formation (P4. We integrate evidence that P4 may prevent and, with antiresorptives, treat women's osteoporosis. P4 stimulates osteoblast differentiation in vitro. Menarche (E2 and onset of ovulation (P4 both contribute to peak BMD. Meta-analysis of 5 studies confirms that regularly cycling premenopausal women lose bone mineral density (BMD related to subclinical ovulatory disturbances (SODs. Cyclic progestin prevents bone loss in healthy premenopausal women with amenorrhea or SOD. BMD loss is more rapid in perimenopause than postmenopause—decreased bone formation due to P4 deficiency contributes. In 4 placebo-controlled RCTs, BMD loss is not prevented by P4 in postmenopausal women with increased bone turnover. However, 5 studies of E2-MPA co-therapy show greater BMD increases versus E2 alone. P4 fracture data are lacking. P4 prevents bone loss in pre- and possibly perimenopausal women; progesterone co-therapy with antiresorptives may increase bone formation and BMD.

  8. Rapid isolation of bone marrow mesenchymal stromal cells using integrated centrifuge-based technology.

    Science.gov (United States)

    Meppelink, Amanda M; Wang, Xing-Hua; Bradica, Gino; Barron, Kathryn; Hiltz, Kathleen; Liu, Xiang-Hong; Goldman, Scott M; Vacanti, Joseph P; Keating, Armand; Hoganson, David M

    2016-06-01

    The use of bone marrow-derived mesenchymal stromal cells (MSCs) in cell-based therapies is currently being developed for a number of diseases. Thus far, the clinical results have been inconclusive and variable, in part because of the variety of cell isolation procedures and culture conditions used in each study. A new isolation technique that streamlines the method of concentration and demands less time and attention could provide clinical and economic advantages compared with current methodologies. In this study, we evaluated the concentrating capability of an integrated centrifuge-based technology compared with standard Ficoll isolation. MSCs were concentrated from bone marrow aspirate using the new device and the Ficoll method. The isolation capabilities of the device and the growth characteristics, secretome production, and differentiation capacity of the derived cells were determined. The new MSC isolation device concentrated the bone marrow in 90 seconds and resulted in a mononuclear cell yield 10-fold higher and with a twofold increase in cell retention compared with Ficoll. The cells isolated using the device were shown to exhibit similar morphology and functional activity as assessed by growth curves and secretome production compared to the Ficoll-isolated cells. The surface marker and trilineage differentiation profile of the device-isolated cells was consistent with the known profile of MSCs. The faster time to isolation and greater cell yield of the integrated centrifuge-based technology may make this an improved approach for MSC isolation from bone marrow aspirates. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  9. 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

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

    Science.gov (United States)

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

    2012-04-01

    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. Twenty-four male Japanese white rabbits were randomly divided into three groups (Group A, B, C) in this study. Under anesthesia, defects of four sizes (1.2, 1.5, 2.0 and 2.5 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-Plus 6.0 software after animal was sacrificed at 4th(Group A), 6th(Group B) and 8th(Group C) weeks postoperatively. Four samples were analyzed for each size of defect and each healing period. The histological and the radiologic evaluation were performed after sacrification of all rabbits on postoperative 4th and 6th weeks, It showed significant difference between the experimental group and the control group when these defects were less than or equal to 2.0 mm. No statistical difference was observed when these defects were larger than 2.0 mm at all healing periods except at the 4th week. 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. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    Singh Bal Baljinder

    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.

  13. Bone healing and bone substitutes.

    Science.gov (United States)

    Costantino, Peter D; Hiltzik, David; Govindaraj, Satish; Moche, Jason

    2002-02-01

    With the advent of new biomaterials and surgical techniques, the reconstructive surgeon has a wider range of treatment modalities for the rehabilitation and reconstruction of craniofacial skeletal deformities than ever before. These innovative substances act as true bone graft substitutes, thereby allowing the surgeon to avoid the use of autogenous bone grafts and their associated donor site morbidity. Surgeons have long been interested in producing a composite graft that can heal faster by induction, incorporate with surrounding tissues, and be remodeled to resemble native bone. Currently, there are a host of bone graft substitutes available that vary in both their composition and properties. Craniomaxillofacial surgeons must therefore become comfortable with numerous biomaterials to best tailor the treatment for each patient individually. Ongoing investigations into the next phase of tissue engineering will continue to bring us closer to the ability to regenerate or replace bone.

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

    Science.gov (United States)

    de Jonge, E A L; Koromani, F; Hofman, A; Uitterlinden, A G; Franco, O H; Rivadeneira, F; Kiefte-de Jong, J C

    2017-08-01

    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 and if intake of dietary fibre was high. Studies on dietary acid load (DAL) and fractures have shown inconsistent results. Associations between DAL, bone mineral density (BMD) and trabecular bone integrity might play a role in these inconsistencies and might be influenced by renal function and dietary fibre intake. Therefore, our aim was to study (1) associations of DAL with BMD and with the trabecular bone score (TBS) and (2) the potential influence of renal function and dietary fibre in these associations. Dutch individuals aged 45 years and over (n = 4672) participating in the prospective cohort of the Rotterdam study were included. Based on food frequency questionnaires, three indices of DAL were calculated: the net endogenous acid production (NEAP) and the ratios of vegetable or animal protein and potassium (VegPro/K and AnPro/K). Data on lumbar spinal TBS and BMD were derived from dual-energy X-ray absorptiometry measurements. Independent of confounders, NEAP and AnPro/K, but not VegPro/K, were associated with low TBS (standardized β (95%) = -0.04 (-0.07, -0.01) and -0.08 (-0.11, -0.04)) but not with BMD. Associations of AnPro/K and VegPro/K with TBS were non-linear and differently shaped. Unfavourable associations between NEAP, BMD and TBS were mainly present in subgroups with high fibre intake. High NEAP was associated with low TBS. Associations of AnPro/K and VegPro/K and TBS were non-linear and differently shaped. No significant associations of DAL with BMD were observed, nor was there any significant interaction between DAL and renal function. Mainly in participants with high intake of dietary fibre, DAL might be detrimental to bone.

  16. [Bone Cell Biology Assessed by Microscopic Approach. The effect of parathyroid hormone and teriparatide on bone].

    Science.gov (United States)

    Takahata, Masahiko

    2015-10-01

    Continuous exposure to parathyroid hormone (PTH) leads to hypercalcemia and a decrease in bone volume, which is referred to as its catabolic effect, while intermittent exogenously administered PTH leads to an anabolic effect on bone. Intermittent administration of PTH dramatically increases bone remodeling and modeling through their direct and indirect effects on the functional cells of bone remodeling units and their precursors. These effects on bone metabolism differ according to dosing frequency of PTH. Therefore, different dosing frequency of PTH shows different therapeutic effects on bone in terms of bone volume and bone quality in patients with osteoporosis.

  17. 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

  18. Extrinsic Mechanisms Involved in Age-Related Defective Bone Formation

    DEFF Research Database (Denmark)

    Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

    2011-01-01

    Context: Age-related bone loss is associated with progressive changes in bone remodeling characterized by decreased bone formation relative to bone resorption. Both trabecular and periosteal bone formation decline with age in both sexes, which contributes to bone fragility and increased risk of f...

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

    Directory of Open Access Journals (Sweden)

    Rinaldo Florencio-Silva

    2015-01-01

    Full Text Available 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.

  20. 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.

  1. Two types of bone necrosis in the Middle Triassic Pistosaurus longaevus bones: the results of integrated studies

    Science.gov (United States)

    Surmik, Dawid; Rothschild, Bruce M.; Dulski, Mateusz; Janiszewska, Katarzyna

    2017-07-01

    Avascular necrosis, diagnosed on the basis of either a specific pathological modification of the articular surfaces of bone or its radiologic appearance in vertebral centra, has been recognized in many Mesozoic marine reptiles as well as in present-day marine mammals. Its presence in the zoological and paleontologic record is usually associated with decompression syndrome, a disease that affects secondarily aquatic vertebrates that could dive. Bone necrosis can also be caused by infectious processes, but it differs in appearance from decompression syndrome-associated aseptic necrosis. Herein, we report evidence of septic necrosis in the proximal articular surface of the femur of a marine reptile, Pistosaurus longaevus, from the Middle Triassic of Poland and Germany. This is the oldest recognition of septic necrosis associated with septic arthritis in the fossil record so far, and the mineralogical composition of pathologically altered bone is described herein in detail. The occurrence of septic necrosis is contrasted with decompression syndrome-associated avascular necrosis, also described in Pistosaurus longaevus bone from Middle Triassic of Germany.

  2. Bone Marrow Aspirate Concentrate versus Platelet Rich Plasma to Enhance Osseous Integration Potential for Osteochondral Allografts.

    Science.gov (United States)

    Stoker, Aaron M; Baumann, Charles A; Stannard, James P; Cook, James L

    2018-04-01

    Fresh osteochondral allograft (OCA) transplantation is an attractive treatment option for symptomatic articular cartilage lesions in young, healthy patients. Since a lack of OCA bone integration can be a cause of treatment failure, methods for speeding and enhancing OCA bone integration to mitigate this potential complication are highly desirable. This study sought to determine and compare the potential of bone marrow aspirate concentrate (BMC) and leukoreduced platelet rich plasma (PRP) to repopulate the osseous portion of an OCA with cells and deliver osteogenic proteins. It was hypothesized that BMC would have significantly higher colony forming units (CFUs)/mL and seed the osseous portion of OCA with more cells than PRP. Finally, we hypothesized that the media of BMC and PRP treated OCAs would have significantly higher concentrations of osteogenic proteins compared with negative control OCAs. Cylindrical OCAs ( n  = 36) created from tissue stored for 21 days were treated with BMC ( n  = 12) or PRP ( n  = 12) obtained for 6 dogs, or left untreated as a negative control ( n  = 12). After treatment, OCAs were cultured for 7 or 14 days. Media were collected for analysis of osteogenic biomarker concentration. Samples of each BMC and PRP were tested for CFU concentration. On day 7 or 14, the grafts were assessed for cell surface adhesion and penetration using fluorescent microscopy. Significant differences in CFU and media biomarker concentration between the groups were determined using one-way analysis of variance (ANOVA) and Tukey's post-hoc test with the significance set at p  BMC had viable cells detectable on the osseous portion of the allografts at day 7 and 14 of culture. BMC samples had a significantly higher ( p  = 0.029) CFU/mL compared with PRP samples. At day 3 and/or 7 of culture, the concentration of several osteogenic proteins was significantly higher in both BMC and PRP samples. Autogenous BMC can be used to deliver both a cell

  3. Otosclerosis: Temporal Bone Pathology.

    Science.gov (United States)

    Quesnel, Alicia M; Ishai, Reuven; McKenna, Michael J

    2018-04-01

    Otosclerosis is pathologically characterized by abnormal bony remodeling, which includes bone resorption, new bone deposition, and vascular proliferation in the temporal bone. Sensorineural hearing loss in otosclerosis is associated with extension of otosclerosis to the cochlear endosteum and deposition of collagen throughout the spiral ligament. Persistent or recurrent conductive hearing loss after stapedectomy has been associated with incomplete footplate fenestration, poor incus-prosthesis connection, and incus resorption in temporal bone specimens. Human temporal bone pathology has helped to define the role of computed tomography imaging for otosclerosis, confirming that computed tomography is highly sensitive for diagnosis, yet limited in assessing cochlear endosteal involvement. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. 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...

  5. Nanostructured gellan and xanthan hydrogel depot integrated within a baghdadite scaffold augments bone regeneration.

    Science.gov (United States)

    Sehgal, Rekha R; Roohani-Esfahani, S I; Zreiqat, Hala; Banerjee, Rinti

    2017-04-01

    Controlled delivery of biological cues through synthetic scaffolds to enhance the healing capacity of bone defects is yet to be realized clinically. The purpose of this study was development of a bioactive tissue-engineered scaffold providing the sustained delivery of an osteoinductive drug, dexamethasone disodium phosphate (DXP), encapsulated within chitosan nanoparticles (CN). Porous baghdadite (BD; Ca 3 ZrSi 2 O 9 ) scaffolds, a zirconia-modified calcium silicate ceramic, was coated with DXP-encapsulated CN nanoparticles (DXP-CN) using nanostructured gellan and xanthan hydrogel (GX). Crosslinker and GX polymer concentrations were optimized to achieve a homogeneous distribution of hydrogel coating within BD scaffolds. Dynamic laser scattering indicated an average size of 521 ± 21 nm for the DXP-CN nanoparticles. In vitro drug-release studies demonstrated that the developed DXP-CN-GX hydrogel-coated BD scaffolds (DXP-CN-GX-BD) resulted in a sustained delivery of DXP over the 5 days (78 ± 6% of drug release) compared with burst release over 1 h, seen from free DXP loaded in uncoated BD scaffolds (92 ± 8% release in 1 h). To estimate the influence of controlled delivery of DXP from the developed scaffolds, the effect on MG 63 cells was evaluated using various bone differentiation assays. Cell culture within DXP-CN-GX-BD scaffolds demonstrated a significant increase in the expression of early and late osteogenic markers of alkaline phosphatase activity, collagen type 1 and osteocalcin, compared to the uncoated BD scaffold. The results suggest that the DXP-releasing nanostructured hydrogel integrated within the BD scaffold caused sustained release of DXP, improving the potential for osteogenic differentiation. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

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

    International Nuclear Information System (INIS)

    Murata, Masaru; Akazawa, Toshiyuki; Yuasa, Toshihiro; Okayama, Miki; Tazaki, Junichi; Hanawa, Takao; Arisue, Makoto; Mizoguchi, Itaru

    2012-01-01

    Highlights: ► A titanium fixture is implanted into palatal bone of an 18-year-old patient as the unmoved anchorage for the orthodontic treatment. ► The fixture is integrated with compact bone with cortical bone-like osteon. ► Microbeam X-ray diffraction denotes the crystallinity and orientation of HAp. ► X-ray images of c-face in HAp reveal functionally graded distribution of bone quality. ► 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 ® , 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 implant thread to the distant site in all horizontal lines of the map. These results indicated that the X-ray images for the intensity of c

  7. 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

  8. Role of Osteal Macrophages in Bone Metabolism

    Directory of Open Access Journals (Sweden)

    Sun Wook Cho

    2015-03-01

    Full Text Available Macrophages have been shown to have pleiotropic functions in various pathophysiologies, especially in terms of anti-inflammatory and regenerative activity. Recently, the novel functions of bone marrow resident macrophages (called osteal macrophages were intensively studied in bone development, remodeling and tissue repair processes. This review discusses the current evidence for a role of osteal macrophages in bone modeling, remodeling, and fracture healing processes.

  9. PHAGOCYTOSIS AND REMODELING OF COLLAGEN MATRICES

    OpenAIRE

    Abraham, Leah C.; Dice, J Fred.; Lee, Kyongbum; Kaplan, David L.

    2007-01-01

    The biodegradation of collagen and the deposition of new collagen-based extracellular matrices are of central importance in tissue remodeling and function. Similarly, for collagen-based biomaterials used in tissue engineering, the degradation of collagen scaffolds with accompanying cellular infiltration and generation of new extracellular matrix is critical for integration of in vitro grown tissues in vivo. In earlier studies we observed significant impact of collagen structure on primary lun...

  10. Chromatin Remodeling and Plant Immunity.

    Science.gov (United States)

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

    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? © 2017 Elsevier Inc. All rights reserved.

  11. Mechanoactive scaffold induces tendon remodeling and expression of fibrocartilage markers.

    Science.gov (United States)

    Spalazzi, Jeffrey P; Vyner, Moira C; Jacobs, Matthew T; Moffat, Kristen L; Lu, Helen H

    2008-08-01

    Biological fixation of soft tissue-based grafts for anterior cruciate ligament (ACL) reconstruction poses a major clinical challenge. The ACL integrates with subchondral bone through a fibrocartilage enthesis, which serves to minimize stress concentrations and enables load transfer between two distinct tissue types. Functional integration thus requires the reestablishment of this fibrocartilage interface on reconstructed ACL grafts. We designed and characterized a novel mechanoactive scaffold based on a composite of poly-alpha-hydroxyester nanofibers and sintered microspheres; we then used the scaffold to test the hypothesis that scaffold-induced compression of tendon grafts would result in matrix remodeling and the expression of fibrocartilage interface-related markers. Histology coupled with confocal microscopy and biochemical assays were used to evaluate the effects of scaffold-induced compression on tendon matrix collagen distribution, cellularity, proteoglycan content, and gene expression over a 2-week period. Scaffold contraction resulted in over 15% compression of the patellar tendon graft and upregulated the expression of fibrocartilage-related markers such as Type II collagen, aggrecan, and transforming growth factor-beta3 (TGF-beta3). Additionally, proteoglycan content was higher in the compressed tendon group after 1 day. The data suggest the potential of a mechanoactive scaffold to promote the formation of an anatomic fibrocartilage enthesis on tendon-based ACL reconstruction grafts.

  12. Irradiation of bone lining cells from bone-seeking alpha-emitters

    International Nuclear Information System (INIS)

    Kruglikov, I.; Polig, E.

    1993-01-01

    The influence of bone remodeling and the non-uniform distribution of alpha-emitters on the hit statistics is discussed. It is shown that for the first generation of bone lining cells, bone remodeling decreases the probability of no hits to the nuclei of these cells whereas the randomness of the spatial distribution of nuclide increases this probability. For the subsequent generations bone remodeling as well as spatial distribution of nuclide increase the probability of no hits. The most conservative estimations for the variance of hits and probability of no hits, which are defined by the minimums of these values, are obtained. (orig.)

  13. Vascular remodeling and mineralocorticoids.

    Science.gov (United States)

    Weber, K T; Sun, Y; Campbell, S E; Slight, S H; Ganjam, V K

    1995-01-01

    Circulating mineralocorticoid hormones are so named because of their important homeostatic properties that regulate salt and water balance via their action on epithelial cells. A broader range of functions in nonclassic target cellular sites has been proposed for these steroids and includes their contribution to wound healing following injury. A chronic, inappropriate (relative to intravascular volume and dietary sodium intake) elevation of these circulating hormones evokes a wound healing response in the absence of tissue injury--a wound healing response gone awry. The adverse remodeling of vascularized tissues seen in association with chronic mineralocorticoid excess is the focus of this review.

  14. Hydroxyapatite particles maintain peri-implant bone mantle during osseointegration in osteoporotic bone

    NARCIS (Netherlands)

    Tami, A.E.; Leitner, M.M.; Baucke, M.G.; Mueller, T.L.; Lenthe, van G.H.; Müller, R.; Ito, K.

    2009-01-01

    In osteoporotic bones, resorption exceeds formation during the remodelling phase of bone turnover. As a consequence, decreased bone volume and bone contact result in the peri-implant region. This may subsequently lead to loss of fixation. In this study we investigated whether the presence of

  15. 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.

  16. 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.

  17. A Rapid Clinical Perspective on Bone-Mineral Density

    African Journals Online (AJOL)

    Although bone remodeling occurs throughout life, different turnover .... Further, most elderly patients ... health akin to that before suffering from a hip fracture.34 Other fractures ..... calcium absorption, indirectly promoting bone mineralization.

  18. Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras.

    Science.gov (United States)

    Das, Anusuya; Segar, Claire E; Chu, Yihsuan; Wang, Tiffany W; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C; Cui, Quanjun; Botchwey, Edward A

    2015-09-01

    Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    1996-01-01

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

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

    Science.gov (United States)

    Murata, Masaru; Akazawa, Toshiyuki; Yuasa, Toshihiro; Okayama, Miki; Tazaki, Junichi; Hanawa, Takao; Arisue, Makoto; Mizoguchi, Itaru

    2012-12-01

    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®, 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 implant thread to the distant site in all horizontal lines of the map. These results indicated that the X-ray images for the intensity of c-face in HAp revealed functionally graded distribution of cortical bone quality. The micro-scale measurements of HAp structure could be a useful method for evaluating the mechanical stress distribution in human hard tissues.

  1. 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.

  2. Vasotrophic Regulation of Age-Dependent Hypoxic Cerebrovascular Remodeling

    Science.gov (United States)

    Silpanisong, Jinjutha; Pearce, William J.

    2015-01-01

    Hypoxia can induce functional and structural vascular remodeling by changing the expression of trophic factors to promote homeostasis. While most experimental approaches have been focused on functional remodeling, structural remodeling can reflect changes in the abundance and organization of vascular proteins that determine functional remodeling. Better understanding of age-dependent hypoxic macrovascular remodeling processes of the cerebral vasculature and its clinical implications require knowledge of the vasotrophic factors that influence arterial structure and function. Hypoxia can affect the expression of transcription factors, classical receptor tyrosine kinase factors, non-classical G-protein coupled factors, catecholamines, and purines. Hypoxia’s remodeling effects can be mediated by Hypoxia Inducible Factor (HIF) upregulation in most vascular beds, but alterations in the expression of growth factors can also be independent of HIF. PPARγ is another transcription factor involved in hypoxic remodeling. Expression of classical receptor tyrosine kinase ligands, including vascular endothelial growth factor, platelet derived growth factor, fibroblast growth factor and angiopoietins, can be altered by hypoxia which can act simultaneously to affect remodeling. Tyrosine kinase-independent factors, such as transforming growth factor, nitric oxide, endothelin, angiotensin II, catecholamines, and purines also participate in the remodeling process. This adaptation to hypoxic stress can fundamentally change with age, resulting in different responses between fetuses and adults. Overall, these mechanisms integrate to assure that blood flow and metabolic demand are closely matched in all vascular beds and emphasize the view that the vascular wall is a highly dynamic and heterogeneous tissue with multiple cell types undergoing regular phenotypic transformation. PMID:24063376

  3. Investigation of the histology and interfacial bonding between carbonated hydroxyapatite cement and bone

    International Nuclear Information System (INIS)

    Mao Keya; Hao Libo; Tang Peifu; Wang Zheng; Wen Ning; Du Mingkui; Wang Jifang; Wang Yan; Yang Yun; Li Jiangtao

    2009-01-01

    An ideal bone implant should facilitate the formation of a new bone layer as an osteo-integrated interface between bone and the implanted biomaterials. In the present work, the interface between carbonated hydroxyapatite (CHA) cement and bone was evaluated by interfacial bonding strength measurements and histological characterizations. CHA cement was implanted into a mongrel dog's femoral supracondylar and below the tibial plateau area, and was then tested ex vivo by, respectively, detaching and pullout experiments. Polymethylmethacrylate (PMMA) was used as a control. CHA cement could be directly injected and solidified in situ to repair bone defects. Histology results showed that CHA bonded with bone through gradual remodeling and was replaced by new bone tissue, which is an attribute for excellent biocompatibility. The interfacial bonding strength increased with implantation time. After 16 weeks implantation, the measured detaching force and the pullout force between CHA and bone were 281 ± 16 N and 512.5 ± 14.5 N, respectively. These values were several times higher compared to 5 days implantation. In contrast, the control showed a fibrous microstructure between PMMA and bone, and the detaching force and the pullout force decreased with implantation time. The results strongly suggest that CHA can form a better osteo-integrated interface compared to PMMA, and could be used as an ideal biomaterial for bone defect repair.

  4. An animal model to evaluate skin-implant-bone integration and gait with a prosthesis directly attached to the residual limb.

    Science.gov (United States)

    Farrell, Brad J; Prilutsky, Boris I; Kistenberg, Robert S; Dalton, John F; Pitkin, Mark

    2014-03-01

    Despite the number of advantages of bone-anchored prostheses, their use in patients is limited due to the lack of complete skin-implant integration. The objective of the present study was to develop an animal model that would permit both detailed investigations of gait with a bone-anchored limb prosthesis and histological analysis of the skin-implant-bone interface after physiological loading of the implant during standing and walking. Full-body mechanics of walking in two cats were recorded and analyzed before and after implantation of a percutaneous porous titanium pylon into the right tibia and attachment of a prosthesis. The rehabilitation procedures included initial limb casting, progressively increasing loading on the implant, and standing and locomotor training. Detailed histological analysis of bone and skin ingrowth into implant was performed at the end of the study. The two animals adopted the bone-anchored prosthesis for standing and locomotion, although loads on the prosthetic limb during walking decreased by 22% and 62%, respectively, 4months after implantation. The animals shifted body weight to the contralateral side and increased propulsion forces by the contralateral hindlimb. Histological analysis of the limb implants demonstrated bone and skin ingrowth. The developed animal model to study prosthetic gait and tissue integration with the implant demonstrated that porous titanium implants may permit bone and skin integration and prosthetic gait with a bone-anchored prosthesis. Future studies with this model will help optimize the implant and prosthesis properties. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. A tissue engineering solution for segmental defect regeneration in load-bearing long bones.

    Science.gov (United States)

    Reichert, Johannes C; Cipitria, Amaia; Epari, Devakara R; Saifzadeh, Siamak; Krishnakanth, Pushpanjali; Berner, Arne; Woodruff, Maria A; Schell, Hanna; Mehta, Manav; Schuetz, Michael A; Duda, Georg N; Hutmacher, Dietmar W

    2012-07-04

    The reconstruction of large defects (>10 mm) in humans usually relies on bone graft transplantation. Limiting factors include availability of graft material, comorbidity, and insufficient integration into the damaged bone. We compare the gold standard autograft with biodegradable composite scaffolds consisting of medical-grade polycaprolactone and tricalcium phosphate combined with autologous bone marrow-derived mesenchymal stem cells (MSCs) or recombinant human bone morphogenetic protein 7 (rhBMP-7). Critical-sized defects in sheep--a model closely resembling human bone formation and structure--were treated with autograft, rhBMP-7, or MSCs. Bridging was observed within 3 months for both the autograft and the rhBMP-7 treatment. After 12 months, biomechanical analysis and microcomputed tomography imaging showed significantly greater bone formation and superior strength for the biomaterial scaffolds loaded with rhBMP-7 compared to the autograft. Axial bone distribution was greater at the interfaces. With rhBMP-7, at 3 months, the radial bone distribution within the scaffolds was homogeneous. At 12 months, however, significantly more bone was found in the scaffold architecture, indicating bone remodeling. Scaffolds alone or with MSC inclusion did not induce levels of bone formation comparable to those of the autograft and rhBMP-7 groups. Applied clinically, this approach using rhBMP-7 could overcome autograft-associated limitations.

  6. Are bone turnover markers associated with volumetric bone density, size, and strength in older men and women? The AGES-Reykjavik study.

    Science.gov (United States)

    Marques, E A; Gudnason, V; Sigurdsson, G; Lang, T; Johannesdottir, F; Siggeirsdottir, K; Launer, L; Eiriksdottir, G; Harris, T B

    2016-05-01

    Association between serum bone formation and resorption markers and bone mineral, structural, and strength variables derived from quantitative computed tomography (QCT) in a population-based cohort of 1745 older adults was assessed. The association was weak for lumbar spine and femoral neck areal and volumetric bone mineral density. The aim of this study was to examine the relationship between levels of bone turnover markers (BTMs; osteocalcin (OC), C-terminal cross-linking telopeptide of type I collagen (CTX), and procollagen type 1N propeptide (P1NP)) and quantitative computed tomography (QCT)-derived bone density, geometry, and strength indices in the lumbar spine and femoral neck (FN). A total of 1745 older individuals (773 men and 972 women, aged 66-92 years) from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort were studied. QCT was performed in the lumbar spine and hip to estimate volumetric trabecular, cortical, and integral bone mineral density (BMD), areal BMD, bone geometry, and bone strength indices. Association between BTMs and QCT variables were explored using multivariable linear regression. Major findings showed that all BMD measures, FN cortical index, and compressive strength had a low negative correlation with the BTM levels in both men and women. Correlations between BTMs and bone size parameters were minimal or not significant. No associations were found between BTMs and vertebral cross-sectional area in women. BTMs alone accounted for only a relatively small percentage of the bone parameter variance (1-10 %). Serum CTX, OC, and P1NP were weakly correlated with lumbar spine and FN areal and volumetric BMD and strength measures. Most of the bone size indices were not associated with BTMs; thus, the selected bone remodeling markers do not reflect periosteal bone formation. These results confirmed the limited ability of the most sensitive established BTMs to predict bone structural integrity in older adults.

  7. Theoretical analysis of alendronate and risedronate effects on canine vertebral remodeling and microdamage

    OpenAIRE

    Wang, Xiang; Erickson, Antonia M.; Allen, Matthew R.; Burr, David B.; Martin, R. Bruce; Hazelwood, Scott J.

    2009-01-01

    Bisphosphonates suppress bone remodeling activity, increase bone volume, and significantly reduce fracture risk in individuals with osteoporosis and other metabolic bone diseases. The objectives of the current study were to develop a mathematical model that simulates control and 1 year experimental results following bisphosphonate treatment (alendronate or risedronate) in the canine fourth lumbar vertebral body, validate the model by comparing simulation predictions to 3 year experimental res...

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

    International Nuclear Information System (INIS)

    Colnot, C.; Huang, S.; Helms, J.

    2006-01-01

    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

  9. Bioceramics of apatites: an option for bone regeneration

    International Nuclear Information System (INIS)

    Arxer, Eliana Alves; Almeida Filho, Edson de; Guastaldi, Antonio Carlos

    2011-01-01

    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)

  10. Transcriptional networks and chromatin remodeling controlling adipogenesis

    DEFF Research Database (Denmark)

    Siersbæk, Rasmus; Nielsen, Ronni; Mandrup, Susanne

    2012-01-01

    Adipocyte differentiation is tightly controlled by a transcriptional cascade, which directs the extensive reprogramming of gene expression required to convert fibroblast-like precursor cells into mature lipid-laden adipocytes. Recent global analyses of transcription factor binding and chromatin...... remodeling have revealed 'snapshots' of this cascade and the chromatin landscape at specific time-points of differentiation. These studies demonstrate that multiple adipogenic transcription factors co-occupy hotspots characterized by an open chromatin structure and specific epigenetic modifications....... Such transcription factor hotspots are likely to represent key signaling nodes which integrate multiple adipogenic signals at specific chromatin sites, thereby facilitating coordinated action on gene expression....

  11. Progenitor cells in pulmonary vascular remodeling

    Science.gov (United States)

    Yeager, Michael E.; Frid, Maria G.; Stenmark, Kurt R.

    2011-01-01

    Pulmonary hypertension is characterized by cellular and structural changes in the walls of pulmonary arteries. Intimal thickening and fibrosis, medial hypertrophy and fibroproliferative changes in the adventitia are commonly observed, as is the extension of smooth muscle into the previously non-muscularized vessels. A majority of these changes are associated with the enhanced presence of α-SM-actin+ cells and inflammatory cells. Atypical abundances of functionally distinct endothelial cells, particularly in the intima (plexiform lesions), and also in the perivascular regions, are also described. At present, neither the origin(s) of these cells nor the molecular mechanisms responsible for their accumulation, in any of the three compartments of the vessel wall, have been fully elucidated. The possibility that they arise from either resident vascular progenitors or bone marrow–derived progenitor cells is now well established. Resident vascular progenitor cells have been demonstrated to exist within the vessel wall, and in response to certain stimuli, to expand and express myofibroblastic, endothelial or even hematopoietic markers. Bone marrow–derived or circulating progenitor cells have also been shown to be recruited to sites of vascular injury and to assume both endothelial and SM-like phenotypes. Here, we review the data supporting the contributory role of vascular progenitors (including endothelial progenitor cells, smooth muscle progenitor cells, pericytes, and fibrocytes) in vascular remodeling. A more complete understanding of the processes by which progenitor cells modulate pulmonary vascular remodeling will undoubtedly herald a renaissance of therapies extending beyond the control of vascular tonicity and reduction of pulmonary artery pressure. PMID:22034593

  12. 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.

  13. 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

  14. Epigenetic remodeling and modification to preserve skeletogenesis in vivo.

    Science.gov (United States)

    Godfrey, Tanner C; Wildman, Benjamin J; Javed, Amjad; Lengner, Christopher J; Hassan, Mohammad Quamarul

    2018-12-01

    Current studies offer little insight on how epigenetic remodeling of bone-specific chromatin maintains bone mass in vivo. Understanding this gap and precise mechanism is pivotal for future therapeutic innovation to prevent bone loss. Recently, we found that low bone mass is associated with decreased H3K27 acetylation (activating histone modification) of bone specific gene promoters. Here, we aim to elucidate the epigenetic mechanisms by which a miRNA cluster controls bone synthesis and homeostasis by regulating chromatin accessibility and H3K27 acetylation. In order to decipher the epigenetic axis that regulates osteogenesis, we studied a drug inducible anti-miR-23a cluster (miR-23a Cl ZIP ) knockdown mouse model. MiR-23a cluster knockdown (heterozygous) mice developed high bone mass. These mice displayed increased expression of Runx2 and Baf45a, essential factors for skeletogenesis; and decreased expression of Ezh2, a chromatin repressor indispensable for skeletogenesis. ChIP assays using miR-23a Cl knockdown calvarial cells revealed a BAF45A-EZH2 epigenetic antagonistic mechanism that maintains bone formation. Together, our findings support that the miR-23a Cl connection with tissue-specific RUNX2-BAF45A-EZH2 function is a novel molecular epigenetic axis through which a miRNA cluster orchestrates chromatin modification to elicit major effects on osteogenesis in vivo.

  15. The effect of antiresorptives on bone quality.

    Science.gov (United States)

    Recker, Robert R; Armas, Laura

    2011-08-01

    Currently, antiresorptive therapy in the treatment and prevention of osteoporosis includes bisphosphonates, estrogen replacement, selective estrogen receptor modulators (raloxifene), and denosumab (a human antibody that inactivates RANKL). The original paradigm driving the development of antiresorptive therapy was that inhibition of bone resorption would allow bone formation to continue and correct the defect. However, it is now clear increases in bone density account for little of the antifracture effect of these treatments. We examined the antifracture benefit of antiresorptives deriving from bone quality changes. We searched the archive of nearly 30,000 articles accumulated over more than 40 years in our research center library using a software program (Refman™). Approximately 250 publications were identified in locating the 69 cited here. The findings document antiresorptive agents are not primarily anabolic. All cause a modest increase in bone density due to a reduction in the bone remodeling space; however, the majority of their efficacy is due to suppression of the primary cause of osteoporosis, ie, excessive bone remodeling not driven by mechanical need. All of them improve some element(s) of bone quality. Antiresorptive therapy reduces risk of fracture by improving bone quality through halting removal of bone tissue and the resultant destruction of microarchitecture of bone and, perhaps to some extent, by improving the intrinsic material properties of bone tissue. Information presented here may help clinicians to improve selection of patients for antiresorptive therapy by avoiding them in cases clearly not due to excessive bone remodeling.

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

    OpenAIRE

    Ogawa, Takahiro; Yamada,Masahiro; Ueno,; Tsukimura,Naoki; Ikeda,; Nakagawa,; Hori,; Suzuki,

    2012-01-01

    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 integratio...

  17. 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.

  18. Time Simulation of Bone Adaptation

    DEFF Research Database (Denmark)

    Bagge, Mette

    1998-01-01

    The structural adaptation of a three-dimensional finite element model ofthe proximal femur is considered. Presuming the bone possesses the optimalstructure under the given loads, the bone material distribution is foundby minimizing the strain energy averaged over ten load cases with avolume....... The remodeling algorithm is derived directly from theoptimization recurrence formula, and in a time increment the materialdistribution changes towards the optimal structure for the present load case.The speed of remodeling is taken from clinical data.Numerical examples of respectively increasing and reducing...

  19. 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...

  20. Differential Gene Expression in the Otic Capsule and the Middle Ear-An Annotation of Bone-Related Signaling Genes

    DEFF Research Database (Denmark)

    Nielsen, Michelle C.; Martin-Bertelsen, Tomas; Friis, Morten

    2015-01-01

    Hypothesis: A number of bone-related genes may be responsible for the unique suppression of perilabyrinthine bone remodeling. Background: Bone remodeling is highly inhibited around the inner ear space most likely because of osteoprotegerin (OPG), which is a well-known potent inhibitor of osteocla...

  1. Black box integration of computer-aided diagnosis into PACS deserves a second chance: results of a usability study concerning bone age assessment.

    Science.gov (United States)

    Geldermann, Ina; Grouls, Christoph; Kuhl, Christiane; Deserno, Thomas M; Spreckelsen, Cord

    2013-08-01

    Usability aspects of different integration concepts for picture archiving and communication systems (PACS) and computer-aided diagnosis (CAD) were inquired on the example of BoneXpert, a program determining the skeletal age from a left hand's radiograph. CAD-PACS integration was assessed according to its levels: data, function, presentation, and context integration focusing on usability aspects. A user-based study design was selected. Statements of seven experienced radiologists using two alternative types of integration provided by BoneXpert were acquired and analyzed using a mixed-methods approach based on think-aloud records and a questionnaire. In both variants, the CAD module (BoneXpert) was easily integrated in the workflow, found comprehensible and fitting in the conceptual framework of the radiologists. Weak points of the software integration referred to data and context integration. Surprisingly, visualization of intermediate image processing states (presentation integration) was found less important as compared to efficient handling and fast computation. Seamlessly integrating CAD into the PACS without additional work steps or unnecessary interrupts and without visualizing intermediate images may considerably improve software performance and user acceptance with efforts in time.

  2. Can the Hydroxyapatite-Coated Skin-Penetrating Abutment for Bone Conduction Hearing Implants Integrate with the Surrounding Skin?

    Science.gov (United States)

    van Hoof, Marc; Wigren, Stina; Duimel, Hans; Savelkoul, Paul H M; Flynn, Mark; Stokroos, Robert Jan

    2015-01-01

    Percutaneous implants, such as bone conduction hearing implants, suffer from complications that include inflammation of the surrounding skin. A sealed skin-abutment interface can prevent the ingress of bacteria, which should reduce the occurrence of peri-abutment dermatitis. It was hypothesized that a hydroxyapatite (HA)-coated abutment in conjunction with soft tissue preservation surgery should enable integration with the adjacent skin. Previous research has confirmed that integration is never achieved with as-machined titanium abutments. Here, we investigate, in vivo, if skin integration is achievable in patients using a HA-coated abutment. One titanium abutment (control) and one HA-coated abutment (case) together with the surrounding skin were surgically retrieved from two patients who had a medical indication for this procedure. Histological sections of the skin were investigated using light microscopy. The abutment was qualitatively analyzed using scanning electron microscopy. The titanium abutment only had a partial and thin layer of attached amorphous biological material. The HA-coated abutment was almost fully covered by a pronounced thick layer of organized skin, composed of different interconnected structural layers. Proof-of-principle evidence that the HA-coated abutment can achieve integration with the surrounding skin was presented for the first time.

  3. 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,…

  4. Joint remodelling in inflammatory disease

    OpenAIRE

    Schett, Georg

    2007-01-01

    Bone and the immune system share multiple interactions. The skeleton harbours the bone marrow and provides the niche for development of haematopoietic cells including the immune system. The immune system provides cells as well as molecular signals, which regulate bone homeostasis. Understanding the cellular and molecular regulation of the tight interaction between bone and the immune system is crucial for understanding the changes of skeletal architecture during inflammation. Whereas a short ...

  5. Validation of Material Algorithms for Femur Remodelling Using Medical Image Data

    Directory of Open Access Journals (Sweden)

    Shitong Luo

    2017-01-01

    Full Text Available The aim of this study is the utilization of human medical CT images to quantitatively evaluate two sorts of “error-driven” material algorithms, that is, the isotropic and orthotropic algorithms, for bone remodelling. The bone remodelling simulations were implemented by a combination of the finite element (FE method and the material algorithms, in which the bone material properties and element axes are determined by both loading amplitudes and daily cycles with different weight factor. The simulation results showed that both algorithms produced realistic distribution in bone amount, when compared with the standard from CT data. Moreover, the simulated L-T ratios (the ratio of longitude modulus to transverse modulus by the orthotropic algorithm were close to the reported results. This study suggests a role for “error-driven” algorithm in bone material prediction in abnormal mechanical environment and holds promise for optimizing implant design as well as developing countermeasures against bone loss due to weightlessness. Furthermore, the quantified methods used in this study can enhance bone remodelling model by optimizing model parameters to gap the discrepancy between the simulation and real data.

  6. [Remodeling simulation of human femur under bed rest and spaceflight circumstances based on three dimensional finite element analysis].

    Science.gov (United States)

    Yang, Wenting; Wang, Dongmei; Lei, Zhoujixin; Wang, Chunhui; Chen, Shanguang

    2017-12-01

    Astronauts who are exposed to weightless environment in long-term spaceflight might encounter bone density and mass loss for the mechanical stimulus is smaller than normal value. This study built a three dimensional model of human femur to simulate the remodeling process of human femur during bed rest experiment based on finite element analysis (FEA). The remodeling parameters of this finite element model was validated after comparing experimental and numerical results. Then, the remodeling process of human femur in weightless environment was simulated, and the remodeling function of time was derived. The loading magnitude and loading cycle on human femur during weightless environment were increased to simulate the exercise against bone loss. Simulation results showed that increasing loading magnitude is more effective in diminishing bone loss than increasing loading cycles, which demonstrated that exercise of certain intensity could help resist bone loss during long-term spaceflight. At the end, this study simulated the bone recovery process after spaceflight. It was found that the bone absorption rate is larger than bone formation rate. We advise that astronauts should take exercise during spaceflight to resist bone loss.

  7. 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 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.

  8. Bone fatigue and its implications for injuries in racehorses.

    Science.gov (United States)

    Martig, S; Chen, W; Lee, P V S; Whitton, R C

    2014-07-01

    Musculoskeletal injuries are a common cause of lost training days and wastage in racehorses. Many bone injuries are a consequence of repeated high loading during fast work, resulting in chronic damage accumulation and material fatigue of bone. The highest joint loads occur in the fetlock, which is also the most common site of subchondral bone injury in racehorses. Microcracks in the subchondral bone at sites where intra-articular fractures and palmar osteochondral disease occur are similar to the fatigue damage detected experimentally after repeated loading of bone. Fatigue is a process that has undergone much study in material science in order to avoid catastrophic failure of engineering structures. The term 'fatigue life' refers to the numbers of cycles of loading that can be sustained before failure occurs. Fatigue life decreases exponentially with increasing load. This is important in horses as loads within the limb increase with increasing speed. Bone adapts to increased loading by modelling to maintain the strains within the bone at a safe level. Bone also repairs fatigued matrix through remodelling. Fatigue injuries develop when microdamage accumulates faster than remodelling can repair. Remodelling of the equine metacarpus is reduced during race training and accelerated during rest periods. The first phase of remodelling is bone resorption, which weakens the bone through increased porosity. A bone that is porous following a rest period may fail earlier than a fully adapted bone. Maximising bone adaptation is an important part of training young racehorses. However, even well-adapted bones accumulate microdamage and require ongoing remodelling. If remodelling inhibition at the extremes of training is unavoidable then the duration of exposure to high-speed work needs to be limited and appropriate rest periods instituted. Further research is warranted to elucidate the effect of fast-speed work and rest on bone damage accumulation and repair. © 2014 EVJ Ltd.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Fiona R Straehl

    Full Text Available 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.

  11. [Research advances of fluid bio-mechanics in bone].

    Science.gov (United States)

    Chen, Zebin; Huo, Bo

    2017-04-01

    It has been found for more than one century that when experiencing mechanical loading, the structure of bone will adapt to the changing mechanical environment, which is called bone remodeling. Bone remodeling is charaterized as two processes of bone formation and bone resorption. A large number of studies have confirmed that the shear stress is resulted from interstitial fluid flow within bone cavities under mechanical loading and it is the key factor of stimulating the biological responses of bone cells. This review summarizes the major research progress during the past years, including the biological response of bone cells under fluid flow, the pressure within bone cavities, the theoretical modeling, numerical simulation and experiments about fluid flow within bone, and finally analyzes and predicts the possible tendency in this field in the future.

  12. 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 ...

  13. Remodeling of the notochord during development of vertebral fusions in Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Ytteborg, Elisabeth; Torgersen, Jacob Seilø; Pedersen, Mona E; Baeverfjord, Grete; Hannesson, Kirsten O; Takle, Harald

    2010-12-01

    Histological characterization of spinal fusions in Atlantic salmon (Salmo salar) has demonstrated shape alterations of vertebral body endplates, a reduced intervertebral space, and replacement of intervertebral cells by ectopic bone. However, the significance of the notochord during the fusion process has not been addressed. We have therefore investigated structural and cellular events in the notochord during the development of vertebral fusions. In order to induce vertebral fusions, Atlantic salmon were exposed to elevated temperatures from fertilization until they attained a size of 15g. Based on results from radiography, intermediate and terminal stages of the fusion process were investigated by immunohistochemistry and real-time quantitative polymerase chain reaction. Examination of structural extracellular matrix proteins such as Perlecan, Aggrecan, Elastin, and Laminin revealed reduced activity and reorganization at early stages in the pathology. Staining for elastic fibers visualized a thinner elastic membrane surrounding the notochord of developing fusions, and immunohistochemistry for Perlecan showed that the notochordal sheath was stretched during fusion. These findings in the outer notochord correlated with the loss of Aggrecan- and Substance-P-positive signals and the further loss of vacuoles from the chordocytes in the central notochord. At more progressed stages of fusion, chordocytes condensed, and the expression of Aggrecan and Substance P reappeared. The hyperdense regions seem to be of importance for the formation of notochordal tissue into bone. Thus, the remodeling of notochord integrity by reduced elasticity, structural alterations, and cellular changes is probably involved in the development of vertebral fusions.

  14. Age-associated bone loss and intraskeletal variability in the Imperial Romans.

    Science.gov (United States)

    Cho, Helen; Stout, Sam Darrel

    2011-01-01

    An Imperial Roman sample from the Isola Sacra necropolis (100-300 A.D.) offered an opportunity to histologically examine bone loss and intraskeletal variability in an urban archaeological population. Rib and femur samples were analyzed for static indices of bone remodeling and measures of bone mass. The Imperial Romans experienced normal age-associated bone loss via increased intracortical porosity and endosteal expansion, with females exhibiting greater bone loss and bone turnover rates than in males. Life events such as menopause and lactation coupled with cultural attitudes and practices regarding gender and food may have led to increased bone loss in females. Remodeling dynamics differ between the rib and femur and the higher remodeling rates in the rib may be attributed to different effective age of the adult compacta or loading environment. This study demonstrates that combining multiple methodologies to examine bone loss is necessary to shed light on the biocultural factors that influence bone mass and bone loss.

  15. 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 (pchronic periodontitis with 2/3 alveolar bone loss after three months splinting.

  16. Three-dimensional CaP/gelatin lattice scaffolds with integrated osteoinductive surface topographies for bone tissue engineering

    International Nuclear Information System (INIS)

    Nadeem, Danish; Su, Bo; Smith, Carol-Anne; Dalby, Matthew J; Dominic Meek, R M; Lin, Sien; Li, Gang

    2015-01-01

    Surface topography is known to influence stem cells and has been widely used as physical stimuli to modulate cellular behaviour including adhesion, proliferation and differentiation on 2D surfaces. Integration of well-defined surface topography into three-dimensional (3D) scaffolds for tissue engineering would be useful to direct the cell fate for intended applications. Technical challenges are remaining as how to fabricate such 3D scaffolds with controlled surface topography from a range of biodegradable and biocompatible materials. In this paper, a novel fabrication process using computer numerically controlled machining and lamination is reported to make 3D calcium phosphate/gelatin composite scaffolds with integrated surface micropatterns that are introduced by embossing prior to machining. Geometric analysis shows that this method is versatile and can be used to make a wide range of lattices with porosities that meet the basic requirements for bone tissue engineering. Both in vitro and in vivo studies show that micropatterned composite scaffolds with surfaces comprising 40 μm pits and 50 μm grooves were optimal for improved osteogenesis. The results have demonstrated the potential of a novel fabrication process for producing cell-instructive scaffolds with designed surface topographies to induce specific tissue regeneration. (paper)

  17. ECM remodeling and its plasticity

    Science.gov (United States)

    Feng, Jingchen; Jones, Christopher A. R.; Cibula, Matthew; Mao, Xiaoming; Sander, Leonard M.; Levine, Herbert; Sun, Bo

    The mechanical interactions between cells and Extracellular Matrix (ECM) are of great importance in many cellular processes. These interactions are reciprocal, i.e. contracting cells pull and reorganize the surrounding matrix, while the remodeled matrix feeds back to regulate cell activities. Recent experiments show in collagen gels with densely distributed cells, aligned fiber bundles are formed in the direction between neighboring cells. Fibers flow into the center region between contracting cell pairs in this process, which causes the concentration of fibers in the fiber bundles to become significantly enhanced. Using an extended lattice-based model, we show that viscoelasticity plays an essential role in ECM remodeling and contributes to the enhanced concentration in fiber bundles. We further characterize ECM plasticity within our model and verify our results with rheometer experiments.

  18. Identification of trabecular excrescences, novel microanatomical structures, present in bone in osteoarthropathies

    Directory of Open Access Journals (Sweden)

    AM Taylor

    2012-04-01

    Full Text Available It is widely held that bone architecture is finely regulated in accordance with homeostatic requirements. Aberrant remodelling (hyperdensification and/or cyst formation in the immediately subchondral region has previously been described in bone underlying cartilage in arthropathies. The present study examined the trabecular architecture of samples of bone, initially in the severe osteoarthropathy of alkaptonuria, but subsequently in osteoarthritis using a combination of light microscopy, 3D scanning electron microscopy and quantitative backscattered electron scanning electron microscopy. We report an extraordinary and previously unrecognised bone phenotype in both disorders, including novel microanatomical structures. The underlying subchondral trabecular bone contained idiosyncratic architecture. Trabecular surfaces had numerous outgrowths that we have termed "trabecular excrescences", of which three distinct types were recognised. The first type arose from incomplete resorption of branching secondary trabeculae arising from the deposition of immature (woven bone in prior marrow space. These were characterised by very deeply scalloped surfaces and rugged edges. The second type had arisen in a similar way but been smoothed over by new bone deposition. The third type, which resembled coarse stucco, probably arises from resting surfaces that had been focally reactivated. These were poorly integrated with the prior trabecular wall. We propose that these distinctive microanatomical structures are indicative of abnormal osteoclast/osteoblast modelling in osteoarthropathies, possibly secondary to altered mechanical loading or other aberrant signalling. Identification of the mechanisms underlying the formation of trabecular excrescences will contribute to a better understanding of the role of aberrant bone remodelling in arthropathies and development of new therapeutic strategies.

  19. Chromatin remodeling, development and disease

    International Nuclear Information System (INIS)

    Ko, Myunggon; Sohn, Dong H.; Chung, Heekyoung; Seong, Rho H.

    2008-01-01

    Development is a stepwise process in which multi-potent progenitor cells undergo lineage commitment, differentiation, proliferation and maturation to produce mature cells with restricted developmental potentials. This process is directed by spatiotemporally distinct gene expression programs that allow cells to stringently orchestrate intricate transcriptional activation or silencing events. In eukaryotes, chromatin structure contributes to developmental progression as a blueprint for coordinated gene expression by actively participating in the regulation of gene expression. Changes in higher order chromatin structure or covalent modification of its components are considered to be critical events in dictating lineage-specific gene expression during development. Mammalian cells utilize multi-subunit nuclear complexes to alter chromatin structure. Histone-modifying complex catalyzes covalent modifications of histone tails including acetylation, methylation, phosphorylation and ubiquitination. ATP-dependent chromatin remodeling complex, which disrupts histone-DNA contacts and induces nucleosome mobilization, requires energy from ATP hydrolysis for its catalytic activity. Here, we discuss the diverse functions of ATP-dependent chromatin remodeling complexes during mammalian development. In particular, the roles of these complexes during embryonic and hematopoietic development are reviewed in depth. In addition, pathological conditions such as tumor development that are induced by mutation of several key subunits of the chromatin remodeling complex are discussed, together with possible mechanisms that underlie tumor suppression by the complex

  20. 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.

  1. Three dimensional assessment of condylar surface changes and remodeling after orthognathic surgery

    International Nuclear Information System (INIS)

    Lee, Jung Hye; Lee, Jin Woo; Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul; Shin, Jae Myung

    2016-01-01

    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

  2. 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.

  3. Surgical revascularization induces angiogenesis in orthotopic bone allograft

    NARCIS (Netherlands)

    Willems, Wouter F.; Kremer, Thomas; Friedrich, Patricia; Bishop, Allen T.

    2012-01-01

    Remodeling of structural bone allografts relies on adequate revascularization, which can theoretically be induced by surgical revascularization. We developed a new orthotopic animal model to determine the technical feasibility of axial arteriovenous bundle implantation and resultant angiogenesis. We

  4. 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

  5. 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.

  6. 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)

  7. Receptor tyrosine kinase inhibition causes simultaneous bone loss and excess bone formation within growing bone in rats

    International Nuclear Information System (INIS)

    Nurmio, Mirja; Joki, Henna; Kallio, Jenny; Maeaettae, Jorma A.; Vaeaenaenen, H. Kalervo; Toppari, Jorma; Jahnukainen, Kirsi; Laitala-Leinonen, Tiina

    2011-01-01

    During postnatal skeletal growth, adaptation to mechanical loading leads to cellular activities at the growth plate. It has recently become evident that bone forming and bone resorbing cells are affected by the receptor tyrosine kinase (RTK) inhibitor imatinib mesylate (STI571, Gleevec (registered) ). Imatinib targets PDGF, ABL-related gene, c-Abl, c-Kit and c-Fms receptors, many of which have multiple functions in the bone microenvironment. We therefore studied the effects of imatinib in growing bone. Young rats were exposed to imatinib (150 mg/kg on postnatal days 5-7, or 100 mg/kg on postnatal days 5-13), and the effects of RTK inhibition on bone physiology were studied after 8 and 70 days (3-day treatment), or after 14 days (9-day treatment). X-ray imaging, computer tomography, histomorphometry, RNA analysis and immunohistochemistry were used to evaluate bone modeling and remodeling in vivo. Imatinib treatment eliminated osteoclasts from the metaphyseal osteochondral junction at 8 and 14 days. This led to a resorption arrest at the growth plate, but also increased bone apposition by osteoblasts, thus resulting in local osteopetrosis at the osteochondral junction. The impaired bone remodelation observed on day 8 remained significant until adulthood. Within the same bone, increased osteoclast activity, leading to bone loss, was observed at distal bone trabeculae on days 8 and 14. Peripheral quantitative computer tomography (pQCT) and micro-CT analysis confirmed that, at the osteochondral junction, imatinib shifted the balance from bone resorption towards bone formation, thereby altering bone modeling. At distal trabecular bone, in turn, the balance was turned towards bone resorption, leading to bone loss. - Research highlights: → 3-Day imatinib treatment. → Causes growth plate anomalies in young rats. → Causes biomechanical changes and significant bone loss at distal trabecular bone. → Results in loss of osteoclasts at osteochondral junction.

  8. 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...

  9. Osteopontin: Relation between Adipose Tissue and Bone Homeostasis

    OpenAIRE

    De Fusco, Carolina; Messina, Antonietta; Monda, Vincenzo; Viggiano, Emanuela; Moscatelli, Fiorenzo; Valenzano, Anna; Esposito, Teresa; Sergio, Chieffi; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni

    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 se...

  10. 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

  11. Unbiased Stereologic Estimation of the Spatial Distribution of Paget’s Disease in the Human Temporal Bone

    DEFF Research Database (Denmark)

    Bloch, Sune Land; Sørensen, Mads Sølvsten

    2014-01-01

    remodeling around the inner ear space and to compare it with that of otosclerosis in a contemporary context of temporal bone dynamics. MATERIALS AND METHODS: From the temporal bone collection of Massachusetts Eye and Ear Infirmary, 15 of 29 temporal bones with Paget's disease were selected to obtain...... an independent sample. All volume distributions were obtained along the normal axis of capsular bone remodeling activity by the use of vector-based stereology. RESULTS: Pagetic bone remodeling was distributed centrifugally around the inner ear space at the individual and the general level. This pattern...

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  13. Bone dysplasia with optic atrophy, vascular malformation and seizures in a 14-year-old girl - a case report

    International Nuclear Information System (INIS)

    Kuleta-Bosak, E.; Kluczewska, E.; Gibinska, E.; Jamroz, E.; Augustyn, D.; Gluszkiewicz, E.

    2007-01-01

    The heritable skeletal dysplasias or osteochondrodysplasias are a large heterogeneous group of disorders associated with abnormal shape, growth, or integrity of bones. Osteopetrosis is a collective term for a range of sclerosing bone diseases with various degree of defective remodeling. Increased bone density is the predominant radiologic feature. The skull is often involved with basal sclerosis and the sinuses are obliterated. The most serious consequences of the osteopetroses are seen in the nervous system. Because of perturbed remodeling of the skull bones, many aspects of the brain and cranial nerve function are endangered. Cranial nerves, blood vessels and the spinal cord may be compressed by progressive occlusion of cranial foramina. Carious, misplaced teeth, dysplastic fingernails, tendency to pathologic fractures are the other clinical manifestations. The authors present a 14-year-old girl with dysmorphic features, optic atrophy, CNS vessel malformation, pathologic fractures and seizures. The girl had a wide range of clinical and radiographic symptoms of bone dysplasias together with a giant left internal carotid artery aneurysm and epilepsy. On the basis of clinical and radiological features, a disease belonging to the group of skeletal dysplasias was recognized in our patient. The configuration of the presented symptoms does not allow at the moment strict classification to hitherto determined forms of dysplasia. This leads to the necessity of extending diagnostics, especially by molecular tests, and further long-lasting observations, which perhaps would allow classification of the presented syndrome to one of the known groups, or determination of a new clinical entity. (author)

  14. Bone health in cancer patients

    DEFF Research Database (Denmark)

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

    2014-01-01

    There are three distinct areas of cancer management that make bone health in cancer patients of increasing clinical importance. First, bone metastases are common in many solid tumours, notably those arising from the breast, prostate and lung, as well as multiple myeloma, and may cause major...... morbidity including fractures, severe pain, nerve compression and hypercalcaemia. Through optimum multidisciplinary management of patients with bone metastases, including the use of bone-targeted treatments such as potent bisphosphonates or denosumab, it has been possible to transform the course of advanced...... cancer for many patients resulting in a major reduction in skeletal complications, reduced bone pain and improved quality of life. Secondly, many of the treatments we use to treat cancer patients have effects on reproductive hormones, which are critical for the maintenance of normal bone remodelling...

  15. Remodeling the Vascular Microenvironment of Glioblastoma with α-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

    2016-11-01

    Tumors escape antiangiogenic therapy by activation of proangiogenic signaling pathways. Bevacizumab is approved for the treatment of recurrent glioblastoma, but patients inevitably develop resistance to this angiogenic inhibitor. We previously investigated targeted α-particle therapy with 225 Ac-E4G10 as an antivascular approach and showed increased survival and tumor control in a high-grade transgenic orthotopic glioblastoma model. Here, we investigated changes in tumor vascular morphology and functionality caused by 225 Ac-E4G10. We investigated remodeling of the tumor microenvironment in transgenic Ntva glioblastoma mice using a therapeutic 7.4-kBq dose of 225 Ac-E4G10. Immunofluorescence and immunohistochemical analyses imaged morphologic changes in the tumor blood-brain barrier microenvironment. Multicolor flow cytometry quantified the endothelial progenitor cell population in the bone marrow. Diffusion-weighted MR imaged functional changes in the tumor vascular network. The mechanism of drug action is a combination of remodeling of the glioblastoma vascular microenvironment, relief of edema, 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 were lessened, resulting in increased perfusion and reduced diffusion. Pharmacologic uptake of dasatinib into tumor was enhanced after α-particle therapy. Targeted antivascular 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. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  16. 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

  17. Distinct characteristics of mandibular bone collagen relative to long bone collagen: relevance to clinical dentistry.

    Science.gov (United States)

    Matsuura, Takashi; Tokutomi, Kentaro; Sasaki, Michiko; Katafuchi, Michitsuna; Mizumachi, Emiri; Sato, Hironobu

    2014-01-01

    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.

  18. 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.

  19. Immunohistochemical characterization of nanocrystalline hydroxyapatite silica gel (NanoBone(r)) osteogenesis: a study on biopsies from human jaws.

    Science.gov (United States)

    Götz, Werner; Gerber, Thomas; Michel, Barbara; Lossdörfer, Stefan; Henkel, Kai-Olaf; Heinemann, Friedhelm

    2008-10-01

    Bone substitute biomaterials may be osteogenic, osteoconductive or osteoinductive. To test for these probable characteristics in a new nanoporous grafting material consisting of nanocrystalline hydroxyapatite embedded in a porous silica gel matrix (NanoBone(s)), applied in humans, we studied biopsies from 12 patients before dental implantation following various orofacial augmentation techniques with healing times of between 3.5 and 12 months. Sections from decalcified specimens were investigated using histology, histochemistry [periodic acid Schiff, alcian blue staining and tartrate-resistant acid phosphatase (TRAP)] and immunohistochemistry, with markers for osteogenesis, bone remodelling, resorption and vessel walls (alkaline phosphatase, bone morphogenetic protein-2, collagen type I, ED1, osteocalcin, osteopontin, runx2 and Von-Willebrand factor). Histologically, four specific stages of graft transformation into lamellar bone could be characterized. During early stages of healing, bone matrix proteins were absorbed by NanoBone(s) granules, forming a proteinaceous matrix, which was invaded by small vessels and cells. We assume that the deposition of these molecules promotes early osteogenesis in and around NanoBone(s) and supports the concomitant degradation probably by osteoclast-like cells. TRAP-positive osteoclast-like cells were localized directly on the granular surfaces. Runx2-immunoreactive pre-osteoblasts, which are probably involved in direct osteogenesis forming woven bone that is later transformed into lamellar bone, were attracted. Graft resorption and bone apposition around the graft granules appear concomitantly. We postulate that NanoBone(s) has osteoconductive and biomimetic properties and is integrated into the host's physiological bone turnover at a very early stage.

  20. Quantification of skeletal growth, modeling, and remodeling by in vivo micro computed tomography.

    Science.gov (United States)

    Altman, Allison R; Tseng, Wei-Ju; de Bakker, Chantal M J; Chandra, Abhishek; Lan, Shenghui; Huh, Beom Kang; Luo, Shiming; Leonard, Mary B; Qin, Ling; Liu, X Sherry

    2015-12-01

    In this study we established an image analysis scheme for the investigation of cortical and trabecular bone development during skeletal growth and tested this concept on in vivo μCT images of rats. To evaluate its efficacy, we applied the technique to young (1-month-old) and adult (3-month-old) rat tibiae with vehicle (Veh) or intermittent parathyroid hormone (PTH) treatment. By overlaying 2 sequential scans based on their distinct trabecular microarchitecture, we calculated the linear growth rate of young rats to be 0.31 mm/day at the proximal tibia. Due to rapid growth (3.7 mm in 12 days), the scanned bone region at day 12 had no overlap with the bone tissue scanned at day 0. Instead, the imaged bone region at day 12 represented newly generated bone tissue from the growth plate. The new bone of the PTH-treated rats had significantly greater trabecular bone volume fraction, number, and thickness than those of the Veh-treated rats, indicating PTH's anabolic effect on bone modeling. In contrast, the effect of PTH on adult rat trabecular bone was found to be caused by PTH's anabolic effect on bone remodeling. The cortical bone at the proximal tibia of young rats also thickened more in the PTH group (23%) than the Veh group (14%). This was primarily driven by endosteal bone formation and coalescence of trabecular bone into the cortex. This process can be visualized by aligning the local bone structural changes using image registration. As a result, the cortex after PTH treatment was 31% less porous, and had a 22% greater polar moment of inertia compared to the Veh group. Lastly, we monitored the longitudinal bone growth in adult rats by measuring the distance of bone flow away from the proximal tibial growth plate from 3 months to 19 months of age and discovered a total of 3.5mm growth in 16 months. It was demonstrated that this image analysis scheme can efficiently evaluate bone growth, bone modeling, and bone remodeling, and is ready to be translated into a

  1. Adrenocortical zonation, renewal, and remodeling

    Directory of Open Access Journals (Sweden)

    Marjut ePihlajoki

    2015-03-01

    Full Text Available The adrenal cortex is divided into concentric zones. In humans the major cortical zones are the zona glomerulosa, zona fasciculata, and zona reticularis. The adrenal cortex is a dynamic organ in which senescent cells are replaced by newly differentiated ones. This constant renewal facilitates organ remodeling in response to physiological demand for steroids. Cortical zones can reversibly expand, contract, or alter their biochemical profiles to accommodate needs. Pools of stem/progenitor cells in the adrenal capsule, subcapsular region, and juxtamedullary region can differentiate to repopulate or expand zones. Some of these pools appear to be activated only during specific developmental windows or in response to extreme physiological demand. Senescent cells can also be replenished through direct lineage conversion; for example, cells in the zona glomerulosa can transform into cells of the zona fasciculata. Adrenocortical cell differentiation, renewal, and function are regulated by a variety of endocrine/paracrine factors including adrenocorticotropin, angiotensin II, insulin-related growth hormones, luteinizing hormone, activin, and inhibin. Additionally, zonation and regeneration of the adrenal cortex are controlled by developmental signaling pathways, such as the sonic hedgehog, delta-like homologue 1, fibroblast growth factor, and WNT/β-catenin pathways. The mechanisms involved in adrenocortical remodeling are complex and redundant so as to fulfill the offsetting goals of organ homeostasis and stress adaptation.

  2. Inferior tendon graft to bone tunnel healing at the tibia compared to that at the femur after anterior cruciate ligament reconstruction

    International Nuclear Information System (INIS)

    Lui, P.P.Y.; Ho, G.; Shum, W.T.; Lee, Y.W.; Ho, P.Y.; Lo, W.N.; Lo, C.K.

    2010-01-01

    Tunnel widening after anterior cruciate ligament (ACL) reconstruction (ACLR) is commonly reported without a clear understanding of the mechanism. This study aimed to quantify the spatiotemporal change of the newly formed bone mass, bone tunnel diameter, and area along both bone tunnels using micro-computed tomography (μCT) and correlated the result with histology. ACLR was performed in 24 rabbits. At baseline and weeks 2, 6, and 12, the juxta-articular, middle, and exit segments of both tunnels were harvested for μCT and histological evaluation. μCT and histology revealed significant bone tunnel and graft-bone tunnel healing, respectively, only at week 6 after reconstruction. Despite this, the mean tunnel diameter and area remained relatively unchanged with time. The newly formed bone mass [new bone volume/total bone volume (BV/TV) ratio] and its bone mineral density (BMD) were both higher, whereas the mean tunnel diameter and area were significantly smaller at the femoral tunnel compared to those at the tibial tunnel at weeks 6 and 12 and at week 12, respectively. These were consistent with histological findings, which showed inferior graft remodeling and integration at the tibial tunnel at weeks 6 and 12. The BV/TV increased, whereas the mean tunnel diameter and area decreased toward the exit segment of both tunnels. However, whereas better histological healing occurred at the femoral exit segment, poorer graft remodeling and Sharpey's fiber formation occurred at the tibial exit segment. Poor healing was observed during the initial 6 weeks, particularly that of the tibia, after ACLR. Bone resorption was rapid during healing, resulting in unchanged tunnel diameter and area with time. (author)

  3. 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.

  4. Chromatin Remodelers: From Function to Dysfunction

    Directory of Open Access Journals (Sweden)

    Gernot Längst

    2015-06-01

    Full Text Available Chromatin remodelers are key players in the regulation of chromatin accessibility and nucleosome positioning on the eukaryotic DNA, thereby essential for all DNA dependent biological processes. Thus, it is not surprising that upon of deregulation of those molecular machines healthy cells can turn into cancerous cells. Even though the remodeling enzymes are very abundant and a multitude of different enzymes and chromatin remodeling complexes exist in the cell, the particular remodeling complex with its specific nucleosome positioning features must be at the right place at the right time in order to ensure the proper regulation of the DNA dependent processes. To achieve this, chromatin remodeling complexes harbor protein domains that specifically read chromatin targeting signals, such as histone modifications, DNA sequence/structure, non-coding RNAs, histone variants or DNA bound interacting proteins. Recent studies reveal the interaction between non-coding RNAs and chromatin remodeling complexes showing importance of RNA in remodeling enzyme targeting, scaffolding and regulation. In this review, we summarize current understanding of chromatin remodeling enzyme targeting to chromatin and their role in cancer development.

  5. Growth hormone and bone health.

    Science.gov (United States)

    Bex, Marie; Bouillon, Roger

    2003-01-01

    Growth hormone (GH) and insulin-like growth factor-I have major effects on growth plate chondrocytes and all bone cells. Untreated childhood-onset GH deficiency (GHD) markedly impairs linear growth as well as three-dimensional bone size. Adult peak bone mass is therefore about 50% that of adults with normal height. This is mainly an effect on bone volume, whereas true bone mineral density (BMD; g/cm(3)) is virtually normal, as demonstrated in a large cohort of untreated Russian adults with childhood-onset GHD. The prevalence of fractures in these untreated childhood-onset GHD adults was, however, markedly and significantly increased in comparison with normal Russian adults. This clearly indicates that bone mass and bone size matter more than true bone density. Adequate treatment with GH can largely correct bone size and in several studies also bone mass, but it usually requires more than 5 years of continuous treatment. Adult-onset GHD decreases bone turnover and results in a mild deficit, generally between -0.5 and -1.0 z-score, in bone mineral content and BMD of the lumbar spine, radius and femoral neck. Cross-sectional surveys and the KIMS data suggest an increased incidence of fractures. GH replacement therapy increases bone turnover. The three controlled studies with follow-up periods of 18 and 24 months demonstrated a modest increase in BMD of the lumbar spine and femoral neck in male adults with adult-onset GHD, whereas no significant changes in BMD were observed in women. GHD, whether childhood- or adult-onset, impairs bone mass and strength. Appropriate substitution therapy can largely correct these deficiencies if given over a prolonged period. GH therapy for other bone disorders not associated with primary GHD needs further study but may well be beneficial because of its positive effects on the bone remodelling cycle. Copyright 2003 S. Karger AG, Basel

  6. Bone tumors

    International Nuclear Information System (INIS)

    Unni, K.K.

    1988-01-01

    This book contains the proceedings on bone tumors. Topics covered include: Bone tumor imaging: Contribution of CT and MRI, staging of bone tumors, perind cell tumors of bone, and metastatic bone disease

  7. Dynamics of Lung Defense in Pneumonia: Resistance, Resilience, and Remodeling

    Science.gov (United States)

    Quinton, Lee J.; Mizgerd, Joseph P.

    2015-01-01

    Pneumonia is initiated by microbes in the lung, but physiological processes integrating responses across diverse cell types and organ systems dictate the outcome of respiratory infection. Resistance, or actions of the host to eradicate living microbes, in the lungs involves a combination of innate and adaptive immune responses triggered by air-space infection. Resilience, or the ability of the host tissues to withstand the physiologically damaging effects of microbial and immune activities, is equally complex, precisely regulated, and determinative. Both immune resistance and tissue resilience are dynamic and change throughout the lifetime, but we are only beginning to understand such remodeling and how it contributes to the incidence of severe pneumonias, which diminishes as childhood progresses and then increases again among the elderly. Here, we review the concepts of resistance, resilience, and remodeling as they apply to pneumonia, highlighting recent advances and current significant knowledge gaps. PMID:25148693

  8. [Condylar hyperplasia: qualitative and quantitative study of temporomandibular joints remodeling before and after condylectomy].

    Science.gov (United States)

    Rojare, Camille; Wojcik, Thomas; Coussens, Camille; Ferri, Joël; Pertuzon, Bruno; Raoul, Gwénaël

    2014-06-01

    This retrospective study aimed to evaluate bone remodeling of temporo-mandibular joints (TMJ) using computed tomography (CT) before and after condylectomy for condylar hyperplasia. TMJ bone remodeling was studied by comparing the pre and postoperative CT scan of ten patients. Qualitative evaluation was performed by two-dimensional analysis. Three-dimensional analysis superimpositions were done after digital condylar units isolation. Condylar volume modifications were measured and compared on both sides. Lastly, before and after surgery, we studied the radio-clinic correlations. After surgery, all the operated condyles developed a new cortical bone. We noticed also a thickening of the glenoid fossa. Surgical condylectomy leaded to a 43.5% volume reduction on the operated side and 2.14% on the controlateral side. On the controlateral side, most of abnormalities seen preoperatively disappeared after surgery. For two patients, the condylar resection took away over 80% of the initial volume. For these patients, we observed major radiologic modifications on the controlateral TMJ associated with symptoms of dysfunction. These problems did not worsen their quality of life. Both TMJ presented with bone remodelling after condylectomy. In condylar hyperplasia, condylectomy provides orthopaedic results on dysmorphia and removal of the pathological prechondroblastic zone. In the future, an earlier detection of this pathology may help the surgeon to treat in childhood. This would limit surgical excision and would avoid important dysmorphia. © EDP Sciences, SFODF, 2014.

  9. Remodeled articular surface after surgical fixation of patella fracture in a child

    Directory of Open Access Journals (Sweden)

    Moruf Babatunde Yusuf

    2017-01-01

    Full Text Available Patella fracture is uncommon in pediatric age group and their patella is better preserved in any class of patella fracture. We reported a case of a 13-year-old male with right patella fracture nonunion. He had open reduction and internal fixation using tension band wire device. Fracture union was monitored with serial radiographs and he was followed up for 60 weeks. There was articular surface step after surgical fixation of the patella fracture. At 34 weeks postoperative, there was complete remodeling of the articular surface with good knee function after removal of the tension band wire. Children have good capacity of bone remodeling after fracture. Little retropatella step in a child after patella fracture surgical fixation will remodel with healing.

  10. Obesity and carotid artery remodeling

    DEFF Research Database (Denmark)

    Kozakova, M; Palombo, C; Morizzo, C

    2015-01-01

    BACKGROUND/OBJECTIVE: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions...... and CCA LD (266 healthy subjects with wide range of body weight (24-159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese subjects...... without CV complications and 88 non-obese subjects matched for gender and age). RESULTS: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile...

  11. Investigation of a Novel PLGA/CaP Scaffold in the Healing of Tooth Extraction Sockets to Alveolar Bone Preservation in Humans.

    Science.gov (United States)

    Araujo-Pires, Ana Claudia; Mendes, Vanessa Cristina; Ferreira-Junior, Osny; Carvalho, Paulo Sérgio Perri; Guan, Limin; Davies, John Edward

    2016-06-01

    It is expected that 40% to 60% of initial alveolar bone volume will be lost up to 6 months after tooth extraction. OsteoScaf(TM) (TRT, Toronto, ON, Canada) (poly (DL-lactide-co-glycololide/calcium phosphate [PLGA/CaP] scaffold) is a novel bone substitute material and represents a promising alternative for maintaining alveolar bone integrity in this clinical scenario. Here it was hypothesized that OsteoScaf would reduce alveolar bone lost after tooth extraction in patient, acting as a clot-retention device. A total of 10 patients (32 sockets) were included in the study, of which 16 sockets were grafted with OsteoScaf and 16 were used as control (coagulum alone). Cone beam computed tomography (CBCT) was performed both immediately following extraction and also at 120 days postoperatively, at which time biopsy samples were also harvested for histological analyses. Quantitative analysis of CBCT showed less bone resorption in the OsteoScaf groups, being 10.5% to 14.4% less bone lost in the center of the socket, 15.4% in the buccal region, and 12.6% in the palatal. Qualitative histological analysis showed new bone tissue in direct apposition to the scaffold - demonstrating its osteoconductive nature. OsteoScaf diminished the expected bone lost during the postextraction remodeling of the alveolar bone ridge at 120 days postextraction. © 2015 Wiley Periodicals, Inc.

  12. Remodeling process of the streptozotocln-induced diabetic rat's resected condyle

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Jung Pyo; Kim, Won Cheol; Hwang, Eui Hwan; Lee, Sang Rae [Dept. of Oral and Maxillofacial Radiology, Oral Diagnosis and Oral Medicine, College of Dentistry, Kyung Hee University, Seoul (Korea, Republic of)

    1994-08-15

    The purpose of this study was to investigate the remodeling process of the streptozotocin-induced diabetic rat's resected condyle. The experiment was performed with male Sprague-Dawley strain rats weighing approximately 250 gm, which were rendered diabetic by an intravenous injection of streptozotocin (70 mg/kg body weight). After condylectomy, experimental rats were serially terminated on the 1st week, the 2nd week, the 3rd week, and the 4th week. The following termination, the mandible were dissected out to make specimens. Each mandibular condyle was radiographed with Hitex HA-80 (Hitex Co., Ltd. Japan). In addition to radiographic observation, the mandibular condyles, further decalcified and embedded in paraffin, were sectioned and stained with Hematoxylin and Eosin, Toluidine blue and Masson's trichrome. They were observed with a light microscope and a polarizing microscope. The results were as follows. 1. Soft X-ray radiograms revealed proliferation of bone after 1 week in both groups. Irregularly repaired bones and dense trabeculae were clearly observed in experimental group. 2. The resected condyles were repaired by intramembraneous and endochondral bone formation in both groups. 3. Bone tissue repair was initiated from the adjacent margin of resected bone, and cartilaginous tissues were observed at the top of repaired bone in both groups. 4. The number of osteoblasts of experimental group was small, compared with control group. Each osteoblast was small and flat. The thin trabeculae were irregularly formed. 5. Collagens of bone were gradually matured in both groups but the degree of maturation was lower in experimental group. 6. Fibrous tissues covered the upper parts of repaired bone were densely arranged in the both groups. Conclusively, atrophied osteoblasts, immature collagen of bone, and thin and irregular trabeculae function and caused disturbance of remodeling process of bone.

  13. 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.

  14. 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.

  15. Adipose tissue-derived mesenchymal stem cells acquire bone cell-like responsiveness to fluid shear stress on osteogenic stimulation

    NARCIS (Netherlands)

    Knippenberg, M.; Helder, M.N.; Doulabi, B.Z.; Semeins, C.M.; Wuisman, P.I.J.M.; Klein-Nulend, J.

    2005-01-01

    To engineer bone tissue, mechanosensitive cells are needed that are able to perform bone cell-specific functions, such as (re)modeling of bone tissue. In vivo, local bone mass and architecture are affected by mechanical loading, which is thought to provoke a cellular response via loading-induced

  16. Delivery of S1P receptor-targeted drugs via biodegradable polymer scaffolds enhances bone regeneration in a critical size cranial defect.

    Science.gov (United States)

    Das, Anusuya; Tanner, Shaun; Barker, Daniel A; Green, David; Botchwey, Edward A

    2014-04-01

    Biodegradable polymer scaffolds can be used to deliver soluble factors to enhance osseous remodeling in bone defects. To this end, we designed a poly(lactic-co-glycolic acid) (PLAGA) microsphere scaffold to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors. The microsphere scaffolds were created from fast degrading 50:50 PLAGA and/or from slow-degrading 85:15 PLAGA. Temporal and spatial regulation of bone remodeling depended on the use of appropriate scaffolds for drug delivery. The release profiles from the scaffolds were used to design an optimal delivery system to treat critical size cranial defects in a rodent model. The ability of local FTY720 delivery to maximize bone regeneration was evaluated with micro-computed tomography (microCT) and histology. Following 4 weeks of defect healing, FTY720 delivery from 85:15 PLAGA scaffolds resulted in a significant increase in bone volumes in the defect region compared to the controls. A 85:15 microsphere scaffolds maintain their structural integrity over a longer period of time, and cause an initial burst release of FTY720 due to surface localization of the drug. This encourages cellular in-growth and an increase in new bone formation. Copyright © 2013 Wiley Periodicals, Inc.

  17. Delivery of S1P Receptor-Targeted Drugs via Biodegradable Polymer Scaffolds Enhances Bone Regeneration in a Critical Size Cranial Defect*

    Science.gov (United States)

    Das, Anusuya; Tanner, Shaun; Barker, Daniel A.; Green, David; Botchwey, Edward A.

    2014-01-01

    Biodegradable polymer scaffolds can be used to deliver soluble factors to enhance osseous remodeling in bone defects. To this end, we designed a poly(lactic-co-glycolic acid) (PLAGA) microsphere scaffold to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors. The microsphere scaffolds were created from fast degrading 50:50 PLAGA and/or from slow-degrading 85:15 PLAGA. Temporal and spatial regulation of bone remodeling depended on the use of appropriate scaffolds for drug delivery. The release profiles from the scaffolds were used to design an optimal delivery system to treat critical size cranial defects in a rodent model. The ability of local FTY720 delivery to maximize bone regeneration was evaluated with microcomputed tomography (microCT) and histology. Following 4 weeks of defect healing, FTY720 delivery from 85:15 PLAGA scaffolds resulted in a significant increase in bone volumes in the defect region compared to the controls. 85:15 microsphere scaffolds maintain their structural integrity over a longer period of time, and cause an initial burst release of FTY720 due to surface localization of the drug. This encourages cellular in-growth and an increase in new bone formation. PMID:23640833

  18. Remodeling of the methylation landscape in breast cancer metastasis.

    Directory of Open Access Journals (Sweden)

    Marsha Reyngold

    Full Text Available The development of breast cancer metastasis is accompanied by dynamic transcriptome changes and dramatic alterations in nuclear and chromatin structure. The basis of these changes is incompletely understood. The DNA methylome of primary breast cancers contribute to transcriptomic heterogeneity and different metastatic behavior. Therefore we sought to characterize methylome remodeling during regional metastasis. We profiled the DNA methylome and transcriptome of 44 matched primary breast tumors and regional metastases. Striking subtype-specific patterns of metastasis-associated methylome remodeling were observed, which reflected the molecular heterogeneity of breast cancers. These divergent changes occurred primarily in CpG island (CGI-poor areas. Regions of methylome reorganization shared by the subtypes were also observed, and we were able to identify a metastasis-specific methylation signature that was present across the breast cancer subclasses. These alterations also occurred outside of CGIs and promoters, including sequences flanking CGIs and intergenic sequences. Integrated analysis of methylation and gene expression identified genes whose expression correlated with metastasis-specific methylation. Together, these findings significantly enhance our understanding of the epigenetic reorganization that occurs during regional breast cancer metastasis across the major breast cancer subtypes and reveal the nature of methylome remodeling during this process.

  19. Acción fisiopatológica integrada de las hormonas sobre el tejido óseo: Physiopathological integrated action of hormones on the bone tissue

    Directory of Open Access Journals (Sweden)

    Julio César Sánchez Cruz

    2006-08-01

    Full Text Available La estatura definitiva que puede lograr un individuo, así como la adecuada salud e integración de su tejido óseo, dependen en gran medida de su constante interacción con las hormonas, desde la etapa embrionaria hasta los últimos momentos de la vida. Teniendo en cuenta que en los libros de texto la relación entre las hormonas con el hueso solo se describe de forma separada y sin integralidad entre lo fisiológico y lo patológico, se realiza una amplia revisión bibliográfica mediante la unificación de criterios y puntos de vista de diferentes autores, con el objetivo de lograr una comprensión más exacta de las funciones que realizan las hormonas sobre el tejido óseo y tener una visión más integral y razonada de la etiopatogenia de afecciones tales como la osteoporosis, las bajas y altas tallas (de causa endocrina y la craneosinostosis, entre otras. Se obtuvo como resultado un documento que explica, de forma más amena e integral, las acciones fisiopatológicas de las hormonas sobre el tejido óseo de un organismo vivo.The definitive height an individual can reach, as well as the adequate health and integration of his bone tissue depends in a great extent on his constant interaction with hormones from the embrionary stage to the last moments of his life. Taking into consideration that the relation between the hormones and the bone is only described in the textbooks in a separate way and with no integrality between the physiological and the pathological aspect, a wide bibliographic review is made by unifying criteria and points of view of different authors aimed at attaining a more accurate understanding of the functions of the hormones on the bone tissue, and at having a more comprehensive and reasoned vision of the etiopathogenesis of affections such as osteoporosis, short and tall stature (of endocrine cause and craniosinostosis, among others. As a result, it was obtained a document that explained in a clearer and more integral way

  20. On the Mechanistic Origins of Toughness in Bone

    Science.gov (United States)

    2010-01-01

    can fail to function properly and can lead to a rapid breakdown of the tissue (4). Other collagen gene–related diseases include some forms of dwarfism ...and the remodeling properties of bone and, as such, help in the search for new cures and treatment options for a variety of bone diseases. 46 Launey

  1. Recent progress in the differentiation of bone marrow derived ...

    African Journals Online (AJOL)

    ONOS

    2010-08-09

    Aug 9, 2010 ... Bone marrow mesenchymal stem cells (BMMSCs) are one of the cells found in bone marrow stromal. A large number of ..... BMMSCs and myocardial cells using biomimetic electrical ... effect ventricular remodeling after infarction. Meyern et al. ... to small sample sizes and different experimental con- ditions.

  2. Bone regeneration potential of sub-microfibrous membranes with ...

    African Journals Online (AJOL)

    Conclusion: The results indicate that biodegradable PCL sub-microfibrous membrane produced by electrospinning process seems to have excellent biocompatibility, and may be used as a scaffold for bone tissue engineering. Keywords: Biocompatibility, Hard tissue, Biomaterial availability, Bone remodeling, Polylactic acid, ...

  3. Osteopontin: Relation between Adipose Tissue and Bone Homeostasis

    Directory of Open Access Journals (Sweden)

    Carolina De Fusco

    2017-01-01

    Full Text Available 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 most overexpressed genes in the adipose tissue of the obese contributing to osteoporosis, this mini review will highlight recent insights about relation between adipose tissue and bone homeostasis.

  4. Osteopontin: Relation between Adipose Tissue and Bone Homeostasis.

    Science.gov (United States)

    De Fusco, Carolina; Messina, Antonietta; Monda, Vincenzo; Viggiano, Emanuela; Moscatelli, Fiorenzo; Valenzano, Anna; Esposito, Teresa; Sergio, Chieffi; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni

    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 most overexpressed genes in the adipose tissue of the obese contributing to osteoporosis, this mini review will highlight recent insights about relation between adipose tissue and bone homeostasis.

  5. Hypoxia-Induced Mitogenic Factor (HIMF/FIZZ1/RELM?) Recruits Bone Marrow-Derived Cells to the Murine Pulmonary Vasculature

    OpenAIRE

    Angelini, Daniel J.; Su, Qingning; Kolosova, Irina A.; Fan, Chunling; Skinner, John T.; Yamaji-Kegan, Kazuyo; Collector, Michael; Sharkis, Saul J.; Johns, Roger A.

    2010-01-01

    Background Pulmonary hypertension (PH) is a disease of multiple etiologies with several common pathological features, including inflammation and pulmonary vascular remodeling. Recent evidence has suggested a potential role for the recruitment of bone marrow-derived (BMD) progenitor cells to this remodeling process. We recently demonstrated that hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELM?) is chemotactic to murine bone marrow cells in vitro and involved in pulmonary vascular remodeling ...

  6. Bone Tumor Environment as a Potential Therapeutic Target in Ewing Sarcoma

    OpenAIRE

    Redini, Fran?oise; Heymann, Dominique

    2015-01-01

    Ewing sarcoma is the second most common pediatric bone tumor, with three cases per million worldwide. In clinical terms, Ewing sarcoma is an aggressive, rapidly fatal malignancy that mainly develops not only in osseous sites (85%) but also in extra-skeletal soft tissue. It spreads naturally to the lungs, bones, and bone marrow with poor prognosis in the two latter cases. Bone lesions from primary or secondary (metastases) tumors are characterized by extensive bone remodeling, more often due t...

  7. 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.

  8. Quantitating the effect of prosthesis design on femoral remodeling using high-resolution region-free densitometric analysis (DXA-RFA)

    DEFF Research Database (Denmark)

    Farzi, Mohsen; Morris, Richard M; Penny, Jeannette

    2017-01-01

    Dual energy X-ray absorptiometry (DXA) is the reference standard method used to study bone mineral density (BMD) after total hip arthroplasty (THA). However, the subtle, spatially complex changes in bone mass due to strain-adaptive bone remodeling relevant to different prosthesis designs are not ......Dual energy X-ray absorptiometry (DXA) is the reference standard method used to study bone mineral density (BMD) after total hip arthroplasty (THA). However, the subtle, spatially complex changes in bone mass due to strain-adaptive bone remodeling relevant to different prosthesis designs...... using scans acquired during two previous randomized clinical trials (2004 to 2009); one comparing three cemented prosthesis design geometries, and the other comparing a hip resurfacing versus a conventional cementless prosthesis. DXA RFA resolved subtle differences in magnitude and area of bone...... remodeling between prosthesis designs not previously identified in conventional DXA analyses. A mean bone loss of 10.3%, 12.1%, and 11.1% occurred for the three cemented prostheses within a bone area fraction of 14.8%, 14.4%, and 6.2%, mostly within the lesser trochanter (p 

  9. Dynamics of the ethanolamine glycerophospholipid remodeling network.

    Directory of Open Access Journals (Sweden)

    Lu Zhang

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

  10. Diabetes Mellitus Induces Bone Marrow Microangiopathy

    NARCIS (Netherlands)

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

    2010-01-01

    Objective-The impact of diabetes on the bone marrow (BM) microenvironment was not adequately explored. We investigated whether diabetes induces microvascular remodeling with negative consequence for BM homeostasis. Methods and Results-We found profound structural alterations in BM from mice with

  11. Toward mechanical systems biology in bone.

    Science.gov (United States)

    Trüssel, Andreas; Müller, Ralph; Webster, Duncan

    2012-11-01

    Cyclic mechanical loading is perhaps the most important physiological factor regulating bone mass and shape in a way which balances optimal strength with minimal weight. This bone adaptation process spans multiple length and time scales. Forces resulting from physiological exercise at the organ scale are sensed at the cellular scale by osteocytes, which reside inside the bone matrix. Via biochemical pathways, osteocytes orchestrate the local remodeling action of osteoblasts (bone formation) and osteoclasts (bone resorption). Together these local adaptive remodeling activities sum up to strengthen bone globally at the organ scale. To resolve the underlying mechanisms it is required to identify and quantify both cause and effect across the different scales. Progress has been made at the different scales experimentally. Computational models of bone adaptation have been developed to piece together various experimental observations at the different scales into coherent and plausible mechanisms. However additional quantitative experimental validation is still required to build upon the insights which have already been achieved. In this review we discuss emerging as well as state of the art experimental and computational techniques and how they might be used in a mechanical systems biology approach to further our understanding of the mechanisms governing load induced bone adaptation, i.e., ways are outlined in which experimental and computational approaches could be coupled, in a quantitative manner to create more reliable multiscale models of bone.

  12. Deletion of Adseverin in Osteoclasts Affects Cell Structure But Not Bone Metabolism

    NARCIS (Netherlands)

    Cao, Yixuan; Wang, Yongqiang; Sprangers, Sara; Picavet, Daisy I.; Glogauer, Michael; McCulloch, Christopher A.; Everts, Vincent

    2017-01-01

    Adseverin is an actin-severing/capping protein that may contribute to osteoclast differentiation in vitro but its role in bone remodeling of healthy animals is not defined. We analyzed bone and osteoclast structure in adseverin conditional null mice at alveolar and long bone sites. In wild-type and

  13. Adaptive bone formation in acellular vertebrae of sea bass (Dicentrarchus labrax L.)

    NARCIS (Netherlands)

    Kranenbarg, S.; Cleynenbreugel, van T.; Schipper, H.; Leeuwen, van J.L.

    2005-01-01

    Mammalian bone is an active tissue in which osteoblasts and osteoclasts balance bone mass. This process of adaptive modelling and remodelling is probably regulated by strain-sensing osteocytes. Bone of advanced teleosts is acellular yet, despite the lack of osteocytes, it is capable of an adaptive

  14. 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

  15. Distortion of frontal bones results from cell apoptosis by the mechanical force from the up-migrating eye during metamorphosis in Paralichthys olivaceus.

    Science.gov (United States)

    Sun, Mingyan; Wei, Fen; Li, Hui; Xu, Juan; Chen, Xinye; Gong, Xiaoling; Tian, Yongsheng; Chen, Songlin; Bao, Baolong

    2015-05-01

    Craniofacial remodeling during flatfish metamorphosis, including eye migration, is perhaps the most striking example of asymmetric postembryonic development in the vertebrate world. The asymmetry of the cranium mainly results from distortion of the frontal bones, which depends on eye migration during metamorphosis. However, it is unclear how the up-migrating eye causes distortion of the frontal bones. In this study, we first show that distortion of the frontal bones during metamorphosis in Paralichthys olivaceus is the result of cell apoptosis, rather than cell autophagy or cell proliferation. Secondly, we report that cell apoptosis in the frontal bones is induced by the mechanical force transferred from the up-migrating eye. The mechanical force from the up-migrating eye signals through FAK to downstream molecules that are integrated into the BMP-2 signal pathway. Finally, it is shown that cell apoptosis in the frontal bones is activated by the intrinsic mitochondrial pathway; the extrinsic death receptor is not involved in this process. Moreover, cell apoptosis in frontal bones is not induced directly by thyroid hormones, which are thought to mediate metamorphosis in flatfishes and directly mediate cell apoptosis during amphibian metamorphosis. These findings help identify the major signaling route used during regulation of frontal bone distortion during metamorphosis in flatfish, and indicate that the asymmetry of the cranium, or at least the distortion of frontal bones, is the result of rather than the reason underlying eye migration. Copyright © 2015. Published by Elsevier Ireland Ltd.

  16. 3D- Printed Poly(ε-caprolactone) Scaffold Integrated with Cell-laden Chitosan Hydrogels for Bone Tissue Engineering.

    Science.gov (United States)

    Dong, Liang; Wang, Shao-Jie; Zhao, Xin-Rong; Zhu, Yu-Fang; Yu, Jia-Kuo

    2017-10-17

    Synthetic polymeric scaffolds are commonly used in bone tissue engineering (BTE) due to their biocompatibility and adequate mechanical properties. However, their hydrophobicity and the lack of specific cell recognition sites confined their practical application. In this study, to improve the cell seeding efficiency and osteoinductivity, an injectable thermo-sensitive chitosan hydrogel (CSG) was incorporated into a 3D-printed poly(ε-caprolactone) (PCL) scaffold to form a hybrid scaffold. To demonstrate the feasibility of this hybrid system for BTE application, rabbit bone marrow mesenchymal stem cells (BMMSCs) and bone morphogenetic protein-2 (BMP-2) were encapsulated in CSG. Pure PCL scaffolds were used as controls. Cell proliferation and viability were investigated. Osteogenic gene expressions of BMMSCs in various scaffolds were determined with reverse transcription polymerase chain reaction (RT-PCR). Growth factor releasing profile and mechanical tests were performed. CCK-8 assay confirmed greater cell retention and proliferation in chitosan and hybrid groups. Confocal microscopy showed even distribution of cells in the hybrid system. After 2-week osteogenic culture in vitro, BMMSCs in hybrid and chitosan scaffolds showed stronger osteogenesis and bone-matrix formation. To conclude, chitosan/PCL hybrid scaffolds are a favorable platform for BTE due to its capacity to carry cells and drugs, and excellent mechanical strength.

  17. Bone tissue engineering: the role of interstitial fluid flow

    Science.gov (United States)

    Hillsley, M. V.; Frangos, J. A.

    1994-01-01

    It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.

  18. Repair of microdamage in osteonal cortical bone adjacent to bone screw.

    Directory of Open Access Journals (Sweden)

    Lei Wang

    Full Text Available Up to date, little is known about the repair mode of microdamage in osteonal cortical bone resulting from bone screw implantation. In this study, self-tapping titanium cortical bone screws were inserted into the tibial diaphyses of 24 adult male rabbits. The animals were sacrificed at 1 day, 2 weeks, 1 month and 2 months after surgery. Histomorphometric measurement and confocal microscopy were performed on basic fuchsin stained bone sections to examine the morphological characteristics of microdamage, bone resorption activity and spatial relationship between microdamage and bone resorption. Diffuse and linear cracks were coexisted in peri-screw bone. Intracortical bone resorption was significantly increased 2 weeks after screw installation and reach to the maximum at 1 month. There was no significant difference in bone resorption between 1-month and 2-months groups. Microdamage was significantly decreased within 1 month after surgery. Bone resorption was predisposed to occur in the region of <100 µm from the bone-screw interface, where had extensive diffuse damage mixed with linear cracks. Different patterns of resorption cavities appeared in peri-screw bone. These data suggest that 1 the complex microdamage composed of diffuse damage and linear cracks is a strong stimulator for initiating targeted bone remodeling; 2 bone resorption activities taking place on the surfaces of differently oriented Haversian and Volkmann canals work in a team for the repair of extensive microdamage; 3 targeted bone remodeling is a short-term reaction to microdamage and thereby it may not be able to remove all microdamage resulting from bone screw insertion.

  19. ATP-dependent chromatin remodeling in the DNA-damage response

    Directory of Open Access Journals (Sweden)

    Lans Hannes

    2012-01-01

    Full Text Available Abstract The integrity of DNA is continuously challenged by metabolism-derived and environmental genotoxic agents that cause a variety of DNA lesions, including base alterations and breaks. DNA damage interferes with vital processes such as transcription and replication, and if not repaired properly, can ultimately lead to premature aging and cancer. Multiple DNA pathways signaling for DNA repair and DNA damage collectively safeguard the integrity of DNA. Chromatin plays a pivotal role in regulating DNA-associated processes, and is itself subject to regulation by the DNA-damage response. Chromatin influences access to DNA, and often serves as a docking or signaling site for repair and signaling proteins. Its structure can be adapted by post-translational histone modifications and nucleosome remodeling, catalyzed by the activity of ATP-dependent chromatin-remodeling complexes. In recent years, accumulating evidence has suggested that ATP-dependent chromatin-remodeling complexes play important, although poorly characterized, roles in facilitating the effectiveness of the DNA-damage response. In this review, we summarize the current knowledge on the involvement of ATP-dependent chromatin remodeling in three major DNA repair pathways: nucleotide excision repair, homologous recombination, and non-homologous end-joining. This shows that a surprisingly large number of different remodeling complexes display pleiotropic functions during different stages of the DNA-damage response. Moreover, several complexes seem to have multiple functions, and are implicated in various mechanistically distinct repair pathways.

  20. Characterisation of Bone Beneficial Components from Australian Wallaby Bone

    Science.gov (United States)

    Lao, Weiguo; Jin, Xingliang; Tan, Yi; Xiao, Linda; Padula, Matthew P.; Bishop, David P.; Reedy, Brian; Ong, Madeleine; Kamal, Mohammad A.; Qu, Xianqin

    2016-01-01

    Background: Osteoporosis is a condition in which the bones become brittle, increasing the risk of fractures. Complementary medicines have traditionally used animal bones for managing bone disorders, such as osteoporosis. This study aimed to discover new natural products for these types of conditions by determining mineral and protein content of bone extracts derived from the Australian wallaby. Methods: Inductively coupled plasma-mass spectrometry and Fourier transform infrared spectroscopic analysis were used for mineral tests, proteome analysis was using LC/MS/MS and the effects of wallaby bone extracts (WBE)s on calcium deposition and alkaline phosphatase activity were evaluated in osteogenic cells derived from adipose tissue-derived stem cells (ADSCs). Results: Concentrations of calcium and phosphorus were 26.21% and 14.72% in WBE respectively. Additionally, minerals found were wide in variety and high in concentration, while heavy metal concentrations of aluminium, iron, zinc and other elements were at safe levels for human consumption. Proteome analysis showed that extracts contained high amounts of bone remodelling proteins, such as osteomodulin, osteopontin and osteoglycin. Furthermore, in vitro evaluation of WBEs showed increased deposition of calcium in osteoblasts with enhanced alkaline phosphatase activity in differentiated adipose-derived stem cells. Conclusion: Our results demonstrate that wallaby bone extracts possess proteins and minerals beneficial for bone metabolism. WBEs may therefore be used for developing natural products for conditions such as osteoporosis and further investigation to understand biomolecular mechanism by which WBEs prevent osteoporosis is warranted. PMID:28930133

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

    International Nuclear Information System (INIS)

    Herlin, Maria; Finnilä, Mikko A.J.; Zioupos, Peter; Aula, Antti; Risteli, Juha; Miettinen, Hanna M.; Jämsä, Timo; Tuukkanen, Juha; Korkalainen, Merja; Håkansson, Helen; Viluksela, Matti

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Herlin, Maria, E-mail: maria.herlin@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Finnilä, Mikko A.J., E-mail: mikko.finnila@oulu.fi [Department of Medical Technology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Zioupos, Peter, E-mail: p.zioupos@cranfield.ac.uk [Biomechanics Laboratories, Department of Engineering and Applied Science, Cranfield University, Shrivenham SN6 8LA (United Kingdom); Aula, Antti, E-mail: antti.aula@gmail.com [Department of Medical Physics, Imaging Centre, Tampere University Hospital, Tampere (Finland); Department of Biomedical Engineering, Tampere University of Technology, Tampere (Finland); Risteli, Juha, E-mail: juha.risteli@ppshp.fi [Department of Clinical Chemistry, Oulu University Hospital, Oulu (Finland); Miettinen, Hanna M., E-mail: hanna.miettinen@crl.com [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Jämsä, Timo, E-mail: timo.jamsa@oulu.fi [Department of Medical Technology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Department of Diagnostic Radiology, Oulu University Hospital, Oulu (Finland); Tuukkanen, Juha, E-mail: juha.tuukkanen@oulu.fi [Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu (Finland); Korkalainen, Merja, E-mail: merja.korkalainen@thl.fi [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Håkansson, Helen, E-mail: Helen.Hakansson@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Viluksela, Matti, E-mail: matti.viluksela@thl.fi [Department of Environmental Health, National Institute for Health and Welfare, Kuopio (Finland); Department of Environmental Science, University of Eastern Finland, Kuopio (Finland)

    2013-11-15

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

  3. Temporal mechanically-induced signaling events in bone and dorsal root ganglion neurons after in vivo bone loading.

    Directory of Open Access Journals (Sweden)

    Jason A Bleedorn

    Full Text Available Mechanical signals play an integral role in the regulation of bone mass and functional adaptation to bone loading. The osteocyte has long been considered the principle mechanosensory cell type in bone, although recent evidence suggests the sensory nervous system may play a role in mechanosensing. The specific signaling pathways responsible for functional adaptation of the skeleton through modeling and remodeling are not clearly defined. In vitro studies suggest involvement of intracellular signaling through mitogen-activated protein kinase (MAPK, phosphatidylinositol 3-kinase (PI3K/protein kinase B (Akt, and mammalian target of rapamycin (mTOR. However, anabolic signaling responses to bone loading using a whole animal in vivo model have not been studied in detail. Therefore, we examined mechanically-induced signaling events at five time points from 0 to 24 hours after loading using the rat in vivo ulna end-loading model. Western blot analysis of bone for MAPK's, PI3K/Akt, and mTOR signaling, and quantitative reverse transcription polymerase chain reaction (qRT-PCR to estimate gene expression of calcitonin gene-related protein alpha (CGRP-α, brain-derived neurotrophic factor (BDNF, nerve growth factor (NGF, c-jun, and c-fos in dorsal root ganglion (DRG of the brachial intumescence were performed. There was a significant increase in signaling through MAPK's including extracellular signal-related kinase (ERK and c-Jun N-terminal kinase (JNK in loaded limbs at 15 minutes after mechanical loading. Ulna loading did not significantly influence expression of the genes of interest in DRG neurons. Bone signaling and DRG gene expression from the loaded and contralateral limbs was correlated (SR>0.40, P<0.05. However, bone signaling did not correlate with expression of the genes of interest in DRG neurons. These results suggest that signaling through the MAPK pathway may be involved in load-induced bone formation in vivo. Further characterization of the

  4. The Chromatin Remodeler BPTF Activates a Stemness Gene-Expression Program Essential for the Maintenance of Adult Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Bowen Xu

    2018-03-01

    Full Text Available Summary: Self-renewal and differentiation of adult stem cells are tightly regulated partly through configuration of chromatin structure by chromatin remodelers. Using knockout mice, we here demonstrate that bromodomain PHD finger transcription factor (BPTF, a component of the nucleosome remodeling factor (NURF chromatin-remodeling complex, is essential for maintaining the population size of hematopoietic stem/progenitor cells (HSPCs, including long-term hematopoietic stem cells (HSCs. Bptf-deficient HSCs are defective in reconstituted hematopoiesis, and hematopoietic-specific knockout of Bptf caused profound defects including bone marrow failure and anemia. Genome-wide transcriptome profiling revealed that BPTF loss caused downregulation of HSC-specific gene-expression programs, which contain several master transcription factors (Meis1, Pbx1, Mn1, and Lmo2 required for HSC maintenance and self-renewal. Furthermore, we show that BPTF potentiates the chromatin accessibility of key HSC “stemness” genes. These results demonstrate an essential requirement of the chromatin remodeler BPTF and NURF for activation of “stemness” gene-expression programs and proper function of adult HSCs. : Wang and colleagues show that a chromatin remodeler, BPTF, sustains appropriate functions of hematopoietic stem/progenitor cells (HSPCs. BPTF loss causes bone marrow failure and anemia. The authors further define a BPTF-dependent gene-expression program in HSPCs, which contains key HSC stemness factors. These results demonstrate an essential requirement of the BPTF-associated chromatin remodelers for HSC functionality and adult hematopoiesis. Keywords: Bptf, hematopoietic stem cells, chromatin remodeler, Meis1, Pbx1, Mn1, DNA accessibility, NURF, AP1 complex

  5. Association of Apolipoprotein B and Adiponectin Receptor 1 Genes with Carcass, Bone Integrity and Performance Traits in a Paternal Broiler Line.

    Directory of Open Access Journals (Sweden)

    Valdecy Aparecida Rocha da Cruz

    Full Text Available Apolipoprotein B (APOB and Adiponectin Receptor 1 (ADIPOR1 are related to the regulation of feed intake, fat metabolism and protein deposition and are candidate genes for genomic studies in birds. In this study, associations of two single nucleotide polymorphisms (SNPs g.102A>T (APOB and g.729C>T (ADIPOR1 with carcass, bone integrity and performance traits in broilers were investigated. Genotyping was performed on a paternal line of 1,454 broilers. The SNP detection was carried out by PCR-RFLP technique using the restriction enzymes HhaI for the SNP g.729C>T and MslI for the SNP g.102A>T. The association analyses of the two SNPs with 85 traits were performed using the restricted maximum likelihood (REML and Generalized Quasi-Likelihood Score (GQLS methods. For REML the model included the random additive genetic effect of animal and fixed effects of sex, hatch and SNP genotypes. In the GQLS method, a logistic regression was used to associate the genotypes with phenotypes adjusted for fixed effects of sex and hatch. The SNP g.729C>T in the ADIPOR1 gene was associated with thickness of the femur and breast skin yield. Thus, the ADIPOR1 gene seems implicated in the metabolism and/or fat deposition and bone integrity in broilers.

  6. Cranio-facial remodeling in domestic dogs is associated with changes in larynx position.

    Science.gov (United States)

    Plotsky, Kyle; Rendall, Drew; Chase, Kevin; Riede, Tobias

    2016-06-01

    The hyo-laryngeal complex is a multi-segmented structure integrating the oral and pharyngeal cavities and thus a variety of critical functions related to airway control, feeding, and vocal communication. Currently, we lack a complete understanding of how the hyoid complex, and the functions it mediates, can also be affected by changes in surrounding cranio-facial dimensions. Here, we explore these relationships in a breed of domestic dog, the Portuguese Water Dog, which is characterized by strong cranio-facial variation. We used radiographic images of the upper body and head of 55 adult males and 51 adult females to obtain detailed measures of cranio-facial variation and hyoid anatomy. Principal components analysis revealed multiple orthogonal dimensions of cranio-facial variation, some of which were associated with significant differences in larynx position: the larynx occupied a more descended position in individuals with shorter, broader faces than in those with longer, narrower faces. We then tested the possibility that caudal displacement of the larynx in brachycephalic individuals might reflect a degree of tongue crowding resulting from facial shortening and reduction of oral and pharyngeal spaces. A cadaver sample was used to obtain detailed measurements of constituent bones of the hyoid skeleton and of the tongue body, and their relationships to cranio-facial size and shape and overall body size supported the tongue-crowding hypothesis. Considering the presence of descended larynges in numerous mammalian taxa, our findings establish an important precedent for the possibility that laryngeal descent can be initiated, and even sustained, in part in response to remodeling of the face and cranium for selective pressures unrelated to vocal production. These integrated changes could also have been involved in hominin evolution, where the different laryngeal positions in modern humans compared with nonhuman primates have been traditionally linked to the evolution

  7. The biodegradation of hydroxyapatite bone graft substitutes in vivo.

    Science.gov (United States)

    Rumpel, E; Wolf, E; Kauschke, E; Bienengräber, V; Bayerlein, T; Gedrange, T; Proff, P

    2006-02-01

    Hydroxyapatite (HA) ceramics are widely used for bone reconstruction. They are osteoconductive and serve as structural scaffolds for the deposition of new bone. Generally, scaffold materials should be degradable as they affect the mechanical properties of the reconstructed bone negatively. Degradation by osteoclasts during the bone remodelling process is desirable but often does not take place. In the current study we analysed by light microscopy the degradation of two granular HA implants in critically sized defects in the mandibula of Goettingen mini-pigs five weeks after implantation. Bio-Oss consists of sintered bovine bone and NanoBone is a synthetic HA produced in a sol-gel process in the presence of SiO2. We found that both biomaterials were degraded by osteoclasts with ruffled borders and acid phosphatase activity. The osteoclasts created resorption lacunae and resorptive trails and contained mineral particles. Frequently, resorption surfaces were in direct contact with bone formative surfaces on one granule. Granules, especially of NanoBone, were also covered by osteoclasts if located in vascularised connective tissue distant from bone tissue. However, this usually occurred without the creation of resorption lacunae. The former defect margins consisted of newly formed bone often without remnants of bone substitutes. Our results show that the degradation of both biomaterials corresponds to the natural bone degradation processes and suggest the possibility of complete resorption during bone remodelling.

  8. Long bone histology and growth patterns in ankylosaurs: implications for life history and evolution.

    Directory of Open Access Journals (Sweden)

    Martina Stein

    Full Text Available The ankylosaurs are one of the major dinosaur groups and are characterized by unique body armor. Previous studies on other dinosaur taxa have revealed growth patterns, life history and evolutionary mechanisms based on their long bone histology. However, to date nothing is known about long bone histology in the Ankylosauria. This study is the first description of ankylosaurian long bone histology based on several limb elements, which were sampled from different individuals from the Ankylosauridae and Nodosauridae. The histology is compared to that of other dinosaur groups, including other Thyreophora and Sauropodomorpha. Ankylosaur long bone histology is characterized by a fibrolamellar bone architecture. The bone matrix type in ankylosaurs is closest to that of Stegosaurus. A distinctive mixture of woven and parallel-fibered bone together with overall poor vascularization indicates slow growth rates compared to other dinosaurian taxa. Another peculiar characteristic of ankylosaur bone histology is the extensive remodeling in derived North American taxa. In contrast to other taxa, ankylosaurs substitute large amounts of their primary tissue early in ontogeny. This anomaly may be linked to the late ossification of the ankylosaurian body armor. Metabolically driven remodeling processes must have liberated calcium to ossify the protective osteodermal structures in juveniles to subadult stages, which led to further remodeling due to increased mechanical loading. Abundant structural fibers observed in the primary bone and even in remodeled bone may have improved the mechanical properties of the Haversian bone.

  9. 3D- Printed Poly(ε-caprolactone) Scaffold Integrated with Cell-laden Chitosan Hydrogels for Bone Tissue Engineering

    OpenAIRE

    Dong, Liang; Wang, Shao-Jie; Zhao, Xin-Rong; Zhu, Yu-Fang; Yu, Jia-Kuo

    2017-01-01

    Synthetic polymeric scaffolds are commonly used in bone tissue engineering (BTE) due to their biocompatibility and adequate mechanical properties. However, their hydrophobicity and the lack of specific cell recognition sites confined their practical application. In this study, to improve the cell seeding efficiency and osteoinductivity, an injectable thermo-sensitive chitosan hydrogel (CSG) was incorporated into a 3D-printed poly(ε-caprolactone) (PCL) scaffold to form a hybrid scaffold. To de...

  10. Bone Marrow?Derived Mesenchymal Stem Cells Enhance Bacterial Clearance and Preserve Bioprosthetic Integrity in a Model of Mesh Infection

    OpenAIRE

    Criman, Erik T.; Kurata, Wendy E.; Matsumoto, Karen W.; Aubin, Harry T.; Campbell, Carmen E.; Pierce, Lisa M.

    2016-01-01

    Background: The reported incidence of mesh infection in contaminated operative fields is as high as 30% regardless of the material used. Recently, mesenchymal stem cells (MSCs) have been shown to possess favorable immunomodulatory properties and improve tissue incorporation when seeded onto bioprosthetics. The aim of this study was to evaluate whether seeding noncrosslinked bovine pericardium (Veritas Collagen Matrix) with allogeneic bone marrow?derived MSCs improves infection resistance in v...

  11. The Latest Twists in Chromatin Remodeling.

    Science.gov (United States)

    Blossey, Ralf; Schiessel, Helmut

    2018-01-05

    In its most restrictive interpretation, the notion of chromatin remodeling refers to the action of chromatin-remodeling enzymes on nucleosomes with the aim of displacing and removing them from the chromatin fiber (the effective polymer formed by a DNA molecule and proteins). This local modification of the fiber structure can have consequences for the initiation and repression of the transcription process, and when the remodeling process spreads along the fiber, it also results in long-range effects essential for fiber condensation. There are three regulatory levels of relevance that can be distinguished for this process: the intrinsic sequence preference of the histone octamer, which rules the positioning of the nucleosome along the DNA, notably in relation to the genetic information coded in DNA; the recognition or selection of nucleosomal substrates by remodeling complexes; and, finally, the motor action on the nucleosome exerted by the chromatin remodeler. Recent work has been able to provide crucial insights at each of these three levels that add new twists to this exciting and unfinished story, which we highlight in this perspective. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  12. Estimating the whole bone-marrow asset in humans by a computational approach to integrated PET/CT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Sambuceti, Gianmario [University of Genoa, Nuclear Medicine, Department of Internal Medicine, Genova (Italy); CNR Institute of Bioimages and Molecular Physiology, Genova (Italy); Advanced Biotechnology Center, Genova (Italy); Brignone, Massimo [University of Genoa, Nuclear Medicine, Department of Internal Medicine, Genova (Italy); University of Genoa, Department of Mathematics, Genoa (Italy); Marini, Cecilia [CNR Institute of Bioimages and Molecular Physiology, Genova (Italy); Massollo, Michela; Fiz, Francesco; Morbelli, Silvia; Buschiazzo, Ambra; Piva, Roberta [University of Genoa, Nuclear Medicine, Department of Internal Medicine, Genova (Italy); Campi, Cristina [University of Helsinki, Department of Computer Science, Helsinki (Finland); Massone, Anna Maria [CNR-SPIN, Genova (Italy); Piana, Michele [University of Genoa, Department of Mathematics, Genoa (Italy); CNR-SPIN, Genova (Italy); Frassoni, Francesco [Istituto Giannina Gaslini, Genoa (Italy); Advanced Biotechnology Center, Genova (Italy)

    2012-08-15

    Despite their relevance in clinical medicine, the extension and activity of the bone marrow (BM) cannot be directly evaluated in vivo. We propose a new method to estimate these variables by combining structural and functional maps provided by CT and PET. BM extension and glucose uptake were estimated in 102 patients undergoing whole-body PET/CT because of a history of nonmetastatic melanoma. Image analysis assumed that the BM is surrounded by compact bone. An iterative optimization scheme was applied to each CT slice to identify the external border of the bone. To identify compact bone, the algorithm measured the average Hounsfield coefficient within a two-pixel ring located just inside the bone contour. All intraosseous pixels with an attenuation coefficient lower than this cut-off were flagged as 1, while the remaining pixels were set at 0. Binary masks created from all CT slices were thus applied to the PET data to determine the metabolic activity of the intraosseous volume (IBV). Estimated whole-body IBV was 1,632 {+-} 587 cm{sup 3} and was higher in men than in women (2,004 {+-} 498 cm{sup 3} vs. 1,203 {+-} 354 cm{sup 3}, P < 0.001). Overall, it was strictly correlated with ideal body weight (r = 0.81, P = 0.001) but only loosely with measured body weight (r = 0.43, P = 0.01). The average FDG standardized uptake value (SUV) in the thoracic and lumbar vertebrae was 2.01 {+-} 0.36, Accordingly, intraosseous voxels with SUV {>=}1.11 (mean spine SUV - 2.5 x SD) were considered as active ''red'' BM and those with SUV <1.11 as ''yellow'' BM. Estimated red BM volume was 541 {+-} 195 ml, with a higher prevalence in the axial than in the appendicular skeleton (87 {+-} 8 % vs. 10 {+-} 8 %, P < 0.001). Again, red BM volume was higher in men than in women (7.8 {+-} 2.2 vs. 6.7 {+-} 2.1 ml/kg body weight, P < 0.05), but in women it occupied a greater fraction of the IBV (32 {+-} 7 % vs. 36 {+-} 10 %, P < 0.05). Patient age modestly

  13. Molecular nanomechanics of nascent bone: fibrillar toughening by mineralization

    Science.gov (United States)

    Buehler, Markus J.

    2007-07-01

    Mineralized collagen fibrils are highly conserved nanostructural building blocks of bone. By a combination of molecular dynamics simulation and theoretical analysis it is shown that the characteristic nanostructure of mineralized collagen fibrils is vital for its high strength and its ability to sustain large deformation, as is relevant to the physiological role of bone, creating a strong and tough material. An analysis of the molecular mechanisms of protein and mineral phases under large deformation of mineralized collagen fibrils reveals a fibrillar toughening mechanism that leads to a manifold increase of energy dissipation compared to fibrils without mineral phase. This fibrillar toughening mechanism increases the resistance to fracture by forming large local yield regions around crack-like defects, a mechanism that protects the integrity of the entire structure by allowing for localized failure. As a consequence, mineralized collagen fibrils are able to tolerate microcracks of the order of several hundred micrometres in size without causing any macroscopic failure of the tissue, which may be essential to enable bone remodelling. The analysis proves that adding nanoscopic small platelets to collagen fibrils increases their Young's modulus and yield strength as well as their fracture strength. We find that mineralized collagen fibrils have a Young's modulus of 6.23 GPa (versus 4.59 GPa for the collagen fibril), yield at a tensile strain of 6.7% (versus 5% for the collagen fibril) and feature a fracture stress of 0.6 GPa (versus 0.3 GPa for the collagen fibril).

  14. Molecular nanomechanics of nascent bone: fibrillar toughening by mineralization

    International Nuclear Information System (INIS)

    Buehler, Markus J

    2007-01-01

    Mineralized collagen fibrils are highly conserved nanostructural building blocks of bone. By a combination of molecular dynamics simulation and theoretical analysis it is shown that the characteristic nanostructure of mineralized collagen fibrils is vital for its high strength and its ability to sustain large deformation, as is relevant to the physiological role of bone, creating a strong and tough material. An analysis of the molecular mechanisms of protein and mineral phases under large deformation of mineralized collagen fibrils reveals a fibrillar toughening mechanism that leads to a manifold increase of energy dissipation compared to fibrils without mineral phase. This fibrillar toughening mechanism increases the resistance to fracture by forming large local yield regions around crack-like defects, a mechanism that protects the integrity of the entire structure by allowing for localized failure. As a consequence, mineralized collagen fibrils are able to tolerate microcracks of the order of several hundred micrometres in size without causing any macroscopic failure of the tissue, which may be essential to enable bone remodelling. The analysis proves that adding nanoscopic small platelets to collagen fibrils increases their Young's modulus and yield strength as well as their fracture strength. We find that mineralized collagen fibrils have a Young's modulus of 6.23 GPa (versus 4.59 GPa for the collagen fibril), yield at a tensile strain of 6.7% (versus 5% for the collagen fibril) and feature a fracture stress of 0.6 GPa (versus 0.3 GPa for the collagen fibril)

  15. Proteomic Analysis of Gingival Tissue and Alveolar Bone during Alveolar Bone Healing*

    OpenAIRE

    Yang, Hee-Young; Kwon, Joseph; Kook, Min-Suk; Kang, Seong Soo; Kim, Se Eun; Sohn, Sungoh; Jung, Seunggon; Kwon, Sang-Oh; Kim, Hyung-Seok; Lee, Jae Hyuk; Lee, Tae-Hoon

    2013-01-01

    Bone tissue regeneration is orchestrated by the surrounding supporting tissues and involves the build-up of osteogenic cells, which orchestrate remodeling/healing through the expression of numerous mediators and signaling molecules. Periodontal regeneration models have proven useful for studying the interaction and communication between alveolar bone and supporting soft tissue. We applied a quantitative proteomic approach to analyze and compare proteins with altered expression in gingival sof...

  16. Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation.

    Science.gov (United States)

    Huang, Cynthia; Das, Anusuya; Barker, Daniel; Tholpady, Sunil; Wang, Tiffany; Cui, Quanjun; Ogle, Roy; Botchwey, Edward

    2012-03-01

    Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5 μg) after 5 days. Following 2 weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9 mm(3), respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL®) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls.

  17. Review of vascularised bone tissue-engineering strategies with a focus on co-culture systems.

    Science.gov (United States)

    Liu, Yuchun; Chan, Jerry K Y; Teoh, Swee-Hin

    2015-02-01

    Poor angiogenesis within tissue-engineered grafts has been identified as a main challenge limiting the clinical introduction of bone tissue-engineering (BTE) approaches for the repair of large bone defects. Thick BTE grafts often exhibit poor cellular viability particularly at the core, leading to graft failure and lack of integration with host tissues. Various BTE approaches have been explored for improving vascularisation in tissue-engineered constructs and are briefly discussed in this review. Recent investigations relating to co-culture systems of endothelial and osteoblast-like cells have shown evidence of BTE efficacy in increasing vascularization in thick constructs. This review provides an overview of key concepts related to bone formation and then focuses on the current state of engineered vascularized co-culture systems using bone repair as a model. It will also address key questions regarding the generation of clinically relevant vascularized bone constructs as well as potential directions and considerations for research with the objective of pursuing engineered co-culture systems in other disciplines of vascularized regenerative medicine. The final objective is to generate serious and functional long-lasting vessels for sustainable angiogenesis that will enable enhanced cellular survival within thick voluminous bone grafts, thereby aiding in bone formation and remodelling in the long term. However, more evidence about the quality of blood vessels formed and its associated functional improvement in bone formation as well as a mechanistic understanding of their interactions are necessary for designing better therapeutic strategies for translation to clinical settings. Copyright © 2012 John Wiley & Sons, Ltd.

  18. The Role of Extracellular Vesicles in Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Michela Rossi

    2018-04-01

    Full Text Available Multiple types of cancer have the specific ability to home to the bone microenvironment and cause metastatic lesions. Despite being the focus of intense investigation, the molecular and cellular mechanisms that regulate the metastasis of disseminated tumor cells still remain largely unknown. Bone metastases severely impact quality of life since they are associated with pain, fractures, and bone marrow aplasia. In this review, we will summarize the recent discoveries on the role of extracellular vesicles (EV in the regulation of bone remodeling activity and bone metastasis occurrence. Indeed, it was shown that extracellular vesicles, including exosomes and microvesicles, released from tumor cells can modify the bone microenvironment, allowing the formation of osteolytic, osteosclerotic, and mixed mestastases. In turn, bone-derived EV can stimulate the proliferation of tumor cells. The inhibition of EV-mediated crosstalk between cancer and bone cells could represent a new therapeutic target for bone metastasis.

  19. Biomechanical Remodeling of the Diabetic Gastrointestinal Tract

    DEFF Research Database (Denmark)

    Zhao, Jingbo; Liao, Donghua; Yang, Jian

    2010-01-01

    several years, several studies demonstrated that experimental diabetes induces GI morphological and biomechanical remodeling. Following the development of diabetes, the GI wall becomes thicker and the stiffness of the GI wall increases in a time-dependent manner. It is well known that mechanosensitive...... the biomechanical environment of the mechanosensitive nerve endings, therefore, the structure as well as the tension, stress and strain distribution in the GI wall is important for the sensory and motor function. Biomechanical remodeling of diabetic GI tract including alterations of residual strain and increase...

  20. Does methamphetamine affect bone metabolism?

    International Nuclear Information System (INIS)

    Tomita, Masafumi; Katsuyama, Hironobu; Watanabe, Yoko; Okuyama, Toshiko; Fushimi, Shigeko; Ishikawa, Takaki; Nata, Masayuki; Miyamoto, Osamu

    2014-01-01

    There is a close relationship between the central nervous system activity and bone metabolism. Therefore, methamphetamine (METH), which stimulates the central nervous system, is expected to affect bone turnover. The aim of this study was to investigate the role of METH in bone metabolism. Mice were divided into 3 groups, the control group receiving saline injections, and the 5 and 10 mg/kg METH groups (n = 6 in each group). All groups received an injection of saline or METH every other day for 8 weeks. Bone mineral density (BMD) was assessed by X-ray computed tomography. We examined biochemical markers and histomorphometric changes in the second cancellous bone of the left femoral distal end. The animals that were administered 5 mg/kg METH showed an increased locomotor activity, whereas those receiving 10 mg/kg displayed an abnormal and stereotyped behavior. Serum calcium and phosphorus concentrations were normal compared to the controls, whereas the serum protein concentration was lower in the METH groups. BMD was unchanged in all groups. Bone formation markers such as alkaline phosphatase and osteocalcin significantly increased in the 5 mg/kg METH group, but not in the 10 mg/kg METH group. In contrast, bone resorption markers such as C-terminal telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b did not change in any of the METH groups. Histomorphometric analyses were consistent with the biochemical markers data. A significant increase in osteoblasts, especially in type III osteoblasts, was observed in the 5 mg/kg METH group, whereas other parameters of bone resorption and mineralization remained unchanged. These results indicate that bone remodeling in this group was unbalanced. In contrast, in the 10 mg/kg METH group, some parameters of bone formation were significantly or slightly decreased, suggesting a low turnover metabolism. Taken together, our results suggest that METH had distinct dose-dependent effects on bone turnover and that

  1. Complete resolution and remodeling of chronic recurrent multifocal osteomyelitis on MRI and radiographs

    Energy Technology Data Exchange (ETDEWEB)

    Berkowitz, Y.J.; Greenwood, S.J.; Cassar-Pullicino, V.N. [Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Department of Diagnostic Imaging, Oswestry, Shropshire (United Kingdom); Cribb, G. [Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Department of Orthopaedic Oncology, Oswestry, Shropshire (United Kingdom); Davies, K. [Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Department of Medicine, Oswestry, Shropshire (United Kingdom)

    2018-04-15

    Chronic recurrent multifocal osteomyelitis (CRMO) is a rare condition thought to be under-diagnosed, with a true prevalence of more than the 1 in 10,000 estimated. It is a condition that is classically described as polyostotic with a relapsing and remitting course, preferentially affecting the metaphyses of tubular bones in the pediatric population. Lesions have characteristic appearances of cortical hyperostosis and mixed lytic/sclerotic medullary appearances radiographically, with active osteitis and periostitis best seen with fluid-sensitive sequences on magnetic resonance imaging (MRI). There are reports of lesions resolving on follow-up radiographs and MRI scans, but no supporting images. In particular, although the marrow appearances and degree of osteitis have been shown to improve on MRI, complete resolution and remodeling back to normal has never been demonstrated. We present a case of a lesion that has completely healed and remodeled back to normal appearances on both radiographs and MRI, and consider this the standard for the often loosely used terms ''normalization'' and ''resolution''. We discuss the implications of this for our understanding of the natural history of CRMO, and how this adds weight to the condition being significantly under-diagnosed. It provides a ''gold standard'' to be aimed for when assessing treatments for CRMO, and the optimal outcomes that are possible. It also provides further insight into the potential of pediatric bone to recover and remodel when affected by inflammatory conditions. (orig.)

  2. Bone Adaptation as an Evolutionary Process

    DEFF Research Database (Denmark)

    Bagge, Mette

    1998-01-01

    . The memory of past loadings is included in themodel to account for the delay in the bone response from the loadchanges. The remodeling rate equation is derived from the structuraloptimization task of maximizing the stiffness in each time step. Additional informationscan be extracted from the optimization...... process; the remodelingequilibrium parameter where no apposition or resorption takes place is defined asthe element optimality conditions and the optimal design is used as aninitial design for the onset ofthe remodeling simulation. Some examples of boneadaptation resulting from load changes is given....

  3. Pulmonary venous remodeling in COPD-pulmonary hypertension and idiopathic pulmonary arterial hypertension

    DEFF Research Database (Denmark)

    Andersen, Kasper Hasseriis; Andersen, Claus Bøgelund; Gustafsson, Finn

    2017-01-01

    Pulmonary vascular arterial remodeling is an integral and well-understood component of pulmonary hypertension (PH). In contrast, morphological alterations of pulmonary veins in PH are scarcely described. Explanted lungs (n = 101) from transplant recipients with advanced chronic obstructive...... pulmonary disease (COPD) and idiopathic pulmonary arterial hypertension (IPAH) were analyzed for venous vascular involvement according to a pre-specified, semi-quantitative grading scheme, which categorizes the intensity of venous remodeling in three groups of incremental severity: venous hypertensive (VH......) grade 0 = characterized by an absence of venous vascular remodeling; VH grade 1 = defined by a dominance of either arterialization or intimal fibrosis; and VH grade 2 = a substantial composite of arterialization and intimal fibrosis. Patients were grouped according to clinical and hemodynamic...

  4. Scaffold microstructure effects on functional and mechanical performance: Integration of theoretical and experimental approaches for bone tissue engineering applications.

    Science.gov (United States)

    Cavo, Marta; Scaglione, Silvia

    2016-11-01

    The really nontrivial goal of tissue engineering is combining all scaffold micro-architectural features, affecting both fluid-dynamical and mechanical performance, to obtain a fully functional implant. In this work we identified an optimal geometrical pattern for bone tissue engineering applications, best balancing several graft needs which correspond to competing design goals. In particular, we investigated the occurred changes in graft behavior by varying pore size (300μm, 600μm, 900μm), interpore distance (equal to pore size or 300μm fixed) and pores interconnection (absent, 45°-oriented, 90°-oriented). Mathematical considerations and Computational Fluid Dynamics (CFD) tools, here combined in a complete theoretical model, were carried out to this aim. Poly-lactic acid (PLA) based samples were realized by 3D printing, basing on the modeled architectures. A collagen (COL) coating was also realized on grafts surface and the interaction between PLA and COL, besides the protein contribution to graft bioactivity, was evaluated. Scaffolds were extensively characterized; human articular cells were used to test their biocompatibility and to evaluate the theoretical model predictions. Grafts fulfilled both the chemical and physical requirements. Finally, a good agreement was found between the theoretical model predictions and the experimental data, making these prototypes good candidates for bone graft replacements. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  6. Bone Diseases

    Science.gov (United States)

    Your bones help you move, give you shape and support your body. They are living tissues that rebuild constantly ... childhood and your teens, your body adds new bone faster than it removes old bone. After about ...

  7. Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum.

    LENUS (Irish Health Repository)

    Gobius, Ilan

    2016-01-01

    The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of callosal axons is dependent upon the prior remodeling and degradation of the intervening interhemispheric fissure. This remodeling event is initiated by astroglia on either side of the interhemispheric fissure, which intercalate with one another and degrade the intervening leptomeninges. Callosal axons then preferentially extend over these specialized astroglial cells to cross the midline. A key regulatory step in interhemispheric remodeling is the differentiation of these astroglia from radial glia, which is initiated by Fgf8 signaling to downstream Nfi transcription factors. Crucially, our findings from human neuroimaging studies reveal that developmental defects in interhemispheric remodeling are likely to be a primary etiology underlying human callosal agenesis.

  8. Markers of Airway Remodeling in Bronchopulmonary Diseases

    Directory of Open Access Journals (Sweden)

    O.Ye. Chernyshova

    2014-10-01

    Full Text Available The article presents information about markers of airway remodeling in bronchopulmonary diseases. There is described the influence of matrix metalloproteinases, tissue inhibitor of matrix metalloproteinase, transforming growth factor, collagen autoantibodies III type, endothelin-1 on the processes of morphological airway reconstruction as smooth muscle hypertrophy, enhanced neovascularization, epithelial cell hyperplasia, collagen deposition, compaction of the basal membrane, observed in bronchial asthma.

  9. Link between vitamin D and airway remodeling

    Directory of Open Access Journals (Sweden)

    Berraies A

    2014-04-01

    Full Text Available Anissa Berraies, Kamel Hamzaoui, Agnes HamzaouiPediatric Respiratory Diseases Department, Abderrahmen Mami Hospital, Ariana, and Research Unit 12SP15 Tunis El Manar University, Tunis, TunisiaAbstract: In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma.Keywords: vitamin D, asthma, airway remodeling, airway smooth muscle, supplementation

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

    Directory of Open Access Journals (Sweden)

    Baoping Zhang

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

  11. Increased autophagy in ephrinB2 deficient osteocytes is associated with hypermineralized, brittle bones

    OpenAIRE

    Crimeen-Irwin, Blessing; Sims, Natalie; Martin, T; Oakhill, Jonathan; Smyth, Gordon; Tobin, Mark; Petibois, Cyril; Bambery, Keith; Ikegame, Mika; Hu, Yifang; Forwood, Mark; Nguyen, Huynh; Ansari, Niloufar; Dite, Toby; Vrahnas, Christina

    2018-01-01

    Mineralized bone forms when collagen-containing osteoid accrues hydroxyapatite crystals. This process has two phases: a rapid initiation (primary mineralization), followed by slower accrual of mineral (secondary mineralization) that continues until that portion of bone is renewed by remodelling. Within the bone matrix is an interconnected network of cells termed osteocytes. These cells are derived from bone-forming osteoblasts. Osteoblast differentiation requires expression of ephrinB2, and w...

  12. A cellular automata model of bone formation.

    Science.gov (United States)

    Van Scoy, Gabrielle K; George, Estee L; Opoku Asantewaa, Flora; Kerns, Lucy; Saunders, Marnie M; Prieto-Langarica, Alicia

    2017-04-01

    Bone remodeling is an elegantly orchestrated process by which osteocytes, osteoblasts and osteoclasts function as a syncytium to maintain or modify bone. On the microscopic level, bone consists of cells that create, destroy and monitor the bone matrix. These cells interact in a coordinated manner to maintain a tightly regulated homeostasis. It is this regulation that is responsible for the observed increase in bone gain in the dominant arm of a tennis player and the observed increase in bone loss associated with spaceflight and osteoporosis. The manner in which these cells interact to bring about a change in bone quality and quantity has yet to be fully elucidated. But efforts to understand the multicellular complexity can ultimately lead to eradication of metabolic bone diseases such as osteoporosis and improved implant longevity. Experimentally validated mathematical models that simulate functional activity and offer eventual predictive capabilities offer tremendous potential in understanding multicellular bone remodeling. Here we undertake the initial challenge to develop a mathematical model of bone formation validated with in vitro data obtained from osteoblastic bone cells induced to mineralize and quantified at 26 days of culture. A cellular automata model was constructed to simulate the in vitro characterization. Permutation tests were performed to compare the distribution of the mineralization in the cultures and the distribution of the mineralization in the mathematical models. The results of the permutation test show the distribution of mineralization from the characterization and mathematical model come from the same probability distribution, therefore validating the cellular automata model. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. A quantification strategy for missing bone mass in case of osteolytic bone lesions

    International Nuclear Information System (INIS)

    Fränzle, Andrea; Giske, Kristina; Bretschi, Maren; Bäuerle, Tobias; Hillengass, Jens; Bendl, Rolf

    2013-01-01

    Purpose: Most of the patients who died of breast cancer have developed bone metastases. To understand the pathogenesis of bone metastases and to analyze treatment response of different bone remodeling therapies, preclinical animal models are examined. In breast cancer, bone metastases are often bone destructive. To assess treatment response of bone remodeling therapies, the volumes of these lesions have to be determined during the therapy process. The manual delineation of missing structures, especially if large parts are missing, is very time-consuming and not reproducible. Reproducibility is highly important to have comparable results during the therapy process. Therefore, a computerized approach is needed. Also for the preclinical research, a reproducible measurement of the lesions is essential. Here, the authors present an automated segmentation method for the measurement of missing bone mass in a preclinical rat model with bone metastases in the hind leg bones based on 3D CT scans. Methods: The affected bone structure is compared to a healthy model. Since in this preclinical rat trial the metastasis only occurs on the right hind legs, which is assured by using vessel clips, the authors use the left body side as a healthy model. The left femur is segmented with a statistical shape model which is initialised using the automatically segmented medullary cavity. The left tibia and fibula are segmented using volume growing starting at the tibia medullary cavity and stopping at the femur boundary. Masked images of both segmentations are mirrored along the median plane and transferred manually to the position of the affected bone by rigid registration. Affected bone and healthy model are compared based on their gray values. If the gray value of a voxel indicates bone mass in the healthy model and no bone in the affected bone, this voxel is considered to be osteolytic. Results: The lesion segmentations complete the missing bone structures in a reasonable way. The mean

  14. Effect of cisplatin on bone transport osteogenesis in dogs.

    Science.gov (United States)

    Ehrhart, Nicole; Eurell, Jo Ann C; Tommasini, Matteo; Constable, Peter D; Johnson, Ann L; Feretti, Antonio

    2002-05-01

    To document effects of cisplatin on regenerate bone formation during the distraction and consolidation phases of bone transport osteogenesis. 10 skeletally mature hounds. Bone transport osteogenesis was performed to reconstruct a 3-cm defect in the radius of each dog. Five dogs were randomly selected to receive cisplatin (70 mg/m2, IV, q 21 d for 4 cycles), and 5 were administered saline (0.9% NaCl) solution. Bone mineral density was measured by use of dual-energy x-ray absorptiometry (DEXA) on days 24, 55, and 90 after surgery. Dogs were euthanatized 90 days after surgery. Histomorphometry was performed on nondecalcified sections of regenerate bone. Bone mineral density and histomorphometric indices of newly formed bone were compared between groups. Densitometric differences in regenerate bone mineral density were not detected between groups at any time period. Cisplatin-treated dogs had decreased mineralized bone volume, decreased percentage of woven bone volume, decreased percentage of osteoblast-covered bone, increased porosity, and increased percentage of osteoblast-covered surfaces, compared with values for control dogs. Lamellar bone volume and osteoid volume did not differ significantly between groups. Regenerate bone will form and remodel during administration of cisplatin. Results of histomorphometric analysis suggest that bone formation and resorption may be uncoupled in cisplatin-treated regenerate bone as a result of increased osteoclast activity or delayed secondary bone formation during remodeling. These histomorphometric differences were modest in magnitude and did not result in clinically observable complications or decreased bone mineral density as measured by use of DEXA.

  15. An adaptation model for trabecular bone at different mechanical levels

    Directory of Open Access Journals (Sweden)

    Lv Linwei

    2010-07-01

    Full Text Available Abstract Background Bone has the ability to adapt to mechanical usage or other biophysical stimuli in terms of its mass and architecture, indicating that a certain mechanism exists for monitoring mechanical usage and controlling the bone's adaptation behaviors. There are four zones describing different bone adaptation behaviors: the disuse, adaptation, overload, and pathologic overload zones. In different zones, the changes of bone mass, as calculated by the difference between the amount of bone formed and what is resorbed, should be different. Methods An adaptation model for the trabecular bone at different mechanical levels was presented in this study based on a number of experimental observations and numerical algorithms in the literature. In the proposed model, the amount of bone formation and the probability of bone remodeling activation were proposed in accordance with the mechanical levels. Seven numerical simulation cases under different mechanical conditions were analyzed as examples by incorporating the adaptation model presented in this paper with the finite element method. Results The proposed bone adaptation model describes the well-known bone adaptation behaviors in different zones. The bone mass and architecture of the bone tissue within the adaptation zone almost remained unchanged. Although the probability of osteoclastic activation is enhanced in the overload zone, the potential of osteoblasts to form bones compensate for the osteoclastic resorption, eventually strengthening the bones. In the disuse zone, the disuse-mode remodeling removes bone tissue in disuse zone. Conclusions The study seeks to provide better understanding of the relationships between bone morphology and the mechanical, as well as biological environments. Furthermore, this paper provides a computational model and methodology for the numerical simulation of changes of bone structural morphology that are caused by changes of mechanical and biological

  16. Comparison of recombinant human bone morphogenetic protein-2-infused absorbable collagen sponge, recombinant human bone morphogenetic protein-2-coated tricalcium phosphate, and platelet-rich fibrin-mixed tricalcium phosphate for sinus augmentation in rabbits

    Directory of Open Access Journals (Sweden)

    Chul-Hun Kim

    2017-09-01

    Conclusion: Our histological evaluation demonstrates that Type I ACS can be used as a carrier of rhBMP-2, and rhBMP-2+ACS showed rapid bone formation, remodeling, and calcification at Week 2 in rabbit.

  17. Controlled release pharmaceutical composition useful for the treatment of diseases and conditions affecting metabolism and/or structural integrity of cartilage and/or bone in male comprises strontium salt

    DEFF Research Database (Denmark)

    2004-01-01

    , hyperparathyroidism, periarticular erosions in rheumatoid arthritis, osteodystrophy, myositis ossificans, Bechterew's disease, osteolytic lesions produced by bone metastasis, bone pain due to bone metastasis, bone loss due to sex steroid hormone deficiency, bone abnormalities due to steroid hormone treatment, bone...

  18. Textural versus electrostatic exclusion-enrichment effects in the effective chemical transport within the cortical bone: a numerical investigation.

    Science.gov (United States)

    Lemaire, T; Kaiser, J; Naili, S; Sansalone, V

    2013-11-01

    Interstitial fluid within bone tissue is known to govern the remodelling signals' expression. Bone fluid flow is generated by skeleton deformation during the daily activities. Due to the presence of charged surfaces in the bone porous matrix, the electrochemical phenomena occurring in the vicinity of mechanosensitive bone cells, the osteocytes, are key elements in the cellular communication. In this study, a multiscale model of interstitial fluid transport within bone tissues is proposed. Based on an asymptotic homogenization method, our modelling takes into account the physicochemical properties of bone tissue. Thanks to this multiphysical approach, the transport of nutrients and waste between the blood vessels and the bone cells can be quantified to better understand the mechanotransduction of bone remodelling. In particular, it is shown that the electrochemical tortuosity may have stronger implications in the mass transport within the bone than the purely morphological one. Copyright © 2013 John Wiley & Sons, Ltd.

  19. Short-range intercellular calcium signaling in bone

    DEFF Research Database (Denmark)

    Jørgensen, Niklas R

    2005-01-01

    The regulation of bone turnover is a complex and finely tuned process. Many factors regulate bone remodeling, including hormones, growth factors, cytokines etc. However, little is known about the signals coupling bone formation to bone resorption, and how mechanical forces are translated...... into biological effects in bone. Intercellular calcium waves are increases in intracellular calcium concentration in single cells, subsequently propagating to adjacent cells, and can be a possible mechanism for the coupling of bone formation to bone resorption. The aim of the present studies was to investigate...... whether bone cells are capable of communicating via intercellular calcium signals, and determine by which mechanisms the cells propagate the signals. First, we found that osteoblastic cells can propagate intercellular calcium transients upon mechanical stimulation, and that there are two principally...

  20. The Multifactorial role of Peripheral Nervous System in Bone Growth

    Science.gov (United States)

    Gkiatas, Ioannis; Papadopoulos, Dimitrios; Pakos, Emilios E.; Kostas-Agnantis, Ioannis; Gelalis, Ioannis; Vekris, Marios; Korompilias, Anastasios

    2017-09-01

    Bone alters its metabolic and anabolic activities in response to the variety of systemic and local factors such as hormones and growth factors. Classical observations describing abundance of the nerve fibers in bone also predict a paradigm that the nervous system influences bone metabolism and anabolism. Since 1916 several investigators tried to analyze the effect of peripheral nervous system in bone growth and most of them advocated for the positive effect of innervation in the bones of growing organisms. Moreover, neuronal tissue controls bone formation and remodeling. The purpose of this mini-review is to present the most recent data concerning the influence of innervation on bone growth, the current understanding of the skeletal innervation and their proposed physiological effects on bone metabolism as well as the implication of denervation in human skeletal biology in the developing organism since the peripheral neural trauma as well as peripheral neuropathies are common and they have impact on the growing skeleton.

  1. FGF-21 and skeletal remodeling during and after lactation in C57BL/6J mice.

    Science.gov (United States)

    Bornstein, Sheila; Brown, Sue A; Le, Phuong T; Wang, Xunde; DeMambro, Victoria; Horowitz, Mark C; MacDougald, Ormond; Baron, Roland; Lotinun, Sutada; Karsenty, Gerard; Wei, Wei; Ferron, Mathieu; Kovacs, Christopher S; Clemmons, David; Wan, Yihong; Rosen, Clifford J

    2014-09-01

    Lactation is associated with significant alterations in both body composition and bone mass. Systemic and local skeletal factors such as receptor activator of nuclear factor κ-B ligand (RANKL), PTHrP, calcitonin, and estrogen are known to regulate bone remodeling during and after lactation. Fibroblast growth factor 21 (FGF-21) may function as an endocrine factor to regulate body composition changes during lactation by inducing gluconeogenesis and fatty acid oxidation. In this study, we hypothesized that the metabolic changes during lactation were due in part to increased circulating FGF-21, which in turn could accentuate bone loss. We longitudinally characterized body composition in C57BL/6J (B6) mice during (day 7 and day 21 of lactation) and after normal lactation (day 21 postlactation). At day 7 of lactation, areal bone density declined by 10% (P < .001), bone resorption increased (P < .0001), percent fat decreased by 20%, energy expenditure increased (P < .01), and markers of brown-like adipogenesis were suppressed in the inguinal depot and in preformed brown adipose tissue. At day 7 of lactation there was a 2.4-fold increase in serum FGF-21 vs baseline (P < .0001), a 8-fold increase in hepatic FGF-21 mRNA (P < .03), a 2-fold increase in undercarboxylated osteocalcin (Glu13 OCn) (P < .01), and enhanced insulin sensitivity. Recovery of total areal bone density was noted at day 21 of lactation, whereas the femoral trabecular bone volume fraction was still reduced (P < .01). Because FGF-21 levels rose rapidly at day 7 of lactation in B6 lactating mice, we next examined lactating mice with a deletion in the Fgf21 gene. Trabecular and cortical bone masses were maintained throughout lactation in FGF-21(-/-) mice, and pup growth was normal. Compared with lactating control mice, lactating FGF-21(-/-) mice exhibited an increase in bone formation, but no change in bone resorption. In conclusion, in addition to changes in calciotropic hormones, systemic FGF-21 plays a

  2. Integration

    DEFF Research Database (Denmark)

    Emerek, Ruth

    2004-01-01

    Bidraget diskuterer de forskellige intergrationsopfattelse i Danmark - og hvad der kan forstås ved vellykket integration......Bidraget diskuterer de forskellige intergrationsopfattelse i Danmark - og hvad der kan forstås ved vellykket integration...

  3. Bone turnover markers: Emerging tool in the management of osteoporosis

    Directory of Open Access Journals (Sweden)

    Sahana Shetty

    2016-01-01

    Full Text Available Bone is a dynamic tissue which undergoes constant remodeling throughout the life span. Bone turnover is balanced with coupling of bone formation and resorption at various rates leading to continuous remodeling of bone. A study of bone turnover markers (BTMs provides an insight of the dynamics of bone turnover in many metabolic bone disorders. An increase in bone turnover seen with aging and pathological states such as osteoporosis leads to deterioration of bone microarchitecture and thus contributes to an increase in the risk of fracture independent of low bone mineral density (BMD. These microarchitectural alterations affecting the bone quality can be assessed by BTMs and thus may serve as a complementary tool to BMD in the assessment of fracture risk. A systematic search of literature regarding BTMs was carried out using the PubMed database for the purpose of this review. Various reliable, rapid, and cost-effective automated assays of BTMs with good sensitivity are available for the management of osteoporosis. However, BTMs are subjected to various preanalytical and analytical variations necessitating strict sample collection and assays methods along with utilizing ethnicity-based reference standards for different populations. Estimation of fracture risk and monitoring the adherence and response to therapy, which is a challenge in a chronic, asymptomatic disease such as osteoporosis, are the most important applications of measuring BTMs. This review describes the physiology of bone remodeling, various conventional and novel BTMs, and BTM assays and their role in the assessment of fracture risk and monitoring response to treatment with antiresorptive or anabolic agents.

  4. [Impact of thyroid diseases on bone].

    Science.gov (United States)

    Tsourdi, E; Lademann, F; Siggelkow, H

    2018-05-09

    Thyroid hormones are key regulators of skeletal development in childhood and bone homeostasis in adulthood, and thyroid diseases have been associated with increased osteoporotic fractures. Hypothyroidism in children leads to an impaired skeletal maturation and mineralization, but an adequate and timely substitution with thyroid hormones stimulates bone growth. Conversely, hyperthyroidism at a young age accelerates skeletal development, but may also cause short stature because of a premature fusion of the growth plates. Hypothyroidism in adults causes an increase in the duration of the remodeling cycle and, thus, leads to low bone turnover and enhanced mineralization, but an association with a higher fracture risk is less well established. In adults, a surplus of thyroid hormones enhances bone turnover, mostly due to an increased bone resorption driven by osteoclasts. Thus, hyperthyroidism is a well-recognized cause of high-bone turnover secondary osteoporosis, resulting in an increased susceptibility to fragility fractures. Subclinical hyperthyroidism, especially resulting from endogenous disease, also has an adverse effect on bone mineral density and is associated with fractures. In most patients with overt or subclinical hyperthyroidism restoration of the euthyroid status reverses bone loss. In postmenopausal women who receive thyroid-stimulating hormone suppression therapy because of thyroid cancer, antiresorptive treatments may be indicated. Overall, extensive data support the importance of a euthyroid status for bone mineral accrual and growth in childhood as well as maintenance of bone health in adulthood.

  5. Bone bonding at natural and biomaterial surfaces.

    Science.gov (United States)

    Davies, John E

    2007-12-01

    Bone bonding is occurring in each of us and all other terrestrial vertebrates throughout life at bony remodeling sites. The surface created by the bone-resorbing osteoclast provides a three-dimensionally complex surface with which the cement line, the first matrix elaborated during de novo bone formation, interdigitates and is interlocked. The structure and composition of this interfacial bony matrix has been conserved during evolution across species; and we have known for over a decade that this interfacial matrix can be recapitulated at a biomaterial surface implanted in bone, given appropriate healing conditions. No evidence has emerged to suggest that bone bonding to artificial materials is any different from this natural biological process. Given this understanding it is now possible to explain why bone-bonding biomaterials are not restricted to the calcium-phosphate-based bioactive materials as was once thought. Indeed, in the absence of surface porosity, calcium phosphate biomaterials are not bone bonding. On the contrary, non-bonding materials can be rendered bone bonding by modifying their surface topography. This paper argues that the driving force for bone bonding is bone formation by contact osteogenesis, but that this has to occur on a sufficiently stable recipient surface which has micron-scale surface topography with undercuts in the sub-micron scale-range.

  6. Decreased bone turnover with balanced resorption and formation prevent cortical bone loss during disuse (hibernation) in grizzly bears (Ursus arctos horribilis).

    Science.gov (United States)

    McGee, Meghan E; Maki, Aaron J; Johnson, Steven E; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2008-02-01

    Disuse uncouples bone formation from resorption, leading to increased porosity, decreased bone geometrical properties, and decreased bone mineral content which compromises bone mechanical properties and increases fracture risk. However, black bear bone properties are not adversely affected by aging despite annual periods of disuse (i.e., hibernation), which suggests that bears either prevent bone loss during disuse or lose bone and subsequently recover it at a faster rate than other animals. Here we show decreased cortical bone turnover during hibernation with balanced formation and resorption in grizzly bear femurs. Hibernating grizzly bear femurs were less porous and more mineralized, and did not demonstrate any changes in cortical bone geometry or whole bone mechanical properties compared to active grizzly bear femurs. The activation frequency of intracortical remodeling was 75% lower during hibernation than during periods of physical activity, but the normalized mineral apposition rate was unchanged. These data indicate that bone turnover decreases during hibernation, but osteons continue to refill at normal rates. There were no changes in regional variation of porosity, geometry, or remodeling indices in femurs from hibernating bears, indicating that hibernation did not preferentially affect one region of the cortex. Thus, grizzly bears prevent bone loss during disuse by decreasing bone turnover and maintaining balanced formation and resorption, which preserves bone structure and strength. These results support the idea that bears possess a biological mechanism to prevent disuse osteoporosis.

  7. Diabetes mellitus induces bone marrow microangiopathy

    Science.gov (United States)

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

    2010-01-01

    Objective The impact of diabetes on the bone marrow (BM) microenvironment was not adequately explored. We investigated whether diabetes induces microvascular remodeling with negative consequence for BM homeostasis. Methods and results We found profound structural alterations in BM from type-1 diabetic mice, with depletion of the hematopoietic component and fatty degeneration. Blood flow (fluorescent microspheres) and microvascular density (immunohistochemistry) were remarkably reduced. Flow cytometry verified the depletion of MECA-32pos endothelial cells (ECs). Cultured ECs from BM of diabetic mice showed higher levels of oxidative stress, increased activity of the senescence marker β-galactosidase, reduced migratory and network-formation capacities and increased permeability and adhesiveness to BM mononuclear cells. Flow cytometry analysis of lineageneg c-Kitpos Sca-1pos (LSK) cell distribution along an in vivo Hoechst-33342 dye perfusion gradient documented that diabetes depletes LSK cells predominantly in the low-perfused part of the marrow. Cell depletion was associated to increased oxidative stress, DNA damage and activation of apoptosis. Boosting the anti-oxidative pentose phosphate pathway by benfotiamine supplementation prevented microangiopathy, hypoperfusion and LSK cell depletion. Conclusions We provide novel evidence for the presence of microangiopathy impinging on the integrity of diabetic BM. These discoveries offer the framework for mechanistic solutions of BM dysfunction in diabetes. PMID:20042708

  8. Brassinosteroid Mediated Cell Wall Remodeling in Grasses under Abiotic Stress

    Directory of Open Access Journals (Sweden)

    Xiaolan Rao

    2017-05-01

    Full Text Available Unlike animals, plants, being sessile, cannot escape from exposure to severe abiotic stresses such as extreme temperature and water deficit. The dynamic structure of plant cell wall enables them to undergo compensatory changes, as well as maintain physical strength, with changing environments. Plant hormones known as brassinosteroids (BRs play a key role in determining cell wall expansion during stress responses. Cell wall deposition differs between grasses (Poaceae and dicots. Grass species include many important food, fiber, and biofuel crops. In this article, we focus on recent advances in BR-regulated cell wall biosynthesis and remodeling in response to stresses, comparing our understanding of the mechanisms in grass species with those in the more studied dicots. A more comprehensive understanding of BR-mediated changes in cell wall integrity in grass species will benefit the development of genetic tools to improve crop productivity, fiber quality and plant biomass recalcitrance.

  9. Recovery of the proliferative and functional integrity of mouse bone marrow in long-term cultures established after whole-body irradiation at different doses and dose rates

    International Nuclear Information System (INIS)

    Bierkens, J.G.; Hendry, J.H.; Testa, N.G.

    1991-01-01

    Injury inflicted upon the bone marrow stroma following whole-body irradiation and its repair over a 1-year period has been assessed in murine long-term bone marrow cultures established at increasing time intervals after irradiation. Different doses at different dose rates (10 Gy at 0.05 cGy/min, 4.5 Gy and 10 Gy at 1.6 cGy/min, and 4 x 4.5 Gy [3 weeks between doses] at 60 cGy/min) were chosen so as to maximize differences in effect in the stroma. The cellularity of the adherent layer in long-term cultures established 1 month after irradiation was reduced by 40%-90% depending on the dose and dose rate. Simultaneous with the poor ability of the marrow to form adherent layers, the cumulative spleen colony-forming unit (CFU-S) and granulocyte-macrophage colony-forming cell (GM-CFC) production over a 7-week period was reduced to 0% and 30% of control cultures, respectively. The slow recovery of the adherent layer was paralleled by an increase in the numbers of CFU-S and GM-CFC in the supernatant. Cultures established from repeatedly irradiated mice performed poorly over the entire 1-year period. Whereas the regeneration of the stroma was near complete 1 year after irradiation, the CFU-S and GM-CFC levels reached only between 50% and 80% of control cultures, respectively. Also, the concentration of CFU-S and GM-CFC in the supernatant remained persistently lower in cultures established from irradiated mice as compared to control cultures. The levels of sulfated glycosaminoglycans, which have been implicated in the establishment of the functional integrity of the microenvironment, were not reduced in the adherent layers at any time after irradiation. These results indicate that the regeneration of the stroma is accompanied by an incomplete recovery of active hemopoiesis in vitro

  10. New mechanisms and targets in the treatment of bone fragility.

    Science.gov (United States)

    Martin, T John; Seeman, Ego

    2007-01-01

    Bone modelling and remodelling are cell-mediated processes responsible for the construction and reconstruction of the skeleton throughout life. These processes are chiefly mediated by locally generated cytokines and growth factors that regulate the differentiation, activation, work and life span of osteoblasts and osteoclasts, the cells that co-ordinate the volumes of bone resorbed and formed. In this way, the material composition and structural design of bone is regulated in accordance with its loading requirements. Abnormalities in this regulatory system compromise the material and structural determinants of bone strength producing bone fragility. Understanding the intercellular control processes that regulate bone modelling and remodelling is essential in planning therapeutic approaches to prevention and treatment of bone fragility. A great deal has been learnt in the last decade. Clinical trials carried out exclusively with drugs that inhibit bone resorption have identified the importance of reducing the rate of bone remodelling and so the progression of bone fragility to achieved fracture reductions of approx. 50%. These trials have also identified limitations that should be placed upon interpretation of bone mineral density changes in relation to treatment. New resorption inhibitors are being developed, based on mechanisms of action that are different from existing drugs. Some of these might offer resorption inhibition without reducing bone formation. More recent research has provided the first effective anabolic therapy for bone reconstruction. Daily injections of PTH (parathyroid hormone)-(1-34) have been shown in preclinical studies and in a large clinical trial to increase bone tissue mass and reduce the risk of fractures. The action of PTH differs from that of the resorption inhibitors, but whether it is more effective in fracture reduction is not known. Understanding the cellular and molecular mechanisms of PTH action, particularly its interactions with

  11. Bone marrow aspiration

    Science.gov (United States)

    Iliac crest tap; Sternal tap; Leukemia - bone marrow aspiration; Aplastic anemia - bone marrow aspiration; Myelodysplastic syndrome - bone marrow aspiration; Thrombocytopenia - bone marrow aspiration; Myelofibrosis - bone marrow aspiration

  12. Treatment of active unicameral bone cysts with percutaneous injection of demineralized bone matrix and autogenous bone marrow.

    Science.gov (United States)

    Rougraff, Bruce T; Kling, Thomas J

    2002-06-01

    The treatment of unicameral bone cysts varies from open bone-grafting procedures to percutaneous injection of corticosteroids or bone marrow. The purpose of this study was to evaluate the feasibility and effectiveness of percutaneous injection of a mixture of demineralized bone matrix and autogenous bone marrow for the treatment of simple bone cysts. Twenty-three patients with an active unicameral bone cyst were treated with trephination and injection of allogeneic demineralized bone matrix and autogenous bone marrow. The patients were followed for an average of fifty months (range, thirty to eighty-one months), at which time pain, function, and radiographic signs of resolution of the cyst were assessed. The average time until the patients had pain relief was five weeks, and the average time until the patients returned to full, unrestricted activities was six weeks. Bone-healing at the site of the injection was first seen radiographically at three to six months. No patient had a pathologic fracture during this early bone-healing stage. Cortical remodeling was seen radiographically by six to nine months, and after one year the response was usually complete, changing very little from then on. Five patients required a second injection because of recurrence of the cyst, and all five had a clinically and radiographically quiescent cyst after an average of thirty-six additional months of follow-up. Seven of the twenty-three patients had incomplete healing manifested by small, persistent radiolucent areas within the original cyst. None of these cysts increased in size or resulted in pain or fracture. Percutaneous injection of allogeneic demineralized bone matrix and autogenous bone marrow is an effective treatment for unicameral bone cysts.

  13. Force-induced bone growth and adaptation: A system theoretical approach to understanding bone mechanotransduction

    International Nuclear Information System (INIS)

    Maldonado, Solvey; Findeisen, Rolf

    2010-01-01

    The modeling, analysis, and design of treatment therapies for bone disorders based on the paradigm of force-induced bone growth and adaptation is a challenging task. Mathematical models provide, in comparison to clinical, medical and biological approaches an structured alternative framework to understand the concurrent effects of the multiple factors involved in bone remodeling. By now, there are few mathematical models describing the appearing complex interactions. However, the resulting models are complex and difficult to analyze, due to the strong nonlinearities appearing in the equations, the wide range of variability of the states, and the uncertainties in parameters. In this work, we focus on analyzing the effects of changes in model structure and parameters/inputs variations on the overall steady state behavior using systems theoretical methods. Based on an briefly reviewed existing model that describes force-induced bone adaptation, the main objective of this work is to analyze the stationary behavior and to identify plausible treatment targets for remodeling related bone disorders. Identifying plausible targets can help in the development of optimal treatments combining both physical activity and drug-medication. Such treatments help to improve/maintain/restore bone strength, which deteriorates under bone disorder conditions, such as estrogen deficiency.

  14. Function of Matrix IGF-1 in Coupling Bone Resorption and Formation

    Science.gov (United States)

    Crane, Janet L.; Cao, Xu

    2013-01-01

    Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space and time dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of MSCs and HSCs and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis. PMID:24068256

  15. Function of matrix IGF-1 in coupling bone resorption and formation.

    Science.gov (United States)

    Crane, Janet L; Cao, Xu

    2014-02-01

    Balancing bone resorption and formation is the quintessential component for the prevention of osteoporosis. Signals that determine the recruitment, replication, differentiation, function, and apoptosis of osteoblasts and osteoclasts direct bone remodeling and determine whether bone tissue is gained, lost, or balanced. Therefore, understanding the signaling pathways involved in the coupling process will help develop further targets for osteoporosis therapy, by blocking bone resorption or enhancing bone formation in a space- and time-dependent manner. Insulin-like growth factor type 1 (IGF-1) has long been known to play a role in bone strength. It is one of the most abundant substances in the bone matrix, circulates systemically and is secreted locally, and has a direct relationship with bone mineral density. Recent data has helped further our understanding of the direct role of IGF-1 signaling in coupling bone remodeling which will be discussed in this review. The bone marrow microenvironment plays a critical role in the fate of mesenchymal stem cells and hematopoietic stem cells and thus how IGF-1 interacts with other factors in the microenvironment are equally important. While previous clinical trials with IGF-1 administration have been unsuccessful at enhancing bone formation, advances in basic science studies have provided insight into further mechanisms that should be considered for future trials. Additional basic science studies dissecting the regulation and the function of matrix IGF-1 in modeling and remodeling will continue to provide further insight for future directions for anabolic therapies for osteoporosis.

  16. [Integrity].

    Science.gov (United States)

    Gómez Rodríguez, Rafael Ángel

    2014-01-01

    To say that someone possesses integrity is to claim that that person is almost predictable about responses to specific situations, that he or she can prudentially judge and to act correctly. There is a closed interrelationship between integrity and autonomy, and the autonomy rests on the deeper moral claim of all humans to integrity of the person. Integrity has two senses of significance for medical ethic: one sense refers to the integrity of the person in the bodily, psychosocial and intellectual elements; and in the second sense, the integrity is the virtue. Another facet of integrity of the person is la integrity of values we cherish and espouse. The physician must be a person of integrity if the integrity of the patient is to be safeguarded. The autonomy has reduced the violations in the past, but the character and virtues of the physician are the ultimate safeguard of autonomy of patient. A field very important in medicine is the scientific research. It is the character of the investigator that determines the moral quality of research. The problem arises when legitimate self-interests are replaced by selfish, particularly when human subjects are involved. The final safeguard of moral quality of research is the character and conscience of the investigator. Teaching must be relevant in the scientific field, but the most effective way to teach virtue ethics is through the example of the a respected scientist.

  17. Bone changes from prostaglandin therapy

    International Nuclear Information System (INIS)

    Poznanski, A.K.; Fernbach, S.K.; Berry, T.E.; Northwestern Univ., Chicago, IL

    1985-01-01

    Prostaglandin E therapy in infants causes periosteal elevation. Although the changes usually take 30-40 days to become visible, we have seen them as early as nine days. In 15 infants who had prostaglandin E therapy for over six days, three developed periosteal elevation. Three other cases are described in greater detail, with long-term follow-up in two in which the bone remodeled to normal. Gallium scan in one showed increased uptake in areas involved. The periosteal cloaking may mimic Caffey disease but the pattern of involvement is different, since the mandible, which is commonly affected in Caffey disease, is rarely involved in prostaglandin E therapy. (orig.)

  18. Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly

    DEFF Research Database (Denmark)

    Rahme, Maya; Sharara, Sima Lynn; Baddoura, Rafic

    2017-01-01

    The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double-blind trial we randomized 257 ove...

  19. The manufacture of synthetic non-sintered and degradable bone grafting substitutes.

    Science.gov (United States)

    Gerike, W; Bienengräber, V; Henkel, K-O; Bayerlein, T; Proff, P; Gedrange, T; Gerber, Th

    2006-02-01

    A new synthetic bone grafting substitute (NanoBone, ARTOSS GmbH, Germany) is presented. This is produced by a new technique, the sol-gel-method. This bone grafting substitute consists of nanocrystalline hydroxyapatite (HA) and nanostructured silica (SiO2). By achieving a highly porous structure good osteoconductivity can be seen. In addition, the material will be completely biodegraded and new own bone is formed. It has been demonstrated that NanoBone is biodegraded by osteoclasts in a manner comparable to the natural bone remodelling process.

  20. Low Bone Density

    Science.gov (United States)

    ... Density Exam/Testing › Low Bone Density Low Bone Density Low bone density is when your bone density ... people with normal bone density. Detecting Low Bone Density A bone density test will determine whether you ...

  1. The role of connectivity and stochastic osteocyte behavior in the distribution of perilabyrinthine bone degeneration

    DEFF Research Database (Denmark)

    Bloch, Sune Land; Sørensen, Mads Sølvsten

    2016-01-01

    as the candidate inhibiter of perilabyrinthine bone resorption. Resulting age related excessive matrix microdamage, osteocyte death and degeneration of the OPG signaling pathway is expected to trigger bone remodeling in the otic capsule, but when this happens the morphology of the remodeling bone is abnormal...... this information is used to generate a virtual computer representation of the cellular signaling network, the fate of the aging network can be studied by 'virtual histology' in any number of simulated 'individuals'. We demonstrate how a combination of simple osteocyte survival functions derived from histological...

  2. Remodeling of ACL Allografts is Inhibited by Peracetic Acid Sterilization

    Science.gov (United States)

    Gonnermann, Johannes; Kamp, Julia; Przybilla, Dorothea; Pruss, Axel

    2008-01-01

    Sterilization of allografts for anterior cruciate ligament (ACL) reconstruction has become an important prerequisite to prevent disease transmission. However, current sterilization techniques impair the biological or mechanical properties of such treated grafts. Peracetic acid (PAA) has been successfully used to sterilize bone allografts without these disadvantages and does not impair the mechanical properties of soft tissue grafts in vitro. We asked whether PAA sterilization would influence recellularization, restoration of crimp length and pattern, and revascularization of ACL grafts during early healing. We used an in vivo sheep model for open ACL reconstruction. We also correlated the histologic findings with the restoration of anteroposterior stability and structural properties during load-to-failure testing. PAA slowed remodeling activity at 6 and 12 weeks compared to nonsterilized allografts and autografts. The mechanical properties of PAA grafts were also reduced compared to these control groups at both time points. We conclude PAA sterilization currently should not be used to sterilize soft tissue grafts typically used in ACL reconstruction. PMID:18491201

  3. Therapeutic actions of curcumin in bone disorders

    OpenAIRE

    Rohanizadeh, Ramin; Deng, Yi; Verron, Elise

    2016-01-01

    Curcumin is the active component of turmeric extract derived from the Curcuma longa plant. In the last decade, curcumin has raised a considerable interest in medicine owing to its negligible toxicity and multiple therapeutic actions including anti-cancer, anti-inflammatory and anti-microbial activities. Among the various molecular targets of curcumin, some are involved in bone remodeling, which strongly suggests that curcumin can affect the skeletal system. The review sheds light on the curre...

  4. Trabecular meshwork ECM remodeling in glaucoma: could RAS be a target?

    Science.gov (United States)

    Agarwal, Puneet; Agarwal, Renu

    2018-06-14

    Disturbances of extracellular matrix (ECM) homeostasis in trabecular meshwork (TM) cause increased aqueous outflow resistance leading to elevated intraocular pressure (IOP) in glaucomatous eyes. Therefore, restoration of ECM homeostasis is a rational approach to prevent disease progression. Since renin-angiotensin system (RAS) inhibition positively alters ECM homeostasis in cardiovascular pathologies involving pressure and volume overload, it is likely that RAS inhibitors reduce IOP primarily by restoring ECM homeostasis. Areas covered: Current evidence showing the presence of RAS components in ocular tissue and its role in regulating aqueous humor dynamics is briefly summarized. The role of RAS in ECM remodeling is discussed both in terms of its effects on ECM synthesis and its breakdown. The mechanisms of ECM remodeling involving interactions of RAS with transforming growth factor-β, Wnt/β-catenin signaling, bone morphogenic proteins, connective tissue growth factor, and matrix metalloproteinases in ocular tissue are discussed. Expert opinion: Current literature strongly indicates a significant role of RAS in ECM remodeling in TM of hypertensive eyes. Hence, IOP-lowering effect of RAS inhibitors may primarily be attributed to restoration of ECM homeostasis in aqueous outflow pathways rather than its vascular effects. However, the mechanistic targets for RAS inhibitors have much wider distribution and consequences, which remain relatively unexplored in TM.

  5. Osteoporosis: Modern Paradigms for Last Century's Bones.

    Science.gov (United States)

    Kruger, Marlena C; Wolber, Frances M

    2016-06-17

    The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a "brittle bone" disease that occurs in post-menopausal, thin, Caucasian women with low calcium intakes and/or vitamin D insufficiency. However, a study of black women in Africa demonstrated that higher proportions of body fat did not protect bone health. Isoflavone interventions in Asian postmenopausal women have produced inconsistent bone health benefits, due in part to population heterogeneity in enteric bacterial metabolism of daidzein. A comparison of women and men in several Asian countries identified significant differences between countries in the rate of bone health decline, and a high incidence rate of osteoporosis in both sexes. These studies have revealed significant differences in genetic phenotypes, debunking long-held beliefs and leading to new paradigms in study design. Current studies are now being specifically designed to assess genotype differences between Caucasian, Asian, African, and other phenotypes, and exploring alternative methodology to measure bone architecture.

  6. Fiber architecture in remodeled myocardium revealed with a quantitative diffusion CMR tractography framework and histological validation.

    Science.gov (United States)

    Mekkaoui, Choukri; Huang, Shuning; Chen, Howard H; Dai, Guangping; Reese, Timothy G; Kostis, William J; Thiagalingam, Aravinda; Maurovich-Horvat, Pal; Ruskin, Jeremy N; Hoffmann, Udo; Jackowski, Marcel P; Sosnovik, David E

    2012-10-12

    The study of myofiber reorganization in the remote zone after myocardial infarction has been performed in 2D. Microstructural reorganization in remodeled hearts, however, can only be fully appreciated by considering myofibers as continuous 3D entities. The aim of this study was therefore to develop a technique for quantitative 3D diffusion CMR tractography of the heart, and to apply this method to quantify fiber architecture in the remote zone of remodeled hearts. Diffusion Tensor CMR of normal human, sheep, and rat hearts, as well as infarcted sheep hearts was performed ex vivo. Fiber tracts were generated with a fourth-order Runge-Kutta integration technique and classified statistically by the median, mean, maximum, or minimum helix angle (HA) along the tract. An index of tract coherence was derived from the relationship between these HA statistics. Histological validation was performed using phase-contrast microscopy. In normal hearts, the subendocardial and subepicardial myofibers had a positive and negative HA, respectively, forming a symmetric distribution around the midmyocardium. However, in the remote zone of the infarcted hearts, a significant positive shift in HA was observed. The ratio between negative and positive HA variance was reduced from 0.96 ± 0.16 in normal hearts to 0.22 ± 0.08 in the remote zone of the remodeled hearts (p layers of the myocardium. Tractography-based quantification, performed here for the first time in remodeled hearts, may provide a framework for assessing regional changes in the left ventricle following infarction.

  7. Aging and the cardiac collagen matrix: Novel mediators of fibrotic remodelling.

    Science.gov (United States)

    Horn, Margaux A; Trafford, Andrew W

    2016-04-01

    Cardiovascular disease is a leading cause of death worldwide and there is a pressing need for new therapeutic strategies to treat such conditions. The risk of developing cardiovascular disease increases dramatically with age, yet the majority of experimental research is executed using young animals. The cardiac extracellular matrix (ECM), consisting predominantly of fibrillar collagen, preserves myocardial integrity, provides a means of force transmission and supports myocyte geometry. Disruptions to the finely balanced control of collagen synthesis, post-synthetic deposition, post-translational modification and degradation may have detrimental effects on myocardial functionality. It is now well established that the aged heart is characterized by fibrotic remodelling, but the mechanisms responsible for this are incompletely understood. Furthermore, studies using aged animal models suggest that interstitial remodelling with disease may be age-dependent. Thus with the identification of new therapeutic strategies targeting fibrotic remodelling, it may be necessary to consider age-dependent mechanisms. In this review, we discuss remodelling of the cardiac collagen matrix as a function of age, whilst highlighting potential novel mediators of age-dependent fibrotic pathways. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. μCT-based, in vivo dynamic bone histomorphometry allows 3D evaluation of the early responses of bone resorption and formation to PTH and alendronate combination therapy.

    Science.gov (United States)

    de Bakker, Chantal M J; Altman, Allison R; Tseng, Wei-Ju; Tribble, Mary Beth; Li, Connie; Chandra, Abhishek; Qin, Ling; Liu, X Sherry

    2015-04-01

    Current osteoporosis treatments improve bone mass by increasing net bone formation: anti-resorptive drugs such as bisphosphonates block osteoclast activity, while anabolic agents such as parathyroid hormone (PTH) increase bone remodeling, with a greater effect on formation. Although these drugs are widely used, their role in modulating formation and resorption is not fully understood, due in part to technical limitations in the ability to longitudinally assess bone remodeling. Importantly, it is not known whether or not PTH-induced bone formation is independent of resorption, resulting in controversy over the effectiveness of combination therapies that use both PTH and an anti-resorptive. In this study, we developed a μCT-based, in vivo dynamic bone histomorphometry technique for rat tibiae, and applied this method to longitudinally track changes in bone resorption and formation as a result of treatment with alendronate (ALN), PTH, or combination therapy of both PTH and ALN (PTH+ALN). Correlations between our μCT-based measures of bone formation and measures of bone formation based on calcein-labeled histology (r=0.72-0.83) confirm the accuracy of this method. Bone remodeling parameters measured through μCT-based in vivo dynamic bone histomorphometry indicate an increased rate of bone formation in rats treated with PTH and PTH+ALN, together with a decrease in bone resorption measures in rats treated with ALN and PTH+ALN. These results were further supported by traditional histology-based measurements, suggesting that PTH was able to induce bone formation while bone resorption was suppressed. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. A coupled mechano-biochemical model for bone adaptation

    Czech Academy of Sciences Publication Activity Database

    Klika, Václav; Pérez, M. A.; García-Aznar, J. M.; Maršík, F.; Doblaré, M.

    2014-01-01

    Roč. 69, 6-7 (2014), s. 1383-1429 ISSN 0303-6812 Institutional support: RVO:61388998 Keywords : mechano-biochemical model * bone remodelling * BMU Subject RIV: BJ - Thermodynamics Impact factor: 1.846, year: 2014 http://link.springer.com/article/10.1007%2Fs00285-013-0736-9

  10. Life-history traits of the Miocene Hipparion concudense (Spain inferred from bone histological structure.

    Directory of Open Access Journals (Sweden)

    Cayetana Martinez-Maza

    Full Text Available Histological analyses of fossil bones have provided clues on the growth patterns and life history traits of several extinct vertebrates that would be unavailable for classical morphological studies. We analyzed the bone histology of Hipparion to infer features of its life history traits and growth pattern. Microscope analysis of thin sections of a large sample of humeri, femora, tibiae and metapodials of Hipparion concudense from the upper Miocene site of Los Valles de Fuentidueña (Segovia, Spain has shown that the number of growth marks is similar among the different limb bones, suggesting that equivalent skeletochronological inferences for this Hipparion population might be achieved by means of any of the elements studied. Considering their abundance, we conducted a skeletechronological study based on the large sample of third metapodials from Los Valles de Fuentidueña together with another large sample from the Upper Miocene locality of Concud (Teruel, Spain. The data obtained enabled us to distinguish four age groups in both samples and to determine that Hipparion concudense tended to reach skeletal maturity during its third year of life. Integration of bone microstructure and skeletochronological data allowed us to identify ontogenetic changes in bone structure and growth rate and to distinguish three histologic ontogenetic stages corresponding to immature, subadult and adult individuals. Data on secondary osteon density revealed an increase in bone remodeling throughout the ontogenetic stages and a lesser degree thereof in the Concud population, which indicates different biomechanical stresses in the two populations, likely due to environmental differences. Several individuals showed atypical growth patterns in the Concud sample, which may also reflect environmental differences between the two localities. Finally, classification of the specimens' age within groups enabled us to characterize the age structure of both samples, which is

  11. Bone mass regulation of leptin and postmenopausal osteoporosis with obesity.

    Science.gov (United States)

    Legiran, Siswo; Brandi, Maria Luisa

    2012-09-01

    Leptin has been known to play a role in weight regulation through food intake and energy expenditure. Leptin also has an important role in bone metabolism. The role of leptin is determined by leptin receptors, either central or peripheral to the bones. We discuss the role of leptin on bone and molecular genetics of osteoporosis in postmenopausal obese women. The role of leptin in bone preserves bone mineral density (BMD) through increased OPG levels leading to bind RANKL, resulting in reducing osteoclast activity. The estrogen role on bone is also mediated by RANKL and OPG. In postmenopausal women who have estrogen deficiency, it increases the rate of RANKL, which increases osteoclastogenesis. Obese individuals who have a high level of leptin will be effected by bone protection. There are similarities in the mechanism between estrogen and leptin in influencing the process of bone remodeling. It may be considered that the role of estrogen can be replaced by leptin. Molecular genetic aspects that play a role in bone remodeling, such as leptin, leptin receptors, cytokines (e.g. RANK, RANKL, and OPG), require further study to be useful, especially regarding osteoporosis therapy based on genetic analysis.

  12. Bone scintigraphy in bone stress. A technical consideration and correlation of the findings to clinical symptoms especially to the pain

    International Nuclear Information System (INIS)

    Kuusela, T.; Vorne, M.; Vahatalo, S.

    1983-01-01

    The purpose of this investigation was to find out a reliable scintigraphic method to investigate different fatigue phenomena in bone and to correlate the scintigraphic findings to the development of clinical symptoms. The gamma-imaging after the injection of bone seeking tracers is recommended to be performed after a period of 1-3 hours. The experiments indicate that in active bone tissue, might it be a healing fracture or a remodeling bone, the tracer uptake still increases after 1-3 hours. The delayed gamma-imaging can therefore be useful, especially if it is important to investigate faint physiological changes in bone tissue. It seems, that the capacity of emission energy in the diagnosis of bone affections is superior to the radiology because of its excellent histo-functional resolution especially in detecting and localizing bone affections

  13. Netrin-1 overexpression promotes white matter repairing and remodeling after focal cerebral ischemia in mice

    OpenAIRE

    He, Xiaosong; Li, Yaning; Lu, Haiyan; Zhang, Zhijun; Wang, Yongting; Yang, Guo-Yuan

    2013-01-01

    Damage of oligodendrocytes after ischemia has negative impact on white matter integrity and neuronal function. In this work, we explore whether Netrin-1 (NT-1) overexpression facilitates white matter repairing and remodeling. Adult CD-1 mice received stereotactic injection of adeno-associated virus carrying NT-1 gene (AAV-NT-1). One week after gene transfer, mice underwent 60 minutes of middle cerebral artery occlusion. The effect of NT-1 on neural function was evaluated by neurobehavioral te...

  14. In vivo imaging of extracellular matrix remodeling by tumor-associated fibroblasts

    DEFF Research Database (Denmark)

    Perentes, Jean Y; McKee, Trevor D; Ley, Carsten D

    2009-01-01

    Here we integrated multiphoton laser scanning microscopy and the registration of second harmonic generation images of collagen fibers to overcome difficulties in tracking stromal cell-matrix interactions for several days in live mice. We show that the matrix-modifying hormone relaxin increased...... tumor-associated fibroblast (TAF) interaction with collagen fibers by stimulating beta1-integrin activity, which is necessary for fiber remodeling by matrix metalloproteinases....

  15. Bone tumors

    International Nuclear Information System (INIS)

    Moylan, D.J.; Yelovich, R.M.

    1991-01-01

    Primary bone malignancies are relatively rare with less than 4,000 new cases per year. Multiple myeloma (more correctly a hematologic malignancy) accounts for 40%; osteosarcomas, 28%; chondrosarcomas, 13%; fibrosarcomas arising in bone, 4%; and Ewing's sarcoma, 7%. The authors discuss various treatments for bone tumors, including radiotherapy, chemotherapy and surgery

  16. Vitamin D Content and the State of Bone Metabolism in Patients with Syndrome of Hyperthyroidism (Review of Literature

    Directory of Open Access Journals (Sweden)

    І.V. Pankiv

    2016-10-01

    Full Text Available The literature review presents data of researches on the content of vitamin D and the state of bone metabolism in patients with syndrome of hyperthyroidism. Overt hyperthyroidism is associated with accelerated bone remodeling, reduced bone density, osteoporosis, and an increase in fracture rate. Summarizing the results of the studies conducted by different authors, there should be noted the value of normal balance of thyroid hormones for a skeletogeny and providing bone mineral density.

  17. De Novo Mutations in CHD4, an ATP-Dependent Chromatin Remodeler Gene, Cause an Intellectual Disability Syndrome with Distinctive Dysmorphisms.

    Science.gov (United States)

    Weiss, Karin; Terhal, Paulien A; Cohen, Lior; Bruccoleri, Michael; Irving, Melita; Martinez, Ariel F; Rosenfeld, Jill A; Machol, Keren; Yang, Yaping; Liu, Pengfei; Walkiewicz, Magdalena; Beuten, Joke; Gomez-Ospina, Natalia; Haude, Katrina; Fong, Chin-To; Enns, Gregory M; Bernstein, Jonathan A; Fan, Judith; Gotway, Garrett; Ghorbani, Mohammad; van Gassen, Koen; Monroe, Glen R; van Haaften, Gijs; Basel-Vanagaite, Lina; Yang, Xiang-Jiao; Campeau, Philippe M; Muenke, Maximilian

    2016-10-06

    Chromodomain helicase DNA-binding protein 4 (CHD4) is an ATP-dependent chromatin remodeler involved in epigenetic regulation of gene transcription, DNA repair, and cell cycle progression. Also known as Mi2β, CHD4 is an integral subunit of a well-characterized histone deacetylase complex. Here we report five individuals with de novo missense substitutions in CHD4 identified through whole-exome sequencing and web-based gene matching. These individuals have overlapping phenotypes including developmental delay, intellectual disability, hearing loss, macrocephaly, distinct facial dysmorphisms, palatal abnormalities, ventriculomegaly, and hypogonadism as well as additional findings such as bone fusions. The variants, c.3380G>A (p.Arg1127Gln), c.3443G>T (p.Trp1148Leu), c.3518G>T (p.Arg1173Leu), and c.3008G>A, (p.Gly1003Asp) (GenBank: NM_001273.3), affect evolutionarily highly conserved residues and are predicted to be deleterious. Previous studies in yeast showed the equivalent Arg1127 and Trp1148 residues to be crucial for SNF2 function. Furthermore, mutations in the same positions were reported in malignant tumors, and a de novo missense substitution in an equivalent arginine residue in the C-terminal helicase domain of SMARCA4 is associated with Coffin Siris syndrome. Cell-based studies of the p.Arg1127Gln and p.Arg1173Leu mutants demonstrate normal localization to the nucleus and HDAC1 interaction. Based on these findings, the mutations potentially alter the complex activity but not its formation. This report provides evidence for the role of CHD4 in human development and expands an increasingly recognized group of Mendelian disorders involving chromatin remodeling and modification. Published by Elsevier Inc.

  18. Bone scan in pediatrics

    International Nuclear Information System (INIS)

    Gordon, I.; Peters, A.M.

    1987-01-01

    In 1984, a survey carried out in 21 countries in Europe showed that bone scintigraphy comprised 16% of all paediatric radioisotope scans. Although the value of bone scans in paediatrics is potentially great, their quality varies greatly, and poor-quality images are giving this valuable technique a bad reputation. The handling of children requires a sensitive staff and the provision of a few simple inexpensive items of distraction. Attempting simply to scan a child between two adult patients in a busy general department is a recipe for an unhappy, uncooperative child with the probable result of poor images. The intravenous injection of isotope should be given adjacent to the gamma camera room, unless dynamic scans are required, so that the child does not associate the camera with the injection. This injection is best carried out by someone competent in paediatric venipunture; the entire procedure should be explained to the child and parent, who should remain with child throughout. It is naive to think that silence makes for a cooperative child. The sensitivity of bone-seeking radioisotope tracers and the marked improvement in gamma camera resolution has allowed the bone scanning to become an integrated technique in the assessment of children suspected of suffering from pathological bone conditions. The tracer most commonly used for routine bone scanning is 99m Tc diphosphonate (MDP); other isotopes used include 99m Tc colloid for bone marrow scans and 67 Ga citrate and 111 In white blood cells ( 111 In WBC) for investigation of inflammatory/infective lesions

  19. Age changes in human bone: an overview

    Energy Technology Data Exchange (ETDEWEB)

    Sharpe, W.D.

    1977-12-03

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

  20. Role of arginase in vessel wall remodeling

    Directory of Open Access Journals (Sweden)

    William eDurante

    2013-05-01

    Full Text Available Arginase metabolizes the semi-essential amino acid L-arginine to L-ornithine and urea. There are two distinct isoforms of arginase, arginase I and II, which are encoded by separate genes and display differences in tissue distribution, subcellular localization, and molecular regulation. Blood vessels express both arginase I and II but their distribution appears to be cell-, vessel-, and species-specific. Both isoforms of arginase are induced by numerous pathologic stimuli and contribute to vascular cell dysfunction and vessel wall remodeling in several diseases. Clinical and experimental studies have documented increases in the expression and/or activity of arginase I or II in blood vessels following arterial injury and in pulmonary and arterial hypertension, aging, and atherosclerosis. Significantly, pharmacological inhibition or genetic ablation of arginase in animals ameliorates abnormalities in vascular cells and normalizes blood vessel architecture and function in all of these pathological states. The detrimental effect of arginase in vascular remodeling is attributable to its ability to stimulate vascular smooth muscle cell and endothelial cell proliferation, and collagen deposition by promoting the synthesis of polyamines and L-proline, respectively. In addition, arginase adversely impacts arterial remodeling by directing macrophages towards an inflammatory phenotype. Moreover, the proliferative, fibrotic, and inflammatory actions of arginase in the vasculature are further amplified by its capacity to inhibit nitric oxide synthesis by competing with nitric oxide synthase for substrate, L-arginine. Pharmacologic or molecular approaches targeting specific isoforms of arginase represent a promising strategy in treating obstructive fibroproliferative vascular disease.

  1. Characterizing brain structures and remodeling after TBI based on information content, diffusion entropy.

    Science.gov (United States)

    Fozouni, Niloufar; Chopp, Michael; Nejad-Davarani, Siamak P; Zhang, Zheng Gang; Lehman, Norman L; Gu, Steven; Ueno, Yuji; Lu, Mei; Ding, Guangliang; Li, Lian; Hu, Jiani; Bagher-Ebadian, Hassan; Hearshen, David; Jiang, Quan

    2013-01-01

    To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat. Thirteen healthy subjects were investigated using a Q-ball based DTI data sampling scheme. FA and entropy values were measured in white matter bundles, white matter fiber crossing areas, different gray matter (GM) regions and cerebrospinal fluid (CSF). Axonal densities' from the same regions of interest (ROIs) were evaluated in Bielschowsky and Luxol fast blue stained autopsy (n = 30) brain sections by light microscopy. As a case demonstration, a Wistar rat subjected to TBI and treated with bone marrow stromal cells (MSC) 1 week after TBI was employed to illustrate the superior ability of entropy over FA in detecting reorganized crossing axonal bundles as confirmed by histological analysis with Bielschowsky and Luxol fast blue staining. Unlike FA, entropy was less affected by axonal orientation and more affected by axonal density. A significant agreement (r = 0.91) was detected between entropy values from in vivo human brain and histologically measured axonal density from post mortum from the same brain structures. The MSC treated TBI rat demonstrated that the entropy approach is superior to FA in detecting axonal remodeling after injury. Compared with FA, entropy detected new axonal remodeling regions with crossing axons, confirmed with immunohistological staining. Entropy measurement is more effective in distinguishing axonal remodeling after injury, when compared with FA. Entropy is also more sensitive to axonal density than axonal orientation, and thus may provide a more accurate reflection of axonal changes that occur in neurological injury and disease.

  2. Characterizing Brain Structures and Remodeling after TBI Based on Information Content, Diffusion Entropy

    Science.gov (United States)

    Fozouni, Niloufar; Chopp, Michael; Nejad-Davarani, Siamak P.; Zhang, Zheng Gang; Lehman, Norman L.; Gu, Steven; Ueno, Yuji; Lu, Mei; Ding, Guangliang; Li, Lian; Hu, Jiani; Bagher-Ebadian, Hassan; Hearshen, David; Jiang, Quan

    2013-01-01

    Background To overcome the limitations of conventional diffusion tensor magnetic resonance imaging resulting from the assumption of a Gaussian diffusion model for characterizing voxels containing multiple axonal orientations, Shannon's entropy was employed to evaluate white matter structure in human brain and in brain remodeling after traumatic brain injury (TBI) in a rat. Methods Thirteen healthy subjects were investigated using a Q-ball based DTI data sampling scheme. FA and entropy values were measured in white matter bundles, white matter fiber crossing areas, different gray matter (GM) regions and cerebrospinal fluid (CSF). Axonal densities' from the same regions of interest (ROIs) were evaluated in Bielschowsky and Luxol fast blue stained autopsy (n = 30) brain sections by light microscopy. As a case demonstration, a Wistar rat subjected to TBI and treated with bone marrow stromal cells (MSC) 1 week after TBI was employed to illustrate the superior ability of entropy over FA in detecting reorganized crossing axonal bundles as confirmed by histological analysis with Bielschowsky and Luxol fast blue staining. Results Unlike FA, entropy was less affected by axonal orientation and more affected by axonal density. A significant agreement (r = 0.91) was detected between entropy values from in vivo human brain and histologically measured axonal density from post mortum from the same brain structures. The MSC treated TBI rat demonstrated that the entropy approach is superior to FA in detecting axonal remodeling after injury. Compared with FA, entropy detected new axonal remodeling regions with crossing axons, confirmed with immunohistological staining. Conclusions Entropy measurement is more effective in distinguishing axonal remodeling after injury, when compared with FA. Entropy is also more sensitive to axonal density than axonal orientation, and thus may provide a more accurate reflection of axonal changes that occur in neurological injury and disease

  3. CHD chromatin remodelers and the transcription cycle

    Science.gov (United States)

    Murawska, Magdalena

    2011-01-01

    It is well established that ATP-dependent chromatin remodelers modulate DNA access of transcription factors and RNA polymerases by “opening” or “closing” chromatin structure. However, this view is far too simplistic. Recent findings have demonstrated that these enzymes not only set the stage for the transcription machinery to act but also are actively involved at every step of the transcription process. As a consequence, they affect initiation, elongation, termination and RNA processing. In this review we will use the CHD family as a paradigm to illustrate the progress that has been made in revealing these new concepts. PMID:22223048

  4. Chromatin remodelling: the industrial revolution of DNA around histones.

    Science.gov (United States)

    Saha, Anjanabha; Wittmeyer, Jacqueline; Cairns, Bradley R

    2006-06-01

    Chromatin remodellers are specialized multi-protein machines that enable access to nucleosomal DNA by altering the structure, composition and positioning of nucleosomes. All remodellers have a catalytic ATPase subunit that is similar to known DNA-translocating motor proteins, suggesting DNA translocation as a unifying aspect of their mechanism. Here, we explore the diversity and specialization of chromatin remodellers, discuss how nucleosome modifications regulate remodeller activity and consider a model for the exposure of nucleosomal DNA that involves the use of directional DNA translocation to pump 'DNA waves' around the nucleosome.

  5. Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice

    DEFF Research Database (Denmark)

    Barascuk, N; Vassiliadis, E; Zheng, Qiuju

    2011-01-01

    Arterial extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) is one of the major hallmarks of atherosclerosis. Mimecan, also known as osteoglycin has been implicated in the integrity of the ECM. This study assessed the validity of an enzyme-linked immunosorbent assay (ELISA...

  6. Grizzly bears (Ursus arctos horribilis) and black bears (Ursus americanus) prevent trabecular bone loss during disuse (hibernation).

    Science.gov (United States)

    McGee-Lawrence, Meghan E; Wojda, Samantha J; Barlow, Lindsay N; Drummer, Thomas D; Castillo, Alesha B; Kennedy, Oran; Condon, Keith W; Auger, Janene; Black, Hal L; Nelson, O Lynne; Robbins, Charles T; Donahue, Seth W

    2009-12-01

    Disuse typically causes an imbalance in bone formation and bone resorption, leading to losses of cortical and trabecular bone. In contrast, bears maintain balanced intracortical remodeling and prevent cortical bone loss during disuse (hibernation). Trabecular bone, however, is more detrimentally affected than cortical bone in other animal models of disuse. Here we investigated the effects of hibernation on bone remodeling, architectural properties, and mineral density of grizzly bear (Ursus arctos horribilis) and black bear (Ursus americanus) trabecular bone in several skeletal locations. There were no differences in bone volume fraction or tissue mineral density between hibernating and active bears or between pre- and post-hibernation bears in the ilium, distal femur, or calcaneus. Though indices of cellular activity level (mineral apposition rate, osteoid thickness) decreased, trabecular bone resorption and formation indices remained balanced in hibernating grizzly bears. These data suggest that bears prevent bone loss during disuse by maintaining a balance between bone formation and bone resorption, which consequently preserves bone structure and strength. Further investigation of bone metabolism in hibernating bears may lead to the translation of mechanisms preventing disuse-induced bone loss in bears into novel treatments for osteoporosis.

  7. Bone banking.

    Science.gov (United States)

    Howard, W

    1999-04-01

    The use of human organs and tissues for transplantation in Australia has increased significantly over the past 30 years. In 1997, the Australian Coordinating Committee on Organ Registries and Donation (ACCORD) reported a total number of 190 organ donors, 636 corneal donors and 1509 bone donors Australia wide. Of the 1509 bone donations, 143 came from cadaveric sources and 1366 were made by living donors. Bone transplantation is not as widely recognised as solid organ or corneal transplantation. Due to improved technology and surgical skills, the demand for bone transplantation has increased markedly. This Clinical Update will provide an overview of the physiological aspects of bone transplantation and explore bone banking, a key step in the complex and critical process of bone transplantation.

  8. The role of bone marrow-derived cells during the bone healing process in the GFP mouse bone marrow transplantation model.

    Science.gov (United States)

    Tsujigiwa, Hidetsugu; Hirata, Yasuhisa; Katase, Naoki; Buery, Rosario Rivera; Tamamura, Ryo; Ito, Satoshi; Takagi, Shin; Iida, Seiji; Nagatsuka, Hitoshi

    2013-03-01

    Bone healing is a complex and multistep process in which the origin of the cells participating in bone repair is still unknown. The involvement of bone marrow-derived cells in tissue repair has been the subject of recent studies. In the present study, bone marrow-derived cells in bone healing were traced using the GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) were transplanted into C57BL/6 J wild mice. After transplantation, bone injury was created using a 1.0-mm drill. Bone healing was histologically assessed at 3, 7, 14, and 28 postoperative days. Immunohistochemistry for GFP; double-fluorescent immunohistochemistry for GFP-F4/80, GFP-CD34, and GFP-osteocalcin; and double-staining for GFP and tartrate-resistant acid phosphatase were performed. Bone marrow transplantation successfully replaced the hematopoietic cells into GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts or osteocytes in the repair stage were GFP-negative, whereas osteoclasts in the repair and remodeling stages and hematopoietic cells were GFP-positive. The results indicated that bone marrow-derived cells might not differentiate into osteoblasts. The role of bone marrow-derived cells might be limited to adjustment of the microenvironment by differentiating into inflammatory cells, osteoclasts, or endothelial cells in immature blood vessels.

  9. Fiber architecture in remodeled myocardium revealed with a quantitative diffusion CMR tractography framework and histological validation

    Directory of Open Access Journals (Sweden)

    Mekkaoui Choukri

    2012-10-01

    Full Text Available Abstract Background The study of myofiber reorganization in the remote zone after myocardial infarction has been performed in 2D. Microstructural reorganization in remodeled hearts, however, can only be fully appreciated by considering myofibers as continuous 3D entities. The aim of this study was therefore to develop a technique for quantitative 3D diffusion CMR tractography of the heart, and to apply this method to quantify fiber architecture in the remote zone of remodeled hearts. Methods Diffusion Tensor CMR of normal human, sheep, and rat hearts, as well as infarcted sheep hearts was performed ex vivo. Fiber tracts were generated with a fourth-order Runge-Kutta integration technique and classified statistically by the median, mean, maximum, or minimum helix angle (HA along the tract. An index of tract coherence was derived from the relationship between these HA statistics. Histological validation was performed using phase-contrast microscopy. Results In normal hearts, the subendocardial and subepicardial myofibers had a positive and negative HA, respectively, forming a symmetric distribution around the midmyocardium. However, in the remote zone of the infarcted hearts, a significant positive shift in HA was observed. The ratio between negative and positive HA variance was reduced from 0.96 ± 0.16 in normal hearts to 0.22 ± 0.08 in the remote zone of the remodeled hearts (p Conclusions A significant reorganization of the 3D fiber continuum is observed in the remote zone of remodeled hearts. The positive (rightward shift in HA in the remote zone is greatest in the subepicardium, but involves all layers of the myocardium. Tractography-based quantification, performed here for the first time in remodeled hearts, may provide a framework for assessing regional changes in the left ventricle following infarction.

  10. Comparison of new bone formation, implant integration, and biocompatibility between RGD-hydroxyapatite and pure hydroxyapatite coating for cementless joint prostheses--an experimental study in rabbits.

    Science.gov (United States)

    Bitschnau, Achim; Alt, Volker; Böhner, Felicitas; Heerich, Katharina Elisabeth; Margesin, Erika; Hartmann, Sonja; Sewing, Andreas; Meyer, Christof; Wenisch, Sabine; Schnettler, Reinhard

    2009-01-01

    This is the first work to report on additional Arginin-Glycin-Aspartat (RGD) coating on precoated hydroxyapatite (HA) surfaces regarding new bone formation, implant bone contact, and biocompatibility compared to pure HA coating and uncoated stainless K-wires. There were 39 rabbits in total with 6 animals for the RGD-HA and HA group for the 4 week time period and 9 animals for each of the 3 implant groups for the 12 week observation. A 2.0 K-wire either with RGD-HA or with pure HA coating or uncoated was placed into the intramedullary canal of the tibia. After 4 and 12 weeks, the tibiae were harvested and three different areas of the tibia were assessed for quantitative and qualitative histology for new bone formation, direct implant bone contact, and formation of multinucleated giant cells. Both RGD-HA and pure HA coating showed statistically higher new bone formation and implant bone contact after 12 weeks than the uncoated K-wire. There were no significant differences between the RGD-HA and the pure HA coating in new bone formation and direct implant bone contact after 4 and 12 weeks. The number of multinucleated giant did not differ significantly between the RGD-HA and HA group after both time points. Overall, no significant effects of an additional RGD coating on HA surfaces were detected in this model after 12 weeks. (c) 2008 Wiley Periodicals, Inc.

  11. Effects of aging and Parkinson's disease on motor unit remodeling: influence of resistance exercise training.

    Science.gov (United States)

    Kelly, Neil A; Hammond, Kelley G; Bickel, C Scott; Windham, Samuel T; Tuggle, S Craig; Bamman, Marcas M

    2018-04-01

    Aging muscle atrophy is in part a neurodegenerative process revealed by denervation/reinnervation events leading to motor unit remodeling (i.e., myofiber type grouping). However, this process and its physiological relevance are poorly understood, as is the wide-ranging heterogeneity among aging humans. Here, we attempted to address 1) the relation between myofiber type grouping and molecular regulators of neuromuscular junction (NMJ) stability; 2) the impact of motor unit remodeling on recruitment during submaximal contractions; 3) the prevalence and impact of motor unit remodeling in Parkinson's disease (PD), an age-related neurodegenerative disease; and 4) the influence of resistance exercise training (RT) on regulators of motor unit remodeling. We compared type I myofiber grouping, molecular regulators of NMJ stability, and the relative motor unit activation (MUA) requirement during a submaximal sit-to-stand task among untrained but otherwise healthy young (YA; 26 yr, n = 27) and older (OA; 66 yr, n = 91) adults and OA with PD (PD; 67 yr, n = 19). We tested the effects of RT on these outcomes in OA and PD. PD displayed more motor unit remodeling, alterations in NMJ stability regulation, and a higher relative MUA requirement than OA, suggesting PD-specific effects. The molecular and physiological outcomes tracked with the severity of type I myofiber grouping. Together these findings suggest that age-related motor unit remodeling, manifested by type I myofiber grouping, 1) reduces MUA efficiency to meet submaximal contraction demand, 2) is associated with disruptions in NMJ stability, 3) is further impacted by PD, and 4) may be improved by RT in severe cases. NEW & NOTEWORTHY Because the physiological consequences of varying amounts of myofiber type grouping are unknown, the current study aims to characterize the molecular and physiological correlates of motor unit remodeling. Furthermore, because exercise training has demonstrated neuromuscular benefits in aged

  12. Advances in Osteobiologic Materials for Bone Substitutes.

    Science.gov (United States)

    Hasan, Anwarul; Byambaa, Batzaya; Morshed, Mahboob; Cheikh, Mohammad Ibrahim; Shakoor, Rana Abdul; Mustafy, Tanvir; Marei, Hany

    2018-04-27

    A significant challenge in the current orthopedics is the development of suitable osteobiologic materials that can replace the conventional allografts, autografts and xenografts, and thereby serve as implant materials as bone substitutes for bone repair or remodeling. The complex biology behind the nano-microstructure of bones and their repair mechanisms, which involve various types of chemical and biomechanical signaling amongst different cells, has set strong requirements for biomaterials to be used in bone tissue engineering. This review presents an overview of various types of osteobiologic materials to facilitate the formation of the functional bone tissue and healing of the bone, covering metallic, ceramic, polymeric and cell-based graft substitutes, as well as some biomolecular strategies including stem cells, extracellular matrices, growth factors and gene therapies. Advantages and disadvantages of each type, particularly from the perspective of osteoinductive and osteoconductive capabilities, are discussed. Although the numerous challenges of bone regeneration in tissue engineering and regenerative medicine are yet to be entirely addressed, further advancements in osteobiologic materials will pave the way towards engineering fully functional bone replacement grafts. This article is protected by copyright. All rights reserved.

  13. Centriole Remodeling during Spermiogenesis in Drosophila.

    Science.gov (United States)

    Khire, Atul; Jo, Kyoung H; Kong, Dong; Akhshi, Tara; Blachon, Stephanie; Cekic, Anthony R; Hynek, Sarah; Ha, Andrew; Loncarek, Jadranka; Mennella, Vito; Avidor-Reiss, Tomer

    2016-12-05

    The first cell of an animal (zygote) requires centrosomes that are assembled from paternally inherited centrioles and maternally inherited pericentriolar material (PCM) [1]. In some animals, sperm centrioles with typical ultrastructure are the origin of the first centrosomes in the zygote [2-4]. In other animals, however, sperm centrioles lose their proteins and are thought to be degenerated and non-functional during spermiogenesis [5, 6]. Here, we show that the two sperm centrioles (the giant centriole [GC] and the proximal centriole-like structure [PCL]) in Drosophila melanogaster are remodeled during spermiogenesis through protein enrichment and ultrastructure modification in parallel to previously described centrosomal reduction [7]. We found that the ultrastructure of the matured sperm (spermatozoa) centrioles is modified dramatically and that the PCL does not resemble a typical centriole. We also describe a new phenomenon of Poc1 enrichment of the atypical centrioles in the spermatozoa. Using various mutants, protein expression during spermiogenesis, and RNAi knockdown of paternal Poc1, we found that paternal Poc1 enrichment is essential for the formation of centrioles during spermiogenesis and for the formation of centrosomes after fertilization in the zygote. Altogether, these findings demonstrate that the sperm centrioles are remodeled both in their protein composition and in ultrastructure, yet they are functional and are essential for normal embryogenesis in Drosophila. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. MicroRNAs in right ventricular remodelling.

    Science.gov (United States)

    Batkai, Sandor; Bär, Christian; Thum, Thomas

    2017-10-01

    Right ventricular (RV) remodelling is a lesser understood process of the chronic, progressive transformation of the RV structure leading to reduced functional capacity and subsequent failure. Besides conditions concerning whole hearts, some pathology selectively affects the RV, leading to a distinct RV-specific clinical phenotype. MicroRNAs have been identified as key regulators of biological processes that drive the progression of chronic diseases. The role of microRNAs in diseases affecting the left ventricle has been studied for many years, however there is still limited information on microRNAs specific to diseases in the right ventricle. Here, we review recently described details on the expression, regulation, and function of microRNAs in the pathological remodelling of the right heart. Recently identified strategies using microRNAs as pharmacological targets or biomarkers will be highlighted. Increasing knowledge of pathogenic microRNAs will finally help improve our understanding of underlying distinct mechanisms and help utilize novel targets or biomarkers to develop treatments for patients suffering from right heart diseases. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  15. The Chromatin Remodeler BPTF Activates a Stemness Gene-Expression Program Essential for the Maintenance of Adult Hematopoietic Stem Cells.

    Science.gov (United States)

    Xu, Bowen; Cai, Ling; Butler, Jason M; Chen, Dongliang; Lu, Xiongdong; Allison, David F; Lu, Rui; Rafii, Shahin; Parker, Joel S; Zheng, Deyou; Wang, Gang Greg

    2018-03-13

    Self-renewal and differentiation of adult stem cells are tightly regulated partly through configuration of chromatin structure by chromatin remodelers. Using knockout mice, we here demonstrate that bromodomain PHD finger transcription factor (BPTF), a component of the nucleosome remodeling factor (NURF) chromatin-remodeling complex, is essential for maintaining the population size of hematopoietic stem/progenitor cells (HSPCs), including long-term hematopoietic stem cells (HSCs). Bptf-deficient HSCs are defective in reconstituted hematopoiesis, and hematopoietic-specific knockout of Bptf caused profound defects including bone marrow failure and anemia. Genome-wide transcriptome profiling revealed that BPTF loss caused downregulation of HSC-specific gene-expression programs, which contain several master transcription factors (Meis1, Pbx1, Mn1, and Lmo2) required for HSC maintenance and self-renewal. Furthermore, we show that BPTF potentiates the chromatin accessibility of key HSC "stemness" genes. These results demonstrate an essential requirement of the chromatin remodeler BPTF and NURF for activation of "stemness" gene-expression programs and proper function of adult HSCs. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Influence of mastication and edentulism on mandibular bone density.

    Science.gov (United States)

    Chou, Hsuan-Yu; Satpute, Devesh; Müftü, Ali; Mukundan, Srinivasan; Müftü, Sinan

    2015-01-01

    The aim of this study was to demonstrate that external loading due to daily activities, including mastication, speech and involuntary open-close cycles of the jaw contributes to the internal architecture of the mandible. A bone remodelling algorithm that regulates the bone density as a function of stress and loading cycles is incorporated into finite element analysis. A three-dimensional computational model is constructed on the basis of computerised tomography (CT) images of a human mandible. Masticatory muscle activation involved during clenching is modelled by static analysis using linear optimisation. Other loading conditions are approximated by imposing mandibular flexure. The simulations predict that mandibular bone density distribution results in a tubular structure similar to what is observed in the CT images. Such bone architecture is known to provide the bone optimum strength to resist bending and torsion during mastication while reducing the bone mass. The remodelling algorithm is used to simulate the influence of edentulism on mandibular bone loss. It is shown that depending on the location and number of missing teeth, up to one-third of the mandibular bone mass can be lost due to lack of adequate mechanical stimulation.

  17. Does methamphetamine affect bone metabolism?

    Science.gov (United States)

    Tomita, Masafumi; Katsuyama, Hironobu; Watanabe, Yoko; Okuyama, Toshiko; Fushimi, Shigeko; Ishikawa, Takaki; Nata, Masayuki; Miyamoto, Osamu

    2014-05-07

    There is a close relationship between the central nervous system activity and bone metabolism. Therefore, methamphetamine (METH), which stimulates the central nervous system, is expected to affect bone turnover. The aim of this study was to investigate the role of METH in bone metabolism. Mice were divided into 3 groups, the control group receiving saline injections, and the 5 and 10mg/kg METH groups (n=6 in each group). All groups received an injection of saline or METH every other day for 8 weeks. Bone mineral density (BMD) was assessed by X-ray computed tomography. We examined biochemical markers and histomorphometric changes in the second cancellous bone of the left femoral distal end. The animals that were administered 5mg/kg METH showed an increased locomotor activity, whereas those receiving 10mg/kg displayed an abnormal and stereotyped behavior. Serum calcium and phosphorus concentrations were normal compared to the controls, whereas the serum protein concentration was lower in the METH groups. BMD was unchanged in all groups. Bone formation markers such as alkaline phosphatase and osteocalcin significantly increased in the 5mg/kg METH group, but not in the 10mg/kg METH group. In contrast, bone resorption markers such as C-terminal telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b did not change in any of the METH groups. Histomorphometric analyses were consistent with the biochemical markers data. A significant increase in osteoblasts, especially in type III osteoblasts, was observed in the 5mg/kg METH group, whereas other parameters of bone resorption and mineralization remained unchanged. These results indicate that bone remodeling in this group was unbalanced. In contrast, in the 10mg/kg METH group, some parameters of bone formation were significantly or slightly decreased, suggesting a low turnover metabolism. Taken together, our results suggest that METH had distinct dose-dependent effects on bone turnover and that METH might

  18. Bone marrow cavity segmentation using graph-cuts with wavelet-based texture feature.

    Science.gov (United States)

    Shigeta, Hironori; Mashita, Tomohiro; Kikuta, Junichi; Seno, Shigeto; Takemura, Haruo; Ishii, Masaru; Matsuda, Hideo

    2017-10-01

    Emerging bioimaging technologies enable us to capture various dynamic cellular activities [Formula: see text]. As large amounts of data are obtained these days and it is becoming unrealistic to manually process massive number of images, automatic analysis methods are required. One of the issues for automatic image segmentation is that image-taking conditions are variable. Thus, commonly, many manual inputs are required according to each image. In this paper, we propose a bone marrow cavity (BMC) segmentation method for bone images as BMC is considered to be related to the mechanism of bone remodeling, osteoporosis, and so on. To reduce manual inputs to segment BMC, we classified the texture pattern using wavelet transformation and support vector machine. We also integrated the result of texture pattern classification into the graph-cuts-based image segmentation method because texture analysis does not consider spatial continuity. Our method is applicable to a particular frame in an image sequence in which the condition of fluorescent material is variable. In the experiment, we evaluated our method with nine types of mother wavelets and several sets of scale parameters. The proposed method with graph-cuts and texture pattern classification performs well without manual inputs by a user.

  19. [Three-dimensional evaluation of condylar morphology remodeling after orthognathic surgery in mandibular retrognathism by cone-beam computed tomography].

    Science.gov (United States)

    Chen, Shuo; Liu, Xiao-jing; Li, Zi-li; Liang, Cheng; Wang, Xiao-xia; Fu, Kai-yuan; Yi, Biao

    2015-08-18

    To evaluate the effect of orthognathic surgery on condylar morphology changes by comparing three-dimension surface reconstructions of condyles using cone-beam computed tomography (CBCT) data. In the study, 18 patients with mandible retrognathism deformities were included and CBCT data of 36 temporomandibular joints were collected before surgery and 12 months after surgery. Condyles were reconstructed and superimposed pre- and post-operatively to compare the changes of condylar surfaces. One-sample t test and χ2 test were performed for the analysis of three-dimension metric measurement and condylar head remodeling signs. P<0.05 was considered significant. The root-mean-square (RMS) of condylar surface changes before and after the surgery was (0.37±0.11) mm, which was significant statistically (P<0.05). The distribution of condylar remodeling signs showed significant difference (P<0.05). Bone resorption occurred predominantly in the posterior area of condylar head and bone formation occurred mainly in the anterior area. Three-dimension superimposition method based on CBCT data showed that condylar morphology had undergone remodeling after mandibular advancement.

  20. Aging and bone. X-ray bone densitometry

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Rikushi (Shiga Univ. of Medical Sciences, Otsu (Japan))

    1994-01-01

    Bone mass at all ages of the individuals is the integration of genetic factors, nutrition, physical exercise, hormonal environments, and other factors influencing the bone. It is also a measurable risk factor for osteoporosis which may subsequently cause bone fractures. Thus measuring bone mass is required to predict the probability of developing bone fractures subsequent to osteoporosis, and to diagnose osteoporosis, and to manage the osteoporosis patient. This paper discusses bone mineral measurements according to their characteristics and clinical application. Methodology for measuring bone mass has rapidly progressed during the past 15 years, which covers photodensitometry, photon absorptiometry (single energy X-ray absorptiometry and dual energy X-ray absorptiometry), quantitative CT, and ultrasound. These techniques have allowed noninvasive measurement of bone mineral density in any site of the skeleton with high accuracy and precision, although a single use of the technique cannot satisfy the complete clinical requirements. Thus the most appropriate method for measuring bone mineral density is important to monitor bone mass change and according to the specific site. (N.K.).

  1. Aging and bone. X-ray bone densitometry

    International Nuclear Information System (INIS)

    Morita, Rikushi

    1994-01-01

    Bone mass at all ages of the individuals is the integration of genetic factors, nutrition, physical exercise, hormonal environments, and other factors influencing the bone. It is also a measurable risk factor for osteoporosis which may subsequently cause bone fractures. Thus measuring bone mass is required to predict the probability of developing bone fractures subsequent to osteoporosis, and to diagnose osteoporosis, and to manage the osteoporosis patient. This paper discusses bone mineral measurements according to their characteristics and clinical application. Methodology for measuring bone mass has rapidly progressed during the past 15 years, which covers photodensitometry, photon absorptiometry (single energy X-ray absorptiometry and dual energy X-ray absorptiometry), quantitative CT, and ultrasound. These techniques have allowed noninvasive measurement of bone mineral density in any site of the skeleton with high accuracy and precision, although a single use of the technique cannot satisfy the complete clinical requirements. Thus the most appropriate method for measuring bone mineral density is important to monitor bone mass change and according to the specific site. (N.K.)

  2. Quantification of osteolytic bone lesions in a preclinical rat trial

    Science.gov (United States)

    Fränzle, Andrea; Bretschi, Maren; Bäuerle, Tobias; Giske, Kristina; Hillengass, Jens; Bendl, Rolf

    2013-10-01

    In breast cancer, most of the patients who died, have developed bone metastasis as disease progression. Bone metastases in case of breast cancer are mainly bone destructive (osteolytic). To understand pathogenesis and to analyse response to different treatments, animal models, in our case rats, are examined. For assessment of treatment response to bone remodelling therapies exact segmentations of osteolytic lesions are needed. Manual segmentations are not only time-consuming but lack in reproducibility. Computerized segmentation tools are essential. In this paper we present an approach for the computerized quantification of osteolytic lesion volumes using a comparison to a healthy reference model. The presented qualitative and quantitative evaluation of the reconstructed bone volumes show, that the automatically segmented lesion volumes complete missing bone in a reasonable way.

  3. Bone and adipose tissue – more and more interdependence

    Directory of Open Access Journals (Sweden)

    Joanna Dytfeld

    2014-11-01

    Full Text Available In bone marrow, osteoblasts and adipocytes originate from common progenitor cells – mesenchymal stem cells (MSCs. The further cell differentiation towards one of the two lines, depending on numerous factors, might have an impact on pathologies of bone in further life. Evidence from experimental and clinical studies indicates multiple reciprocal links between skeleton and adipose tissue. Numerous adipocyte products – leptin, adiponectin, etc. – directly or indirectly affect bone formation and resorption, which take place constantly. This knowledge verifies our views on obesity, osteoporosis and fragility fractures. We also know that bone remodeling, a process that requires energy, is heavily dependent on insulin; moreover, bone is a source of osteocalcin, a hormone whose role goes far beyond determining the level of bone turnover. The endocrine role of the skeleton becomes a reality.

  4. Galectin-3 and post-myocardial infarction cardiac remodeling

    NARCIS (Netherlands)

    Meijers, Wouter C.; van der Velde, A. Rogier; Pascual-Figal, Domingo A.; de Boer, Rudolf A.

    2015-01-01

    This review summarizes the current literature regarding the involvement and the putative role(s) of galectin-3 in post-myocardial infarction cardiac remodeling. Post-myocardial infarction remodeling is characterized by acute loss of myocardium, which leads to structural and biomechanical changes in

  5. Negative remodeling at the ostium of the left circumflex artery.

    Science.gov (United States)

    Kobayashi, Y; Mehran, R; Moussa, I; Reyes, A; Moses, J W

    2001-12-01

    We report an ostial lesion with negative remodeling. Coronary angiography revealed a 60% stenosis at the ostium of the left circumflex artery (LCX). Intravascular ultrasound (IVUS)-guided directional atherectomy followed by stenting was planned. However, IVUS images revealed no significant stenosis and negative remodeling at the ostium of the LCX. The lesion did not undergo intervention.

  6. Bone mineral measurements of subchondral and trabecular bone in healthy and osteoporotic rabbits

    International Nuclear Information System (INIS)

    Castaneda, S; Largo, R.; Marcos, M.E.; Herrero-Beaumont, G.; Calvo, E.; Rodriguez-Salvanes, F.; Diaz-Curiel, M.

    2006-01-01

    Experimental models of osteoporosis in rabbits are useful to investigate anabolic agents because this animal has a fast bone turnover with predominant remodelling over the modelling processes. For that purpose, it is necessary to characterize the densitometric values of each type of bony tissue. To determine areal bone mass measurement in the spine and in trabecular, cortical and subchondral bone of the knee in healthy and osteoporotic rabbits. Bone mineral content and bone mineral density were measured in lumbar spine, global knee, and subchondral and cortical bone of the knee with dual energy X-ray absorptiometry using a Hologic QDR-1000/W densitometer in 29 skeletally mature female healthy New Zealand rabbits. Ten rabbits underwent triplicate scans for evaluation of the effect of repositioning. Osteoporosis was experimentally induced in 15 rabbits by bilateral ovariectomy and postoperative corticosteroid treatment for 4 weeks. Identical dual energy X-ray absorptiometry (DXA) studies were performed thereafter. Mean values of bone mineral content at the lumbar spine, global knee, subchondral bone and cortical tibial metaphysis were: 1934±217 mg, 878±83 mg, 149±14 mg and 29±7.0 mg, respectively. The mean values of bone mineral density at the same regions were: 298±24 mg/cm 2 , 455±32 mg/cm 2 , 617±60 mg/cm 2 and 678±163 mg/cm 2 , respectively. (orig.)

  7. Coupling of Bone Resorption and Formation in Real Time

    DEFF Research Database (Denmark)

    Lassen, Nicolai Ernlund; Andersen, Thomas Levin; Pløen, Gro Grunnet

    2017-01-01

    measurements show that the latter contribute the most to overall resorption. Of note, the density of osteoprogenitors continuously grew along the "reversal/resorption" surface, reaching at least 39 cells/mm on initiation of bone formation. This value was independent of the length of the reversal......It is well known that bone remodeling starts with a resorption event and ends with bone formation. However, what happens in between and how resorption and formation are coupled remains mostly unknown. Remodeling is achieved by so-called basic multicellular units (BMUs), which are local teams...... of osteoclasts, osteoblasts, and reversal cells recently proven identical with osteoprogenitors. Their organization within a BMU cannot be appropriately analyzed in common histology. The originality of the present study is to capture the events ranging from initiation of resorption to onset of formation...

  8. Mechanical Intervention for Maintenance of Cartilage and Bone

    Directory of Open Access Journals (Sweden)

    Hui B. Sun

    2011-01-01

    Full Text Available Mechanical loading provides indispensible stimuli for growth and development of the articular cartilage and bone. Interestingly, depending on loading conditions loads applied to the joint can be beneficial as well as harmful to skeletal maintenance and remodeling. Moderate loads to the synovial joint, for instance, suppress the expression levels of matrix metallproteinases (MMPs, while loads above a threshold tend to increase their destructive activities. This report focuses on two recently developed loading modalities from animal studies, joint motion and joint loading. Their unique characteristics and potential usages for maintenance of the articular cartilage and stimulation of bone remodeling are reviewed. Also described are biophysical and molecular mechanisms which likely are responsible for the load-driven maintenance of cartilage and bone, and a possibility of developing load-mediated treatments of osteoporosis and osteoarthritis.

  9. Bone development

    DEFF Research Database (Denmark)

    Tatara, M.R.; Tygesen, Malin Plumhoff; Sawa-Wojtanowicz, B.

    2007-01-01

    The objective of this study was to determine the long-term effect of alpha-ketoglutarate (AKG) administration during early neonatal life on skeletal development and function, with emphasis on bone exposed to regular stress and used to serve for systemic changes monitoring, the rib. Shropshire ram.......01). Furthermore, AKG administration induced significantly higher bone mineral density of the cortical bone by 7.1% (P

  10. Bone scintigraphy in children

    International Nuclear Information System (INIS)

    Mann, M.D.

    2004-01-01

    Full text: Bone scintigraphy is an integral part of the evaluation of bone disease in children. Common indications are suspected infection or inflammation, bone tumours and metastases, trauma and avascular necrosis. In all these disorders the sensitivity of scintigraphy is high. Gallium scintigraphy is often useful in children with clinical signs of infection not responding to treatment but the radiation dose is high. High quality images are essential. They depend on the full participation and co-operation of the child, parents and radiographers, the administration of appropriate analgesics, gentle but firm handling of the child, the injection of the appropriate amount of radiopharmaceutical, good positioning and immobilization, optimised equipment, and the acquisition of a suitable number of counts in an appropriate matrix size. Unless there are specific reasons for not doing so, we routinely perform two phase bone scintigraphy. This usually involves whole body blood pool and delayed images followed by static images of selected areas and, less often, pinhole images or SPECT. The interpretation of bone scan images in children requires knowledge of the age dependent differences in bone metabolism in the developing skeleton and the effect on the appearance of the maturing skeleton. (author)

  11. The BRCA1 Ubiquitin ligase function sets a new trend for remodelling in DNA repair.

    Science.gov (United States)

    Densham, Ruth M; Morris, Joanna R

    2017-03-04

    The protein product of the breast and ovarian cancer gene, BRCA1, is part of an obligate heterodimer with BARD1. Together these RING bearing proteins act as an E3 ubiquitin ligase. Several functions have been attributed to BRCA1 that contribute to genome integrity but which of these, if any, require this enzymatic function was unclear. Here we review recent studies clarifying the role of BRCA1 E3 ubiquitin ligase in DNA repair. Perhaps the most surprising finding is the narrow range of BRCA1 functions this activity relates to. Remarkably ligase activity promotes chromatin remodelling and 53BP1 positioning through the remodeller SMARCAD1, but the activity is dispensable for the cellular survival in response to cisplatin or replication stressing agents. Implications for therapy response and tumor susceptibility are discussed.

  12. ATM-dependent pathways of chromatin remodelling and oxidative DNA damage responses.

    Science.gov (United States)

    Berger, N Daniel; Stanley, Fintan K T; Moore, Shaun; Goodarzi, Aaron A

    2017-10-05

    Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase with a master regulatory function in the DNA damage response. In this role, ATM commands a complex biochemical network that signals the presence of oxidative DNA damage, including the dangerous DNA double-strand break, and facilitates subsequent repair. Here, we review the current state of knowledge regarding ATM-dependent chromatin remodelling and epigenomic alterations that are required to maintain genomic integrity in the presence of DNA double-strand breaks and/or oxidative stress. We will focus particularly on the roles of ATM in adjusting nucleosome spacing at sites of unresolved DNA double-strand breaks within complex chromatin environments, and the impact of ATM on preserving the health of cells within the mammalian central nervous system.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'. © 2017 The Author(s).

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

    DEFF Research Database (Denmark)

    Ding, Ming

    2000-01-01

    , such as apparent, apparent ash and collagen densities of human tibial trabecular bone have significant relationships with age. Tissue density and mineral concentration remain constant throughout life. Trabecular bone is tougher in the younger age, i.e. fracture requires more energy. Collagen density was the single......Initiated and motivated by clinical and scientific problems such as age-related bone fracture, prosthetic loosening, bone remodeling, and degenerative bone diseases, much significant research on the properties of trabecular bone has been carried out over the last two decades. This work has mainly...... focused on the central vertebral trabecular bone, while little is known about age-related changes in the properties of human peripheral (tibial) trabecular bone. Knowledge of the properties of peripheral (tibial) trabecular bone is of major importance for the understanding of degenerative diseases...

  14. Current options for the treatment of Paget’s disease of the bone

    Directory of Open Access Journals (Sweden)

    Daniela Merlotti

    2009-07-01

    Full Text Available Daniela Merlotti, Luigi Gennari, Giuseppe Martini, Ranuccio NutiDepartment of Internal Medicine, Endocrine-Metabolic Sciences and Biochemistry, University of Siena, Siena, ItalyAbstract: Paget’s disease of bone (PDB is a chronic bone remodeling disorder characterized by increased osteoclast-mediated bone resorption, with subsequent compensatory increases in new bone formation, resulting in a disorganized mosaic of woven and lamellar bone at affected skeletal sites. This disease is most often asymptomatic but can be associated with bone pain or deformity, fractures, secondary arthritis, neurological complications, deafness, contributing to substantial morbidity and reduced quality of life. Neoplastic degeneration of pagetic bone is a relatively rare event, occurring with an incidence of less than 1%, but has a grave prognosis. Specific therapy for PDB is aimed at decreasing the abnormal bone turnover and bisphosphonates are currently considered the treatment of choice. These treatments are associated with a reduction in plasma alkaline phosphatase (ALP activity and an improvement in radiological and scintigraphic appearance and with a reduction in bone pain and bone deformity, Recently, the availability of newer, more potent nitrogen-containing bisphosphonates has improved treatment outcomes, allowing a more effective and convenient management of this debilitating disorder.Keywords: Paget’s disease of bone, bisphosphonates, aminobisphosphonates, bone remodeling

  15. Bulk physicochemical, interconnectivity, and mechanical properties of calcium phosphate cements-fibrin glue composites for bone substitute applications

    NARCIS (Netherlands)

    Lopez-Heredia, M.A.; Pattipeilohy, J.; Hsu, S.; Grykien, M.; Weijden, B. van der; Leeuwenburgh, S.C.G.; Salmon, P.; Wolke, J.G.C.; Jansen, J.A.

    2013-01-01

    Calcium phosphate cements (CPCs) and fibrin glue (FG) are used for surgical applications. Their combination is promising to create bone substitutes able to promote cell attachment and bone remodeling. This study proposes a novel approach to create CPC-FG composites by simultaneous CPC setting and FG

  16. Dynamics of bone graft healing around implants

    Directory of Open Access Journals (Sweden)

    Narayan Venkataraman

    2015-01-01

    A few questions arise pertaining to the use of bone grafts along with implants are whether these are successful in approximation with implant. Do they accelerate bone regeneration? Are all defects ultimately regenerated with new viable bone? Is the bone graft completely resorbed or integrated in new bone? Does the implant surface characteristic positively affect osseointegration when used with a bone graft? What type of graft and implant surface can be used that will have a positive effect on the healing type and time? Finally, what are the dynamics of bone graft healing around an implant? This review discusses the cellular and molecular mechanisms of bone graft healing in general and in vicinity of another foreign, avascular body, namely the implant surface, and further, the role of bone grafts in osseointegration and/or clinical success of the implants.

  17. Hydroxyapatite/collagen bone-like nanocomposite.

    Science.gov (United States)

    Kikuchi, Masanori

    2013-01-01

    Our group has succeeded to synthesize material with bone-like nanostructure and bone-like inorganic and organic composition via self-organization mechanism between them using simultaneous titration method under controlled pH and temperature. The hydroxyapatite/collagen (HAp/Col) bone-like nanocomposite completely incorporated into bone remodeling process to be substituted by new bone. Cells cultured on the HAp/Col revealed very interesting reactions. Osteoblast-like MG63 cells showed upregulation of alkaline phosphatase >3 times greater than MG63 cells cultured on tissue culture polystyrene (TCPS). MG63 cells 3-dimensionally cultured in a "HAp/Col sponge," a porous HAp/Col having sponge-like viscoelasticity, accumulated calcium phosphate nodules on extracellular matrices they secreted. Bone marrow cells co-cultured with osteoblasts on HAp/Col differentiated to osteoclasts without differentiation supplements. This phenomenon is not found in cells cultured on hydroxyapatite ceramics and TCPS, and rarely in cells cultured on dentin. These results suggest that HAp/Col is a good candidate for tissue engineering of bone as well as bone filler. In a clinical test as a bone filler, the HAp/Col sponge was significantly better than porous β-tricalcium phosphate. The HAp/Col sponge has been approved by the Japanese government and will be used as greatly needed bone filler in patients. In addition to the above, HAp/Col coating on titanium revealed higher osteo-conductivity than HAp-coated titanium and bare titanium and improved direct bonding between titanium and newly formed bone. The HAp/Col coating may be used for metal devices requiring osseointegration.

  18. Molecular mechanisms of synaptic remodeling in alcoholism.

    Science.gov (United States)

    Kyzar, Evan J; Pandey, Subhash C

    2015-08-05

    Alcohol use and alcohol addiction represent dysfunctional brain circuits resulting from neuroadaptive changes during protracted alcohol exposure and its withdrawal. Alcohol exerts a potent effect on synaptic plasticity and dendritic spine formation in specific brain regions, providing a neuroanatomical substrate for the pathophysiology of alcoholism. Epigenetics has recently emerged as a critical regulator of gene expression and synaptic plasticity-related events in the brain. Alcohol exposure and withdrawal induce changes in crucial epigenetic processes in the emotional brain circuitry (amygdala) that may be relevant to the negative affective state defined as the "dark side" of addiction. Here, we review the literature concerning synaptic plasticity and epigenetics, with a particular focus on molecular events related to dendritic remodeling during alcohol abuse and alcoholism. Targeting epigenetic processes that modulate synaptic plasticity may yield novel treatments for alcoholism. Published by Elsevier Ireland Ltd.

  19. Matrix Remodeling in Pulmonary Fibrosis and Emphysema

    Science.gov (United States)

    O’Reilly, Philip; Antony, Veena B.; Gaggar, Amit

    2016-01-01

    Pulmonary fibrosis and emphysema are chronic lung diseases characterized by a progressive decline in lung function, resulting in significant morbidity and mortality. A hallmark of these diseases is recurrent or persistent alveolar epithelial injury, typically caused by common environmental exposures such as cigarette smoke. We propose that critical determinants of the outcome of the injury-repair processes that result in fibrosis versus emphysema are mesenchymal cell fate and associated extracellular matrix dynamics. In this review, we explore the concept that regulation of mesenchymal cells under the influence of soluble factors, in particular transforming growth factor-β1, and the extracellular matrix determine the divergent tissue remodeling responses seen in pulmonary fibrosis and emphysema. PMID:26741177

  20. Haloperidol Selectively Remodels Striatal Indirect Pathway Circuits

    Science.gov (United States)

    Sebel, Luke E; Graves, Steven M; Chan, C Savio; Surmeier, D James

    2017-01-01

    Typical antipsychotic drugs are widely thought to alleviate the positive symptoms of schizophrenia by antagonizing dopamine D2 receptors expressed by striatal spiny projection neurons (SPNs). What is less clear is why antipsychotics have a therapeutic latency of weeks. Using a combination of physiological and anatomical approaches in ex vivo brain slices from transgenic mice, it was found that 2 weeks of haloperidol treatment induced both intrinsic and synaptic adaptations specifically within indirect pathway SPNs (iSPNs). Perphenazine treatment had similar effects. Some of these adaptations were homeostatic, including a drop in intrinsic excitability and pruning of excitatory corticostriatal glutamatergic synapses. However, haloperidol treatment also led to strengthening of a subset of excitatory corticostriatal synapses. This slow remodeling of corticostriatal iSPN circuitry is likely to play a role in mediating the delayed therapeutic action of neuroleptics. PMID:27577602