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Sample records for bone formation capacity

  1. Assessment of bone formation capacity using in vivo transplantation assays: procedure and tissue analysis

    DEFF Research Database (Denmark)

    Abdallah, Basem; Ditzel, Nicholas; Kassem, Moustapha

    2008-01-01

    In vivo assessment of bone formation (osteogenesis) potential by isolated cells is an important method for analysis of cells and factors control ling bone formation. Currently, cell implantation mixed with hydroxyapa-tite/tricalcium phosphate in an open system (subcutaneous implantation) in immun...... transplantation methods in testing bone formationpotential of human mesenchymal stem cells.......In vivo assessment of bone formation (osteogenesis) potential by isolated cells is an important method for analysis of cells and factors control ling bone formation. Currently, cell implantation mixed with hydroxyapa-tite/tricalcium phosphate in an open system (subcutaneous implantation......) in immunodeficient mice is the standard method for in vivo assessment of bone formation capacity of a particular cell type. The method is easy to perform and provides reproducible results. Assessment of the donor origin of tissue formation is possible, especially in the case of human-to-mouse transplanta tion...

  2. Association between in vivo bone formation and ex vivo migratory capacity of human bone marrow stromal cells

    DEFF Research Database (Denmark)

    Andersen, Rikke K; Zaher, Walid; Larsen, Kenneth H

    2015-01-01

    INTRODUCTION: There is a clinical need for developing systemic transplantation protocols for use of human skeletal stem cells (also known bone marrow stromal stem cells) (hBMSC) in tissue regeneration. In systemic transplantation studies, only a limited number of hBMSC home to injured tissues...... by bioluminescence imaging (BLI). In order to identify the molecular phenotype associated with enhanced migration, we carried out comparative DNA microarray analysis of gene expression of hBMSC-derived high bone forming (HBF) clones versus low bone forming (LBF) clones. RESULTS: HBF clones were exhibited higher ex...... vivo transwell migration and following intravenous injection, better in vivo homing ability to bone fracture when compared to LBF clones. Comparative microarray analysis of HBF versus LBF clones identified enrichment of gene categories of chemo-attraction, adhesion and migration associated genes. Among...

  3. Identifying A Molecular Phenotype for Bone Marrow Stromal Cells With In Vivo Bone Forming Capacity

    DEFF Research Database (Denmark)

    Larsen, Kenneth H; Frederiksen, Casper M; Burns, Jorge S

    2009-01-01

    Abstract The ability of bone marrow stromal cells (BMSCs) to differentiate into osteoblasts is being exploited in cell-based therapy for repair of bone defects. However, the phenotype of ex vivo cultured BMSCs predicting their bone forming capacity is not known. Thus, we employed DNA microarrays...... comparing two human bone marrow stromal cell (hBMSC) populations: one is capable of in vivo heterotopic bone formation (hBMSC-TERT(+Bone)) and the other is not (hBMSC-TERT(-Bone)). Compared to hBMSC-TERT(-Bone), the hBMSC-TERT(+Bone) cells had an increased over-representation of extracellular matrix genes...... (17% versus 5%) and a larger percentage of genes with predicted SP3 transcription factor binding sites in their promoter region (21% versus 8%). On the other hand, hBMSC-TERT(-Bone) cells expressed a larger number of immune-response related genes (26% versus 8%). In order to test for the predictive...

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

    DEFF Research Database (Denmark)

    Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

    2011-01-01

    of fractures. Studies in rodents and humans revealed that, independent of sex hormone deficiency, the age-related decline in bone formation is characterized by decreased osteoblast number and lifespan and reduced bone-forming capacity of individual osteoblasts. An important clinical question is to identify...

  5. Understanding coupling between bone resorption and formation

    DEFF Research Database (Denmark)

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

    2013-01-01

    Bone remodeling requires bone resorption by osteoclasts, bone formation by osteoblasts, and a poorly investigated reversal phase coupling resorption to formation. Likely players of the reversal phase are the cells recruited into the lacunae vacated by the osteoclasts and presumably preparing...... these lacunae for bone formation. These cells, called herein reversal cells, cover >80% of the eroded surfaces, but their nature is not identified, and it is not known whether malfunction of these cells may contribute to bone loss in diseases such as postmenopausal osteoporosis. Herein, we combined...... physiological status. Their prevalence correlated with decreased trabecular bone volume and osteoid and osteoblast surfaces in postmenopausal osteoporosis. They were, however, virtually absent in primary hyperparathyroidism, in which the transition between bone resorption and formation occurs optimally...

  6. Bone formation in axial spondyloarthritis.

    Science.gov (United States)

    Lories, Rik J; Haroon, Nigil

    2014-10-01

    The success of targeted therapies directed against tumor necrosis factor for patients with spondyloarthritis has shifted the focus of physicians and scientists towards the prevention of structural damage to the involved structures, in particular the sacroiliac joints and the spine, to avoid loss of function and disability. Structural damage to the skeleton as witnessed by radiography mainly consists of new bone formation potentially progressively leading to spine or joint ankylosis. This important long-term outcome parameter has been difficult to study, not alone because the time window for change may be long but also because human tissues with direct translational relevance are rarely available. Data from rodent models have identified growth factor signaling pathways as relevant targets. Both human and animal studies have tried to understand the link between inflammation and new bone formation. At the current moment, most evidence points towards a strong link between both but with the question still lingering about the sequence of events, disease triggers, and the interdependence of both features of disease. New discoveries such as a masterswitch T cell population that carries the IL23 receptor and the analysis of auto-antibodies directed again noggin and sclerostin are contributing to innovative insights into the pathophysiology of disease. Long-term data with tumor necrosis factor (TNF) inhibitors also suggest that some window of opportunity may exist to inhibit structural disease progression. All these data provide support for a further critical analysis of the available datasets and boost research in the field. The introduction of novel disease definitions, in particular the characterization of non-radiographic axial spondyloarthritis patients, will likely be instrumental in our further understanding of structural damage. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Lutein Enhances Bone Mass by Stimulating Bone Formation and Suppressing Bone Resorption in Growing Mice.

    Science.gov (United States)

    Takeda, Hiroshi; Tominari, Tsukasa; Hirata, Michiko; Watanabe, Kenta; Matsumoto, Chiho; Grundler, Florian M W; Inada, Masaki; Miyaura, Chisato

    2017-01-01

    Lutein is a member of the xanthophyll family of carotenoids, which are known to prevent hypoxia-induced cell damage in the eye by removing free radicals. However, its role in other tissues is controversial, and the effects of lutein on bone tissues are unknown. To identify a possible role of lutein in bone tissues, we examined the effects of lutein on bone formation and bone resorption and on femoral bone mass in mice. Lutein enhanced the formation of mineralized bone nodules in cultures of osteoblasts. On the other hand, lutein clearly suppressed 1α, 25-dihydroxyvitamin D 3 -induced bone resorption as measured by pit formation in organ culture of mouse calvaria. In co-cultures of bone marrow cells and osteoblasts, lutein suppressed 1α, 25-dihydroxyvitamin D 3 -induced osteoclast formation. In cultures of bone marrow macrophages, lutein suppressed soluble RANKL, the receptor activator of nuclear factor-kappaB (NF-κB) ligand, induced osteoclast formation. When five-week-old male mice were orally administered lutein for 4 weeks, the femoral bone mass was clearly enhanced in cortical bone, as measured by bone mineral density in dual X-ray absorptiometry and micro computed tomography (µCT) analyses. The present study indicates that lutein enhances bone mass in growing mice by suppressing bone resorption and stimulating bone formation. Lutein may be a natural agent that promotes bone turnover and may be beneficial for bone health in humans.

  8. Local induction of inflammation affects bone formation

    NARCIS (Netherlands)

    Croes, M.; Kruyt, M. C.; Loozen, L.; Kragten, A. H M; Yuan, H.; Dhert, W. J.; Öner, F. C.; Alblas, Jacqueline

    2017-01-01

    To explore the influence of inflammatory processes on bone formation, we applied a new in vivo screening model. Confined biological pockets were first created in rabbits as a response to implanted bone cement discs. These biomembrane pockets were subsequently used to study the effects of

  9. Biomimetic matrices self-initiating the induction of bone formation.

    Science.gov (United States)

    Ripamonti, Ugo; Roden, Laura C; Ferretti, Carlo; Klar, Roland M

    2011-09-01

    intelligent scaffolds for tissue engineering of bone. The concavities assembled in the bioceramic constructs biomimetize the remodeling cycle of the corticocancellous bone and are endowed with multifunctional pleiotropic self-assembly capacities, initiating angiogenesis and bone formation by induction without the exogenous applications of the osteogenic-soluble molecular signals of the transforming growth factor β supergene family. The incorporation of specific biologic activities into biomimetic matrices by manipulating the geometry of the substratum, defined as geometric induction of bone formation, is now helping to engineer therapeutic osteogenesis in clinical contexts.

  10. Heterotopic bone formation following total shoulder arthroplasty

    DEFF Research Database (Denmark)

    Kjaersgaard-Andersen, P.; Frich, Lars Henrik; Sjøbjerg, J.O.

    1989-01-01

    the glenohumeral and/or the glenoacromial space. There was no correlation between shoulder pain and the development of ossification. Shoulders with grade III heterotopic bone formation had a limited range of active elevation compared with shoulders without or with only a milder lesion. Men and patients......The incidence and location of heterotopic bone formation following total shoulder arthroplasty were evaluated in 58 Neer Mark-II total shoulder replacements. One year after surgery, 45% had developed some ectopic ossification. In six shoulders (10%) the ossifications roentgenographically bridged...... with osteoarthritis of the shoulder joint were significantly disposed to the development of heterotopic bone. Heterotopic bone formation following total shoulder arthroplasty is frequent, but disabling heterotopic ossifications seem to be rare....

  11. Bioactivity And Bone Formation In Silicon-Substituted Hydroxyapatite

    Directory of Open Access Journals (Sweden)

    Ulvan Ozad

    2012-06-01

    Full Text Available Bioactivity and successful bone formation in silicon-substituted hydroxyapatite bone grafts were investigated by using scanning electron microscopy and electron dispersive x-ray spectroscopy. Areas of bone formation have been detected in scanning electron microscopy; and, arranged lamellar collagen has been observed. 20.8% average carbon content rise has been detected between bone graft and the produced bone; and, this has been confirmed to be a gradual increase throughout the interphase. Obvious bone formation and maturation were observed in the samples. Carbon content gradually increased from bone graft to the bone formed, confirming formation of new bone and dissociation of silicon-substituted bone graft.

  12. Histologic evaluation of bone healing capacity following application of inorganic bovine bone and a new allograft material in rabbit calvaria.

    Directory of Open Access Journals (Sweden)

    Mojgan Paknejad

    2015-02-01

    Full Text Available Considering the importance of bone augmentation prior to implant placement in order to obtain adequate bone quality and quantity, many studies have been conducted to evaluate different techniques and materials regarding new bone formation. In this study, we investigated the bone healing capacity of two different materials deproteinized bovine bone mineral (DBBM with the trade name of Bio-Oss and demineralized freeze-dried bone allograft (DFDBA with the trade name of DynaGraft.This randomized blinded prospective study was conducted on twelve New Zealand white rabbits. Three cranial defects with an equal diameter were created on their calvarium. Subsequently, they were distributed into three groups: 1. The control group without any treatment; 2. The Bio-Oss group; 3. The DynaGraft group. After 30 days, the animals were sacrificed for histologic and histomorphometric analysis.Substantial new bone formation was observed in both groups. DynaGraft: 56/1 % ± 15/1 and Bio-Oss: 53/55 % ± 13/5 compared to the control group: 28/6 % ± 11/2. All groups showed slight inflammation and a small amount of residual biomaterial was observed.Considerable new bone formation was demonstrated in both DynaGraft and Bio-Oss groups in comparison with the control group. Both materials are considered biocompatible regarding the negligible foreign body reaction.

  13. Does simvastatin stimulate bone formation in vivo?

    Directory of Open Access Journals (Sweden)

    Chorev Michael

    2003-04-01

    Full Text Available Abstract Background Statins, potent compounds that inhibit cholesterol synthesis in the liver have been reported to induce bone formation, both in tissue culture and in rats and mice. To re-examine potential anabolic effects of statins on bone formation, we compared the activity of simvastatin (SVS to the known anabolic effects of PTH in an established model of ovariectomized (OVX Swiss-Webster mice. Methods Mice were ovariectomized at 12 weeks of age (T0, remained untreated for 5 weeks to allow development of osteopenia (T5, followed by treatment for 8 weeks (T13. Whole, trabecular and cortical femoral bone was analyzed by micro-computed tomography (micro CT. Liquid chromatography/mass spectrometry (LC/MS was used to detect the presence of SVS and its active metabolite, simvastatin β-hydroxy acid (SVS-OH in the mouse serum. Results Trabecular BV/TV at T13 was 4.2 fold higher in animals treated with PTH (80 micro-g/kg/day compared to the OVX-vehicle treated group (p in vivo study. Conclusions While PTH demonstrated the expected anabolic effect on bone, SVS failed to stimulate bone formation, despite our verification by LC/MS of the active SVS-OH metabolite in mouse serum. While statins have clear effects on bone formation in vitro, the formulation of existing 'liver-targeted' statins requires further refinement for efficacy in vivo.

  14. Bone marrow-derived mesenchymal cells can rescue osteogenic capacity of devitalized autologous bone.

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    Tohma, Yasuaki; Ohgushi, Hajime; Morishita, Toru; Dohi, Yoshiko; Tadokoro, Mika; Tanaka, Yasuhito; Takakura, Yoshinori

    2008-01-01

    In clinical cases, many orthopaedists have been troubled with bone fragility, such as fractures after devitalization therapy for bone tumour, pathological fractures and metastatic tumours. The aim of this study was to determine whether loss of osteogenic capacity of devitalized autologous bones can be rescued using cultured bone marrow-derived mesenchymal cells. A devitalized bone model was produced from rat femur by irradiation and three groups were prepared: intact bone, irradiated bone and irradiated bone combined with cultured mesenchymal cells. Each bone was transplanted subcutaneously into a syngeneic rat. At 2 or 4 weeks after transplantation, biochemical analyses [alkaline phosphatase (ALP) activity and osteocalcin mRNA expression] and histological measurement were performed. Moreover, we verified the origin of newly formed bone, using the sex-determining region Y (sry) gene as a marker to distinguish between donor and recipient. In both intact bone and irradiated bone with mesenchymal cells, ALP activity and osteocalcin mRNA expression were detected and living osteoblasts together with newly formed bone were clearly seen histologically. Furthermore, analysis of the origin of de novo formed bone indicated that newly formed bone in irradiated bone with mesenchymal cells was derived from cultured bone marrow-derived mesenchymal cells. These results proved that the osteogenic capacity of devitalized autologous bone can be rescued using tissue-engineering techniques. This procedure should contribute to various clinical treatments, such as local metastatic tumours, pathological fracture after devitalization therapy and reconstruction after wide-margin tumour resection. The benefits would be applicable to all types of devitalized bone. Copyright (c) 2008 John Wiley & Sons, Ltd.

  15. Bone formation using human demineralised bone matrix (Grafton) for the treatment of bone cysts in children.

    Science.gov (United States)

    Hass, H-J; Krause, H; Kroker, S; Wagemann, W; Meyer, F

    2007-02-01

    Bone cysts, in particular solitary bone cysts, are the most frequent cause of pathological fractures in children. However, there is still a great variety of regimens used to treat these lesions. Since demineralised bone matrix (DBM) is commercially available, we aimed to use this material for the consolidation of bones diagnosed as fragile because of cyst formation. Each of the 7 bone cysts as well as one enchondroma filled with DBM showed a continuous decrease in bone transparency over a period of two years (mean 8 months). A significant decrease in bone transparency and simultaneous cortical remodelling was radiographically detected in these cases as the specific hallmark of an initiated graft incorporation after 3 to 4 months. It was demonstrated that it is possible to heal children within an acceptable period of time using DBM to fill the cystic lesion. DBM appears to be a reasonable and beneficial alternative for the treatment of bone cysts offering both osteoinduction and osteoconductive features.

  16. Regenerative capacity of augmented bone in rat calvarial guided bone augmentation model.

    Science.gov (United States)

    Kubota, Tatsuya; Hasuike, Akira; Ozawa, Yasumasa; Yamamoto, Takanobu; Tsunori, Katsuyoshi; Yamada, Yutaka; Sato, Shuichi

    2017-04-01

    Guided bone regeneration (GBR) is the most widely used technique to regenerate and augment bones. Even though augmented bones (ABs) have been examined histologically in many studies, few studies have been conducted to examine the biological potential of these bones and the healing dynamics following their use. Moreover, whether the bone obtained from the GBR procedure possesses the same functions as the existing autogenous bone is uncertain. In particular, little attention has been paid to the regenerative ability of GBR bone. Therefore, the present study histologically evaluated the regenerative capacity of AB in the occlusive space of a rat guided bone augmentation (GBA) model. The calvaria of 30 rats were exposed, and plastic caps were placed on the right of the calvaria in 10 of the 30 rats. After a 12-week healing phase, critical-sized calvarial bone defects (diameter: 5.0 mm) were trephined into the dorsal parietal bone on the left of the calvaria. Bone particles were harvested from the AB or the cortical bone (CB) using a bone scraper and transplanted into the critical defects. The newly generated bone at the defects' edge was evaluated using micro-computed tomography (micro-CT) and histological sections. In the micro-CT analysis, the radiopacity in both the augmented and the CB groups remained high throughout the observational period. In the histological analysis, the closure rate of the CB was significantly higher than in the AB group. The numbers of cells positive for runt-related transcription factor 2 (Runx2) and tartrate-resistant acid phosphatase (TRAP) in the AB group were larger than in the CB group. The regenerative capacity of AB in the occlusive space of the rat GBA model was confirmed. Within the limitations of this study, the regenerative ability of the AB particulate transplant was inferior to that of the CB particulate transplant.

  17. Bone char quality and defluoridation capacity in contact precipitation

    DEFF Research Database (Denmark)

    Albertus, J.; Bregnhøj, Henrik; Kongpun, M.

    2002-01-01

    Samples from six different brands of bone char are tested for their capacity to remove fluoride from water in batch. Initial concentrations of 10 mg/L and contact times of 6 hours are used. The removal capacities observed are 0.6-1.1 mg/g on an average, s.d. being 0.16. Addition of calcium...... and phosphate compounds to the jar experiments results in more than doubling of these capacities, on average 1.9 mg/g, s.d. being 0.14. One of bone char products is setup in columns are fed with water, 100 mg/L, for saturation. Hereafter the coloumns are fed with water of 10 mgF/L where calcium and phosphate...

  18. Osteoclasts secrete non-bone derived signals that induce bone formation

    DEFF Research Database (Denmark)

    Karsdal, Morten A; Neutzsky-Wulff, Anita V; Dziegiel, Morten Hanefeld

    2008-01-01

    Bone turnover is a highly regulated process, where bone resorption in the normal healthy individual always is followed by bone formation in a manner referred to as coupling. Patients with osteopetrosis caused by defective acidification of the resorption lacuna have severely decreased resorption......, in face of normal or even increased bone formation. This suggests that osteoclasts, not their resorptive activity, are important for sustaining bone formation. To investigate whether osteoclasts mediate control of bone formation by production of bone anabolic signals, we collected conditioned media (CM...

  19. Enhancement of bone formation in rabbits by recombinant human growth hormone

    International Nuclear Information System (INIS)

    Ehrnberg, A.; Brosjoe, O.; Laaftman, P.; Nilsson, O.; Stroemberg, L.

    1993-01-01

    We studied the effect of human recombinant growth hormone on diaphyseal bone in 40 adult rabbits. The diaphyseal periosteum of one femur in each animal was mechanically stimulated by a nylon cerclage band. The bands induced an increase in bone formation, bone mineral content, and maximum torque capacity of the diaphyseal bone at 1 and 2 months. Growth hormone enhanced the anabolic effect of the cerclage bands on bone metabolism, evidenced by a further increase in torsional strength of the femurs. (au) (32 refs.)

  20. Hydroxyapatite formation from cuttlefish bones: kinetics.

    Science.gov (United States)

    Ivankovic, H; Tkalcec, E; Orlic, S; Ferrer, G Gallego; Schauperl, Z

    2010-10-01

    Highly porous hydroxyapatite (Ca(10)(PO(4))(6)·(OH)(2), HA) was prepared through hydrothermal transformation of aragonitic cuttlefish bones (Sepia officinalis L. Adriatic Sea) in the temperature range from 140 to 220°C for 20 min to 48 h. The phase composition of converted hydroxyapatite was examined by quantitative X-ray diffraction (XRD) using Rietveld structure refinement and Fourier transform infrared spectroscopy (FTIR). Johnson-Mehl-Avrami (JMA) approach was used to follow the kinetics and mechanism of transformation. Diffusion controlled one dimensional growth of HA, predominantly along the a-axis, could be defined. FTIR spectroscopy determined B-type substitutions of CO(3) (2-) groups. The morphology and microstructure of converted HA was examined by scanning electron microscopy. The general architecture of cuttlefish bones was preserved after hydrothermal treatment and the cuttlefish bones retained its form with the same channel size (~80 × 300 μm). The formation of dandelion-like HA spheres with diameter from 3 to 8 μm were observed on the surface of lamellae, which further transformed into various radially oriented nanoplates and nanorods with an average diameter of about 200-300 nm and an average length of about 8-10 μm.

  1. Human decellularized bone scaffolds from aged donors show improved osteoinductive capacity compared to young donor bone.

    Directory of Open Access Journals (Sweden)

    Christopher A Smith

    Full Text Available To improve the safe use of allograft bone, decellularization techniques may be utilized to produce acellular scaffolds. Such scaffolds should retain their innate biological and biomechanical capacity and support mesenchymal stem cell (MSC osteogenic differentiation. However, as allograft bone is derived from a wide age-range, this study aimed to determine whether donor age impacts on the ability an osteoinductive, acellular scaffold produced from human bone to promote the osteogenic differentiation of bone marrow MSCs (BM-MSC. BM-MSCs from young and old donors were seeded on acellular bone cubes from young and old donors undergoing osteoarthritis related hip surgery. All combinations resulted in increased osteogenic gene expression, and alkaline phosphatase (ALP enzyme activity, however BM-MSCs cultured on old donor bone displayed the largest increases. BM-MSCs cultured in old donor bone conditioned media also displayed higher osteogenic gene expression and ALP activity than those exposed to young donor bone conditioned media. ELISA and Luminex analysis of conditioned media demonstrated similar levels of bioactive factors between age groups; however, IGF binding protein 1 (IGFBP1 concentration was significantly higher in young donor samples. Additionally, structural analysis of old donor bone indicated an increased porosity compared to young donor bone. These results demonstrate the ability of a decellularized scaffold produced from young and old donors to support osteogenic differentiation of cells from young and old donors. Significantly, the older donor bone produced greater osteogenic differentiation which may be related to reduced IGFBP1 bioavailability and increased porosity, potentially explaining the excellent clinical results seen with the use of allograft from aged donors.

  2. Roles of Chondrocytes in Endochondral Bone Formation and Fracture Repair.

    Science.gov (United States)

    Hinton, R J; Jing, Y; Jing, J; Feng, J Q

    2017-01-01

    The formation of the mandibular condylar cartilage (MCC) and its subchondral bone is an important but understudied topic in dental research. The current concept regarding endochondral bone formation postulates that most hypertrophic chondrocytes undergo programmed cell death prior to bone formation. Under this paradigm, the MCC and its underlying bone are thought to result from 2 closely linked but separate processes: chondrogenesis and osteogenesis. However, recent investigations using cell lineage tracing techniques have demonstrated that many, perhaps the majority, of bone cells are derived via direct transformation from chondrocytes. In this review, the authors will briefly discuss the history of this idea and describe recent studies that clearly demonstrate that the direct transformation of chondrocytes into bone cells is common in both long bone and mandibular condyle development and during bone fracture repair. The authors will also provide new evidence of a distinct difference in ossification orientation in the condylar ramus (1 ossification center) versus long bone ossification formation (2 ossification centers). Based on our recent findings and those of other laboratories, we propose a new model that contrasts the mode of bone formation in much of the mandibular ramus (chondrocyte-derived) with intramembranous bone formation of the mandibular body (non-chondrocyte-derived).

  3. Impact of bone graft harvesting techniques on bone formation and graft resorption

    DEFF Research Database (Denmark)

    Saulacic, Nikola; Bosshardt, Dieter D; Jensen, Simon S

    2015-01-01

    in the mandibles of 12 minipigs. The animals were sacrificed after 1, 2, 4 and 8 weeks of healing. Histology and histomorphometrical analyses were performed to assess bone formation and graft resorption. An explorative statistical analysis was performed. RESULTS: The amount of new bone increased, while the amount......: Transplantation of autogenous bone particles harvested with four techniques in the present model resulted in moderate differences in terms of bone formation and graft resorption....

  4. Biomimetism, biomimetic matrices and the induction of bone formation.

    Science.gov (United States)

    Ripamonti, Ugo

    2009-09-01

    the induction of bone formation, the emergence of the skeleton, of the vertebrates and of Homo species * Different strategies for the induction of bone formation. Biological significance of redundancy and synergistic induction of bone formation. Biomimetism and biomimetic matrices self-assembling the induction of bone formation The concavity: the shape of life and the induction of bone formation. Influence of geometry on the expression of the osteogenic phenotype. Conclusion and therapeutic perspectives on porous biomimetic matrices with intrinsic osteoinductivity Bone formation by induction initiates by invocation of osteogenic soluble molecular signals of the transforming growth factor-beta (TGF-beta) superfamily; when combined with insoluble signals or substrata, the osteogenic soluble signals trigger the ripple-like cascade of cell differentiation into osteoblastic cell lines secreting bone matrix at site of surgical implantation. A most exciting and novel strategy to initiate bone formation by induction is to carve smart self-inducing geometric concavities assembled within biomimetic constructs. The assembly of a series of repetitive concavities within the biomimetic constructs is endowed with the striking prerogative of differentiating osteoblast-like cells attached to the biomimetic matrices initiating the induction of bone formation as a secondary response. Importantly, the induction of bone formation is initiated without the exogenous application of the osteogenic soluble molecular signals of the TGF-beta superfamily. This manuscript reviews the available data on this fascinating phenomenon, i.e. biomimetic matrices that arouse and set into motion the mammalian natural ability to heal thus constructing biomimetic matrices that in their own right set into motion inductive regenerative phenomena initiating the cascade of bone differentiation by induction biomimetizing the remodelling cycle of the primate cortico-cancellous bone.

  5. Investigating bone chip formation in craniotomy.

    Science.gov (United States)

    Huiyu, He; Chengyong, Wang; Yue, Zhang; Yanbin, Zheng; Linlin, Xu; Guoneng, Xie; Danna, Zhao; Bin, Chen; Haoan, Chen

    2017-10-01

    In a craniotomy, the milling cutter is one of the most important cutting tools. The operating performance, tool durability and cutting damage to patients are influenced by the tool's sharpness, intensity and structure, whereas the cutting characteristics rely on interactions between the tool and the skull. In this study, an orthogonal cutting experiment during a craniotomy of fresh pig skulls was performed to investigate chip formation on the side cutting and face cutting of the skull using a high-speed camera. The cutting forces with different combinations of cutting parameters, such as the rake angle, clearance angle, depth of cut and cutting speed, were measured. The skull bone microstructure and cutting damage were observed by scanning electron microscope. Cutting models for different cutting approaches and various depths of cut were constructed and analyzed. The study demonstrated that the effects of shearing, tension and extrusion occur during chip formation. Various chip types, such as unit chips, splintering chips and continuous chips, were generated. Continuous pieces of chips, which are advisable for easy removal from the field of operation, were formed at greater depths of cut and tool rake angles greater than 10°. Cutting damage could be relieved with a faster recovery with clearance angles greater than 20°.

  6. Biomimetism, biomimetic matrices and the induction of bone formation

    OpenAIRE

    Ripamonti, Ugo

    2008-01-01

    Bone formation by induction initiates by invocation of osteogenic soluble molecular signals of the transforming growth factor-? (TGF-?) superfamily; when combined with insoluble signals or substrata, the osteogenic soluble signals trigger the ripple-like cascade of cell differentiation into osteoblastic cell lines secreting bone matrix at site of surgical implantation. A most exciting and novel strategy to initiate bone formation by induction is to carve smart self-inducing geometric concavit...

  7. Glucocorticoids and inhibition of bone formation induced by skeletal unloading

    Energy Technology Data Exchange (ETDEWEB)

    Halloran, B.P.; Bikle, D.D.; Cone, C.M.; Morey-Holton, E. (Univ. of California, San Francisco (USA) Veterans Administration Medical Center, San Francisco, CA (USA) NASA-Ames Research Center, Moffett Field, CA (USA))

    1988-12-01

    Skeletal unloading or loss of normal weight bearing in the growing animal inhibits bone formation and reduces bone calcium. To determine whether the inhibition of bone formation induced by skeletal unloading is a consequence of an increase in plasma glucocorticoids and/or an increase in bone sensitivity to glucocorticoids, the authors measured plasma corticosterone throughout the day in unloaded and normally loaded rats (hindlimb elevation model) and examined the effect of adrenalectomy on the response of bone to skeletal unloading. Plasma corticosterone levels were similar in normally loaded and unloaded rats at all times. Skeletal unloading in sham-adrenalectomized animals reduced tibial and vertebral calcium by 11.5 and 11.1%, respectively, and in adrenalectomized animals by 15.3 and 20.3%, respectively. Uptake of {sup 45}Ca and ({sup 3}H)proline in the tibia was reduced by 8 and 14%, respectively, in the sham-adrenalectomized animals and by 13 and 19% in the adrenalectomized animals. Bone formation and apposition rates were reduced to the same level in sham- and adrenalectomized animals. These results suggest that the inhibition of bone formation induced by skeletal unloading is not a consequence of increased plasma glucocorticoids or an increase in bone sensitivity to the glucocorticoids but, rather, point to a local mediator in bone that senses mechanical load and transmits that information to the bone-forming cells directly.

  8. Lutein, a carotenoid, suppresses osteoclastic bone resorption and stimulates bone formation in cultures.

    Science.gov (United States)

    Tominari, Tsukasa; Matsumoto, Chiho; Watanabe, Kenta; Hirata, Michiko; Grundler, Florian M W; Inada, Masaki; Miyaura, Chisato

    2017-02-01

    Lutein, a member of the xanthophyll family of carotenoids, suppressed IL-1-induced osteoclast differentiation and bone resorption. The survival of mature osteoclasts was also suppressed by lutein in cultures. When lutein was added to the cultures of osteoblasts, lutein enhanced the formation of mineralized bone nodules by elevating BMP2 expression and inhibiting sclerostin expression. Lutein may be beneficial for bone health.

  9. Effect of coating Straumann Bone Ceramic with Emdogain on mesenchymal stromal cell hard tissue formation.

    Science.gov (United States)

    Mrozik, Krzysztof Marek; Gronthos, Stan; Menicanin, Danijela; Marino, Victor; Bartold, P Mark

    2012-06-01

    Periodontal tissue engineering requires a suitable biocompatible scaffold, cells with regenerative capacity, and instructional molecules. In this study, we investigated the capacity of Straumann Bone Ceramic coated with Straumann Emdogain, a clinical preparation of enamel matrix protein (EMP), to aid in hard tissue formation by post-natal mesenchymal stromal cells (MSCs) including bone marrow stromal cells (BMSCs) and periodontal ligament fibroblasts (PDLFs). MSCs were isolated and ex vivo-expanded from human bone marrow and periodontal ligament and, in culture, allowed to attach to Bone Ceramic in the presence or absence of Emdogain. Gene expression of bone-related proteins was investigated by real time RT-PCR for 72 h, and ectopic bone formation was assessed histologically in subcutaneous implants of Bone Ceramic containing MSCs with or without Emdogain in NOD/SCID mice. Alkaline phosphatase activity was also assessed in vitro, in the presence or absence of Emdogain. Collagen-I mRNA was up-regulated in both MSC populations over the 72-h time course with Emdogain. Expression of BMP-2 and the osteogenic transcription factor Cbfa-1 showed early stimulation in both MSC types after 24 h. In contrast, expression of BMP-4 was consistently down-regulated in both MSC types with Emdogain. Up-regulation of osteopontin and periostin mRNA was restricted to BMSCs, while higher levels of bone sialoprotein-II were observed in PDLFs with Emdogain. Furthermore, alkaline phosphatase activity levels were reduced in both BMSCs and PDLFs in the presence of Emdogain. Very little evidence was found for ectopic bone formation following subcutaneous implantation of MSCs with Emdogain-coated or -uncoated Bone Ceramic in NOD/SCID mice. The early up-regulation of several important bone-related genes suggests that Emdogain may have a significant stimulatory effect in the commitment of mesenchymal cells to osteogenic differentiation in vitro. While Emdogain inhibited AP activity and appeared

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...... 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...

  11. HIF-1α Regulates Bone Formation after Osteogenic Mechanical Loading

    Science.gov (United States)

    Tomlinson, Ryan E.; Silva, Matthew J.

    2015-01-01

    HIF-1 is a transcription factor typically associated with angiogenic gene transcription under hypoxic conditions. In this study, mice with HIF-1α deleted in the osteoblast lineage (ΔHIF-1α) were subjected to damaging or non-damaging mechanical loading known to produce woven or lamellar bone, respectively, at the ulnar diaphysis. By microCT, ΔHIF-1α mice produced significantly less woven bone than wild type (WT) mice 7 days after damaging loading. This decrease in woven bone volume and extent was accompanied by a significant decrease in vascularity measured by immunohistochemistry against vWF. Additionally, osteocytes, rather than osteoblasts, appear to be the main bone cell expressing HIF-1α following damaging loading. In contrast, 10 days after non-damaging mechanical loading, dynamic histomorphometry measurements demonstrated no impairment in loading-induced lamellar bone formation in ΔHIF-1α mice. In fact, both non-loaded and loaded ulnae from ΔHIF-1α mice had increased bone formation compared to WT ulnae. When comparing the relative increase in periosteal bone formation in loaded vs. non-loaded ulnae, it was not different between ΔHIF-1α mice and controls. There were no significant differences observed between WT and ΔHIF-1α mice in endosteal bone formation parameters. The increases in periosteal lamellar bone formation in ΔHIF-1α mice are attributed to non-angiogenic effects of the knockout. In conclusion, these results demonstrate that HIF-1α is a pro-osteogenic factor for woven bone formation after damaging loading, but an anti-osteogenic factor for lamellar bone formation under basal conditions and after non-damaging loading. PMID:25541207

  12. 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.

  13. Effect of Dual Treatment with SDF-1 and BMP-2 on Ectopic and Orthotopic Bone Formation

    Science.gov (United States)

    Jung, Hong-Moon; Lee, Jung-Tae; Kwon, Tae-Geon

    2015-01-01

    Purposes The potent stem cell homing factor stromal cell-derived factor-1 (SDF-1) actively recruits mesenchymal stem cells from circulation and from local bone marrow. It is well established that bone morphogenetic protein-2 (BMP-2) induces ectopic and orthotopic bone formation. However, the exact synergistic effects of BMP-2 and SDF-1 in ectopic and orthotopic bone regeneration models have not been fully investigated. The purpose of this study was to evaluate the potential effects of simultaneous SDF-1 and BMP-2 treatment on bone formation. Materials and Methods Various doses of SDF-1 were loaded onto collagen sponges with or without BMP-2.These sponges were implanted into subcutaneous pockets and critical-size calvarial defects in C57BL/6 mice. The specimens were harvested 4 weeks post-surgery and the degree of bone formation in specimens was evaluated by histomorphometric and radiographic density analyses. Osteogenic potential and migration capacity of mesenchymal cells and capillary tube formation of endothelial cells following dual treatment with SDF-1 and BMP-2 were evaluated with in vitro assays. Results SDF-1-only-treated implants did not yield significant in vivo bone formation and SDF-1 treatment did not enhance BMP-2-induced ectopic and orthotopic bone regeneration. In vitro experiments showed that concomitant use of BMP-2 and SDF-1 had no additive effect on osteoblastic differentiation, cell migration or angiogenesis compared to BMP-2 or SDF-1 treatment alone. Conclusions These findings imply that sequence-controlled application of SDF-1 and BMP-2 must be further investigated for the enhancement of robust osteogenesis in bone defects. PMID:25781922

  14. Bone Formation Rate in Experimental Disuse Osteoporosis in Monkeys

    Science.gov (United States)

    Cann, Christopher; Young, Donald R.

    1976-01-01

    Specific mechanisms underlying weightless and hypodynamic bone loss are obscure. A principal relationship which must be affected is the balance between bone formation and bone resorption rates. In order to better define the influence of those parameters on bone loss, and also to develop measurements in other species as a useful adjunct to human research, studies were undertaken with experimental monkeys. Tests were conducted with a total of 6 adult male monkeys, weighing 10-13 kg, and approximately 10-12 yrs. of age to evaluate specifically bone formation rate during the development of disuse osteoporosis and osteopenia. Three animals were restrained in a semi-recumbent position for six months; three animals served as normal caged controls. Food intake (Purina) was held relatively constant at 200g/day for each animal. Using a Norland Bone Mineral Analyzer, bone mineral losses of 3.5 to 6% were seen in the mid-shaft of the tibia and in the distal radius. Bone loss was confirmed radiographically, with observation of thinning of the proximal tibial cortex and trabeculae in the calcaneus. Bone formation rate was determined using standard Ca-47 kinetics under metabolic balance conditions. After six months of restraint, accretion was 7.2-13.2 mg Ca/kg/day, compared to 3.2-4.1 mg Ca/kg/day in caged controls and 3-8 mg Ca/kg/day in normal adult humans. Fecal and urine calcium was 25-40% higher in restrained animals than in controls. Dietary calcium absorption decreases during restraint, and calcium turnover increases, implying a rise in bone resorption rate concommitant with the observed rise in bone accretion rate. Further studies dealing specifically with bone resorption are underway to define this more fully.

  15. Lrp5 and bone formation : A serotonin-dependent pathway.

    Science.gov (United States)

    Yadav, Vijay K; Ducy, Patricia

    2010-03-01

    Lrp5, the mutated gene in osteoporosis pseudoglioma (OPPG) and the high bone-mass syndrome (HBM), regulates bone formation, while beta-catenin, the molecular node of Wnt signaling, regulates bone resorption, suggesting that Lrp5 could act in a Wnt-independent manner. Using microarray and conditional gene deletion in mice, we showed that Lrp5 actually enhances bone formation by inhibiting the expression, in duodenum, of tryptophan hydroxylase 1, the rate-limiting enzyme in the serotonin biosynthetic pathway. Accordingly, serotonin circulating levels are high in Lrp5(-/-) mice and OPPG patients but low in HBM patients, and normalizing serum serotonin levels rescues the bone phenotype of the Lrp5(-/-) mice. We also showed that serotonin acts on osteoblasts through the Htr1b receptor and the transcription factor cAMP responsive element binding to inhibit their proliferation. This study shows that Lrp5 acts in gut cells, not in osteoblasts, to control bone formation via a Wnt-independent pathway and identifies a new hormone, serotonin, and a novel endocrine axis regulating bone mass. These findings may have important therapeutic implications for the treatment of low bone-mass disorders.

  16. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis.

    Science.gov (United States)

    Li, Xiaodong; Ominsky, Michael S; Warmington, Kelly S; Morony, Sean; Gong, Jianhua; Cao, Jin; Gao, Yongming; Shalhoub, Victoria; Tipton, Barbara; Haldankar, Raj; Chen, Qing; Winters, Aaron; Boone, Tom; Geng, Zhaopo; Niu, Qing-Tian; Ke, Hua Zhu; Kostenuik, Paul J; Simonet, W Scott; Lacey, David L; Paszty, Chris

    2009-04-01

    The development of bone-rebuilding anabolic agents for potential use in the treatment of bone loss conditions, such as osteoporosis, has been a long-standing goal. Genetic studies in humans and mice have shown that the secreted protein sclerostin is a key negative regulator of bone formation, although the magnitude and extent of sclerostin's role in the control of bone formation in the aging skeleton is still unclear. To study this unexplored area of sclerostin biology and to assess the pharmacologic effects of sclerostin inhibition, we used a cell culture model of bone formation to identify a sclerostin neutralizing monoclonal antibody (Scl-AbII) for testing in an aged ovariectomized rat model of postmenopausal osteoporosis. Six-month-old female rats were ovariectomized and left untreated for 1 yr to allow for significant estrogen deficiency-induced bone loss, at which point Scl-AbII was administered for 5 wk. Scl-AbII treatment in these animals had robust anabolic effects, with marked increases in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. This not only resulted in complete reversal, at several skeletal sites, of the 1 yr of estrogen deficiency-induced bone loss, but also further increased bone mass and bone strength to levels greater than those found in non-ovariectomized control rats. Taken together, these preclinical results establish sclerostin's role as a pivotal negative regulator of bone formation in the aging skeleton and, furthermore, suggest that antibody-mediated inhibition of sclerostin represents a promising new therapeutic approach for the anabolic treatment of bone-related disorders, such as postmenopausal osteoporosis.

  17. Extraskeletal and intraskeletal new bone formation induced by demineralized bone matrix combined with bone marrow cells

    International Nuclear Information System (INIS)

    Lindholm, T.S.; Nilsson, O.S.; Lindholm, T.C.

    1982-01-01

    Dilutions of fresh autogenous bone marrow cells in combination with allogeneic demineralized cortical bone matrix were tested extraskeletally in rats using roentgenographic, histologic, and 45 Ca techniques. Suspensions of bone marrow cells (especially diluted 1:2 with culture media) combined with demineralized cortical bone seemed to induce significantly more new bone than did demineralized bone, bone marrow, or composite grafts with whole bone marrow, respectively. In a short-term spinal fusion experiment, demineralized cortical bone combined with fresh bone marrow produced new bone and bridged the interspace between the spinous processes faster than other transplantation procedures. The induction of undifferentiated host cells by demineralized bone matrix is further complemented by addition of autogenous, especially slightly diluted, bone marrow cells

  18. De novo alveolar bone formation adjacent to endosseous implants.

    Science.gov (United States)

    Berglundh, Tord; Abrahamsson, Ingemar; Lang, Niklaus P; Lindhe, Jan

    2003-06-01

    To describe a model for the investigation of different phases of wound healing that are involved in the process resulting in osseointegration. The implants used for the study of early healing had a geometry that corresponded to that of a solid screw implant with an SLA surface configuration. A circumferential trough had been prepared within the thread region (intra-osseous portion) that established a geometrically well-defined wound compartment. Twenty Labrador dogs received 160 experimental devices totally to allow the evaluation of healing between 2 h and 12 weeks. Both ground sections and decalcified sections were prepared from different implant sites. The experimental chamber used appeared to be conducive for the study of early phases of bone formation. The ground sections provided an overview of the various phases of soft and hard tissue formation, while the decalcified, thin sections enabled a more detailed study of events involved in bone tissue modeling and remodeling. The initially empty wound chamber became occupied with a coagulum and a granulation tissue that was replaced by a provisional matrix. The process of bone formation started already during the first week. The newly formed bone present at the lateral border of the cut bony bed appeared to be continuous with the parent bone, but woven bone was also found on the SLA surface at a distance from the parent bone. This primary bone that included trabeculae of woven bone was replaced by parallel-fibered and/or lamellar bone and marrow. Between 1 and 2 weeks, the bone tissue immediately lateral to the pitch region, responsible for primary mechanical stability of the device, became resorbed and replaced with newly formed viable bone. Despite this temporary loss of hard tissue contact, the implants remained clinically stable at all times. Osseointegration represents a dynamic process both during its establishment and its maintenance. In the establishment phase, there is a delicate interplay between bone

  19. Nanocrystalline hydroxyapatite bone substitute leads to sufficient bone tissue formation already after 3 months: histological and histomorphometrical analysis 3 and 6 months following human sinus cavity augmentation.

    Science.gov (United States)

    Ghanaati, Shahram; Barbeck, Mike; Willershausen, Ines; Thimm, Benjamin; Stuebinger, Stefan; Korzinskas, Tadas; Obreja, Karina; Landes, Constantin; Kirkpatrick, Charles J; Sader, Robert A

    2013-12-01

    In this study the de novo bone formation capacity of a nanocrystalline hydroxyapatite bone substitute was assessed 3 and 6 months after its insertion into the human sinus cavity. Sinus cavity augmentation was performed in a total of 14 patients (n = 7 implantation after 3 months; n = 7 implantation after 6 months) with severely atrophic maxillary bone. The specimens obtained after 3 and 6 months were analyzed histologically and histomorphometrically with special focus on bone metabolism within the residual bone and the augmented region. This study revealed that bone tissue formation started from the bone-biomaterial-interface and was directed into the most cranial parts of the augmented region. There was no statistically significant difference in new bone formation after 3 and 6 months (24.89 ± 10.22% vs 31.29 ± 2.29%), respectively. Within the limits of the present study and according to previously published data, implant insertion in regions augmented with this bone substitute material could be considered already after 3 months. Further clinical studies with bone substitute materials are necessary to validate these findings. © 2012 Wiley Periodicals, Inc.

  20. 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

    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...... as a functional continuum. It was based on the position of specific cell markers in longitudinal sections of Haversian BMUs generating new canals through human long bones. It showed that initial resorption at the tip of the canal is followed by a period where newly recruited reversal/osteoprogenitor cells...... 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...

  1. Functional Diversity of Fibroblast Growth Factors in Bone Formation

    Directory of Open Access Journals (Sweden)

    Yuichiro Takei

    2015-01-01

    Full Text Available The functional significance of fibroblast growth factor (FGF signaling in bone formation has been demonstrated through genetic loss-of-function and gain-of-function approaches. FGFs, comprising 22 family members, are classified into three subfamilies: canonical, hormone-like, and intracellular. The former two subfamilies activate their signaling pathways through FGF receptors (FGFRs. Currently, intracellular FGFs appear to be primarily involved in the nervous system. Canonical FGFs such as FGF2 play significant roles in bone formation, and precise spatiotemporal control of FGFs and FGFRs at the transcriptional and posttranscriptional levels may allow for the functional diversity of FGFs during bone formation. Recently, several research groups, including ours, have shown that FGF23, a member of the hormone-like FGF subfamily, is primarily expressed in osteocytes/osteoblasts. This polypeptide decreases serum phosphate levels by inhibiting renal phosphate reabsorption and vitamin D3 activation, resulting in mineralization defects in the bone. Thus, FGFs are involved in the positive and negative regulation of bone formation. In this review, we focus on the reciprocal roles of FGFs in bone formation in relation to their local versus systemic effects.

  2. Inflammatory response and bone healing capacity of two porous calcium phosphate ceramics in critical size cortical bone defects.

    Science.gov (United States)

    Chatterjea, Anindita; van der Stok, Johan; Danoux, Charlène B; Yuan, Huipin; Habibovic, Pamela; van Blitterswijk, Clemens A; Weinans, Harrie; de Boer, Jan

    2014-05-01

    In the present study, two open porous calcium phosphate ceramics, β-tricalcium phosphate (β-TCP), and hydroxyapatite (HA) were compared in a critical-sized femoral defect in rats. Previous comparisons of these two ceramics showed significantly greater osteoinductive potential of β-TCP upon intramuscular implantation and a better performance in a spinal fusion model in dogs. Results of the current study also showed significantly more bone formation in defects grafted with β-TCP compared to HA; however, both the ceramics were not capable of increasing bone formation to such extend that it bridges the defect. Furthermore, a more pronounced degradation of β-TCP was observed as compared to HA. Progression of inflammation and initiation of new bone formation were assessed for both materials at multiple time points by histological and fluorochrome-based analyses. Until 12 days postimplantation, a strong inflammatory response in absence of new bone formation was observed in both ceramics, without obvious differences between the two materials. Four weeks postimplantation, signs of new bone formation were found in both β-TCP and HA. At 6 weeks, inflammation had subsided in both ceramics while bone deposition continued. In conclusion, the two ceramics differed in the amount of bone formed after 8 weeks of implantation, whereas no differences were found in the duration of the inflammatory phase after implantation or initiation of new bone formation. Copyright © 2013 Wiley Periodicals, Inc.

  3. Clay-Enriched Silk Biomaterials for Bone Formation

    Science.gov (United States)

    Mieszawska, Aneta J.; Llamas, Jabier Gallego; Vaiana, Christopher A.; Kadakia, Madhavi P.; Naik, Rajesh R.; Kaplan, David L.

    2011-01-01

    The formation of silk protein/clay composite biomaterials for bone tissue formation is described. Silk fibroin serves as an organic scaffolding material offering mechanical stability suitable for bone specific uses. Clay montmorillonite (Cloisite ® Na+) and sodium silicate are sources of osteoinductive silica-rich inorganic species, analogous to bioactive bioglass-like bone repair biomaterial systems. Different clay particle-silk composite biomaterial films were compared to silk films doped with sodium silicate as controls for support of human bone marrow derived mesenchymal stem cells (hMSCs) in osteogenic culture. The cells adhered and proliferated on the silk/clay composites over two weeks. Quantitative real-time RT-PCR analysis revealed increased transcript levels for alkaline phosphatase (ALP), bone sialoprotein (BSP), and collagen type 1 (Col I) osteogenic markers in the cells cultured on the silk/clay films in comparison to the controls. Early evidence for bone formation based on collagen deposition at the cell-biomaterial interface was also found, with more collagen observed for the silk films with higher contents of clay particles. The data suggest that the silk/clay composite systems may be useful for further study toward bone regenerative needs. PMID:21549864

  4. Granulation Tissue Eroding the Subchondral Bone Also Promotes New Bone Formation in Ankylosing Spondylitis.

    Science.gov (United States)

    Bleil, Janine; Maier, Rene; Hempfing, Axel; Sieper, Joachim; Appel, Heiner; Syrbe, Uta

    2016-10-01

    We previously suggested that fibroblast-rich granulation tissue eroding the subchondral bone is instrumental in the joint remodeling that occurs in ankylosing spondylitis (AS). The purpose of this study was to determine if this granulation tissue also carries bone-forming capabilities, which we approached by searching for bone-forming cells (hypertrophic chondrocytes, osteoblasts) in its vicinity. We also assessed adipogenic tissue transformation, which has been suggested to be an intermediate feature in AS bone formation based on imaging studies. The facet joints of AS patients, osteoarthritis (OA) patients, and autopsy subjects (controls) were screened for subchondral granulation tissue. We searched for hypertrophic chondrocytes by assessing RUNX-2, type X collagen, and matrix metalloproteinase 13 (MMP-13) expression, for osteoblasts by analyzing RUNX-2, CD56, and type I collagen expression, as well as for signs of new bone formation. Adipocytes and lipid accumulation were assessed in Safranin O-stained sections. In the joints of AS and OA patients, RUNX-2-positive cells were found to be lining the granulation tissue. These cells coexpressed type I collagen but lacked type X collagen and MMP-13 expression, confirming their osteoblastic nature. In 91% of AS joints and in 20% of OA joints (P granulation tissue and the cartilage. Joints containing bony spots showed greater replacement of the adjacent bone marrow by granulation tissue than did joints without bone formation (P granulation tissue often contained adipocytes and lipid accumulations. Replacement of the subchondral bone marrow by fat tissue was also frequently found but was not associated with new bone formation. The subchondral granulation tissue carries osteoblasts, which promote new bone formation, leading to intraarticular ankylosis of the facet joints in AS. © 2016, American College of Rheumatology.

  5. In vitro induction of alkaline phosphatase levels predicts in vivo bone forming capacity of human bone marrow stromal cells

    Directory of Open Access Journals (Sweden)

    Henk-Jan Prins

    2014-03-01

    Full Text Available One of the applications of bone marrow stromal cells (BMSCs that are produced by ex vivo expansion is for use in in vivo bone tissue engineering. Cultured stromal cells are a mixture of cells at different stages of commitment and expansion capability, leading to a heterogeneous cell population that each time can differ in the potential to form in vivo bone. A parameter that predicts for in vivo bone forming capacity is thus far lacking. We employed single colony-derived BMSC cultures to identify such predictive parameters. Using limiting dilution, we have produced sixteen single CFU-F derived BMSC cultures from human bone marrow and found that only five of these formed bone in vivo. The single colony-derived BMSC strains were tested for proliferation, osteogenic-, adipogenic- and chondrogenic differentiation capacity and the expression of a variety of associated markers. The only robust predictors of in vivo bone forming capacity were the induction of alkaline phosphatase, (ALP mRNA levels and ALP activity during in vitro osteogenic differentiation. The predictive value of in vitro ALP induction was confirmed by analyzing “bulk-cultured” BMSCs from various bone marrow biopsies. Our findings show that in BMSCs, the additional increase in ALP levels over basal levels during in vitro osteogenic differentiation is predictive of in vivo performance.

  6. The Effect of Aloe, Gelfoam, Plaster on Bone Formation in applying to the bone defect

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Eui Hwan [Dept. of Oral and Maxillofacial Radiology, College of Dentistry, Chosun University and Oral Biology Research Center, Kwangju (Korea, Republic of); Kim, Su Gwan [Dept. of Oral and Maxillofacial Surgery, College of Dentistry, Chosun University and Oral Biology Research Center, Kwangju (Korea, Republic of)

    1999-08-15

    This study was to evaluate the effects of Aloe, Gelfoam, and Plaster of Paris on bone healing. Four experimental defects were created for placement of the three materials in the right femur of dogs. One defect served as an empty control site. The evaluation was performed at 1-, 6-, and 12-weeks by light microscopy and NIH image program. Radiographic and Histologic examinations showed new bone formation in the presence of Aloe, Gelfoam, and Plaster of Paris and similar bone healing reactions. On the basis of these findings, it was concluded that Aloe, Gelfoam, and Plaster of Paris may be adequate agents for use in bone procurement.

  7. The Effect of Aloe, Gelfoam, Plaster on Bone Formation in applying to the bone defect

    International Nuclear Information System (INIS)

    Choi, Eui Hwan; Kim, Su Gwan

    1999-01-01

    This study was to evaluate the effects of Aloe, Gelfoam, and Plaster of Paris on bone healing. Four experimental defects were created for placement of the three materials in the right femur of dogs. One defect served as an empty control site. The evaluation was performed at 1-, 6-, and 12-weeks by light microscopy and NIH image program. Radiographic and Histologic examinations showed new bone formation in the presence of Aloe, Gelfoam, and Plaster of Paris and similar bone healing reactions. On the basis of these findings, it was concluded that Aloe, Gelfoam, and Plaster of Paris may be adequate agents for use in bone procurement.

  8. Biomimetic Functionalized Surfaces and the Induction of Bone Formation.

    Science.gov (United States)

    Ripamonti, Ugo

    2017-11-01

    Tissue engineering still needs to assign the molecular basis of pattern formation, tissue induction, and morphogenesis: What next to morphogens and stem cells? Macroporous biomimetic matrices per se, without the addition of the soluble osteogenic molecular signals of the transforming growth factor-β (TGF-β) supergene family, remarkably initiate the induction of bone formation. Carving geometries within different calcium phosphate-based macroporous bioreactors we show that geometric cues imprinted within the macroporous spaces initiate the spontaneous induction of bone. Concavities biomimetize the remodeling cycle of the primate osteonic bone and are endowed with functionalized smart geometric cues that per se initiate osteoblasts' differentiation with the expression and secretion of osteogenic molecular signals that induce bone as a secondary response. To study the role of calcium ions (Ca ++ ) and osteoclastogenesis, coral-derived calcium carbonate (CC)/hydroxyapatite (HA) bioreactors with limited conversion to HA (7% HA/CC) were preloaded with 500 μg of the L-type voltage gated calcium channel blocker verapamil hydrochloride. Bioreactors were also loaded with 240 μg of the bisphosphonate zoledronate, an osteoclast inhibitor, and implanted in heterotopic sites of the rectus abdominis muscle of Papio ursinus. Bisphosphonate-treated specimens were characterized by a delayed profoundly inhibited induction of tissue patterning with limited induction of bone. Macroporous constructs pretreated with verapamil hydrochloride yielded limited bone formation. Similarly, 125 or 150 μg human Noggin previously adsorbed onto the macroporous bioreactors resulted in minimal bone formation by induction, indirectly showing that the initiation of bone formation is through the bone morphogenetic protein (BMP) pathway. Downregulation of BMP-2 and osteogenic protein-1 (OP-1) with upregulation of Noggin correlated with limited bone induction. Angiogenesis, capillary sprouting

  9. Effect of distraction frequency on bone formation during bone lengthening: a study in chickens.

    Science.gov (United States)

    Mizuta, Hiroshi; Nakamura, Eiichi; Mizumoto, Yoshihiko; Kudo, Satoshi; Takagi, Katsumasa

    2003-12-01

    We compared the effects of two distraction frequencies on bone formation during tibial lengthening by evaluating radiographs, bone mineral density, and histological findings. In 15 mature White Leghorn chickens, both tibiae were distracted at a rate of 0.75 mm/day for 10 days. The distraction frequency was 2 steps (0.375 mm/12 hour) by hand on the right side and 120 steps (0.00625 mm/12 min) by autodistractor on the left. Serial radiographs showed faster bone formation on the 120-step side than on the 2-step side. Bone mineral density on the 120-step side was also higher than that on the 2-step side at all times. On the 2-step side, endochondral ossification was marked in the early stage of distraction; then intramembranous ossification became the main mechanism of bone formation. On the 120-step side, however, intramembranous bone formation predominated throughout the study. Our findings support the contention that, at least in skeletally mature chickens, an increase in the distraction frequency improves osteogenesis during bone lengthening.

  10. Knee loading stimulates cortical bone formation in murine femurs

    Directory of Open Access Journals (Sweden)

    Tanaka Shigeo M

    2006-09-01

    Full Text Available Abstract Background Bone alters its architecture and mass in response to the mechanical environment, and thus varying loading modalities have been examined for studying load-driven bone formation. The current study aimed to evaluate the anabolic effects of knee loading on diaphyseal cortical bone in the femur. Methods Using a custom-made piezoelectric loader, 0.5-N loads were laterally applied to the left knee of C57/BL/6 mice at 5, 10, 15, and 20 Hz for 3 minutes per day for 3 consecutive days. Animals were sacrificed for examination 13 days after the last loading. The contralateral femur was used as a non-loading control, and the statistical significance of loading effects was evaluated with p Results Although diaphyseal strains were measured as small as 12 μstrains, bone histomorphometry clearly demonstrated frequency-dependent enhancement of bone formation. Compared to a non-loading control, bone formation on the periosteal surface was significantly enhanced. The loading at 15 Hz was most effective in elevating the mineralizing surface (1.7 x; p p p p p p Conclusion The results support the anabolic effects of knee loading on diaphyseal cortical bone in the femur with small in situ strain, and they extend our knowledge on the interplay between bone and joints. Strengthening the femur contributes to preventing femoral fractures, and the discovery about the described knee loading might provide a novel strategy to strengthen osteoporotic bones. Further analyses are required to understand the biophysical and molecular mechanism behind knee loading.

  11. Cellular Therapy to Obtain Rapid Endochondral Bone Formation

    Science.gov (United States)

    2012-03-01

    were removed from the rat fibula starting with a simple fracture (1mm), and systematically increasing in one millimeter increments to a maximum of 10 mm...bone formation, and fracture healing is a collaborative effort between a bio-engineering/biomaterials group at Rice University and Baylor College of...for fracture healing. This set of proposed experiments will provide significant knowledge to the field of bone tissue engineering. Proposed

  12. Appositional bone formation in marginal defects at implants.

    Science.gov (United States)

    Botticelli, Daniele; Berglundh, Tord; Buser, Daniel; Lindhe, Jan

    2003-02-01

    In a previous experiment, it was demonstrated that a wide marginal defect around an implant can heal with a high degree of osseointegration. The present experiment was performed to evaluate the degree and quality of de novo bone formation and osseointegration in marginal defects adjacent to submerged titanium implants. All mandibular premolars and 1st molars were extracted in four Labrador dogs. Four experimental sites were identified in the right side of the mandible. In two sites, custom-made implants with a sandblasted, large grit, acid-etched (SLA) surface were installed without further ostectomy (control sites). In the two remaining sites (test sites), a specially designed step drill was used to widen the marginal 5 mm of the canal. A barrier membrane was used to cover the implants in the defect sites. All implants were submerged. One month later, an identical procedure, including site preparation and implant installation, was performed in the left side of the mandible. Two months following the first implant installation procedure, biopsies were collected and prepared for sectioning. Ostectomy and implant installation in the control location resulted in a series of bone tissue alterations which eventually allowed newly formed bone to establish contact with the SLA surface. The marginal defect lateral to the implant in the test locations gradually became filled with newly formed bone. De novo bone formation started within the walls of the surgically prepared defect. Bone-to-implant contact was first established in the apical portion of the gap. This new bone tissue was in the coronal direction continuous with a dense, non-mineralized 'implant attached' soft tissue which, over time, also became mineralized to increase the height of the zone of bone-to-implant contact. The results suggest that healing of a wide marginal defect around an implant is characterized by appositional bone growth from the lateral and apical bone walls of the defect.

  13. Sclerostin Antibody Reverses Bone Loss by Increasing Bone Formation and Decreasing Bone Resorption in a Rat Model of Male Osteoporosis.

    Science.gov (United States)

    Li, Xiaodong; Ominsky, Michael S; Villasenor, Kelly S; Niu, Qing-Tian; Asuncion, Frank J; Xia, Xuechun; Grisanti, Mario; Wronski, Thomas J; Simonet, W Scott; Ke, Hua Zhu

    2018-01-01

    Sclerostin antibody (Scl-Ab) restored bone mass and strength in the ovariectomized rat model of postmenopausal osteoporosis. Increased bone mineral density (BMD) and decreased skeletal fragility fracture risk have been reported in postmenopausal osteoporotic women receiving Scl-Ab. In males, loss of androgen leads to rapid decreases in BMD and an increased risk of fragility fractures. We hypothesized that Scl-Ab could reverse the loss of bone mass and strength caused by androgen ablation in the orchiectomized (ORX) rat model of male osteoporosis. We treated 9-month-old ORX Sprague Dawley rats (3 months after ORX) subcutaneously twice weekly with vehicle or Scl-Ab (5 or 25 mg/kg) for 6 weeks (n = 10 per group). Both doses of Scl-Ab fully reversed the BMD deficit in the lumbar spine and femur and tibia in ORX rats. Microcomputed tomography showed that the bone mass in the fifth lumbar vertebral body, femur diaphysis, and femoral neck were dose-dependently restored by Scl-Ab. The bone strength at these sites increased significantly with Scl-Ab to levels matching those of sham-operated controls and correlated positively with improvements in bone mineral content, demonstrating bone quality maintenance. Dynamic histomorphometry of the tibial diaphysis and second lumbar vertebral body demonstrated that Scl-Ab significantly increased bone formation on periosteal, endocortical, and trabecular surfaces and significantly decreased bone resorption on endocortical and trabecular surfaces. The effects of Scl-Ab on increasing bone formation and decreasing bone resorption led to restoration of bone mass and strength in androgen-deficient rats. These findings support the ongoing evaluation of Scl-Ab as a potential therapeutic agent for osteoporosis in men. Copyright © 2018 Endocrine Society.

  14. Non-linear pattern formation in bone growth and architecture.

    Science.gov (United States)

    Salmon, Phil

    2014-01-01

    The three-dimensional morphology of bone arises through adaptation to its required engineering performance. Genetically and adaptively bone travels along a complex spatiotemporal trajectory to acquire optimal architecture. On a cellular, micro-anatomical scale, what mechanisms coordinate the activity of osteoblasts and osteoclasts to produce complex and efficient bone architectures? One mechanism is examined here - chaotic non-linear pattern formation (NPF) - which underlies in a unifying way natural structures as disparate as trabecular bone, swarms of birds flying, island formation, fluid turbulence, and others. At the heart of NPF is the fact that simple rules operating between interacting elements, and Turing-like interaction between global and local signals, lead to complex and structured patterns. The study of "group intelligence" exhibited by swarming birds or shoaling fish has led to an embodiment of NPF called "particle swarm optimization" (PSO). This theoretical model could be applicable to the behavior of osteoblasts, osteoclasts, and osteocytes, seeing them operating "socially" in response simultaneously to both global and local signals (endocrine, cytokine, mechanical), resulting in their clustered activity at formation and resorption sites. This represents problem-solving by social intelligence, and could potentially add further realism to in silico computer simulation of bone modeling. What insights has NPF provided to bone biology? One example concerns the genetic disorder juvenile Pagets disease or idiopathic hyperphosphatasia, where the anomalous parallel trabecular architecture characteristic of this pathology is consistent with an NPF paradigm by analogy with known experimental NPF systems. Here, coupling or "feedback" between osteoblasts and osteoclasts is the critical element. This NPF paradigm implies a profound link between bone regulation and its architecture: in bone the architecture is the regulation. The former is the emergent

  15. Vibration acceleration promotes bone formation in rodent models.

    Directory of Open Access Journals (Sweden)

    Ryohei Uchida

    Full Text Available All living tissues and cells on Earth are subject to gravitational acceleration, but no reports have verified whether acceleration mode influences bone formation and healing. Therefore, this study was to compare the effects of two acceleration modes, vibration and constant (centrifugal accelerations, on bone formation and healing in the trunk using BMP 2-induced ectopic bone formation (EBF mouse model and a rib fracture healing (RFH rat model. Additionally, we tried to verify the difference in mechanism of effect on bone formation by accelerations between these two models. Three groups (low- and high-magnitude vibration and control-VA groups were evaluated in the vibration acceleration study, and two groups (centrifuge acceleration and control-CA groups were used in the constant acceleration study. In each model, the intervention was applied for ten minutes per day from three days after surgery for eleven days (EBF model or nine days (RFH model. All animals were sacrificed the day after the intervention ended. In the EBF model, ectopic bone was evaluated by macroscopic and histological observations, wet weight, radiography and microfocus computed tomography (micro-CT. In the RFH model, whole fracture-repaired ribs were excised with removal of soft tissue, and evaluated radiologically and histologically. Ectopic bones in the low-magnitude group (EBF model had significantly greater wet weight and were significantly larger (macroscopically and radiographically than those in the other two groups, whereas the size and wet weight of ectopic bones in the centrifuge acceleration group showed no significant difference compared those in control-CA group. All ectopic bones showed calcified trabeculae and maturated bone marrow. Micro-CT showed that bone volume (BV in the low-magnitude group of EBF model was significantly higher than those in the other two groups (3.1±1.2mm3 v.s. 1.8±1.2mm3 in high-magnitude group and 1.3±0.9mm3 in control-VA group, but

  16. In vitro formation of osteoclasts from long-term cultures of bone marrow mononuclear phagocytes

    International Nuclear Information System (INIS)

    Burger, E.H.; Van der Meer, J.W.; van de Gevel, J.S.; Gribnau, J.C.; Thesingh, G.W.; van Furth, R.

    1982-01-01

    The origin of osteoclasts was studied in an in vitro model using organ cultures of periosteum-free embryonic mouse long-bone primordia, which were co-cultured with various cell populations. The bone rudiments were freed of their periosteum-perichondrium by collagenase treatment in a stage before cartilage erosion and osteoclast formation, and co-cultured for 7 d with either embryonic liver or mononuclear phagocytes from various sources. Light and electron microscopic examination of the cultures showed that mineralized matrix-resorbing osteoclasts developed only in bones co-cultured with embryonic liver or with cultured bone marrow mononuclear phagocytes but not when co-cultured with blood monocytes or resident or exudate peritoneal macrophages. Osteoclasts developed from the weakly adherent, but not from the strongly adherent cells of bone marrow cultures, whereas 1,000 rad irradiation destroyed the capacity of such cultures to form osteoclasts. In bone cultures to which no other cells were added, osteoclasts were virtually absent. Bone-resorbing activity of in vitro formed osteoclasts was demonstrated by 45 Ca release studies. These studies demonstrate that osteoclasts develop from cells present in cultures of proliferating mononuclear phagocytes and that, at least in our system, monocytes and macrophages are unable to form osteoclasts. The most likely candidates for osteoclast precursor cells seem to be monoblasts and promonocytes

  17. PTH-IGF SIGNALING PROMOTES BONE FORMATION THROUGH GLYCOLYSIS

    Science.gov (United States)

    Esen, Emel; Lee, Seung-Yon; Wice, Burton M; Long, Fanxin

    2016-01-01

    Teriparatide, a recombinant peptide corresponding to amino acids 1-34 of human parathyroid hormone (PTH), has been an effective bone anabolic drug for over a decade. However, the mechanism whereby PTH stimulates bone formation remains poorly understood. Here we report that in cultures of osteoblast-lineage cells, PTH stimulates glucose consumption and lactate production in the presence of oxygen, a hallmark of aerobic glycolysis, also known as Warburg effect. Experiments with radioactively labeled glucose demonstrate that PTH suppresses glucose entry into the tricarboxylic acid cycle (TCA cycle). Mechanistically, the increase in aerobic glycolysis is secondary to insulin-like growth factor (Igf) signaling induced by PTH, whereas the metabolic effect of Igf is dependent on activation of mammalian target of rapamycin complex 2 (mTORC2). Importantly, pharmacological perturbation of glycolysis suppresses the bone anabolic effect of intermittent PTH in the mouse. Thus, stimulation of aerobic glycolysis via Igf signaling contributes to bone anabolism in response to PTH. PMID:25990470

  18. Ultraviolet light-irradiated photocrosslinkable chitosan hydrogel to prevent bone formation in both rat skull and fibula bone defects.

    Science.gov (United States)

    Tsuda, Yoshifumi; Hattori, Hidemi; Tanaka, Yoshihiro; Ishihara, Masayuki; Kishimoto, Satoko; Amako, Masatoshi; Arino, Hiroshi; Nemoto, Koichi

    2013-09-01

    In the field of orthopaedic surgery, an orthopaedic surgeon sometimes requires to suppress excessive bone formation, such as ectopic bone formation, ossifying myositis and radio-ulnar synostosis, etc. Ultraviolet (UV) light irradiation of a photocrosslinkable chitosan (Az-CH-LA) generates an insoluble hydrogel within 30 s. The purpose of this study was to evaluate the ability of the photocrosslinked chitosan hydrogel (PCH) to inhibit bone formation in an experimental model of bone defect. Rat calvarium and fibula were surgically injured and PCH was implanted into the resultant bone defects. The PCH implants significantly prevented bone formation in the bone defects during the 4 and 8 week observation periods. In the PCH-treated defects, fibrous tissues infiltrated by inflammatory cells were formed by day 7, completely filling the bone defects. In addition to these findings, expression of osteocalcin and runt-related gene 2 (RUNX2) mRNA, both markers of bone formation, was lower in the PCH-treated defects than in the controls. In contrast, collagen type 1α2 and α-smooth muscle actin (α-SMA) mRNA levels were significantly higher in the PCH-treated defects after 1 week. PCH stimulated the formation of fibrous tissue in bone defects while inhibiting bone formation. Thus, PCH might be a promising new therapeutic biomaterial for the prevention of bone formation in orthopaedic surgery. Copyright © 2012 John Wiley & Sons, Ltd.

  19. Demineralized Bone Matrix Injection in Consolidation Phase Enhances Bone Regeneration in Distraction Osteogenesis via Endochondral Bone Formation.

    Science.gov (United States)

    Kim, Ji-Beom; Lee, Dong Yeon; Seo, Sang Gyo; Kim, Eo Jin; Kim, Ji Hye; Yoo, Won Joon; Cho, Tae-Joon; Choi, In Ho

    2015-09-01

    Distraction osteogenesis (DO) is a promising tool for bone and tissue regeneration. However, prolonged healing time remains a major problem. Various materials including cells, cytokines, and growth factors have been used in an attempt to enhance bone formation. We examined the effect of percutaneous injection of demineralized bone matrix (DBM) during the consolidation phase on bone regeneration after distraction. The immature rabbit tibial DO model (20 mm length-gain) was used. Twenty-eight animals received DBM 100 mg percutaneously at the end of distraction. Another 22 animals were left without further procedure (control). Plain radiographs were taken every week. Postmortem bone dual-energy X-ray absorptiometry and micro-computed tomography (micro-CT) studies were performed at the third and sixth weeks of the consolidation period and histological analysis was performed. The regenerate bone mineral density was higher in the DBM group when compared with that in the saline injection control group at the third week postdistraction. Quantitative analysis using micro-CT revealed larger trabecular bone volume, higher trabecular number, and less trabecular separation in the DBM group than in the saline injection control group. Cross-sectional area and cortical thickness at the sixth week postdistraction, assessed using micro-CT, were greater in the regenerates of the DBM group compared with the control group. Histological evaluation revealed higher trabecular bone volume and trabecular number in the regenerate of the DBM group. New bone formation was apparently enhanced, via endochondral ossification, at the site and in the vicinity of the injected DBM. DBM was absorbed slowly, but it remained until the sixth postoperative week after injection. DBM administration into the distraction gap at the end of the distraction period resulted in a significantly greater regenerate bone area, trabecular number, and cortical thickness in the rabbit tibial DO model. These data suggest

  20. Disassociation of bone resorption and formation by GLP-2

    DEFF Research Database (Denmark)

    Henriksen, Dennis B; Alexandersen, Peter; Hartmann, Bolette

    2007-01-01

    We have previously shown that a single subcutaneous injection of glucagon-like peptide-2 (GLP-2) at 10 p.m. in postmenopausal women results in a dose-dependent decrease in the nocturnal serum and urine concentrations of fragments derived from the degradation of the C-terminal telopeptide region...... of collagen type I (s-CTX and u-CTX) and u-DPD, markers of bone resorption. In contrast, bone formation, as assessed by serum osteocalcin and procollagen type I N-terminal propeptide (PINP), appeared to be unaffected by treatment with exogenous GLP-2. These effects were further investigated in a 14-day study...

  1. Novel Resorbable and Osteoconductive Calcium Silicophosphate Scaffold Induced Bone Formation

    Directory of Open Access Journals (Sweden)

    Patricia Ros-Tárraga

    2016-09-01

    Full Text Available This aim of this research was to develop a novel ceramic scaffold to evaluate the response of bone after ceramic implantation in New Zealand (NZ rabbits. Ceramics were prepared by the polymer replication method and inserted into NZ rabbits. Macroporous scaffolds with interconnected round-shaped pores (0.5–1.5 mm = were prepared. The scaffold acted as a physical support where cells with osteoblastic capability were found to migrate, develop processes, and newly immature and mature bone tissue colonized on the surface (initially and in the material’s interior. The new ceramic induced about 62.18% ± 2.28% of new bone and almost complete degradation after six healing months. An elemental analysis showed that the gradual diffusion of Ca and Si ions from scaffolds into newly formed bone formed part of the biomaterial’s resorption process. Histological and radiological studies demonstrated that this porous ceramic scaffold showed biocompatibility and excellent osteointegration and osteoinductive capacity, with no interposition of fibrous tissue between the implanted material and the hematopoietic bone marrow interphase, nor any immune response after six months of implantation. No histological changes were observed in the various organs studied (para-aortic lymph nodes, liver, kidney and lung as a result of degradation products being released.

  2. Novel Resorbable and Osteoconductive Calcium Silicophosphate Scaffold Induced Bone Formation

    Science.gov (United States)

    Ros-Tárraga, Patricia; Mazón, Patricia; Rodríguez, Miguel A.; Meseguer-Olmo, Luis; De Aza, Piedad N.

    2016-01-01

    This aim of this research was to develop a novel ceramic scaffold to evaluate the response of bone after ceramic implantation in New Zealand (NZ) rabbits. Ceramics were prepared by the polymer replication method and inserted into NZ rabbits. Macroporous scaffolds with interconnected round-shaped pores (0.5–1.5 mm = were prepared). The scaffold acted as a physical support where cells with osteoblastic capability were found to migrate, develop processes, and newly immature and mature bone tissue colonized on the surface (initially) and in the material’s interior. The new ceramic induced about 62.18% ± 2.28% of new bone and almost complete degradation after six healing months. An elemental analysis showed that the gradual diffusion of Ca and Si ions from scaffolds into newly formed bone formed part of the biomaterial’s resorption process. Histological and radiological studies demonstrated that this porous ceramic scaffold showed biocompatibility and excellent osteointegration and osteoinductive capacity, with no interposition of fibrous tissue between the implanted material and the hematopoietic bone marrow interphase, nor any immune response after six months of implantation. No histological changes were observed in the various organs studied (para-aortic lymph nodes, liver, kidney and lung) as a result of degradation products being released. PMID:28773906

  3. Marginal zinc deficiency in pregnant rats impairs bone matrix formation and bone mineralization in their neonates.

    Science.gov (United States)

    Nagata, Masashi; Kayanoma, Megumu; Takahashi, Takeshi; Kaneko, Tetsuo; Hara, Hiroshi

    2011-08-01

    Zinc (Zn) deficiency during pregnancy may result in a variety of defects in the offspring. We evaluated the influence of marginal Zn deficiency during pregnancy on neonatal bone status. Nine-week-old male Sprague-Dawley rats were divided into two groups and fed AIN-93G-based experimental diets containing 35 mg Zn/kg (Zn adequately supplied, N) or 7 mg Zn/kg (low level of Zn, L) from 14-day preconception to 20 days of gestation, that is, 1 day before normal delivery. Neonates were delivered by cesarean section. Litter size and neonate weight were not different between the two groups. However, in the L-diet-fed dam group, bone matrix formation in isolated neonatal calvaria culture was clearly impaired and was not recovered by the addition of Zn into the culture media. Additionally, serum concentration of osteocalcin, as a bone formation parameter, was lower in neonates from the L-diet-fed dam group. Impaired bone mineralization was observed with a significantly lower content of phosphorus in neonate femurs from L-diet-fed dams compared with those from N-diet-fed dams. Moreover, Zn content in the femur and calvaria of neonates from the L-diet group was lower than that of the N-diet-fed group. In the marginally Zn-deficient dams, femoral Zn content, serum concentrations of Zn, and osteocalcin were reduced when compared with control dams. We conclude that maternal Zn deficiency causes impairment of bone matrix formation and bone mineralization in neonates, implying the importance of Zn intake during pregnancy for proper bone development of offspring.

  4. Osteoclast formation from peripheral blood of patients with bone-lytic diseases

    NARCIS (Netherlands)

    de Vries, T.J.; Everts, V.

    2009-01-01

    Recent literature indicates that osteoclast formation in vitro from peripheral blood of patients with diseases associated with bone loss such as rheumatoid arthritis, osteoporosis, periodontitis and bone metastatic cancer may occur spontaneously being independent of addition of osteoclast formation

  5. Bone cutting capacity and osseointegration of surface-treated orthodontic mini-implants.

    Science.gov (United States)

    Kim, Ho-Young; Kim, Sang-Cheol

    2016-11-01

    The objective of the study was to evaluate the practicality and the validity of different surface treatments of self-drilling orthodontic mini-implants (OMIs) by comparing bone cutting capacity and osseointegration. Self-drilling OMIs were surface-treated in three ways: Acid etched (Etched), resorbable blasting media (RBM), partially resorbabla balsting media (Hybrid). We compared the bone cutting capacity by measuring insertion depths into artificial bone (polyurethane foam). To compare osseointegration, OMIs were placed in the tibia of 25 rabbits and the removal torque value was measured at 1, 2, 4, and 8 weeks after placement. The specimens were analyzed by optical microscopy, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDS). The bone cutting capacity of the etched and hybrid group was lower than the machined (control) group, and was most inhibited in the RBM group ( p < 0.05). At 4 weeks, the removal torque in the machined group was significantly decreased ( p < 0.05), but was increased in the etched group ( p < 0.05). In the hybrid group, the removal torque significantly increased at 2 weeks, and was the highest among all measured values at 8 weeks ( p < 0.05). The infiltration of bone-like tissue surface was evaluated by SEM, and calcium and phosphorus were detected via EDS only in the hybrid group. Partial RBM surface treatment (hybrid type in this study) produced the most stable self-drilling OMIs, without a corresponding reduction in bone cutting capacity.

  6. Multi-protein delivery by nanodiamonds promotes bone formation.

    Science.gov (United States)

    Moore, L; Gatica, M; Kim, H; Osawa, E; Ho, D

    2013-11-01

    Bone morphogenetic proteins (BMPs) are well-studied regulators of cartilage and bone development that have been Food and Drug Administration (FDA)-approved for the promotion of bone formation in certain procedures. BMPs are seeing more use in oral and maxillofacial surgeries because of recent FDA approval of InFUSE(®) for sinus augmentation and localized alveolar ridge augmentation. However, the utility of BMPs in medical and dental applications is limited by the delivery method. Currently, BMPs are delivered to the surgical site by the implantation of bulky collagen sponges. Here we evaluate the potential of detonation nanodiamonds (NDs) as a delivery vehicle for BMP-2 and basic fibroblast growth factor (bFGF). Nanodiamonds are biocompatible, 4- to 5-nm carbon nanoparticles that have previously been used to deliver a wide variety of molecules, including proteins and peptides. We find that both BMP-2 and bFGF are readily loaded onto NDs by physisorption, forming a stable colloidal solution, and are triggered to release in slightly acidic conditions. Simultaneous delivery of BMP-2 and bFGF by ND induces differentiation and proliferation in osteoblast progenitor cells. Overall, we find that NDs provide an effective injectable alternative for the delivery of BMP-2 and bFGF to promote bone formation.

  7. Lipoic acid increases the expression of genes involved in bone formation in mice fed a high-fat diet.

    Science.gov (United States)

    Xiao, Ying; Cui, Jue; Shi, Yonghui; Le, Guowei

    2011-04-01

    Antioxidant lipoic acid (LA) has been reported to have a potential prophylactic effect on bone loss induced by high-fat diet (HFD). The aim of this work was to examine the hypothesis that LA decreases bone resorption-related gene expression and increases bone formation-related gene expression in HFD-fed mice, preventing a shift in the bone metabolism balance toward resorption. Male C57BL/6 mice were fed a normal diet, HFD, or HFD plus 0.1% LA for 12 weeks. The bone metabolism-related genes differentially expressed between mice fed HFD and those fed HFD supplemented with LA were identified through complementary DNA microarray. The supplemental LA significantly increased bone mineral density and bone antioxidant capacity in mice fed HFD (P LA induced the decreased expression of genes associated with bone resorption, such as Mmp9 (1.9-fold) and Ctsk (2.3-fold), and increased those genes associated with bone formation, such as Col1a1 (1.3-fold) and Alp1 (1.5-fold). Furthermore, LA upregulated many genes involved in the Igf signaling pathway, such as Igf-1 (increased 1.7-fold), and downregulated genes involved in the p53 apoptotic pathway, such as p53 (decreased 2.3-fold), thus attenuating the HFD-induced inhibition of bone formation. Lipoic acid induced upregulation of Il12a (2.1-fold) and downregulation of Tgfbr1 (4.3-fold) and Il17a (11.3-fold), which may reduce bone resorption. In summary, LA supplementation during HFD could affect bone density, altering gene expression. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. CHARACTERIZATION OF REACTIVE FORMATIONS: A VISION FOR THE CAPACITY EXPANSION

    Directory of Open Access Journals (Sweden)

    Danielly Vieira de Lucena

    2013-12-01

    Full Text Available All classes of clay minerals absorb water, but the smectite absorb much larger volumes than the other classes because of its expanded network. During the drilling of oil wells it is common for the detection of layers consisting of clay minerals high grade of hydration arranged in laminar packages. When in contact with water, the packets are separated clay as the water enters the basal spacing. This phenomenon is known as expansion or swelling. Given this, this paper aims to characterize shales in two regions of the country to explain the susceptibility of hydration of each of these formations. The characterization was done by making use of Exchange cation capacity (ECC, X-ray fluorescence (XRF, diferential thermal analysis (DTA, Thermogravimetry (TGA and X-ray diffraction (XRD. The results obtained showed that among the shales studied, those with the greatest degree of clay fractions (smectite in its composition showed higher swelling index according to the methodology of Foster.

  9. Hypoxia inhibits the growth, differentiation and bone-forming capacity of rat osteoblasts

    International Nuclear Information System (INIS)

    Utting, J.C.; Robins, S.P.; Brandao-Burch, A.; Orriss, I.R.; Behar, J.; Arnett, T.R.

    2006-01-01

    We investigated the effect of hypoxia on rat osteoblast function in long-term primary cultures. Reduction of pO 2 from 20% to 5% and 2% decreased formation of mineralized bone nodules 1.7-fold and 11-fold, respectively. When pO 2 was reduced further to 0.2%, bone nodule formation was almost abolished. The inhibitory effect of hypoxia on bone formation was partly due to decreased osteoblast proliferation, as measured by 3 H-thymidine incorporation. Hypoxia also sharply reduced osteoblast alkaline phosphatase (ALP) activity and expression of mRNAs for ALP and osteocalcin, suggesting inhibition of differentiation to the osteogenic phenotype. Hypoxia did not increase the apoptosis of osteoblasts but induced a reversible state of quiescence. Transmission electron microscopy revealed that collagen fibrils deposited by osteoblasts cultured in 2% O 2 were less organized and much less abundant than in 20% O 2 cultures. Furthermore, collagen produced by hypoxic osteoblasts contained a lower percentage of hydroxylysine residues and exhibited an increased sensitivity to pepsin degradation. These data demonstrate the absolute oxygen requirement of osteoblasts for successful bone formation and emphasize the importance of the vasculature in maintaining bone health. We recently showed that hypoxia also acts in a reciprocal manner as a powerful stimulator of osteoclast formation. Considered together, our results help to explain the bone loss that occurs at the sites of fracture, tumors, inflammation and infection, and in individuals with vascular disease or anemia

  10. Botulinum Toxin-induced Muscle Paralysis Inhibits Heterotopic Bone Formation.

    Science.gov (United States)

    Ausk, Brandon J; Gross, Ted S; Bain, Steven D

    2015-09-01

    Short-term muscle atrophy induced by botulinum toxin A (BTxA) has been observed to impair osteogenesis in a rat closed femur fracture model. However, it is unclear whether the underlying mechanism is a direct effect of BTxA on muscle-bone interactions or an indirect effect that is driven by skeletal unloading. Because skeletal trauma in the closed fracture model also leads to disuse atrophy, we sought to mitigate this confounding variable by examining BTxA effects on muscle-bone interactions in two complementary in vivo models in which osteogenesis is induced in the absence of skeletal unloading. The overall aim of this study was to identify a potential strategy to inhibit pathological bone formation and heterotopic ossification (HO). (1) Does muscle paralysis inhibit periosteal osteogenesis induced by a transcortical defect? (2) Does muscle paralysis inhibit heterotopic bone formation stimulated by intramuscular bone morphogenetic protein (BMP) injection? Focal osteogenesis was induced in the right hindlimb of mice through surgical initiation of a small transcortical defect in the tibia (fracture callus; n = 7/group) or intramuscular injection of BMP-2 (HO lesion; n = 6/group), both in the presence/absence of adjacent calf paralysis. High-resolution micro-CT images were obtained in all experimental groups 21 days postinduction and total volume (ie, perimeter of periosteal callus or HO lesion) and bone volume (calcified tissue within the total volume) were quantified as primary outcome measures. Finally, these outcome measures were compared to determine the effect of muscle paralysis on inhibition of local osteogenesis in both studies. After a transcortical defect, BTxA-treated mice showed profound inhibition of osteogenesis in the periosteal fracture callus 21 days postsurgery compared with saline-treated mice (total volume: 0.08 ± 0.06 versus 0.42 ± 0.11 mm(3), p paralysis at the same time point (total volume: 1.42 ± 0.31 versus 3.42 ± 2.11 mm(3), p = 0

  11. Mechanical Vibration Mitigates the Decrease of Bone Quantity and Bone Quality of Leptin Receptor-Deficient Db/Db Mice by Promoting Bone Formation and Inhibiting Bone Resorption.

    Science.gov (United States)

    Jing, Da; Luo, Erping; Cai, Jing; Tong, Shichao; Zhai, Mingming; Shen, Guanghao; Wang, Xin; Luo, Zhuojing

    2016-09-01

    Leptin, a major hormonal product of adipocytes, is involved in regulating appetite and energy metabolism. Substantial studies have revealed the anabolic actions of leptin on skeletons and bone cells both in vivo and in vitro. Growing evidence has substantiated that leptin receptor-deficient db/db mice exhibit decreased bone mass and impaired bone microstructure despite several conflicting results previously reported. We herein systematically investigated bone microarchitecture, mechanical strength, bone turnover and its potential molecular mechanisms in db/db mice. More importantly, we also explored an effective approach for increasing bone mass in leptin receptor-deficient animals in an easy and noninvasive manner. Our results show that deterioration of trabecular and cortical bone microarchitecture and decreases of skeletal mechanical strength-including maximum load, yield load, stiffness, energy, tissue-level modulus and hardness-in db/db mice were significantly ameliorated by 12-week, whole-body vibration (WBV) with 0.5 g, 45 Hz via micro-computed tomography (μCT), three-point bending, and nanoindentation examinations. Serum biochemical analysis shows that WBV significantly decreased serum tartrate-resistant acid phosphatase 5b (TRACP5b) and CTx-1 levels and also mitigated the reduction of serum osteocalcin (OCN) in db/db mice. Bone histomorphometric analysis confirmed that decreased bone formation-lower mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone-in db/db mice were suppressed by WBV. Real-time PCR assays show that WBV mitigated the reductions of tibial alkaline phosphatase (ALP), OCN, Runt-related transcription factor 2 (RUNX2), type I collagen (COL1), BMP2, Wnt3a, Lrp6, and β-catenin mRNA expression, and prevented the increases of tibial sclerostin (SOST), RANK, RANKL, RANL/osteoprotegerin (OPG) gene levels in db/db mice. Our results show that WBV promoted bone quantity and quality in db/db mice with obvious

  12. Functionalized Surface Geometries Induce: “Bone: Formation by Autoinduction”

    Directory of Open Access Journals (Sweden)

    Ugo Ripamonti

    2018-02-01

    Full Text Available The induction of tissue formation, and the allied disciplines of tissue engineering and regenerative medicine, have flooded the twenty-first century tissue biology scenario and morphed into high expectations of a fulfilling regenerative dream of molecularly generated tissues and organs in assembling human tissue factories. The grand conceptualization of deploying soluble molecular signals, first defined by Turing as forms generating substances, or morphogens, stemmed from classic last century studies that hypothesized the presence of morphogens in several mineralized and non-mineralized mammalian matrices. The realization of morphogens within mammalian matrices devised dissociative extractions and chromatographic procedures to isolate, purify, and finally reconstitute the cloned morphogens, found to be members of the transforming growth factor-β (TGF-β supergene family, with insoluble signals or substrata to induce de novo tissue induction and morphogenesis. Can we however construct macroporous bioreactors per se capable of inducing bone formation even without the exogenous applications of the osteogenic soluble molecular signals of the TGF-β supergene family? This review describes original research on coral-derived calcium phosphate-based macroporous constructs showing that the formation of bone is independent of the exogenous application of the osteogenic soluble signals of the TGF-β supergene family. Such signals are the molecular bases of the induction of bone formation. The aim of this review is to primarily describe today's hottest topic of biomaterials' science, i.e., to construct and define osteogenetic biomaterials' surfaces that per se, in its own right, do initiate the induction of bone formation. Biomaterials are often used to reconstruct osseous defects particularly in the craniofacial skeleton. Edentulism did spring titanium implants as tooth replacement strategies. No were else that titanium surfaces require functionalized

  13. Cancer cell expression of autotaxin controls bone metastasis formation in mouse through lysophosphatidic acid-dependent activation of osteoclasts.

    Directory of Open Access Journals (Sweden)

    Marion David

    2010-03-01

    Full Text Available Bone metastases are highly frequent complications of breast cancers. Current bone metastasis treatments using powerful anti-resorptive agents are only palliative indicating that factors independent of bone resorption control bone metastasis progression. Autotaxin (ATX/NPP2 is a secreted protein with both oncogenic and pro-metastatic properties. Through its lysosphospholipase D (lysoPLD activity, ATX controls the level of lysophosphatidic acid (LPA in the blood. Platelet-derived LPA promotes the progression of osteolytic bone metastases of breast cancer cells. We asked whether ATX was involved in the bone metastasis process. We characterized the role of ATX in osteolytic bone metastasis formation by using genetically modified breast cancer cells exploited on different osteolytic bone metastasis mouse models.Intravenous injection of human breast cancer MDA-B02 cells with forced expression of ATX (MDA-B02/ATX to immunodeficiency BALB/C nude mice enhanced osteolytic bone metastasis formation, as judged by increased bone loss, tumor burden, and a higher number of active osteoclasts at the metastatic site. Mouse breast cancer 4T1 cells induced the formation of osteolytic bone metastases after intracardiac injection in immunocompetent BALB/C mice. These cells expressed active ATX and silencing ATX expression inhibited the extent of osteolytic bone lesions and decreased the number of active osteoclasts at the bone metastatic site. In vitro, osteoclast differentiation was enhanced in presence of MDA-B02/ATX cell conditioned media or recombinant autotaxin that was blocked by the autotaxin inhibitor vpc8a202. In vitro, addition of LPA to active charcoal-treated serum restored the capacity of the serum to support RANK-L/MCSF-induced osteoclastogenesis.Expression of autotaxin by cancer cells controls osteolytic bone metastasis formation. This work demonstrates a new role for LPA as a factor that stimulates directly cancer growth and metastasis, and

  14. Reciprocal Interactions between Multiple Myeloma Cells and Osteoprogenitor Cells Affect Bone Formation and Tumor Growth

    Science.gov (United States)

    2014-10-01

    SUBJECT TERMS Multiple Myeloma, Blood Cancer , Hematological Malignancy , Bone Metastasis, 3D Model, In vitro, silk scaffolds, osteogenic microRNAs...platform to study cancer -bone interactions. Keywords Multiple Myeloma, Blood Cancer , Hematological Malignancy , Bone Metastasis, 3D Model, In vitro...Affect Bone Formation and Tumor Growth” PRINCIPAL INVESTIGATOR: Michaela Reagan CONTRACTING ORGANIZATION: Dana-Farber Cancer Institute, Inc

  15. Direct bone formation during distraction osteogenesis does not require TNF alpha receptors and elevated serum TNF alpha fails to inhibit bone formation in TNFR1 deficient mice

    Science.gov (United States)

    Distraction osteogenesis (DO) is a process which induces direct new bone formation as a result of mechanical distraction. Tumor necrosis factor-alpha (TNF) is a cytokine that can modulate osteoblastogenesis. The direct effects of TNF on direct bone formation in rodents are hypothetically mediated th...

  16. New bone formation in a bone defect associated to dental implant using absorbable or non-absorbable membrane in a dog model

    Science.gov (United States)

    Lopez, Maria de Almeida; Olate, Sergio; Lanata-Flores, Antonio; Pozzer, Leandro; Cavalieri-Pereira, Lucas; Cantín, Mario; Vásquez, Bélgica; de Albergaria-Barbosa, José

    2013-01-01

    The aim of this research was to determine the bone formation capacity in fenestration defects associated with dental implants using absorbable and non-absorbable membranes. Six dogs were used in the study. In both tibias of each animal 3 implants were installed, and around these 5 mm circular defects were created. The defects were covered with absorbable membranes (experimental group 1), non-absorbable membranes (experimental group 2), and the third defect was not covered (control group). At 3 and 8 weeks post-surgery, the animals were euthanized and the membranes with the bone tissue around the implants were processed for histological analysis. The statistical analysis was conducted with Tukey’s test, considering statistical significance when p0.1). In the defects without membrane, continuous connective tissue invasions and bone repair deficiency were observed. There were no significant differences in the characteristics and volume of the neoformed bone in the defects around the implants covered by the different membranes, whereas the control defects produced significantly less bone. The use of biological membranes contributes to bone formation in three-wall defects. PMID:24228090

  17. Kaempferol-immobilized titanium dioxide promotes formation of new bone: effects of loading methods on bone marrow stromal cell differentiation in vivo and in vitro.

    Science.gov (United States)

    Tsuchiya, Shuhei; Sugimoto, Keisuke; Kamio, Hisanobu; Okabe, Kazuto; Kuroda, Kensuke; Okido, Masazumi; Hibi, Hideharu

    2018-01-01

    Surface modification of titanium dioxide (TiO 2 ) implants promotes bone formation and shortens the osseointegration period. Kaempferol is a flavonoid that has the capacity to promote osteogenic differentiation in bone marrow stromal cells. The aim of this study was to promote bone formation around kaempferol immobilized on TiO 2 implants. There were four experimental groups. Alkali-treated TiO 2 samples (implants and discs) were used as a control and immersed in Dulbecco's phosphate-buffered saline (DPBS) (Al-Ti). For the coprecipitation sample (Al-cK), the control samples were immersed in DPBS containing 50 µg kaempferol/100% ethanol. For the adsorption sample (Al-aK), 50 µg kaempferol/100% ethanol was dropped onto control samples. The surface topography of the TiO 2 implants was observed by scanning electron microscopy with energy-dispersive X-ray spectroscopy, and a release assay was performed. For in vitro experiments, rat bone marrow stromal cells (rBMSCs) were cultured on each of the TiO 2 samples to analyze cell proliferation, alkaline phosphatase activity, calcium deposition, and osteogenic differentiation. For in vivo experiments, TiO 2 implants placed on rat femur bones were analyzed for bone-implant contact by histological methods. Kaempferol was detected on the surface of Al-cK and Al-aK. The results of the in vitro study showed that rBMSCs cultured on Al-cK and Al-aK promoted alkaline phosphatase activity, calcium deposition, and osteogenic differentiation. The in vivo histological analysis revealed that Al-cK and Al-aK stimulated new bone formation around implants. TiO 2 implant-immobilized kaempferol may be an effective tool for bone regeneration around dental implants.

  18. Abaloparatide, a novel PTH receptor agonist, increased bone mass and strength in ovariectomized cynomolgus monkeys by increasing bone formation without increasing bone resorption.

    Science.gov (United States)

    Doyle, N; Varela, A; Haile, S; Guldberg, R; Kostenuik, P J; Ominsky, M S; Smith, S Y; Hattersley, G

    2018-03-01

    Abaloparatide, a novel PTH1 receptor agonist, increased bone formation in osteopenic ovariectomized cynomolgus monkeys while increasing cortical and trabecular bone mass. Abaloparatide increased bone strength and maintained or enhanced bone mass-strength relationships, indicating preserved or improved bone quality. Abaloparatide is a selective PTH1R activator that is approved for the treatment of postmenopausal osteoporosis. The effects of 16 months of abaloparatide administration on bone formation, resorption, density, and strength were assessed in adult ovariectomized (OVX) cynomolgus monkeys (cynos). Sixty-five 9-18-year-old female cynos underwent OVX surgery, and 15 similar cynos underwent sham surgery. After a 9-month period without treatments, OVX cynos were allocated to four groups that received 16 months of daily s.c. injections with either vehicle (n = 17) or abaloparatide (0.2, 1, or 5 μg/kg/day; n = 16/dose level), while Sham controls received s.c. vehicle (n = 15). Bone densitometry (DXA, pQCT, micro-CT), qualitative bone histology, serum calcium, bone turnover markers, bone histomorphometry, and bone strength were among the key measures assessed. At the end of the 9-month post-surgical bone depletion period, just prior to the treatment phase, the OVX groups exhibited increased bone turnover markers and decreased bone mass compared with sham controls. Abaloparatide administration to OVX cynos led to increased bone formation parameters, including serum P1NP and endocortical bone formation rate. Abaloparatide administration did not influence serum calcium levels, bone resorption markers, cortical porosity, or eroded surfaces. Abaloparatide increased bone mass at the whole body, lumbar spine, tibial diaphysis, femoral neck, and femoral trochanter. Abaloparatide administration was associated with greater lumbar vertebral strength, and had no adverse effects on bone mass-strength relationships for the vertebrae, femoral neck, femoral

  19. Trauma-induced heterotopic bone formation and the role of the immune system: A review.

    Science.gov (United States)

    Kraft, Casey T; Agarwal, Shailesh; Ranganathan, Kavitha; Wong, Victor W; Loder, Shawn; Li, John; Delano, Matthew J; Levi, Benjamin

    2016-01-01

    Extremity trauma, spinal cord injuries, head injuries, and burn injuries place patients at high risk of pathologic extraskeletal bone formation. This heterotopic bone causes severe pain, deformities, and joint contractures. The immune system has been increasingly implicated in this debilitating condition. This review summarizes the various roles immune cells and inflammation play in the formation of ectopic bone and highlights potential areas of future investigation and treatment. Cell types in both the innate and adaptive immune system such as neutrophils, macrophages, mast cells, B cells, and T cells have all been implicated as having a role in ectopic bone formation through various mechanisms. Many of these cell types are promising areas of therapeutic investigation for potential treatment. The immune system has also been known to also influence osteoclastogenesis, which is heavily involved in ectopic bone formation. Chronic inflammation is also known to have an inhibitory role in the formation of ectopic bone, whereas acute inflammation is necessary for ectopic bone formation.

  20. Bone Marrow Stromal Cells Contribute to Bone Formation Following Infusion into Femoral Cavities of a Mouse Model of Osteogenesis Imperfecta

    Science.gov (United States)

    Li, Feng; Wang, Xujun; Niyibizi, Christopher

    2010-01-01

    Currently, there are conflicting data in literature regarding contribution of bone marrow stromal cells (BMSCs) to bone formation when the cells are systemically delivered in recipient animals. To understand if BMSCs contribute to bone cell phenotype and bone formation in osteogenesis imperfecta bones (OI), MSCs marked with GFP were directly infused into the femurs of a mouse model of OI (oim). The contribution of the cells to the cell phenotype and bone formation was assessed by histology, immunohistochemistry and biomechanical loading of recipient bones. Two weeks following infusion of BMSCs, histological examination of the recipient femurs demonstrated presence of new bone when compared to femurs injected with saline which showed little or no bone formation. The new bone contained few donor cells as demonstrated by GFP fluorescence. At six weeks following cell injection, new bone was still detectable in the recipient femurs but was enhanced by injection of the cells suspended in pepsin solublized type I collagen. Immunofluorescence and immunohistochemical staining showed that donor GFP positive cells in the new bone were localized with osteocalcin expressing cells suggesting that the cells differentiated into osteoblasts in vivo. Biomechanical loading to failure in thee point bending, revealed that, femurs infused with BMSCs in PBS or in soluble type I collagen were biomechanically stronger than those injected with PBS or type I collagen alone. Taken together, the results indicate that transplanted cells differentiated into osteoblasts in vivo and contributed to bone formation in vivo; we also speculate that donor cells induced differentiation or recruitment of endogenous cells to initiate reparative process at early stages following transplantation. PMID:20570757

  1. Radiologic study of the experimentally produced bone destruction and bone formation

    International Nuclear Information System (INIS)

    Chei, Soon Chul; Ahn, Hyung Kyu

    1988-01-01

    Bone destruction was induced experimentally by the insertion of a bit of the arsenic compound into the pulp chambers of the right premolars and the artificial bone defects were produced in the periapical regions of the left premolars in 7 dogs. The serial standardized periapical radiographs using aluminum stepwedge attached to the XCP instruments and resin bite blocks were taken following insertion of arsenic compound and at 2, 4, 7, 10, 14, 17, 21, 24 and 28 days in case of bone destruction and following bone injury and weekly thereafter for a total of 14 weeks in case of bone formation . The errors of the method were determined with error estimators described by the Duinkerke. All radiographs were evaluated by the visual examination after joint evaluation by three dental radiologists and analysed with densitometer. The following results were obtained; 1. Analysis of the bone destruction process 1) The error of the method in estimating two distances proved to be small (S.D. for the measuring error; 0.04 mm, S.D. for the over-all error; 0.06 mm, S.D. for the positioning error; 0.05 mm) 2) The radiographic changes were observed after 7 days in 6 cases, 4 days in 1 case and 10 days in 1 case by the visual examination. 3) Aluminum equivalent values were diminished after 2 days and the diminution of 0.58 ± 0.19 mm was demanded to be detected by the visual examination. 2. Analysis of the bone formation process 1) The error of the method in estimating two distances proved to be small (S.D. for the measuring error; 0.03 mm, S.D. for the over-all error; 0.04 mm, S.D. for the positioning error; 0.04 mm) 2) The radiographic changes were observed after 2 weeks in 5 cases and 3 weeks in 2 cases by the visual examination. 3) Aluminum equivalent values were increased after 1 week and the increase of 0.45 ± 0.15 mm was demanded to be detected by the visual examination. 4) Aluminum equivalent values were increased continuously for 7 or 9 weeks but there was only extremely small

  2. Impaired bone formation in Pdia3 deficient mice.

    Directory of Open Access Journals (Sweden)

    Yun Wang

    Full Text Available 1α,25-Dihydroxyvitamin D3 [1α,25(OH2D3] is crucial for normal skeletal development and bone homeostasis. Protein disulfide isomerase family A, member 3 (PDIA3 mediates 1α,25(OH2D3 initiated-rapid membrane signaling in several cell types. To understand its role in regulating skeletal development, we generated Pdia3-deficient mice and examined the physiologic consequence of Pdia3-disruption in embryos and Pdia3+/- heterozygotes at different ages. No mice homozygous for the Pdia3-deletion were found at birth nor were there embryos after E12.5, indicating that targeted disruption of the Pdia3 gene resulted in early embryonic lethality. Pdia3-deficiency also resulted in skeletal manifestations as revealed by µCT analysis of the tibias. In comparison to wild type mice, Pdia3 heterozygous mice displayed expanded growth plates associated with decreased tether formation. Histomorphometry also showed that the hypertrophic zone in Pdia3+/- mice was more cellular than seen in wild type growth plates. Metaphyseal trabecular bone in Pdia3+/- mice exhibited an age-dependent phenotype with lower BV/TV and trabecular numbers, which was most pronounced at 15 weeks of age. Bone marrow cells from Pdia3+/- mice exhibited impaired osteoblastic differentiation, based on reduced expression of osteoblast markers and mineral deposition compared to cells from wild type animals. Collectively, our findings provide in vivo evidence that PDIA3 is essential for normal skeletal development. The fact that the Pdia3+/- heterozygous mice share a similar growth plate and bone phenotype to nVdr knockout mice, suggests that PDIA3-mediated rapid membrane signaling might be an alternative mechanism responsible for 1α,25(OH2D3's actions in regulating skeletal development.

  3. Osteocytes subjected to fluid flow inhibit osteoclast formation and bone resorption.

    NARCIS (Netherlands)

    Tan, S.D.; Vries, T.J. de; Kuijpers-Jagtman, A.M.; Semeins, C.M.; Everts, V.; Klein-Nulend, J.

    2007-01-01

    Bone has the capacity to alter its mass and structure to its mechanical environment. Osteocytes are the predominant bone cells and it is generally accepted that the osteocytes are the professional mechanosensors of bone. A strain-derived fluid flow through the lacuno-canalicular porosity seems to

  4. Low Bone Mineral Mass Is Associated with Decreased Bone Formation and Diet in Females with Rett Syndrome

    Science.gov (United States)

    Motil, Kathleen J.; Barrish, Judy O.; Neul, Jeffrey L.; Glaze, Daniel G.

    2014-01-01

    Objective To characterize biomarkers of bone turnover and their relation with bone mineral mass in a cross-sectional cohort of females with Rett syndrome (RTT) and to examine the role of dietary, biochemical, hormonal, and inflammatory factors on bone mineral mass and bone biomarkers in this disorder. Methods Total body bone mineral content (BMC) and density (BMD) were determined by dual-energy x-ray absorptiometry. Dietary nutrient intakes were determined from 3-day food records. Biomarkers of bone turnover, bone metabolites, vitamin D metabolites, hormones, and inflammatory markers were measured by standard clinical laboratory methods. Results Serum osteocalcin, bone alkaline phosphatase, and C-telopeptide showed significant inverse relations with age in the RTT cohort. Mean osteocalcin concentrations were significantly lower and mean bone alkaline phosphatase concentrations were significantly higher for individual age groups in the RTT cohort than mean values for their respective age ranges in the reference population. Significant inverse associations were identified between urinary calcium losses, expressed as calcium:creatinine ratios, and total body BMC and BMD z-scores. Dietary protein, calcium, and phosphorus intakes, expressed as a proportion of Dietary Reference Intakes for age and gender, showed significant positive associations with total body BMD z-scores. Conclusion This study suggests decreased bone formation rather than increased bone resorption may explain in part the deficits in bone mineral mass in RTT and that attention to the adequacy of dietary protein, calcium and phosphorus intakes may offer an opportunity to improve bone health in RTT. PMID:25144778

  5. Predicting Diaphyseal Cortical Bone Status Using Measures of Muscle Force Capacity.

    Science.gov (United States)

    Higgins, Simon; Sokolowski, Chester M; Vishwanathan, Megha; Anderson, Jessica G; Schmidt, Michael D; Lewis, Richard D; Evans, Ellen M

    2018-02-16

    Muscle cross sectional area (MCSA) is often used as a surrogate for the forces applied to bones during physical activity. Though MCSA is a strong predictor of cortical bone status, its use makes assumptions about the relationship between muscle size and force that are inaccurate. Furthermore, to measure MCSA and other muscle force surrogates typically requires expensive and/or radiative laboratory equipment. Thus, this study aimed to determine whether clinical lab- and field-based methodologies for measuring muscular force capacity accounted for similar variance in diaphyseal cortical bone status as a commonly used muscular force surrogate; MCSA, at the mid-tibia in young men and women. Healthy young adults (n = 142, 19.7 ± 0.7 yo, 52.8% female) were assessed via peripheral quantitative computed tomography at the mid-tibia for cortical bone status and MCSA. Muscle force capacity was measured via Biodex dynamometer, Nottingham leg extensor power rig, and Vertec vertical jump. Regression analysis compared the independent variance predicted by each muscle force measure to that of MCSA, accounting for relevant confounders. MCSA, knee extension peak torque, and peak anaerobic power from vertical jump were independent predictors of select cortical structural outcomes (cortical thickness and area, periosteal and endosteal circumference, and estimated strength) accounting for up to 78.4% of the variance explained (all p<.05). However, cortical volumetric bone mineral density was unrelated to any measure or surrogate of muscle force capacity. MCSA is a strong independent predictor of cortical bone structure; however, both lab- and field-based measures of peak torque and/or peak anaerobic power are promising alternatives, explaining similar and sometimes greater variance than MCSA.

  6. Bone formation is not impaired by hibernation (disuse) in black bears Ursus americanus.

    Science.gov (United States)

    Donahue, Seth W; Vaughan, Michael R; Demers, Laurence M; Donahue, Henry J

    2003-12-01

    Disuse by bed rest, limb immobilization or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. This net bone loss increases the risk of fracture upon remobilization. Bone loss also occurs in hibernating ground squirrels, golden hamsters, and little brown bats by arresting bone formation and accelerating bone resorption. There is some histological evidence to suggest that black bears Ursus americanus do not lose bone mass during hibernation (i.e. disuse). There is also evidence suggesting that muscle mass and strength are preserved in black bears during hibernation. The question of whether bears can prevent bone loss during hibernation has not been conclusively answered. The goal of the current study was to further assess bone metabolism in hibernating black bears. Using the same serum markers of bone remodeling used to evaluate human patients with osteoporosis, we assayed serum from five black bears, collected every 10 days over a 196-day period, for bone resorption and formation markers. Here we show that bone resorption remains elevated over the entire hibernation period compared to the pre-hibernation period, but osteoblastic bone formation is not impaired by hibernation and is rapidly accelerated during remobilization following hibernation.

  7. Self-assembling bisphosphonates into nanofibers to enhance their inhibitory capacity on bone resorption

    Science.gov (United States)

    Tang, Anming; Qian, Yu; Liu, Shuang; Wang, Weijuan; Xu, Bing; Qin, An; Liang, Gaolin

    2016-05-01

    Osteoporosis (OP) is an important aging-related disease and the effective prevention/treatment of this disease remains challenging. Considering the acidic microenvironment of bone resorption lacunae, herein, we rationally designed two pamidronate (Pami)-derivative and alendronate (Alen)-derivative hydrogelators Pami-D and Alen-D which self-assemble into nanofibers to form supramolecular hydrogels under acidic conditions. Cell viability assay, osteoclastogenesis, osteoclastic gene expression, and in vitro bone resorption results indicated that both Pami-D and Alen-D have better inhibitory effects on osteoclastic formation and bone resorption than Pami and Alen, respectively. We anticipate that our new drugs Pami-D and Alen-D could ``smartly'' self-assemble and locally concentrate the drugs at bone resorption lacunae in vivo and subsequently prevent/treat osteoporosis more efficiently.Osteoporosis (OP) is an important aging-related disease and the effective prevention/treatment of this disease remains challenging. Considering the acidic microenvironment of bone resorption lacunae, herein, we rationally designed two pamidronate (Pami)-derivative and alendronate (Alen)-derivative hydrogelators Pami-D and Alen-D which self-assemble into nanofibers to form supramolecular hydrogels under acidic conditions. Cell viability assay, osteoclastogenesis, osteoclastic gene expression, and in vitro bone resorption results indicated that both Pami-D and Alen-D have better inhibitory effects on osteoclastic formation and bone resorption than Pami and Alen, respectively. We anticipate that our new drugs Pami-D and Alen-D could ``smartly'' self-assemble and locally concentrate the drugs at bone resorption lacunae in vivo and subsequently prevent/treat osteoporosis more efficiently. Electronic supplementary information (ESI) available: Experiment methods and details; syntheses and characterization of Pami-D and Alen-D; HPLC conditions; Fig. S1-S15, Schemes S1 and S2, Tables S1 and S2

  8. Osteoblast Differentiation and Bone Formation Gene Expression in Strontium-inducing Bone Marrow Mesenchymal Stem Cell

    OpenAIRE

    SILA-ASNA, MONNIPHA; BUNYARATVEJ, AHNOND; Maeda, Sakan; Kitaguchi, Hiromichi; BUNYARATAVEJ, NARONG

    2007-01-01

    Osteoblastic differentiation from human mesenchymal stem cell (hMSCs) is animportant step of bone formation. We studied the in vitro induction of hMSCs byusing strontium ranelate, a natural trace amount in water, food and human skeleton.The mRNA synthesis of various osteoblast specific genes was assessed by means ofreverse transcription polymerase chain reaction (RT-PCR). In the hMSCs culture,strontium ranelate could enhance the induction of hMSCs to differentiate intoosteoblasts. Cbfa1 gene ...

  9. Mice deficient in 11beta-hydroxysteroid dehydrogenase type 1 lack bone marrow adipocytes, but maintain normal bone formation

    DEFF Research Database (Denmark)

    Justesen, Jeannette; Mosekilde, Lis; Holmes, Megan

    2004-01-01

    Glucocorticoids (GCs) exert potent, but poorly characterized, effects on the skeleton. The cellular activity of GCs is regulated at a prereceptor level by 11beta-hydroxysteroid dehydrogenases (11betaHSDs). The type 1 isoform, which predominates in bone, functions as a reductase in intact cells...... and regenerates active cortisol (corticosterone) from circulating inert 11-keto forms. The aim of the present study was to investigate the role of this intracrine activation of GCs on normal bone physiology in vivo using mice deficient in 11betaHSD1 (HSD1(-/-)). The HSD1(-/-) mice exhibited no significant changes...... in cortical or trabecular bone mass compared with wild-type (Wt) mice. Aged HSD1(-/-) mice showed age-related bone loss similar to that observed in Wt mice. Histomorphometric analysis showed similar bone formation and bone resorption parameters in HSD1(-/-) and Wt mice. However, examination of bone marrow...

  10. The chloride channel inhibitor NS3736 [corrected] prevents bone resorption in ovariectomized rats without changing bone formation

    DEFF Research Database (Denmark)

    Schaller, Sophie; Henriksen, Kim; Sveigaard, Christina

    2004-01-01

    Chloride channel activity is essential for osteoclast function. Consequently, inhibition of the osteoclastic chloride channel should prevent bone resorption. Accordingly, we tested a chloride channel inhibitor on bone turnover and found that it inhibits bone resorption without affecting bone...... for osteoporosis, daily treatment with 30 mg/kg orally protected bone strength and BMD by approximately 50% 6 weeks after surgery. Most interestingly, bone formation assessed by osteocalcin, mineral apposition rate, and mineralized surface index was not inhibited. MATERIALS AND METHODS: Analysis of chloride......, appearing mainly in osteoclasts, ovaries, appendix, and Purkinje cells. This highly selective distribution predicts that inhibition of ClC-7 should specifically target osteoclasts in vivo. We suggest that NS3736 is inhibiting ClC-7, leading to a bone-specific effect in vivo. RESULTS AND CONCLUSION...

  11. Synergistic effect of parathyroid hormone and growth hormone on trabecular and cortical bone formation in hypophysectomized rats.

    Science.gov (United States)

    Guevarra, Maria Sarah N; Yeh, James K; Castro Magana, Mariano; Aloia, John F

    2010-01-01

    Growth hormone (GH) deficiency in pediatric patients results in short stature and osteopenia. We postulated that the GH and parathyroid hormone (PTH) combination would result in improvement in bone growth and bone formation. Forty hypophysectomized female rats at age 8 weeks were divided into hypophysectomy (HX), HX + PTH (62.5 microg/kg, s.c. daily), HX + GH (3.33 mg/kg, s.c. daily), and HX + PTH + GH for a 4-week study. GH increased body weight, bone growth, bone mineral content (BMC) and bone mineral density (BMD), whereas PTH increased BMC and BMD without a significant effect on bone size. GH increased both periosteal and endocortical bone formation and cortical size, while PTH increased only endocortical bone formation. GH mitigated the trabecular bone loss by increasing bone formation, while PTH increased bone mass by increasing bone formation and suppressing osteoclast number per bone area. The result of combined intervention shows an increase in trabecular, periosteal and endocortical bone formation and suppression of bone resorption resulting in a synergistic effect on increasing trabecular and cortical bone volume and BMD. The combination treatment of PTH and GH increases bone growth, bone formation, decreases bone resorption and has a synergistic effect on increasing bone density and bone mass. Copyright (c) 2010 S. Karger AG, Basel.

  12. Acidification of the osteoclastic resorption compartment provides insight into the coupling of bone formation to bone resorption

    DEFF Research Database (Denmark)

    Karsdal, M.A.; Henriksen, K.; Sorensen, M.G.

    2005-01-01

    evaluated by osteocalcin. We speculate that attenuated acidification inhibits dissolution of the inorganic phase of bone and results in an increased number of nonresorbing osteoclasts that are responsible for the coupling to normal bone formation. Thus, we suggest that acidification is essential for normal...

  13. Bisphosphonates enhance bacterial adhesion and biofilm formation on bone hydroxyapatite.

    Science.gov (United States)

    Kos, Marcin; Junka, Adam; Smutnicka, Danuta; Szymczyk, Patrycja; Gluza, Karolina; Bartoszewicz, Marzenna

    2015-07-01

    Because of the suspicion that bisphosphonates enhance bacterial colonization, this study evaluated adhesion and biofilm formation by Streptococcus mutans 25175, Staphylococcus aureus 6538, and Pseudomonas aeruginosa 14454 reference strains on hydroxyapatite coated with clodronate, pamidronate, or zoledronate. Bacterial strains were cultured on bisphosphonate-coated and noncoated hydroxyapatite discs. After incubation, nonadhered bacteria were removed by centrifugation. Biofilm formation was confirmed by scanning electron microscopy. Bacterial colonization was estimated using quantitative cultures compared by means with Kruskal-Wallis and post-hoc Student-Newman-Keuls tests. Modeling of the interactions between bisphosphonates and hydroxyapatite was performed using the Density Functional Theory method. Bacterial colonization of the hydroxyapatite discs was significantly higher for all tested strains in the presence of bisphosphonates vs. Adherence in the presence of pamidronate was higher than with other bisphosphonates. Density Functional Theory analysis showed that the protonated amine group of pamidronate, which are not present in clodronate or zoledronate, forms two additional hydrogen bonds with hydroxyapatite. Moreover, the reactive cationic amino group of pamidronate may attract bacteria by direct electrostatic interaction. Increased bacterial adhesion and biofilm formation can promote osteomyelitis, cause failure of dental implants or bisphosphonate-coated joint prostheses, and complicate bone surgery in patients on bisphosphonates. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  14. The induction of bone formation by smart biphasic hydroxyapatite tricalcium phosphate biomimetic matrices in the non-human primate Papio ursinus

    Science.gov (United States)

    Ripamonti, U; Richter, P W; Nilen, R W N; Renton, L

    2008-01-01

    Long-term studies in the non-human primate Chacma baboon Papio ursinus were set to investigate the induction of bone formation by biphasic hydroxyapatite/p-tricalcium phosphate (HA/β-TCP) biomimetic matrices. HA/β-TCP biomimetic matrices in a pre-sinter ratio (wt%) of 40/60 and 20/80, respectively, were sintered and implanted in the rectus abdominis and in calvarial defects of four adult baboons. The post-sinter phase content ratios were 19/81 and 4/96, respectively. Morphological analyses on day 90 and 365 showed significant induction of bone formation within concavities of the biomimetic matrices with substantial bone formation by induction and resorption/dissolution of the implanted matrices. One year after implantation in calvarial defects, 4/96 biphasic biomimetic constructs showed prominent induction of bone formation with significant dissolution of the implanted scaffolds. The implanted smart biomimetic matrices induce de novo bone formation even in the absence of exogenously applied osteogenic proteins of the transforming growth factor-β(TGF-β) superfamily. The induction of bone formation biomimetizes the remodelling cycle of the cortico-cancellous bone of primates whereby resorption lacunae, pits and concavities cut by osteoclastogenesis are regulators of bone formation by induction. The concavities assembled in HA/β-TCP biomimetic bioceramics are endowed with multifunctional pleiotropic self-assembly capacities initiating and promoting angiogenesis and bone formation by induction. Resident mesenchymal cells differentiate into osteoblastic cell lines expressing, secreting and embedding osteogenic soluble molecular signals of the TGF-β superfamily within the concavities of the biomimetic matrices initiating bone formation as a secondary response. PMID:18363843

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

    OpenAIRE

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

    2007-01-01

    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. ...

  16. CRMP4 Inhibits Bone Formation by Negatively Regulating BMP and RhoA Signaling

    DEFF Research Database (Denmark)

    Abdallah, Basem M.; Figeac, Florence; Larsen, Kenneth H.

    2017-01-01

    % increase in bone mass, increased mineral apposition rate, and bone formation rate, compared to wild-type controls. Increased bone mass in Crmp4(-/-) mice was associated with enhanced BMP2 signaling and BMP2-induced osteoblast differentiation in Crmp4(-/-) osteoblasts (OBs). Furthermore, Crmp4(-/-) OBs...

  17. Effect of unreamed, limited reamed, and standard reamed intramedullary nailing on cortical bone porosity and new bone formation.

    Science.gov (United States)

    Hupel, T M; Weinberg, J A; Aksenov, S A; Schemitsch, E H

    2001-01-01

    To compare the effects of unreamed nail insertion and reamed nail insertion with limited and standard canal reaming on cortical bone porosity and new bone formation. A canine segmental tibial fracture was created in fifteen adult dogs. The tibiae were stabilized with a statically locked 6.5-millimeter intramedullary nail without prior canal reaming (n = 5), after limited reaming to 7.0 millimeters (n = 5), or after standard canal reaming to 9.0 millimeters (n = 5). Porosity, new bone formation, and the mineral apposition rate of cortical bone were directly compared between the three nailing techniques. A significant increase in cortical bone porosity and new bone formation was seen in all three groups of experimental animals compared with the control tibiae. The overall lowest porosity levels were measured in the limited reamed group, with similar porosity levels measured in the unreamed and standard reamed groups. Porosity was lower in the limited reamed group in the entire cortex of the segmental and distal cross sections, as well as the endosteal, anterior, and posterior cortices along the length of the tibia. Overall, there was no difference in the amount of new bone formation or the mineral apposition rate between the three groups of animals at eleven weeks after surgery. The results of this study suggest that limited intramedullary reaming is a biologically sound alternative for the treatment of tibial diaphyseal fractures in which the circulation is already compromised.

  18. Bone loss in rheumatoid arthritis. Influence of disease activity, duration of the disease, functional capacity, and corticosteroid treatment

    DEFF Research Database (Denmark)

    Hansen, M; Florescu, A; Stoltenberg, M

    1996-01-01

    Axial and appendicular bone mass were studied in 95 patients with rheumatoid arthritis. The aims were to quantify bone mineral density (BMD) and to evaluate the importance of disease activity, duration of disease, functional capacity, and corticosteroid treatment for bone loss in patients...... activity at the time of investigation. By contrast, BMDARM was decreased in patients with active disease. BMD in any of the three measured locations was not directly correlated to duration of the disease. However, the bone mass in the appendicular skeleton was already decreased within the first two years...... to clinical improvement, which may counteract the expected negative effect of these drugs on bone in rheumatoid arthritis....

  19. Adenoviral Mediated Expression of BMP2 by Bone Marrow Stromal Cells Cultured in 3D Copolymer Scaffolds Enhances Bone Formation

    Science.gov (United States)

    Sharma, Sunita; Sapkota, Dipak; Xue, Ying; Sun, Yang; Finne-Wistrand, Anna; Bruland, Ove; Mustafa, Kamal

    2016-01-01

    Selection of appropriate osteoinductive growth factors, suitable delivery method and proper supportive scaffold are critical for a successful outcome in bone tissue engineering using bone marrow stromal cells (BMSC). This study examined the molecular and functional effect of a combination of adenoviral mediated expression of bone morphogenetic protein-2 (BMP2) in BMSC and recently developed and characterized, biodegradable Poly(L-lactide-co-є-caprolactone){poly(LLA-co-CL)}scaffolds in osteogenic molecular changes and ectopic bone formation by using in vitro and in vivo approaches. Pathway-focused custom PCR array, validation using TaqMan based quantitative RT-PCR (qRT-PCR) and ALP staining showed significant up-regulation of several osteogenic and angiogenic molecules, including ALPL and RUNX2 in ad-BMP2 BMSC group grown in poly(LLA-co-CL) scaffolds both at 3 and 14 days. Micro CT and histological analyses of the subcutaneously implanted scaffolds in NOD/SCID mice revealed significantly increased radiopaque areas, percentage bone volume and formation of vital bone in ad-BMP2 scaffolds as compared to the control groups both at 2 and 8 weeks. The increased bone formation in the ad-BMP2 group in vivo was paralleled at the molecular level with concomitant over-expression of a number of osteogenic and angiogenic genes including ALPL, RUNX2, SPP1, ANGPT1. The increased bone formation in ad-BMP2 explants was not found to be associated with enhanced endochondral activity as evidenced by qRT-PCR (SOX9 and FGF2) and Safranin O staining. Taken together, combination of adenoviral mediated BMP-2 expression in BMSC grown in the newly developed poly(LLA-co-CL) scaffolds induced expression of osteogenic markers and enhanced bone formation in vivo. PMID:26808122

  20. Assessment of activated porous granules on implant fixation and early bone formation in sheep

    Directory of Open Access Journals (Sweden)

    Ming Ding

    2016-04-01

    Conclusion: In conclusion, despite nice bone formation and implant fixation in all groups, bioreactor activated graft material did not convincingly induce early implant fixation similar to allograft, and neither bioreactor nor by adding BMA credited additional benefit for bone formation in this model.

  1. Abdominal Fat Is Associated With Lower Bone Formation and Inferior Bone Quality in Healthy Premenopausal Women: A Transiliac Bone Biopsy Study

    Science.gov (United States)

    Dempster, David W.; Recker, Robert R.; Lappe, Joan M.; Zhou, Hua; Zwahlen, Alexander; Müller, Ralph; Zhao, Binsheng; Guo, Xiaotao; Lang, Thomas; Saeed, Isra; Liu, X. Sherry; Guo, X. Edward; Cremers, Serge; Rosen, Clifford J.; Stein, Emily M.; Nickolas, Thomas L.; McMahon, Donald J.; Young, Polly; Shane, Elizabeth

    2013-01-01

    Context: The conventional view that obesity is beneficial for bone strength has recently been challenged by studies that link obesity, particularly visceral obesity, to low bone mass and fractures. It is controversial whether effects of obesity on bone are mediated by increased bone resorption or decreased bone formation. Objective: The objective of the study was to evaluate bone microarchitecture and remodeling in healthy premenopausal women of varying weights. Design: We measured bone density and trunk fat by dual-energy x-ray absorptiometry in 40 women and by computed tomography in a subset. Bone microarchitecture, stiffness, remodeling, and marrow fat were assessed in labeled transiliac bone biopsies. Results: Body mass index (BMI) ranged from 20.1 to 39.2 kg/m2. Dual-energy x-ray absorptiometry-trunk fat was directly associated with BMI (r = 0.78, P < .001) and visceral fat by computed tomography (r = 0.79, P < .001). Compared with women in the lowest tertile of trunk fat, those in the highest tertile had inferior bone quality: lower trabecular bone volume (20.4 ± 5.8 vs 29.1 ± 6.1%; P = .001) and stiffness (433 ± 264 vs 782 ± 349 MPa; P = .01) and higher cortical porosity (8.8 ± 3.5 vs 6.3 ± 2.4%; P = .049). Bone formation rate (0.004 ± 0.002 vs 0.011 ± 0.008 mm2/mm · year; P = .006) was 64% lower in the highest tertile. Trunk fat was inversely associated with trabecular bone volume (r = −0.50; P < .01) and bone formation rate (r = −0.50; P < .001). The relationship between trunk fat and bone volume remained significant after controlling for age and BMI. Conclusions: At the tissue level, premenopausal women with more central adiposity had inferior bone quality and stiffness and markedly lower bone formation. Given the rising levels of obesity, these observations require further investigation. PMID:23515452

  2. The effect of enamel matrix proteins and deproteinized bovine bone mineral on heterotopic bone formation.

    Science.gov (United States)

    Donos, Nikolaos; Kostopoulos, Lambros; Tonetti, Maurizio; Karring, Thorkild; Lang, Niklaus P

    2006-08-01

    To evaluate the osteoinductive potential of deproteinized bovine bone mineral (DBBM) and an enamel matrix derivative (EMD) in the muscle of rats. Sixteen rats were used in this study. The animals were divided in three groups. Group A: a pouch was created in one of the pectoralis profundis muscles of the thorax of the rats and DBBM particles (Bio-Oss) were placed into the pouch. Healing: 60 days. Group B: a small pouch was created on both pectoralis profundis muscles at each side of the thorax midline. In one side, a mixture of EMD (Emdogain) mixed with DBBM was placed into one of the pouches, whereas in the contralateral side of the thorax the pouch was implanted with DBBM mixed with the propylene glycol alginate (PGA--carrier for enamel matrix proteins of EMD). Healing: 60 days. Group C: the same procedure as group B, but with a healing period of 120 days. Qualitative histological analysis of the results was performed. At 60 days, the histological appearance of the DBBM particles implanted alone was similar to that of the particles implanted together with EMD or PGA at both 60 and 120 days. The DBBM particles were encapsulated into a connective tissue stroma and an inflammatory infiltrate. At 120 days, the DBBM particles implanted together with EMD or PGA exhibited the presence of resorption lacunae in some cases. Intramuscular bone formation was not encountered in any group. The implantation of DBBM particles alone, combined with EMD or its carrier (PGA) failed to exhibit extraskeletal, bone-inductive properties.

  3. Poly(vinylidene-trifluoroethylene)/barium titanate composite for in vivo support of bone formation.

    Science.gov (United States)

    Lopes, Helena B; Santos, Thiago de S; de Oliveira, Fabiola S; Freitas, Gileade P; de Almeida, Adriana Lg; Gimenes, Rossano; Rosa, Adalberto L; Beloti, Marcio M

    2014-07-01

    In this study, we evaluated the effect of poly(vinylidene fluoride-trifluoroethylene)/barium titanate (P(VDF-TrFE)/BT) membrane on in vivo bone formation. Rat calvarial bone defects were implanted with P(VDF-TrFE)/BT and polytetrafluoroethylene (PTFE) membranes, and at 4 and 8 weeks, histomorphometric and gene expression analyses were performed. A higher amount of bone formation was noticed on P(VDF-TrFE)/BT compared with PTFE. The gene expression of RUNX2, bone sialoprotein, osteocalcin, receptor activator of nuclear factor-kappa B ligand, and osteoprotegerin indicates that P(VDF-TrFE)/BT favored the osteoblast differentiation compared with PTFE. These results evidenced the benefits of using P(VDF-TrFE)/BT to promote new bone formation, which may represent a promising alternative to be employed in guided bone regeneration. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  4. 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.

  5. Thyroid Sporadic Goiter with Adult Heterotopic Bone Formation

    Directory of Open Access Journals (Sweden)

    Adriana Handra-Luca

    2015-01-01

    Full Text Available Thyroid heterotopic bone formation (HBF in goiter is a rare finding. Five thyroid resection specimens were analyzed for HBF. The results were correlated with clinicomorphological features. All patients were women (33–82 years. The preoperative diagnosis was thyroid goiter or nodule. Treatment consisted in thyroidectomy and lobectomy (3 and 2, resp.. Microscopy showed sporadic nodular goiter. Malformative blood vessels and vascular calcifications were seen in intra- and extrathyroid location (5 and 3, resp.. The number and size of HBFs (total: 28 ranged between 1 and 23/thyroid gland (one bilateral and 1 and 10 mm, respectively. Twelve HBFs were in contact with the thyroid capsule. Most were extranodular (21, versus 6 intranodular. The medical history was positive for dyslipidemia, hyperglycemia, renal dysfunction, and hyperuricemia (2, 3, and 3 cases and 1 case, resp. without any parathyroid abnormality. In conclusion, thyroid HBF may be characterized by subcapsular or extranodular location, various size (usually ≥2 mm, and vascular calcifications and malformations. Features of metabolic syndrome and renal dysfunction may be present, but their exact role in the pathogenesis of HBFs remains to be elucidated.

  6. Chinese red yeast rice (Monascus purpureus-fermented rice promotes bone formation

    Directory of Open Access Journals (Sweden)

    Rabie Bakr

    2008-03-01

    Full Text Available Abstract Background Statin can induce the gene expression of bone morphogenetic protein-2. Red yeast rice (RYR, Hongqu, i.e. rice fermented with Monascus purpureus, contains a natural form of statin. This study demonstrates the effects of RYR extract on bone formation. Methods Bone defects were created in the parietal bones of two New Zealand white rabbits. In the test animal, two defects were grafted with collagen matrix mixed with RYR extract. In the control animal, two defects were grafted with collagen matrix alone. UMR 106 cell line was used to test RYR extract in vitro. In the control group, cells were cultured for three durations (24 hours, 48 hours and 72 hours without any intervention. In the RYR group, cells were cultured for the same durations with various concentrations of RYR extract (0.001 g/ml, 0.005 g/ml and 0.01 g/ml. Bicinchoninic acid (BCA assay, 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and alkaline phosphatase (ALP assay were performed to measure total protein, mitochondrial activity and bone cell formation respectively. Results The test animal showed more formation of new bone in the defects than the control animal. RYR significantly increased the optical density in the MTT assay and ALP activity in vitro. Conclusion RYR extract stimulated new bone formation in bone defects in vivo and increased bone cell formation in vitro.

  7. The Paradox of Bone Formation and Bone Loss in Ankylosing Spondylitis: Evolving New Concepts of Bone Formation and Future Trends in Management.

    Science.gov (United States)

    Magrey, Marina N; Khan, Muhammad A

    2017-04-01

    The purpose of the study is to briefly review the molecular mechanisms that leads to structural damage in ankylosing spondylitis (AS), defined as new bone formation resulting in complete or incomplete ankylosis of the spine, and the impact of treatment with biologics to retard this process. The understanding of molecular mechanisms leading to new bone formation in AS has significantly improved but is still incomplete. Availability of biologics has greatly enhanced the treatment of patients with AS, but its impact on slowing the structural damage is still a matter of debate, although a few observational studies have shown that long term use of TNF-α blockers may slow radiographic progression. The availability of newer biologics targeting IL-17/1L23 has shown some promising results in slowing radiographic progression in AS. Although the availability of TNF-inhibitors has greatly enhanced the treatment options for patients with AS, their impact on slowing the structural damage is still not clearly established. However, preliminary results using newer biologics targeting IL-17/1L23 axis are more encouraging but longer follow-up is needed.

  8. GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women

    DEFF Research Database (Denmark)

    Iepsen, Eva Pers Winning; Lundgren, Julie Rehné; Hartmann, Bolette

    2015-01-01

    bone mass reductions. DESIGN: Randomized control study. SETTING: Out-patient research hospital clinic. PARTICIPANTS: Thirty-seven healthy obese women. BMI 34±0.5 kg/m(2), age 46±2 years. INTERVENTION: After a low-calorie diet-induced 12% weight loss, participants were randomized to treatment......CONTEXT: Recent studies indicate that glucagon-like peptide 1 (GLP-1) regulates bone turnover, but the effects of GLP-1 receptor agonists (GLP-1 RAs) on bone in obese weight-reduced individuals are unknown. OBJECTIVE: To investigate the role of GLP-1 RAs on bone formation and weight loss induced...... markers (CTX-1 and P1NP) were investigated before, after weight loss and after 52 weeks weight maintenance. Primary end points: Change in BMC and bone markers after 52 weeks weight maintenance with or without GLP-1 RA treatment. RESULTS: Total, pelvic and arm-leg BMC decreased during weight maintenance...

  9. Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

    Science.gov (United States)

    Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

    1998-01-01

    Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that

  10. The relationship between inflammation and new bone formation in patients with ankylosing spondylitis

    OpenAIRE

    Baraliakos, Xenofon; Listing, Joachim; Rudwaleit, Martin; Sieper, Joachim; Braun, Juergen

    2008-01-01

    Introduction Spinal inflammation as detected by magnetic resonance imaging and new bone formation as identified by conventional radiographs are characteristic of ankylosing spondylitis. Whether and how spondylitis and syndesmophyte formation are linked are unclear. Our objective was to investigate whether and how spinal inflammation are associated with new bone formation in ankylosing spondylitis. Methods Spinal magnetic resonance images and conventional radiographs from 39 ankylosing spondyl...

  11. Method for in situ determination cation exchange capacities of subsurface formations

    International Nuclear Information System (INIS)

    Fertl, W.H.; Welker, D.W.

    1980-01-01

    A method is disclosed for the in situ examination of each subsurface formation penetrated by a borehole to ascertain the cation exchange capacity of such formations within a geological region. Natural γ ray logging is used to develop signals functionally related to the total γ radiation and to the potassium-40, uranium and thorium energy-band radiations. A first borehole is traversed by a potential γ ray spectrometer to provide selected measurements of natural γ radiation. Core samples are taken from the logged formation and laboratory tests performed to determine the cation exchange capacity thereof. The cation exchange capacities thus are developed then correlated with selected parameters provided by the γ ray spectrometer to establish functional relationships. Cation exchange capacities of formations in subsequent boreholes within the region are then determined in situ by use of the natural γ ray spectrometer and these established relationships. (author)

  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. Impact of skeletal unloading on bone formation: Role of systemic and local factors

    Science.gov (United States)

    Bikle, Daniel D.; Halloran, Bernard P.; Morey-Holton, Emily

    We have developed a model of skeletal unloading using growing rats whose hindlimbs are unweighted by tail suspension. The bones in the hindlimbs undergo a transient cessation of bone growth; when reloaded bone formation is accelerated until bone mass is restored. These changes do not occur in the normally loaded bones of the forelimbs. Associated with the fall in bone formation is a fall in 1,25(OH) 2D 3 production and osteocalcin levels. In contrast, no changes in parathyroid hormone, calcium, or corticosterone levels are seen. To examine the role of locally produced growth factors, we have measured the mRNA and protein levels of insulin like growth factor-1 (IGF-1) in bone during tail suspension. Surprisingly, both the mRNA and protein levels of IGF-1 increase during tail suspension as bone formation is reduced. Furthermore, the bones in the hindlimbs of the suspended animals develop a resistance to the growth promoting effects of both growth hormone and IGF-1 when given parenterally. Thus, the cessation of bone growth with skeletal unloading is apparently associated with a resistance to rather than failure to produce local growth factors. The cause of this resistance remains under active investigation.

  14. Negative regulation of bone formation by the transmembrane Wnt antagonist Kremen-2.

    Directory of Open Access Journals (Sweden)

    Jochen Schulze

    Full Text Available Wnt signalling is a key pathway controlling bone formation in mice and humans. One of the regulators of this pathway is Dkk1, which antagonizes Wnt signalling through the formation of a ternary complex with the transmembrane receptors Krm1/2 and Lrp5/6, thereby blocking the induction of Wnt signalling by the latter ones. Here we show that Kremen-2 (Krm2 is predominantly expressed in bone, and that its osteoblast-specific over-expression in transgenic mice (Col1a1-Krm2 results in severe osteoporosis. Histomorphometric analysis revealed that osteoblast maturation and bone formation are disturbed in Col1a1-Krm2 mice, whereas bone resorption is increased. In line with these findings, primary osteoblasts derived from Col1a1-Krm2 mice display a cell-autonomous differentiation defect, impaired canonical Wnt signalling and decreased production of the osteoclast inhibitory factor Opg. To determine whether the observed effects of Krm2 on bone remodeling are physiologically relevant, we analyzed the skeletal phenotype of 24 weeks old Krm2-deficient mice and observed high bone mass caused by a more than three-fold increase in bone formation. Taken together, these data identify Krm2 as a regulator of bone remodeling and raise the possibility that antagonizing KRM2 might prove beneficial in patients with bone loss disorders.

  15. Ciliary neurotrophic factor inhibits bone formation and plays a sex-specific role in bone growth and remodeling.

    Science.gov (United States)

    McGregor, Narelle E; Poulton, Ingrid J; Walker, Emma C; Pompolo, Sueli; Quinn, Julian M W; Martin, T John; Sims, Natalie A

    2010-03-01

    Ciliary neurotrophic factor (CNTF) receptor (CNTFR) expression has been described in osteoblast-like cells, suggesting a role for CNTF in bone metabolism. When bound to CNTF, neuropoietin (NP), or cardiotrophin-like-cytokine (CLC), CNTFR forms a signaling complex with gp130 and the leukemia inhibitory factor receptor, which both play critical roles in bone cell biology. This study aimed to determine the role of CNTFR-signaling cytokines in bone. Immunohistochemistry detected CNTF in osteoblasts, osteocytes, osteoclasts, and proliferating chondrocytes. CNTFR mRNA was detected in primary calvarial osteoblasts and was upregulated during osteoblast differentiation. Treatment of osteoblasts with CNTF or CLC, but not NP, significantly inhibited mineralization and osterix mRNA levels. Twelve-week-old male CNTF ( -/- ) mice demonstrated reduced femoral length, cortical thickness, and periosteal circumference; but femoral trabecular bone mineral density (Tb.BMD) and tibial trabecular bone volume (BV/TV) were not significantly different from wild-type, indicating a unique role for CNTF in bone growth in male mice. In contrast, female CNTF ( -/- ) femora were of normal width, but femoral Tb.BMD, tibial BV/TV, trabecular number, and trabecular thickness were all increased. Female CNTF ( -/- ) tibiae also demonstrated high osteoblast number and mineral apposition rate compared to wild-type littermates, and this was intrinsic to the osteoblast lineage. CNTF is expressed locally in bone and plays a unique role in female mice as an inhibitor of trabecular bone formation and in male mice as a stimulus of cortical growth.

  16. Osteogenic Embryoid Body-Derived Material Induces Bone Formation In Vivo

    Science.gov (United States)

    Sutha, Ken; Schwartz, Zvi; Wang, Yun; Hyzy, Sharon; Boyan, Barbara D.; McDevitt, Todd C.

    2015-01-01

    The progressive loss of endogenous regenerative capacity that accompanies mammalian aging has been attributed at least in part to alterations in the extracellular matrix (ECM) composition of adult tissues. Thus, creation of a more regenerative microenvironment, analogous to embryonic morphogenesis, may be achieved via pluripotent embryonic stem cell (ESC) differentiation and derivation of devitalized materials as an alternative to decellularized adult tissues, such as demineralized bone matrix (DBM). Transplantation of devitalized ESC materials represents a novel approach to promote functional tissue regeneration and reduce the inherent batch-to-batch variability of allograft-derived materials. In this study, the osteoinductivity of embryoid body-derived material (EBM) was compared to DBM in a standard in vivo ectopic osteoinduction assay in nude mice. EBM derived from EBs differentiated for 10 days with osteogenic media (+β-glycerophosphate) exhibited similar osteoinductivity to active DBM (osteoinduction score = 2.50 ± 0.27 vs. 2.75 ± 0.16) based on histological scoring, and exceeded inactive DBM (1.13 ± 0.13, p osteoinductivity of EBM demonstrates that morphogenic factors expressed by ESCs undergoing osteogenic differentiation yield a novel devitalized material capable of stimulating de novo bone formation in vivo. PMID:25961152

  17. In vitro osteogenic capacity of bone marrow MSCs from postmenopausal women reflect the osseointegration of their cementless hip stems

    Directory of Open Access Journals (Sweden)

    Jessica J. Alm

    2016-12-01

    Full Text Available Age-related dysfunction of mesenchymal stromal cells (MSCs is suggested as a main cause of altered bone repair with aging. We recently showed that in postmenopausal women undergoing cementless total hip arthroplasty (THA aging, low bone mineral density (BMD and age-related geometric changes of the proximal femur are risk factors for increased early migration and delayed osseointegration of the femoral stems. Extending these analyses, we have here explored how the in vitro osteogenic capacity of bone marrow MSCs from these patients reflects implant osseointegration, representing the patient's in vivo bone healing capacity. A total of 19 postmenopausal women with primary hip osteoarthritis (mean age 65 years, range 50–78 and well-defined bone quality underwent successful preoperative in vitro analysis of osteogenic capacity of iliac crest bone marrow MSCs as well as two-year radiostereometric (RSA follow-up of femoral stem migration after cementless THA. In patients with MSCs of low osteogenic capacity, the magnitude of cumulative stem subsidence after the settling period of three months was greater (p = 0.028 and the time point for translational osseointegration was significantly delayed (p = 0.030 compared to patients with MSCs of high osteogenic capacity. This study suggests that patients with MSCs of low in vitro osteogenic capacity may display increased stem subsidence after the settling period of 3 months and thereby delayed osseointegration. Our study presents a novel approach for studying the biological progress of hip implant osseointegration and to verify the impact of decreased MSCs function, especially in patients with age-related dysfunction of MSCs and bone healing capacity. Keywords: Human mesenchymal stromal cells, Osteogenic differentiation, Radiostereometric analysis, Total hip arthroplasty, Osseointegration

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

    DEFF Research Database (Denmark)

    Andersen, Thomas Levin; Søndergaard, Teis Esben; Skorzynska, Katarzyna

    2009-01-01

    During skeletal remodeling, pre-osteoclasts and pre-osteoblasts are targeted to critical sites of the bone to resorb and reconstruct bone matrix, respectively. Coordination of site-specific recruitment of these two cell types is a prerequisite to maintain the specific architecture of each bone wi...

  19. Bone formation in cranial, mandibular, tibial and iliac bone grafts in rats

    DEFF Research Database (Denmark)

    Solheim, E; Pinholt, E M; Talsnes, O

    1995-01-01

    Several studies have suggested that grafts from membranous derived bone (e.g., calvarial grafts) retain their volume better than those from endochondral derived bone (e.g., iliac bone grafts). Increased osteogenesis in grafts of the former type has been offered as the explanation. However, simple...

  20. Parathyroid hormone may maintain bone formation in hibernating black bears (Ursus americanus) to prevent disuse osteoporosis.

    Science.gov (United States)

    Donahue, Seth W; Galley, Sarah A; Vaughan, Michael R; Patterson-Buckendahl, Patricia; Demers, Laurence M; Vance, Josef L; McGee, Meghan E

    2006-05-01

    Mechanical unloading of bone causes an imbalance in bone formation and resorption leading to bone loss and increased fracture risk. Black bears (Ursus americanus) are inactive for up to six months during hibernation, yet bone mineral content and strength do not decrease with disuse or aging. To test whether hibernating bears have biological mechanisms to prevent disuse osteoporosis, we measured the serum concentrations of hormones and growth factors involved in bone metabolism and correlated them with the serum concentration of a bone formation marker (osteocalcin). Serum was obtained from black bears over a 7-month duration that included periods of activity and inactivity. Both resorption and formation markers increased during hibernation, suggesting high bone turnover occurred during inactivity. However, bone formation appeared to be balanced with bone resorption. The serum concentration of parathyroid hormone (PTH) was higher in the hibernation (P=0.35) and post-hibernation (P=0.006) seasons relative to pre-hibernation levels. Serum leptin was lower (Phibernation relative to pre-hibernation and hibernation periods. Insulin-like growth factor I (IGF-I) decreased (Phibernation relative to pre-hibernation and reached its highest value during remobilization. There was no difference (P=0.64) in 25-OH vitamin D between the three seasons. Serum osteocalcin (bone formation marker) was significantly correlated with PTH, but not with leptin, IGF-I or 25-OH vitamin D. Osteocalcin and PTH were positively correlated when samples from all seasons were pooled and when only hibernation samples were considered, raising the possibility that the anabolic actions of PTH help maintain bone formation to prevent disuse osteoporosis. Prostaglandin E(2) (PGE(2)) release from MC3T3 osteoblastic cells was significantly affected by treatment with bear serum from different seasons (i.e. hibernation versus active periods). The seasonal changes in PGE(2) release showed trends similar to the

  1. In Vivo Bone Formation Within Engineered Hydroxyapatite Scaffolds in a Sheep Model.

    Science.gov (United States)

    Lovati, A B; Lopa, S; Recordati, C; Talò, G; Turrisi, C; Bottagisio, M; Losa, M; Scanziani, E; Moretti, M

    2016-08-01

    Large bone defects still represent a major burden in orthopedics, requiring bone-graft implantation to promote the bone repair. Along with autografts that currently represent the gold standard for complicated fracture repair, the bone tissue engineering offers a promising alternative strategy combining bone-graft substitutes with osteoprogenitor cells able to support the bone tissue ingrowth within the implant. Hence, the optimization of cell loading and distribution within osteoconductive scaffolds is mandatory to support a successful bone formation within the scaffold pores. With this purpose, we engineered constructs by seeding and culturing autologous, osteodifferentiated bone marrow mesenchymal stem cells within hydroxyapatite (HA)-based grafts by means of a perfusion bioreactor to enhance the in vivo implant-bone osseointegration in an ovine model. Specifically, we compared the engineered constructs in two different anatomical bone sites, tibia, and femur, compared with cell-free or static cell-loaded scaffolds. After 2 and 4 months, the bone formation and the scaffold osseointegration were assessed by micro-CT and histological analyses. The results demonstrated the capability of the acellular HA-based grafts to determine an implant-bone osseointegration similar to that of statically or dynamically cultured grafts. Our study demonstrated that the tibia is characterized by a lower bone repair capability compared to femur, in which the contribution of transplanted cells is not crucial to enhance the bone-implant osseointegration. Indeed, only in tibia, the dynamic cell-loaded implants performed slightly better than the cell-free or static cell-loaded grafts, indicating that this is a valid approach to sustain the bone deposition and osseointegration in disadvantaged anatomical sites.

  2. GLP-1 Receptor Agonist Treatment Increases Bone Formation and Prevents Bone Loss in Weight-Reduced Obese Women.

    Science.gov (United States)

    Iepsen, Eva W; Lundgren, Julie R; Hartmann, Bolette; Pedersen, Oluf; Hansen, Torben; Jørgensen, Niklas R; Jensen, Jens-Erik B; Holst, Jens J; Madsbad, Sten; Torekov, Signe S

    2015-08-01

    Recent studies indicate that glucagon-like peptide (GLP)-1 regulates bone turnover, but the effects of GLP-1 receptor agonists (GLP-1 RAs) on bone in obese weight-reduced individuals are unknown. To investigate the role of GLP-1 RAs on bone formation and weight loss-induced bone mass reduction. Randomized control study. Outpatient research hospital clinic. Thirty-seven healthy obese women with body mass index of 34 ± 0.5 kg/m(2) and age 46 ± 2 years. After a low-calorie-diet-induced 12% weight loss, participants were randomized to treatment with or without administration of the GLP-1 RA liraglutide (1.2 mg/d) for 52 weeks. In case of weight gain, up to two meals per day could be replaced with a low-calorie-diet product to maintain the weight loss. Total, pelvic, and arm-leg bone mineral content (BMC) and bone markers [C-terminal telopeptide of type 1 collagen (CTX-1) and N-terminal propeptide of type 1 procollagen (P1NP)] were investigated before and after weight loss and after 52-week weight maintenance. Primary endpoints were changes in BMC and bone markers after 52-week weight maintenance with or without GLP-1 RA treatment. Total, pelvic, and arm-leg BMC decreased during weight maintenance in the control group (P GLP-1 RA increased bone formation by 16% and prevented bone loss after weight loss obtained through a low-calorie diet, supporting its role as a safe weight-lowering agent.

  3. Effects of designed PLLA and 50:50PLGA scaffold architectures on bone formation in vivo

    OpenAIRE

    Saito, Eiji; Liao, Elly E.; Hu, Wei-Wen; Krebsbach, Paul H.; Hollister, Scott J.

    2011-01-01

    Biodegradable porous scaffolds have been investigated as an alternative approach to current metal, ceramic, and polymer bone graft substitutes for lost or damaged bone tissues. Although there have been many studies investigating the effects of scaffold architecture on bone formation, many of these scaffolds were fabricated using conventional methods, such as salt leaching and phase separation, and were constructed without designed architecture. To study the effects of both designed architectu...

  4. Tricalcium phosphate/hydroxyapatite (TCP-HA) bone scaffold as potential candidate for the formation of tissue engineered bone.

    Science.gov (United States)

    Sulaiman, Shamsul Bin; Keong, Tan Kok; Cheng, Chen Hui; Saim, Aminuddin Bin; Idrus, Ruszymah Bt Hj

    2013-06-01

    Various materials have been used as scaffolds to suit different demands in tissue engineering. One of the most important criteria is that the scaffold must be biocompatible. This study was carried out to investigate the potential of HA or TCP/HA scaffold seeded with osteogenic induced sheep marrow cells (SMCs) for bone tissue engineering. HA-SMC and TCP/HA-SMC constructs were induced in the osteogenic medium for three weeks prior to implantation in nude mice. The HA-SMC and TCP/HA-SMC constructs were implanted subcutaneously on the dorsum of nude mice on each side of the midline. These constructs were harvested after 8 wk of implantation. Constructs before and after implantation were analyzed through histological staining, scanning electron microscope (SEM) and gene expression analysis. The HA-SMC constructs demonstrated minimal bone formation. TCP/HA-SMC construct showed bone formation eight weeks after implantation. The bone formation started on the surface of the ceramic and proceeded to the centre of the pores. H&E and Alizarin Red staining demonstrated new bone tissue. Gene expression of collagen type 1 increased significantly for both constructs, but more superior for TCP/HA-SMC. SEM results showed the formation of thick collagen fibers encapsulating TCP/HA-SMC more than HA-SMC. Cells attached to both constructs surface proliferated and secreted collagen fibers. The findings suggest that TCP/HA-SMC constructs with better osteogenic potential compared to HA-SMC constructs can be a potential candidate for the formation of tissue engineered bone.

  5. 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.

  6. Low-intensity pulsed ultrasound enhances bone formation around miniscrew implants.

    Science.gov (United States)

    Ganzorig, Khaliunaa; Kuroda, Shingo; Maeda, Yuichi; Mansjur, Karima; Sato, Minami; Nagata, Kumiko; Tanaka, Eiji

    2015-06-01

    Miniscrew implants (MSIs) are currently used to provide absolute anchorage in orthodontics; however, their initial stability is an issue of concern. Application of low-intensity pulsed ultrasound (LIPUS) can promote bone healing. Therefore, LIPUS application may stimulate bone formation around MSIs and enhance their initial stability. To investigate the effect of LIPUS exposure on bone formation after implantation of titanium (Ti) and stainless steel (SS) MSIs. MSIs made of Ti-6Al-4V and 316L SS were placed on rat tibiae and treated with LIPUS. The bone morphology around MSIs was evaluated by scanning electron microscopy and three-dimensional micro-computed tomography. MC3T3-E1 cells cultured on Ti and SS discs were treated with LIPUS, and the temporary expression of alkaline phosphatase (ALP) was examined. Bone-implant contact increased gradually from day 3 to day 14 after MSI insertion. LIPUS application increased the cortical bone density, cortical bone thickness, and cortical bone rate after implantation of Ti and SS MSIs (P<0.05). LIPUS exposure induced ALP upregulation in MC3T3-E1 cells at day 3 (P<0.05). LIPUS enhanced bone formation around Ti and SS MSIs, enhancing the initial stability of MSIs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Expansion of Bone Marrow Mesenchymal Stromal Cells in Perfused 3D Ceramic Scaffolds Enhances In Vivo Bone Formation.

    Science.gov (United States)

    Hoch, Allison I; Duhr, Ralph; Di Maggio, Nunzia; Mehrkens, Arne; Jakob, Marcel; Wendt, David

    2017-12-01

    Bone marrow-derived mesenchymal stromal cells (BMSC), when expanded directly within 3D ceramic scaffolds in perfusion bioreactors, more reproducibly form bone when implanted in vivo as compared to conventional expansion on 2D polystyrene dishes/flasks. Since the bioreactor-based expansion on 3D ceramic scaffolds encompasses multiple aspects that are inherently different from expansion on 2D polystyrene, we aimed to decouple the effects of specific parameters among these two model systems. We assessed the effects of the: 1) 3D scaffold vs. 2D surface; 2) ceramic vs. polystyrene materials; and 3) BMSC niche established within the ceramic pores during in vitro culture, on subsequent in vivo bone formation. While BMSC expanded on 3D polystyrene scaffolds in the bioreactor could maintain their in vivo osteogenic potential, results were similar as BMSC expanded in monolayer on 2D polystyrene, suggesting little influence of the scaffold 3D environment. Bone formation was most reproducible when BMSC are expanded on 3D ceramic, highlighting the influence of the ceramic substrate. The presence of a pre-formed niche within the scaffold pores had negligible effects on the in vivo bone formation. The results of this study allow a greater understanding of the parameters required for perfusion bioreactor-based manufacturing of osteogenic grafts for clinical applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Oxytocin promotes bone formation during the alveolar healing process in old acyclic female rats.

    Science.gov (United States)

    Colli, Vilma Clemi; Okamoto, Roberta; Spritzer, Poli Mara; Dornelles, Rita Cássia Menegati

    2012-09-01

    OT was reported to be a direct regulator of bone mass in young rodents, and this anabolic effect on bone is a peripheral action of OT. The goal of this study was to investigate the peripheral action of oxytocin (OT) in the alveolar healing process in old female rats. Females Wistar rats (24-month-old) in permanent diestrus phase, received two ip (12h apart) injections of saline (NaCl 0.15M - control group) or OT (45μg/rat - treated group). Seven days later, the right maxillary incisor was extracted and analyses were performed up to 28 days of the alveolar healing process (35 days after saline or OT administration). Calcium and phosphorus plasma concentrations did not differ between the groups. The plasma biochemical bone formations markers, alkaline phosphatase (ALP) and osteocalcin were significantly higher in the treated group. Histomorphometric analyses confirmed bone formation as the treated group presented the highest mean value of post-extraction bone formation. Tartrate-resistant acid phosphatase (TRAP) was significantly reduced in the treated group indicating an anti-resorptive effect of OT. Immunohistochemistry reactions performed in order to identify the presence of osteocalcin and TRAP in the bone cells of the dental socket confirmed these outcomes. OT was found to promote bone formation and to inhibit bone resorption in old acyclic female rats during the alveolar healing process. Published by Elsevier Ltd.

  9. Energy expenditure and bone formation share a common sensitivity to AP-1 transcription in the hypothalamus

    DEFF Research Database (Denmark)

    Rowe, Glenn C; Vialou, Vincent; Sato, Kazusa

    2012-01-01

    ) whether these effects were due to antagonism to AP1. Our results show that stereotactic injection of an adeno-associated virus vector to restrict overexpression of ¿FosB to the ventral hypothalamus of wildtype mice induced a profound increase in both energy expenditure and bone formation and bone mass...

  10. Effects of low‑level laser therapy on osteoblastic bone formation and ...

    African Journals Online (AJOL)

    were compared. Conclusion: Histologically, LLLT stimulated bone formation, as revealed by analysis after the retention period. LLLT during expansion may accelerate bone healing. Key words: Bio‑stimulation, laser, rapid maxillary expansion. Date of Acceptance: 12‑Jan‑2015. Address for correspondence: Dr. M Demirkol,.

  11. Addition of a Synthetically Fabricated Osteoinductive Biphasic Calcium Phosphate Bone Graft to BMP2 Improves New Bone Formation.

    Science.gov (United States)

    Zhang, Yufeng; Yang, Shuang; Zhou, Wei; Fu, Hang; Qian, Li; Miron, Richard J

    2016-12-01

    Bone morphogenetic protein-2 (BMP2) has been successfully utilized in dentistry to promote new bone formation because of its osteoinductive ability to recruit mesenchymal progenitor cells and induce their differentiation to bone-forming osteoblasts. Recently, novel biphasic calcium phosphate scaffolds have been developed with similar osteoinductive properties capable of forming ectopic bone formation. The aim of the present study was to assess whether the combination of BMP2 with this novel Biphasic Calcium Phosphate (BCP) scaffold may additionally promote new bone regeneration. Cylindrical bone defects measuring 2.5 mm were created bilaterally in the femurs of 18 Wistar rats. After 4 weeks, the following six groups were assessed for new bone formation by micro-computed tomography (CT) as well as histological assessment: 1) collagen scaffolds + 20 μg of BMP2; 2) collagen scaffolds + 50 μg of BMP2; 3) collagen scaffolds + 100 μg of BMP2; 4) BCP scaffolds + 20 μg of BMP2; 5) BCP scaffolds + 50 μg of BMP2; and 6) BCP scaffolds + 100 μg of BMP2. Furthermore, tartrate-resistant acid phosphatase (TRAP) staining was utilized to assess osteoclast activity and osteoclast number. The release kinetics of BMP2 from both BCP and collagen scaffolds was investigated over a 14-day period. The results from present study demonstrate that BMP2 is able to promote new bone formation in a concentration dependant manner when loaded with either a collagen scaffolds or BCP scaffolds. Micro-CT analysis demonstrated significantly higher levels of new bone formation in groups containing BCP + BMP2 when compared with collagen scaffolds + BMP2. BMP2 had little effect on osteoclast activity; however, less TRAP staining and osteoclast number was observed in the defects receiving collagen scaffolds when compared with BCP scaffolds. The release of BMP2 over time was rapidly released after 1 day on BCP scaffolds whereas a gradually release over

  12. Stretch force guides finger-like pattern of bone formation in suture.

    Science.gov (United States)

    Wu, Bo-Hai; Kou, Xiao-Xing; Zhang, Ci; Zhang, Yi-Mei; Cui, Zhen; Wang, Xue-Dong; Liu, Yan; Liu, Da-Wei; Zhou, Yan-Heng

    2017-01-01

    Mechanical tension is widely applied on the suture to modulate the growth of craniofacial bones. Deeply understanding the features of bone formation in expanding sutures could help us to improve the outcomes of clinical treatment and avoid some side effects. Although there are reports that have uncovered some biological characteristics, the regular pattern of sutural bone formation in response to expansion forces is still unknown. Our study was to investigate the shape, arrangement and orientation of new bone formation in expanding sutures and explore related clinical implications. The premaxillary sutures of rat, which histologically resembles the sutures of human beings, became wider progressively under stretch force. Micro-CT detected new bones at day 3. Morphologically, these bones were forming in a finger-like pattern, projecting from the maxillae into the expanded sutures. There were about 4 finger-like bones appearing on the selected micro-CT sections at day 3 and this number increased to about 18 at day 7. The average length of these projections increased from 0.14 mm at day 3 to 0.81 mm at day 7. The volume of these bony protuberances increased to the highest level of 0.12 mm3 at day 7. HE staining demonstrated that these finger-like bones had thick bases connecting with the maxillae and thin fronts stretching into the expanded suture. Nasal sections had a higher frequency of finger-like bones occuring than the oral sections at day 3 and day 5. Masson-stained sections showed stretched fibers embedding into maxillary margins. Osteocalcin-positive osteoblasts changed their shapes from cuboidal to spindle and covered the surfaces of finger-like bones continuously. Alizarin red S and calcein deposited in the inner and outer layers of finger-like bones respectively, which showed that longer and larger bones formed on the nasal side of expanded sutures compared with the oral side. Interestingly, these finger-like bones were almost paralleling with the direction

  13. Effects of low‑level laser therapy on osteoblastic bone formation and ...

    African Journals Online (AJOL)

    2015-01-12

    level laser therapy (LLLT) on osteoblastic bone formation and relapse ... Rapid maxillary expansion (RME) and surgically assisted. RME are used to ... steel wires) were affixed to the maxillary incisors of all animals to expand the ...

  14. Bone morphogenetic protein-induced heterotopic bone formation: What have we learned from the history of a half century?

    Directory of Open Access Journals (Sweden)

    Takenobu Katagiri, PhD

    2015-05-01

    Full Text Available Bone morphogenetic protein (BMP was originally discovered by Marshall Urist a half century ago following the observation of a unique activity that induced heterotopic bone formation in skeletal muscle tissue. The molecular mechanisms underlying the induction of heterotopic bone formation in skeletal muscle by BMPs were elucidated through the purification and molecular cloning of BMPs and identification of their functional receptors and downstream effectors, as well as from genetic disorders related to BMP activity. BMPs are important regulators of not only skeletal development and regeneration but also the homeostasis of normal skeletal muscle mass. There is still much to learn about the physiology and pathology at the interface of BMPs and skeletal muscle.

  15. The effect of semelil (angipars® on bone resorption and bone formation markers in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Hasani-Ranjbar Shirin

    2012-12-01

    Full Text Available Abstract Background and purpose of the study Diabetes mellitus has been recognized as a major risk factor for osteoporosis in which bone turnover is affected by different mechanisms. As the morbidity, mortality and financial cost related to osteoporosis are expected to rise in Iran in coming years, and considering the efficacy of Angipars® for improvement of different ulcers which made it a new herbal drug in diabetic foot ulcer, there is a need to evaluate the effect of this new drug on different organs including bone resorption and bone formation markers. Methods In this randomized, double- blind clinical trial, 61 diabetic patients were included. The subjects were randomly divided into intervention and control groups. Subjects of intervention group received 100 mg of Angipars® twice a day. Laboratory tests including bone resorption and bone formation markers were performed at baseline and after 3 months. Result 31 patients in study group and 30 patients in control group finished the study. The mean age of the study population and the mean disease duration was respectively 51.8 ± 6.2 and 7.5 ± 4.7 years with no significant differences between intervention and control patients. No statistically significant differences between patients and controls were observed in pyridinoline, osteocalcin, urine calcium, bone alkaline phosphatase and tumor necrosis factor (TNF-α. Only urine creatinine level significantly changed between two groups after 3 month of treatment (p-value: 0.029 Conclusion In conclusion, the findings of this study indicate that Semelil (Angipars® had no beneficial or harmful effects on bone. It might be other effects of this new component on bone turnover process which need more studies and more time to be discovered.

  16. The Efect of Semelil (AngiparsW on Bone Resorption and Bone Formation Markers in Type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Shirin Hasani-Ranjbar

    2012-01-01

    Full Text Available Background and purpose of the study: Diabetes mellitus has been recognized as a major risk factor for osteoporosis in which bone turnover is affected by different mechanisms. As the morbidity, mortality and financial cost related to osteoporosis are expected to rise in Iran in coming years, and considering the efficacy of AngiparsW for improvement of different ulcers which made it a new herbal drug in diabetic foot ulcer, there is a need toevaluate the effect of this new drug on different organs including bone resorption and bone formation markers.Methods: In this randomized, double- blind clinical trial, 61 diabetic patients were included. The subjects wererandomly divided into intervention and control groups. Subjects of intervention group received 100 mg of AngiparsW twice a day. Laboratory tests including bone resorption and bone formation markers were performed at baseline and after 3 months.Result: 31 patients in study group and 30 patients in control group finished the study. The mean age of the studypopulation and the mean disease duration was respectively 51.8 ± 6.2 and 7.5 ± 4.7 years with no significant differences between intervention and control patients. No statistically significant differences between patients and controls were observed in pyridinoline, osteocalcin, urine calcium, bone alkaline phosphatase and tumor necrosis factor (TNF-α. Only urine creatinine level significantly changed between two groups after 3 month of treatment (pvalue:0.029Conclusion: In conclusion, the findings of this study indicate that Semelil (AngiparsW had no beneficial or harmfuleffects on bone. It might be other effects of this new component on bone turnover process which need morestudies and more time to be discovered.

  17. Rat bone marrow stem cells isolation and culture as a bone formative experimental system

    Directory of Open Access Journals (Sweden)

    Amer Smajilagić

    2013-02-01

    Full Text Available Bone marrow mesenchymal cells have been identified as a source of pluripotent stem cells with multipotential potential and differentiation in to the different cells types such as are osteoblast, chondroblast, adipoblast. In this research we describe pioneering experiment of tissue engineering in Bosnia and Herzegovina, of the isolation and differentiation rat bone marrow stromal cells in to the osteoblast cells lineages. Rat bone marrow stromal cells were isolated by method described by Maniatopulos using their plastic adherence capatibility. The cells obtained by plastic adherence were cultured and serially passaged in the osteoinductive medium to differentiate into the osteocytes. Bone marrow samples from rats long bones used for isolation of stromal cells (BMSCs. Under determinate culture conditions BMSCs were differentiated in osteogenic cell lines detected by Alizarin red staining three weeks after isolation. BMSCs as autologue cells model showed high osteogenetic potential and calcification capatibility in vitro. In future should be used as alternative method for bone transplantation in Regenerative Medicine.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    A remarkable property of bone remodeling is that osteoblasts form bone matrix exactly where and when osteoclasts have removed it. The bone remodeling compartment (BRC) canopies that cover bone surfaces undergoing remodeling, were proposed to be critical players in this mechanism. Here, we provide...... support to this hypothesis by analyzing the changes in prevalence of BRC canopies during the progress of the remodeling cycle in a cohort of healthy individuals and in patients with endogenous Cushing's syndrome (CS), and by relating these changes in prevalence with the extent of bone forming surfaces....... Both cohorts showed almost 100% canopy coverage above resorbing osteoclasts, and only about 76% above bone forming surfaces. This indicates that BRC canopies are invariably associated with the early stage of the remodeling cycle, but may disappear later. Interestingly, in control and two thirds...

  19. Requirement of alveolar bone formation for eruption of rat molars.

    Science.gov (United States)

    Wise, Gary E; He, Hongzhi; Gutierrez, Dina L; Ring, Sherry; Yao, Shaomian

    2011-10-01

    Tooth eruption is a localized event that requires a dental follicle (DF) to regulate the resorption of alveolar bone to form an eruption pathway. During the intra-osseous phase of eruption, the tooth moves through this pathway. The mechanism or motive force that propels the tooth through this pathway is controversial but many studies have shown that alveolar bone growth at the base of the crypt occurs during eruption. To determine if this bone growth (osteogenesis) was causal, experiments were designed in which the expression of an osteogenic gene in the DF, bone morphogenetic protein-6 (Bmp6), was inhibited by injection of the first mandibular molar of the rat with a small interfering RNA (siRNA) targeted against Bmp6. The injection was followed by electroporation to promote uptake of the siRNA. In 45 first molars injected, eruption was either delayed or completely inhibited (seven molars). In the impacted molars, an eruption pathway formed but bone growth at the base of the crypt was greatly reduced compared with the erupted first-molar controls. These studies show that alveolar bone growth at the base of the crypt is required for tooth eruption and that Bmp6 may be essential for promoting this growth. © 2011 Eur J Oral Sci.

  20. Intermittent PTH administration improves alveolar bone formation in type 1 diabetic rats with periodontitis.

    Science.gov (United States)

    Kim, Ji-Hye; Kim, Ae Ri; Choi, Yun Hui; Kim, Aeryun; Sohn, Yongsung; Woo, Gye-Hyeong; Cha, Jeong-Heon; Bak, Eun-Jung; Yoo, Yun-Jung

    2018-03-15

    Periodontitis is an infectious disease that manifests as alveolar bone loss surrounding the roots of teeth. Diabetes aggravates periodontitis-induced alveolar bone loss via suppression of bone formation. Intermittent parathyroid hormone (PTH) administration displays an anabolic effect on bone. In this study, we investigated the effect of intermittent PTH administration on alveolar bone loss in type 1 diabetic rats with periodontitis. Rats were divided into control (C), periodontitis (P), periodontitis treated with PTH (P + PTH), diabetes with periodontitis (DP), and diabetes with periodontitis treated with PTH (DP + PTH) groups. To induce type 1 diabetes, rats were injected with streptozotocin and periodontitis was induced bilaterally by applying ligatures to the mandibular first molars for 30 days. During the experimental period, the P + PTH and DP + PTH groups were subcutaneously injected with PTH (40 μg/kg) three times per week, whereas the C, P, and DP groups were injected with citrate buffer. To observe the mineralization of the alveolar bone, the DP and DP + PTH groups were injected with calcein on days 10 and 27, and with alizarin red on day 20. Thirty days after ligation, histological findings and fluorescence labeling were analyzed in the furcations of the mandibular first molars. Sclerostin-positive osteocytes were assessed by immunohistochemical analyses. The DP groups had smaller areas of alveolar bone than the other groups, and the DP + PTH group had a larger alveolar bone area than the DP group. The DP group had less osteoid formation than the C group, whereas the DP + PTH had greater osteoid formation than the DP group. Fluorescence labeling results revealed that the DP + PTH group had more mineral deposition on the alveolar bone than the DP group. The DP + PTH group exhibited lower percentage of sclerostin-positive osteocytes in alveolar bone than the DP group. Intermittent PTH administration diminishes

  1. Autologous platelet-rich plasma induces bone formation of tissue-engineered bone with bone marrow mesenchymal stem cells on beta-tricalcium phosphate ceramics.

    Science.gov (United States)

    Yu, Tengbo; Pan, Huazheng; Hu, Yanling; Tao, Hao; Wang, Kai; Zhang, Chengdong

    2017-11-21

    The purpose of the study is to investigate whether autologous platelet-rich plasma (PRP) can serve as bone-inducing factors to provide osteoinduction and improve bone regeneration for tissue-engineered bones fabricated with bone marrow mesenchymal stem cells (MSCs) and beta-tricalcium phosphate (β-TCP) ceramics. The current study will give more insight into the contradictory osteogenic capacity of PRP. The concentration of platelets, platelet-derived growth factor-AB (PDGF-AB), and transforming growth factor-β1 (TGF-β1) were measured in PRP and whole blood. Tissue-engineered bones using MSCs on β-TCP scaffolds in combination with autologous PRP were fabricated (PRP group). Controls were established without the use of autologous PRP (non-PRP group). In vitro, the proliferation and osteogenic differentiation of MSCs on fabricated constructs from six rabbits were evaluated with MTT assay, alkaline phosphatase (ALP) activity, and osteocalcin (OC) content measurement after 1, 7, and 14 days of culture. For in vivo study, the segmental defects of radial diaphyses of 12 rabbits from each group were repaired by fabricated constructs. Bone-forming capacity of the implanted constructs was determined by radiographic and histological analysis at 4 and 8 weeks postoperatively. PRP produced significantly higher concentration of platelets, PDGF-AB, and TGF-β1 than whole blood. In vitro study, MTT assay demonstrated that the MSCs in the presence of autologous PRP exhibited excellent proliferation at each time point. The results of osteogenic capacity detection showed significantly higher levels of synthesis of ALP and OC by the MSCs in combination with autologous PRP after 7 and 14 days of culture. In vivo study, radiographic observation showed that the PRP group produced significantly higher score than the non-PRP group at each time point. For histological evaluation, significantly higher volume of regenerated bone was found in the PRP group when compared with the non

  2. Pulsed electromagnetic fields partially preserve bone mass, microarchitecture, and strength by promoting bone formation in hindlimb-suspended rats.

    Science.gov (United States)

    Jing, Da; Cai, Jing; Wu, Yan; Shen, Guanghao; Li, Feijiang; Xu, Qiaoling; Xie, Kangning; Tang, Chi; Liu, Juan; Guo, Wei; Wu, Xiaoming; Jiang, Maogang; Luo, Erping

    2014-10-01

    A large body of evidence indicates that pulsed electromagnetic fields (PEMF), as a safe and noninvasive method, could promote in vivo and in vitro osteogenesis. Thus far, the effects and underlying mechanisms of PEMF on disuse osteopenia and/or osteoporosis remain poorly understood. Herein, the efficiency of PEMF on osteoporotic bone microarchitecture, bone strength, and bone metabolism, together with its associated signaling pathway mechanism, was systematically investigated in hindlimb-unloaded (HU) rats. Thirty young mature (3-month-old), male Sprague-Dawley rats were equally assigned to control, HU, and HU + PEMF groups. The HU + PEMF group was subjected to daily 2-hour PEMF exposure at 15 Hz, 2.4 mT. After 4 weeks, micro-computed tomography (µCT) results showed that PEMF ameliorated the deterioration of trabecular and cortical bone microarchitecture. Three-point bending test showed that PEMF mitigated HU-induced reduction in femoral mechanical properties, including maximum load, stiffness, and elastic modulus. Moreover, PEMF increased serum bone formation markers, including osteocalcin (OC) and N-terminal propeptide of type 1 procollagen (P1NP); nevertheless, PEMF exerted minor inhibitory effects on bone resorption markers, including C-terminal crosslinked telopeptides of type I collagen (CTX-I) and tartrate-resistant acid phosphatase 5b (TRAcP5b). Bone histomorphometric analysis demonstrated that PEMF increased mineral apposition rate, bone formation rate, and osteoblast numbers in cancellous bone, but PEMF caused no obvious changes on osteoclast numbers. Real-time PCR showed that PEMF promoted tibial gene expressions of Wnt1, LRP5, β-catenin, OPG, and OC, but did not alter RANKL, RANK, or Sost mRNA levels. Moreover, the inhibitory effects of PEMF on disuse-induced osteopenia were further confirmed in 8-month-old mature adult HU rats. Together, these results demonstrate that PEMF alleviated disuse-induced bone loss by promoting skeletal anabolic activities

  3. Identification of Chloride Intracellular Channel Protein 3 as a Novel Gene Affecting Human Bone Formation

    DEFF Research Database (Denmark)

    Brum, A M; Leije, M; J, Schreuders-Koedam

    2017-01-01

    is diminished and more adipocytes are seen in the bone marrow, suggesting a shift in MSC lineage commitment. Identification of specific factors that stimulate osteoblast differentiation from human MSCs may deliver therapeutic targets to treat osteoporosis. The aim of this study was to identify novel genes...... an in vivo human bone formation model in which hMSCs lentivirally transduced with the CLIC3 overexpression construct were loaded onto a scaffold (hydroxyapatite-tricalcium-phosphate), implanted under the skin of NOD-SCID mice, and analyzed for bone formation 8 weeks later. CLIC3 overexpression led to a 15...

  4. 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.

  5. The effect of drill hole location on load bearing capacity of long bones.

    Science.gov (United States)

    Yiachos, Christopher James; Saha, Subrata

    2018-06-01

    We investigated how load bearing capacity (LBC) of long bone differs with a bicortical drill hole in a compressive/tensile location vs. a neutral location. Group I had a hole drilled through 0°/180° ([compressive at 0°/maximum tensile at 180°]), Group II at 90°/270° ([neutral]), and Group III at 135°/315° ([tensile at 135°/compressive at 315°]). Maximum load at failure and stiffness was measured. A significant ([ p  Loss of strength for Group II was statistically insignificant ([ p  > 0.05]). Changes in stiffness for both tibias and fibulas was not statistically significant ([ p >  0.05]).

  6. Local effect of zoledronic acid on new bone formation in posterolateral spinal fusion with demineralized bone matrix in a murine model.

    Science.gov (United States)

    Zwolak, Pawel; Farei-Campagna, Jan; Jentzsch, Thorsten; von Rechenberg, Brigitte; Werner, Clément M

    2018-01-01

    Posterolateral spinal fusion is a common orthopaedic surgery performed to treat degenerative and traumatic deformities of the spinal column. In posteriolateral spinal fusion, different osteoinductive demineralized bone matrix products have been previously investigated. We evaluated the effect of locally applied zoledronic acid in combination with commercially available demineralized bone matrix putty on new bone formation in posterolateral spinal fusion in a murine in vivo model. A posterolateral sacral spine fusion in murine model was used to evaluate the new bone formation. We used the sacral spine fusion model to model the clinical situation in which a bone graft or demineralized bone matrix is applied after dorsal instrumentation of the spine. In our study, group 1 received decortications only (n = 10), group 2 received decortication, and absorbable collagen sponge carrier, group 3 received decortication and absorbable collagen sponge carrier with zoledronic acid in dose 10 µg, group 4 received demineralized bone matrix putty (DBM putty) plus decortication (n = 10), and group 5 received DBM putty, decortication and locally applied zoledronic acid in dose 10 µg. Imaging was performed using MicroCT for new bone formation assessment. Also, murine spines were harvested for histopathological analysis 10 weeks after surgery. The surgery performed through midline posterior approach was reproducible. In group with decortication alone there was no new bone formation. Application of demineralized bone matrix putty alone produced new bone formation which bridged the S1-S4 laminae. Local application of zoledronic acid to demineralized bone matrix putty resulted in significant increase of new bone formation as compared to demineralized bone matrix putty group alone. A single local application of zoledronic acid with DBM putty during posterolateral fusion in sacral murine spine model increased significantly new bone formation in situ in our model. Therefore, our

  7. Normal tempo of bone formation in Turner syndrome despite signs of accelerated bone resorption

    DEFF Research Database (Denmark)

    Cleemann, Line Hartvig; Holm, Kirsten Bagge; Kobbernagel, Hanne

    2011-01-01

    Aims: To evaluate area bone mineral density (aBMD) and volumetric BMD (vBMD) by dual-energy X-ray absorptiometry, and relations to bone markers and hormones in adolescent women with Turner syndrome (TS). Methods: Cross-sectional study in TS patients (n = 37, 16.7 ± 3.4 years) and control group (n...

  8. Normal Tempo of Bone Formation in Turner Syndrome despite Signs of Accelerated Bone Resorption

    DEFF Research Database (Denmark)

    Cleemann, Line; Holm, Kirsten; Kobbernagel, Hanne

    2011-01-01

    Aims: To evaluate area bone mineral density (aBMD) and volumetric BMD (vBMD) by dual-energy X-ray absorptiometry, and relations to bone markers and hormones in adolescent women with Turner syndrome (TS). Methods: Cross-sectional study in TS patients (n = 37, 16.7 ± 3.4 years) and control group (n...

  9. Effects of Weight Loss on Lean Mass, Strength, Bone, and Aerobic Capacity.

    Science.gov (United States)

    Weiss, Edward P; Jordan, Richard C; Frese, Ethel M; Albert, Stewart G; Villareal, Dennis T

    2017-01-01

    This study aimed to evaluate the hypothesis that exercise attenuates the reductions in lean mass, muscle strength, bone mineral density, and V˙O2max that accompany modest weight loss induced by calorie restriction (CR). Overweight, sedentary women and men (n = 52, 45-65 yr) were randomized to 6%-8% weight loss by using CR, endurance exercise training (EX), or both (CREX). The CR and the CREX groups underwent counseling to reduce energy intake by 20% and 10%, respectively. The EX and the CREX groups exercised 7.4 ± 0.5 and 4.4 ± 0.5 h·wk, respectively. Before and after 16.8 ± 1.1 wk of weight loss, lean mass and bone mineral density were measured with dual-energy x-ray absorptiometry, strength was measured with dynamometry, and aerobic capacity (V˙O2max) was measured with indirect calorimetry during maximal-intensity treadmill exercise. Weight loss was ~7% in all groups. Decreases in whole-body (~2%, P = 0.003) and lower extremity (~4%, P weight loss, these reductions were attenuated in the CREX group (~1%, P = 0.44 and ~2%, P = 0.05, respectively) and absent in the EX group. Absolute aerobic capacity decreased ~6% in the CR group (P = 0.04), was unchanged in the CREX group (P = 0.28), and increased ~15% in the EX group (P weight loss (~7%) induced by 20% CR in overweight women and men decreases lean mass and reduces absolute V˙O2max. Exercise protects against these effects. Although the CR-induced changes might be considered physiologically appropriate for a reduced body weight, exercise preserves and/or improves these parameters during weight loss, which likely improves physical function. These findings support the notion of using exercise as an important component of weight loss programs.

  10. Time-dependent changes in bone healing capacity of scaphoid fractures and non-unions.

    Science.gov (United States)

    Schmidle, Gernot; Ebner, Hannes Leonhard; Klima, Günter; Pfaller, Kristian; Fritz, Josef; Hoermann, Romed; Gabl, Markus

    2018-02-27

    The scaphoid is the most frequently fractured carpal bone and prone to non-union due to mechanical and biological factors. Whereas the importance of stability is well documented, the evaluation of biological activity is mostly limited to the assessment of vascularity. The purpose of this study was to select histological and immunocytochemical parameters that could be used to assess healing potential after scaphoid fractures and to correlate these findings with time intervals after fracture for the three parts of the scaphoid (distal, gap and proximal). Samples were taken during operative intervention in 33 patients with delayed or non-union of the scaphoid. Haematoxylin and Eosin (HE), Azan, Toluidine, von Kossa and Tartrate-resistant acid phosphatase (TRAP) staining were used to characterise the samples histologically. We determined distribution of collagen 1 and 2 by immunocytochemistry, and scanning electron microscopy (SEM) was used to investigate the ultrastructure. To analyse the samples, parameters for biological healing status were defined and grouped according to healing capacity in parameters with high, partial and little biological activity. These findings allowed scoring of biological healing capacity, and the ensuing results were correlated with different time intervals after fracture. The results showed reduced healing capacity over time, but not all parts of the scaphoid were affected in the same way. For the distal fragment, regression analysis showed a statistically significant correlation between summarised healing activity scores and time from initial fracture (r = -0.427, P = 0.026) and decreasing healing activity for the gap region (r = -0.339, P = 0.090). In contrast, the analyses of the proximal parts for all patients did not show a correlation (r = 0.008, P = 0.969) or a decrease in healing capacity, with reduced healing capacity already at early stages. The histological and immunocytochemical characterisation of scaphoid non

  11. Bone formation around zirconia implants combined with rhBMP-2 gel in the canine mandible.

    Science.gov (United States)

    Lee, Byung-Chul; Yeo, In-Sung; Kim, Dae-Joon; Lee, Jai-Bong; Kim, Sung-Hun; Han, Jung-Suk

    2013-12-01

    The aim of this study was to estimate the effects of zirconia implants and recombinant human bone morphogenetic protein-2 (rhBMP-2) gel on the acceleration of local bone formation and osseointegration in the canine mandible. Four groups of 48 implants with identical geometry were installed in the mandibles of beagle dogs: alumina-blasted zirconia implants applied with rhBMP-2, alumina-blasted zirconia implants applied with demineralized bone matrix (DBM), alumina-blasted zirconia implants, and resorbable blast media-treated titanium (Ti) implants. For the first two groups, zirconia implants were inserted after the surgical sites were filled with rhBMP-2 or DBM gel. For the other two groups, zirconia or Ti implants were installed with no adjunctive treatment. Fluorescent bone markers were administered to monitor bone remodeling at weeks 2, 4, and 5 postimplantation. After healing periods of 3 weeks and 6 weeks, the animals were sacrificed, and fluorescent microscopy, histology, and histomorphometric analyses were performed. Fluorescent microscopy showed that bone formation around the zirconia implants installed with rhBMP-2 gel was the most prominent at 2 weeks postimplantation, while the Ti implants acquired bone apposition mainly at week 5. No significant differences were found in bone area among the groups (P > 0.05). The zirconia implants showed similar bone-to-implant contact to the Ti implants. There were no significant differences in bone-to-implant contact between the zirconia implants with rhBMP-2 gel and those with DBM (P > 0.05). The zirconia implants with alumina-blasted surfaces may achieve osseointegration in much the same manner as the well-established Ti implants. The area influenced by rhBMP-2 gel, including the alveolar crest, may cause active remodeling and early bone formation. © 2012 John Wiley & Sons A/S.

  12. Does PEEK/HA Enhance Bone Formation Compared With PEEK in a Sheep Cervical Fusion Model?

    Science.gov (United States)

    Walsh, William R; Pelletier, Matthew H; Bertollo, Nicky; Christou, Chris; Tan, Chris

    2016-11-01

    Polyetheretherketone (PEEK) has a wide range of clinical applications but does not directly bond to bone. Bulk incorporation of osteoconductive materials including hydroxyapatite (HA) into the PEEK matrix is a potential solution to address the formation of a fibrous tissue layer between PEEK and bone and has not been tested. Using in vivo ovine animal models, we asked: (1) Does PEEK-HA improve cortical and cancellous bone ongrowth compared with PEEK? (2) Does PEEK-HA improve bone ongrowth and fusion outcome in a more challenging functional ovine cervical fusion model? The in vivo responses of PEEK-HA Enhanced and PEEK-OPTIMA ® Natural were evaluated for bone ongrowth in the form of dowels implanted in the cancellous and cortical bone of adult sheep and examined at 4 and 12 weeks as well as interbody cervical fusion at 6, 12, and 26 weeks. The bone-implant interface was evaluated with radiographic and histologic endpoints for a qualitative assessment of direct bone contact of an intervening fibrous tissue later. Gamma-irradiated cortical allograft cages were evaluated as well. Incorporating HA into the PEEK matrix resulted in more direct bone apposition as opposed to the fibrous tissue interface with PEEK alone in the bone ongrowth as well as interbody cervical fusions. No adverse reactions were found at the implant-bone interface for either material. Radiography and histology revealed resorption and fracture of the allograft devices in vivo. Incorporating HA into PEEK provides a more favorable environment than PEEK alone for bone ongrowth. Cervical fusion was improved with PEEK-HA compared with PEEK alone as well as allograft bone interbody devices. Improving the bone-implant interface with a PEEK device by incorporating HA may improve interbody fusion results and requires further clinical studies.

  13. The effect of patient age on bone formation using a fully synthetic nanocrystalline bone augmentation material in maxillary sinus grafting.

    Science.gov (United States)

    Wolf, Michael; Wurm, Alexander; Heinemann, Friedhelm; Gerber, Thomas; Reichert, Christoph; Jäger, Andreas; Götz, Werner

    2014-01-01

    Maxillary sinus floor augmentation is a treatment that has been proposed for patients in whom the alveolar bone height is insufficient. This procedure is commonly used in patients aged 40 to 70 years and older. However, little information exists whether the factor of age might influence the outcome of augmentation procedures. The aim of this study was to investigate whether the patient's age has an effect on bone formation and incorporation in maxillary sinus floor augmentation procedures. A fully synthetic nanocrystalline bone augmentation material (NanoBone, Artoss) was used for sinus floor augmentation in patients with a subantral vertical bone height of at least 3 mm and maximum of 7 mm. After 7 months healing time, biopsy specimens were taken and were divided into two groups according to the patient's age. Exclusion criteria were poor general health (eg, severe renal/and or liver disease), history of a radiotherapy in the head region, chemotherapy at the time of surgical procedure, noncompensated diabetes mellitus, symptoms of a maxillary sinus disease, active periodontal or systemic diseases, smoking, and poor oral hygiene. Histologic analyses with hematoxylin-eosin stain were performed. Multinucleated osteoclast-like cells were identified by histochemical staining (tartrate-resistant acid phosphatase [TRAP]). Quantitative and age-dependent assessment of bone formation, residual bone grafting material, and soft tissue formation following sinus augmentation was performed using histomorphometric analysis and the Bonferroni adjustment of the Student t test. Twenty biopsy specimens from 17 patients were taken and divided into two groups according to age (group 1: 41 to 52 years; group 2: 66 to 71 years) containing 10 specimens each, which were analyzed in triplicate resulting in a total of 30 specimens per group. A regeneration process with varying amounts of newly formed bone surrounded by marrow-like tissue was present in all augmented regions. No signs of

  14. Ectopic bone formation in rats: the importance of the carrier.

    NARCIS (Netherlands)

    Hartman, E.H.M.; Vehof, J.W.M.; Spauwen, P.H.M.; Jansen, J.A.

    2005-01-01

    Much research has been done to develop the ideal bone graft substitute (BGS). One approach to develop this ideal BGS is the use of growth factors, but for this approach osteoprogenitor cells are needed at the site of reconstruction. An alternative is a cell-based approach, where enough cells are

  15. A Computational Analysis of Bone Formation in the Cranial Vault in the Mouse

    Directory of Open Access Journals (Sweden)

    Chanyoung eLee

    2015-03-01

    Full Text Available Bones of the cranial vault are formed by the differentiation of mesenchymal cells into osteoblasts on a surface that surrounds the brain, eventually forming mineralized bone. Signaling pathways causative for the cell differentiation include the actions of extracellular proteins driven by information from genes. We assume that the interaction of cells and extracellular molecules which are associated with cell differentiation can be modeled using Turing’s reaction-diffusion model, a mathematical model for pattern formation controlled by two interacting molecules (activator and inhibitor. In this study we hypothesize that regions of high concentration of an activator develop into primary centers of ossification, the earliest sites of cranial vault bone. In addition to the Turing model, we use another diffusion equation to model a morphogen (potentially the same as the morphogen associated with formation of ossification centers associated with bone growth. These mathematical models were solved using the finite volume method. The computational domain and model parameters are determined using a large collection of experimental data showing skull bone formation in mouse at different embryonic days in both of normal and defect conditions. The results show that the relative locations of the five ossification centers that form in our model occur at the same position as those identified in experimental data. As bone grows from these ossification centers, sutures form between the bones.

  16. Mate tea (Ilex paraguariensis) improves bone formation in the alveolar socket healing after tooth extraction in rats.

    Science.gov (United States)

    Brasilino, Matheus da Silva; Stringhetta-Garcia, Camila Tami; Pereira, Camila Scacco; Pereira, Ariana Aparecida Ferreira; Stringhetta, Karina; Leopoldino, Andréia Machado; Crivelini, Marcelo Macedo; Ervolino, Edilson; Dornelles, Rita Cássia Menegati; de Melo Stevanato Nakamune, Ana Cláudia; Chaves-Neto, Antonio Hernandes

    2018-04-01

    The objective of this study was to investigate the effects of mate tea (MT) [Ilex paraguariensis] on alveolar socket healing after tooth extraction. Sixteen male rats were divided into MT and control groups. MT was administered by intragastric gavage at a dose of 20 mg/kg/day for 28 days before and 28 days after right maxillary incisor extraction. The control group received an equal volume of water. Histopathological and histometric analysis of the neoformed bone area and osteocyte density were performed, as well as immunohistochemical analysis of osteocalcin (OCN), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), tartrate-resistant acid phosphatase (TRAP), and manganese superoxide dismutase (MnSOD) in the alveolar socket. Calcium, phosphorus, alkaline phosphatase (ALP) activity, total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured in plasma, whereas TRAP activity was determined in serum. Histometry evidenced an increase in bone area (P alveolar socket healing on day 28 after tooth extraction. Regular MT ingestion improves the antioxidant defenses and bone formation, which is beneficial for alveolar socket bone healing after tooth extraction.

  17. In vivo cyclic loading as a potent stimulatory signal for bone formation inside tissue engineering scaffold

    Directory of Open Access Journals (Sweden)

    A Roshan-Ghias

    2010-02-01

    Full Text Available In clinical situations, bone defects are often located at load bearing sites. Tissue engineering scaffolds are future bone substitutes and hence they will be subjected to mechanical stimulation. The goal of this study was to test if cyclic loading can be used as stimulatory signal for bone formation in a bone scaffold. Poly(L-lactic acid (PLA/ 5% beta-tricalcium phosphate (beta-TCP scaffolds were implanted in both distal femoral epiphyses of eight rats. Right knees were stimulated (10N, 4Hz, 5 min five times, every two days, starting from the third day after surgery while left knees served as control. Finite element study of the in vivo model showed that the strain applied to the scaffold is similar to physiological strains. Using micro-computed tomography (CT, all knees were scanned five times after the surgery and the related bone parameters of the newly formed bone were quantified. Statistical modeling was used to estimate the evolution of these parameters as a function of time and loading. The results showed that mechanical stimulation had two effects on bone volume (BV: an initial decrease in BV at week 2, and a long-term increase in the rate of bone formation by 28%. At week 13, the BV was then significantly higher in the loaded scaffolds.

  18. Localized intermittent delivery of simvastatin hydroxyacid stimulates bone formation in rats.

    Science.gov (United States)

    Jeon, Ju Hyeong; Piepgrass, Ward T; Lin, Yi-Ling; Thomas, Mark V; Puleo, David A

    2008-08-01

    The cholesterol-lowering drug simvastatin promotes bone formation in cell cultures and animal models. In previous studies, devices for the controlled, localized delivery of simvastatin hydroxyacid enhanced osteoblastic activity in vitro. The objective of this investigation was to determine bioactivity of the delivery system in vivo. Devices for sustained or intermittent release of simvastatin hydroxyacid were formed using a blend of cellulose acetate phthalate and a poly(ethylene oxide) and poly(propylene oxide) block copolymer, and they were implanted directly over the calvarium of young male rats. Drug-free devices were used as controls. After 9, 18, or 28 days, specimens were histologically evaluated for new bone formation. All three groups showed some level of new bone formation, but the extent of osteogenesis depended on the type of implant. Devices delivering simvastatin hydroxyacid were associated with a 77.5% to 133% increase in new woven bone thickness compared to control devices without a drug (P<0.05). Furthermore, intermittent release stimulated a 32.3% greater response in bone thickness and a 74.1% greater bone area than did sustained delivery (P<0.05). Although a minimal thickness of woven bone was formed directly under the device (up to 36 microm), a significantly thicker layer was observed at the periphery (up to 205 microm), implying mechanical and/or chemical effects directly under the implant. The percentage of lamellar bone area for intermittent and sustained release was higher than that for the control group (P<0.05). Based on the present results of enhanced bone formation, these devices for the intermittent delivery of simvastatin hydroxyacid merit further attention for localized osteogenesis.

  19. Callus formation in bone fractures combined with brain injury in rat

    Directory of Open Access Journals (Sweden)

    Yu-Ping Chen

    2017-01-01

    Full Text Available Objective: The objective of this study was to determine the speed of bony union and the serum levels of biomarkers in the setting of bone fractures combined with brain injury. Materials and Methods: In this study, Sprague–Dawley rats were randomized into four groups: sham, brain injury, bone fracture, and bone fracture plus brain injury groups. The serum levels of biochemical markers, namely, nerve growth factor (NGF, Wnt-3a, Dickkopf-related protein-1, receptor-activator of NF-κB ligand, and adrenocorticotropic hormone (ACTH, were measured on the days 1, 3, 7, and 14 following injury. Bony union was evaluated using radiographs every week for 6 weeks. Results: Compared with the brain injury group and bone fracture group, the radiographs of the bone fracture plus brain injury group revealed enhanced callus formations in week 2. From week 3, the callus formation did not differ significantly among the groups. The serum levels of the biomarkers varied at different time points. The serum levels of NGF on days 1 and 3, Wnt-3a on days 3 and 14, and ACTH on days 1, 3, and 7 were significantly higher in the bone fracture plus brain injury group than in the bone fracture group. Conclusions: Brain injury increases callus formation in simultaneous bone fracture. Considering the time point, early NGF, Wnt-3a, and ACTH elevation might be associated with early callus formation enhancement. The results indicate that these brain injury-induced biomarkers might play crucial role in accelerating bone healing.

  20. Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats

    International Nuclear Information System (INIS)

    Gilmour, Peter S.; O'Shea, Patrick J.; Fagura, Malbinder; Pilling, James E.; Sanganee, Hitesh; Wada, Hiroki; Courtney, Paul F.; Kavanagh, Stefan; Hall, Peter A.; Escott, K. Jane

    2013-01-01

    Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/μCT imaging. GSK-3 inhibitors caused β-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH 1–34 or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/μCT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis and

  1. Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats

    Energy Technology Data Exchange (ETDEWEB)

    Gilmour, Peter S., E-mail: Peter.Gilmour@astrazeneca.com [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); O' Shea, Patrick J.; Fagura, Malbinder [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Pilling, James E. [Discovery Sciences, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Sanganee, Hitesh [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Wada, Hiroki [R and I IMed, AstraZeneca R and D, Molndal (Sweden); Courtney, Paul F. [DMPK, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Kavanagh, Stefan; Hall, Peter A. [Safety Assessment, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Escott, K. Jane [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom)

    2013-10-15

    Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/μCT imaging. GSK-3 inhibitors caused β-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH{sub 1–34} or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/μCT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis

  2. Cellular Therapy to Obtain Rapid Endochondral Bone Formation

    Science.gov (United States)

    2010-02-01

    surgery, and both autografts and allografts have been commonly used in spinal fusion, revision total hip arthroplasty , maxillofacial reconstruction...idiopathic scoliosis. Spine (Phila Pa 1976) 2003 Apr 15;28(8):793-798. 2. Goldberg VM. Selection of bone grafts for revision total hip arthroplasty ...grafting4. This number does not include the millions of total joint arthroplasties , spinal arthrodeses, maxillofacial surgeries and implant

  3. Bone formation: The rules for fabricating a composite ceramic

    Energy Technology Data Exchange (ETDEWEB)

    Caplan, A.I. (Case Western Reserve Univ., Cleveland, OH (USA))

    1990-01-01

    Bone, teeth and shells are complex composite ceramics which are fabricated at low temperature by living organisms. The detailed understanding of this fabrication process is required if we are to attempt to mimic this low temperature assembly process. The guiding principles and major components are outlined with the intent of establishing non-vital fabrication schemes to form a complex composite ceramic consisting of an organix matrix inorganic crystalline phase. 19 refs.

  4. Grape seed proanthocyanidins extract promotes bone formation in rat's mandibular condyle.

    Science.gov (United States)

    Ishikawa, Makoto; Maki, Kenshi; Tofani, Iwan; Kimura, Kyoko; Kimura, Mitsutaka

    2005-02-01

    We studied the effect of dietary supplementation with grape seed proanthocyanidins extract (GSPE) 3 mg added in 100 g high-calcium diet with a calcium content of 1697 mg 100 g(-1) on mandibular condyle bone debility, which was induced by a low-calcium diet. Forty Wistar male rats, 5 week old, were randomly divided into control (Co), low-calcium diet (LC), low-calcium/high-calcium diet (LCH), and low-calcium/high-calcium with supplementary GSPE diet (LCHG) groups for 6 wk. Bone formation of the mandibular condyle was measured using peripheral quantitative computed tomography (pQCT). Significant differences were not seen among the four groups for body weight, measured weekly. The LCHG group scored significantly higher in cortical bone density, total bone cross-sectional area, cortical bone cross-sectional area, cortical bone mineral content, total bone density, total bone mineral content, and in the stress-strain index to the reference axis x when compared with the LCH group. We concluded that a high-calcium diet combined with GSPE supplementation is more effective in reversing mandibular condyle bone debility in rats than is a low-calcium diet, standard diet, or high-calcium diet alone.

  5. Suppression Effect of Astaxanthin on Osteoclast Formation In Vitro and Bone Loss In Vivo

    Directory of Open Access Journals (Sweden)

    Yun-Ho Hwang

    2018-03-01

    Full Text Available Osteoporosis is characterized by a reduction of the bone mineral density (BMD and microarchitectural deterioration of the bone, which lead to bone fragility and susceptibility to fracture. Astaxanthin (AST has a variety of biological activities, such as a protective effect against asthma or neuroinflammation, antioxidant effect, and decrease of the osteoclast number in the right mandibles in the periodontitis model. Although treatment with AST is known to have an effect on inflammation, no studies on the effect of AST exposure on bone loss have been performed. Thus, in the present study, we examined the antiosteoporotic effect of AST on bone mass in ovariectomized (OVX mice and its possible mechanism of action. The administration of AST (5, 10 mg/kg for 6 weeks suppressed the enhancement of serum calcium, inorganic phosphorus, alkaline phosphatase, total cholesterol, and tartrate-resistant acid phosphatase (TRAP activity. The bone mineral density (BMD and bone microarchitecture of the trabecular bone in the tibia and femur were recovered by AST exposure. Moreover, in the in vitro experiment, we demonstrated that AST inhibits osteoclast formation through the expression of the nuclear factor of activated T cells (NFAT c1, dendritic cell-specific transmembrane protein (DC-STAMP, TRAP, and cathepsin K without any cytotoxic effects on bone marrow-derived macrophages (BMMs. Therefore, we suggest that AST may have therapeutic potential for the treatment of postmenopausal osteoporosis.

  6. Teriparatide and bone turnover and formation in a hemodialysis patient with low-turnover bone disease: a case report.

    Science.gov (United States)

    Palcu, Patricia; Dion, Natalie; Ste-Marie, Louis-Georges; Goltzman, David; Radziunas, Ina; Miller, Paul D; Jamal, Sophie A

    2015-06-01

    Teriparatide, a recombinant form of parathyroid hormone, is an anabolic agent approved for use in women and men with osteoporosis. However, it is not well studied in people with chronic kidney disease (CKD). We report on a patient with stage 5 CKD treated with dialysis who presented to our clinic with multiple fractures, including bilateral nondisplaced pelvic fractures resulting in chronic pain and interfering with the patient's ability to work. Bone histomorphometry demonstrated low-turnover bone disease, and he was treated with 20μg of teriparatide (subcutaneous injection) every morning for 24 months. Within 6 months of initiating therapy, the patient's pain resolved and he was able to resume work. Serum calcium and phosphate levels remained within reference ranges throughout his treatment, and he sustained no further fractures. During 24 months of treatment, bone mineral density was maintained at the lumbar spine, and there was an increase of 4% at the femoral neck and total hip. A second transiliac bone biopsy demonstrated improvements in static and dynamic parameters of bone formation. In our patient, 24-month treatment with teriparatide was safe and effective; however, larger studies are needed to determine the efficacy of teriparatide in the dialysis-dependent CKD population. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  7. Youth self-formation and the 'capacity to aspire': The itinerant ...

    African Journals Online (AJOL)

    The article employs the lenses of 'aspiration', 'space', and 'technologies of self' to present the argument that his 'capacity to aspire' has to be understood on the basis of his active self-formation and disciplining, accumulated across the itinerant spaces of his life. The aim of this article is to open a window onto how young ...

  8. Local Application of Isogenic Adipose-Derived Stem Cells Restores Bone Healing Capacity in a Type 2 Diabetes Model.

    Science.gov (United States)

    Wallner, Christoph; Abraham, Stephanie; Wagner, Johannes Maximilian; Harati, Kamran; Ismer, Britta; Kessler, Lukas; Zöllner, Hannah; Lehnhardt, Marcus; Behr, Björn

    2016-06-01

    Bone regeneration is typically a reliable process without scar formation. The endocrine disease type 2 diabetes prolongs and impairs this healing process. In a previous work, we showed that angiogenesis and osteogenesis-essential steps of bone regeneration-are deteriorated, accompanied by reduced proliferation in type 2 diabetic bone regeneration. The aim of the study was to improve these mechanisms by local application of adipose-derived stem cells (ASCs) and facilitate bone regeneration in impaired diabetic bone regeneration. The availability of ASCs in great numbers and the relative ease of harvest offers unique advantages over other mesenchymal stem cell entities. A previously described unicortical tibial defect model was utilized in diabetic mice (Lepr(db-/-)). Isogenic mouse adipose-derived stem cells (mASCs)(db-/db-) were harvested, transfected with a green fluorescent protein vector, and isografted into tibial defects (150,000 living cells per defect). Alternatively, control groups were treated with Dulbecco's modified Eagle's medium or mASCs(WT). In addition, wild-type mice were identically treated. By means of immunohistochemistry, proteins specific for angiogenesis, cell proliferation, cell differentiation, and bone formation were analyzed at early (3 days) and late (7 days) stages of bone regeneration. Additionally, histomorphometry was performed to examine bone formation rate and remodeling. Histomorphometry revealed significantly increased bone formation in mASC(db-/db-)-treated diabetic mice as compared with the respective control groups. Furthermore, locally applied mASCs(db-/db-) significantly enhanced neovascularization and osteogenic differentiation. Moreover, bone remodeling was upregulated in stem cell treatment groups. Local application of mACSs can restore impaired diabetic bone regeneration and may represent a therapeutic option for the future. This study showed that stem cells obtained from fat pads of type 2 diabetic mice are capable of

  9. Cigarette smoke challenges bone marrow mesenchymal stem cell capacities in guinea pig.

    Science.gov (United States)

    Tura-Ceide, Olga; Lobo, Borja; Paul, Tanja; Puig-Pey, Raquel; Coll-Bonfill, Núria; García-Lucio, Jéssica; Smolders, Valérie; Blanco, Isabel; Barberà, Joan A; Peinado, Víctor I

    2017-03-23

    Cigarette smoke (CS) is associated with lower numbers of circulating stem cells and might severely affect their mobilization, trafficking and homing. Our study was designed to demonstrate in an animal model of CS exposure whether CS affects the homing and functional capabilities of bone marrow-derived mesenchymal stem cells (BM-MSCs). Guinea pigs (GP), exposed or sham-exposed to CS, were administered via tracheal instillation or by vascular administration with 2.5 × 10 6 BM-MSCs obtained from CS-exposed or sham-exposed animal donors. Twenty-four hours after cell administration, animals were sacrificed and cells were visualised into lung structures by optical microscopy. BM-MSCs from 8 healthy GP and from 8 GP exposed to CS for 1 month were isolated from the femur, cultured in vitro and assessed for their proliferation, migration, senescence, differentiation potential and chemokine gene expression profile. CS-exposed animals showed greater BM-MSCs lung infiltration than sham-exposed animals regardless of route of administration. The majority of BM-MSCs localized in the alveolar septa. BM-MSCs obtained from CS-exposed animals showed lower ability to engraft and lower proliferation and migration. In vitro, BM-MSCs exposed to CS extract showed a significant reduction of proliferative, cellular differentiation and migratory potential and an increase in cellular senescence in a dose dependent manner. Short-term CS exposure induces BM-MSCs dysfunction. Such dysfunction was observed in vivo, affecting the cell homing and proliferation capabilities of BM-MSCs in lungs exposed to CS and in vitro altering the rate of proliferation, senescence, differentiation and migration capacity. Additionally, CS induced a reduction in CXCL9 gene expression in the BM from CS-exposed animals underpinning a potential mechanistic action of bone marrow dysfunction.

  10. Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ali Murat Tatlı

    2013-01-01

    Full Text Available Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient’s history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage.

  11. Effects of Cynanchum wilfordii on osteoporosis with inhibition of bone resorption and induction of bone formation.

    Science.gov (United States)

    Lee, Haesu; Kim, Mi Hye; Choi, You Yeon; Hong, Jongki; Yang, Woong Mo

    2018-03-01

    Cynanchum wilfordii Hemsley has been used for the treatment of musculoskeletal diseases in traditional Republic of Korean medicine. The present study investigated the effects of C. wilfordii water extract (CW) on postmenopausal osteoporosis. Female mice were used and randomly assigned into a normal group and three ovariectomized (OVX) groups: OVX with vehicle (OVX + vehicle); OVX with 17β‑estradiol (E2; 10 µg/kg/day); and OVX with CW (1 mg/kg/day). Oral administration of CW or E2 intraperitoneal injection began 9 weeks after OVX and continued for 3 weeks. Following sacrifice, bone histology, bone mineral density (BMD) and bone mineral content (BMC) of the femur were observed. Serum osteocalcin concentration was analyzed. In addition, the expression levels of osteoprotegerin (OPG) and osterix were evaluated in human osteoblast‑like Saos‑2 cells. In the lateral and medial epicondyles of the CW‑administrated group, dense and well‑formed bone marrow cells with reduced bone marrow pores were observed. CW decreased the number of tartrate resistant acid phosphatase‑positive multinucleated osteoclasts. BMD and BMC were increased following increased serum osteocalcin levels by CW treatment. The expression levels of OPG and osterix were upregulated by CW treatment in vitro. The results suggested that C. wilfordii has an advantageous effect on osteoporosis and possesses the potential to be used in osteoporosis treatment.

  12. Geochemical and mineralogical studies of dinosaur bone from the Morrison Formation at Dinosaur Ridge

    Science.gov (United States)

    Modreski, P.J.

    2001-01-01

    The dinosaur bones first discovered in 1877 in the Upper Jurassic Morrison Formation at Morrison, Colorado were the first major find of dinosaur skeletons in the western U.S. and led to the recognition of four new dinosaur genera (Apatosaurus, Allosaurus, Diplodocus, and Stegosaurus). Eight articles dealing with these bones which appeared as research reports in the annual reports of the Friends of Dinosaur Ridge from 1990-1999 are condensed and summarized with some additional comments. Two of the articles are about the mineralogy and preservation of the bones; two are about the physical description of the bone occurrence; two are about the history of the site, and two are about use of novel instrumental methods (ground-penetrating radar and a directional scintillometer) to search for new bones.

  13. Differential Effects of Teriparatide and Denosumab on Intact PTH and Bone Formation Indices: AVA Osteoporosis Study

    Science.gov (United States)

    Zhou, Hua; Recker, Robert R.; Brown, Jacques P.; Recknor, Christopher P.; Lewiecki, E. Michael; Miller, Paul D.; Rao, Sudhaker D.; Kendler, David L.; Lindsay, Robert; Krege, John H.; Alam, Jahangir; Taylor, Kathleen A.; Janos, Boris; Ruff, Valerie A.

    2016-01-01

    Context: Denosumab-induced PTH elevation may stimulate early bone formation. Objective: Our objective was to evaluate whether denosumab-induced changes of intact PTH (iPTH) result in early anabolic effects according to histomorphometry and bone turnover markers (BTMs) compared with teriparatide, an established anabolic agent. Design: This open-label, randomized study used quadruple labeling to label bone before/after treatment, with a transiliac bone biopsy at 3 months. Setting: This study took both in both US and Canadian sites. Participants: Sixty-nine postmenopausal women with osteoporosis were included. Interventions: Teriparatide (20 μg/day) for 6 months and denosumab (60 mg once) were used in this study. Main Outcome Measure: Between-treatment comparison of change from baseline to month 3 in cancellous mineralizing surface/bone surface, histomorphometric indices in four bone envelopes, and BTM and iPTH at baseline, 1, 3, and 6 months was undertaken. Results: After denosumab, iPTH peaked at month 1 (P teriparatide, iPTH declined at all time points (P teriparatide and decreased with denosumab and at month 3, was higher with teriparatide. Similar results were observed in other bone envelopes. BTMs increased from baseline in teriparatide-treated subjects (procollagen type 1 N-terminal propeptide at month 1 and carboxyterminal cross-linking telopeptide of type 1 collagen at month 3); procollagen type 1 N-terminal propeptide and carboxyterminal cross-linking telopeptide of type 1 collagen decreased from baseline at all time points in denosumab-treated subjects. Conclusions: Denosumab treatment increased iPTH but inhibited bone formation indices. In contrast, teriparatide treatment decreased iPTH but stimulated bone formation indices. These findings are not consistent with the hypothesis of early indirect anabolic effect with denosumab. PMID:26859106

  14. Effect of Combined Calcium Hydroxide and Accelerated Portland Cement on Bone Formation and Soft Tissue Healing in Dog Bone Lesions

    Directory of Open Access Journals (Sweden)

    Khorshidi H

    2015-09-01

    Full Text Available Statement of Problem: Recent literatures show that accelerated Portland cement (APC and calcium hydroxide Ca (OH2 may have the potential to promote the bone regeneration. However, certain clinical studies reveal consistency of Ca (OH2, as one of the practical drawbacks of the material when used alone. To overcome such inconvenience, the combination of the Ca (OH2 with a bone replacement material could offer a convenient solution. Objectives: To evaluate the soft tissue healing and bone regeneration in the periodontal intrabony osseous defects using accelerated Portland cement (APC in combination with calcium hydroxide Ca (OH2, as a filling material. Materials and Methods: Five healthy adult mongrel dogs aged 2-3 years old (approximately 20 kg in weight with intact dentition and healthy periodontium were selected for this study. Two one-wall defects in both mesial and distal aspects of the 3rd premolars of both sides of the mandible were created. Therefore, four defects were prepared in each dog. Three defects in each dog were randomly filled with one of the following materials: APC alone, APC mixed with Ca (OH2, and Ca (OH2 alone. The fourth defect was left empty (control. Upon clinical examination of the sutured sites, the amount of dehiscence from the adjacent tooth was measured after two and eight weeks, using a periodontal probe mesiodistally. For histometric analysis, the degree of new bone formation was estimated at the end of the eighth postoperative week, by a differential point-counting method. The percentage of the defect volume occupied by new osteoid or trabecular bone was recorded. Results: Measurement of wound dehiscence during the second week revealed that all five APCs had an exposure of 1-2 mm and at the end of the study all samples showed 3-4 mm exposure across the surface of the graft material, whereas the Ca (OH2, control, and APC + Ca (OH2 groups did not show any exposure at the end of the eighth week of the study. The most

  15. Relation between Silver Nanoparticle Formation Rate and Antioxidant Capacity of Aqueous Plant Leaf Extracts

    Directory of Open Access Journals (Sweden)

    Azat Akbal

    2016-01-01

    Full Text Available Correlation between the antioxidant capacity and silver nanoparticle formation rates of pomegranate (Punica granatum, quince (Cydonia oblonga, chestnut (Castanea sativa, fig (Ficus carica, walnut (Juglans cinerea, black mulberry (Morus nigra, and white mulberry (Morus alba leaf extracts is investigated at a fixed illumination. Silver nanoparticles formed in all plant leaf extracts possess round shapes with average particle size of 15 to 25 nm, whereas corresponding surface plasmon resonance peak wavelengths vary between 422 nm and 451 nm. Cupric reducing antioxidant capacity technique is used as a reference method to determine total antioxidant capacity of the plant leaf extracts. Integrated absorbance over the plasmon resonance peaks exhibits better linear relation with antioxidant capacities of various plant leaf extracts compared to peak absorbance values, with correlation coefficient values of 0.9333 and 0.7221, respectively.

  16. A Bile Duct Stone Formation around a Fish Bone as a Nidus after Pancreatoduodenectomy

    Directory of Open Access Journals (Sweden)

    Tomoki Sakakida

    2018-02-01

    Full Text Available We report a rare case of bile duct stone formation around an ingested fish bone as a nidus after pancreatoduodenectomy. A 78-year-old woman was admitted to our department for fever and epigastric pain. Abdominal computed tomography revealed an elongated bile duct stone containing a linearly shaped foreign body of bone density. Enteroscopic lithotomy was performed using single balloon enteroscopy to safely remove the stone and foreign body from the bile duct. The foreign body was determined to be a fish bone by pathological examination and component analysis.

  17. The effect of enamel matrix derivative (Emdogain) on bone formation: a systematic review.

    Science.gov (United States)

    Rathe, Florian; Junker, Rüdiger; Chesnutt, Betsy M; Jansen, John A

    2009-09-01

    This systematic review focused on the question, if and to what extent enamel matrix derivative (Emdogain) [EMD]) promotes the regeneration of bone. The influence of combinations with other biomaterials was additionally evaluated. Twenty histomorphometric studies were included in this systematic review. Main results of the reviewed articles were (i) guide tissue regeneration (GTR) of infrabony defects seems to result in a higher degree of bone regeneration compared to treatment with EMD; (ii) combined therapy (GTR + EMD) of infrabony defects might not lead to better results than GTR therapy alone; (iii) there seems to be no additional benefit of combined therapy (GTR + EMD) in furcation defects over GTR therapy alone; (iv) EMD seems to lead to more bone regeneration of infrabony defects compared to open flap debridement; (v) however, EMD application might result in more bone formation when applied in supporting defects compared to nonsupporting defects; and (vi) EMD does not seem to promote external jaw/parietal bone formation in the titanium capsule model. The results of one study that suggest that EMD increases the initial growth of trabecular bone around endosseous implants by new bone induction need to be confirmed by additional research.

  18. Differential gene expression from microarray analysis distinguishes woven and lamellar bone formation in the rat ulna following mechanical loading.

    Directory of Open Access Journals (Sweden)

    Jennifer A McKenzie

    Full Text Available Formation of woven and lamellar bone in the adult skeleton can be induced through mechanical loading. Although much is known about the morphological appearance and structural properties of the newly formed bone, the molecular responses to loading are still not well understood. The objective of our study was to use a microarray to distinguish the molecular responses between woven and lamellar bone formation induced through mechanical loading. Rat forelimb loading was completed in a single bout to induce the formation of woven bone (WBF loading or lamellar bone (LBF loading. A set of normal (non-loaded rats were used as controls. Microarrays were performed at three timepoints after loading: 1 hr, 1 day and 3 days. Confirmation of microarray results was done for a select group of genes using quantitative real-time PCR (qRT-PCR. The micorarray identified numerous genes and pathways that were differentially regulated for woven, but not lamellar bone formation. Few changes in gene expression were evident comparing lamellar bone formation to normal controls. A total of 395 genes were differentially expressed between formation of woven and lamellar bone 1 hr after loading, while 5883 and 5974 genes were differentially expressed on days 1 and 3, respectively. Results suggest that not only are the levels of expression different for each type of bone formation, but that distinct pathways are activated only for woven bone formation. A strong early inflammatory response preceded an increase in angiogenic and osteogenic gene expression for woven bone formation. Furthermore, at later timepoints there was evidence of bone resorption after WBF loading. In summary, the vast coverage of the microarray offers a comprehensive characterization of the early differences in expression between woven and lamellar bone formation.

  19. Load-sharing through elastic micro-motion accelerates bone formation and interbody fusion.

    Science.gov (United States)

    Ledet, Eric H; Sanders, Glenn P; DiRisio, Darryl J; Glennon, Joseph C

    2018-02-13

    Achieving a successful spinal fusion requires the proper biological and biomechanical environment. Optimizing load-sharing in the interbody space can enhance bone formation. For anterior cervical discectomy and fusion (ACDF), loading and motion are largely dictated by the stiffness of the plate, which can facilitate a balance between stability and load-sharing. The advantages of load-sharing may be substantial for patients with comorbidities and in multilevel procedures where pseudarthrosis rates are significant. We aimed to evaluate the efficacy of a novel elastically deformable, continuously load-sharing anterior cervical spinal plate for promotion of bone formation and interbody fusion relative to a translationally dynamic plate. An in vivo animal model was used to evaluate the effects of an elastically deformable spinal plate on bone formation and spine fusion. Fourteen goats underwent an ACDF and received either a translationally dynamic or elastically deformable plate. Animals were followed up until 18 weeks and were evaluated by plain x-ray, computed tomography scan, and undecalcified histology to evaluate the rate and quality of bone formation and interbody fusion. Animals treated with the elastically deformable plate demonstrated statistically significantly superior early bone formation relative to the translationally dynamic plate. Trends in the data from 8 to 18 weeks postoperatively suggest that the elastically deformable implant enhanced bony bridging and fusion, but these enhancements were not statistically significant. Load-sharing through elastic micro-motion accelerates bone formation in the challenging goat ACDF model. The elastically deformable implant used in this study may promote early bony bridging and increased rates of fusion, but future studies will be necessary to comprehensively characterize the advantages of load-sharing through micro-motion. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Muscle paralysis induces bone marrow inflammation and predisposition to formation of giant osteoclasts.

    Science.gov (United States)

    Ausk, Brandon J; Worton, Leah E; Smigiel, Kate S; Kwon, Ronald Y; Bain, Steven D; Srinivasan, Sundar; Gardiner, Edith M; Gross, Ted S

    2017-11-01

    Transient muscle paralysis engendered by a single injection of botulinum toxin A (BTxA) rapidly induces profound focal bone resorption within the medullary cavity of adjacent bones. While initially conceived as a model of mechanical disuse, osteoclastic resorption in this model is disproportionately severe compared with the modest gait defect that is created. Preliminary studies of bone marrow following muscle paralysis suggested acute upregulation of inflammatory cytokines, including TNF-α and IL-1. We therefore hypothesized that BTxA-induced muscle paralysis would rapidly alter the inflammatory microenvironment and the osteoclastic potential of bone marrow. We tested this hypothesis by defining the time course of inflammatory cell infiltration, osteoinflammatory cytokine expression, and alteration in osteoclastogenic potential in the tibia bone marrow following transient muscle paralysis of the calf muscles. Our findings identified inflammatory cell infiltration within 24 h of muscle paralysis. By 72 h, osteoclast fusion and pro-osteoclastic inflammatory gene expression were upregulated in tibia bone marrow. These alterations coincided with bone marrow becoming permissive to the formation of osteoclasts of greater size and greater nuclei numbers. Taken together, our data are consistent with the thesis that transient calf muscle paralysis induces acute inflammation within the marrow of the adjacent tibia and that these alterations are temporally consistent with a role in mediating muscle paralysis-induced bone resorption. Copyright © 2017 the American Physiological Society.

  1. NRF2 Activation Impairs Quiescence and Bone Marrow Reconstitution Capacity of Hematopoietic Stem Cells.

    Science.gov (United States)

    Murakami, Shohei; Suzuki, Takuma; Harigae, Hideo; Romeo, Paul-Henri; Yamamoto, Masayuki; Motohashi, Hozumi

    2017-10-01

    Tissue stem cells are maintained in quiescence under physiological conditions but proliferate and differentiate to replenish mature cells under stressed conditions. The KEAP1-NRF2 system plays an essential role in stress response and cytoprotection against redox disturbance. To clarify the role of the KEAP1-NRF2 system in tissue stem cells, we focused on hematopoiesis in this study and used Keap1 -deficient mice to examine the effects of persistent activation of NRF2 on long-term hematopoietic stem cells (LT-HSCs). We found that persistent activation of NRF2 due to Keap1 deficiency did not change the number of LT-HSCs but reduced their quiescence in steady-state hematopoiesis. During hematopoietic regeneration after bone marrow (BM) transplantation, persistent activation of NRF2 reduced the BM reconstitution capacity of LT-HSCs, suggesting that NRF2 reduces the quiescence of LT-HSCs and promotes their differentiation, leading to eventual exhaustion. Transient activation of NRF2 by an electrophilic reagent also promotes the entry of LT-HSCs into the cell cycle. Taken together, our findings show that NRF2 drives the cell cycle entry and differentiation of LT-HSCs at the expense of their quiescence and maintenance, an effect that appears to be beneficial for prompt recovery from blood loss. We propose that the appropriate control of NRF2 activity by KEAP1 is essential for maintaining HSCs and guarantees their stress-induced regenerative response. Copyright © 2017 American Society for Microbiology.

  2. Effects of designed PLLA and 50:50 PLGA scaffold architectures on bone formation in vivo.

    Science.gov (United States)

    Saito, Eiji; Liao, Elly E; Hu, Wei-Wen; Krebsbach, Paul H; Hollister, Scott J

    2013-02-01

    Biodegradable porous scaffolds have been investigated as an alternative approach to current metal, ceramic, and polymer bone graft substitutes for lost or damaged bone tissues. Although there have been many studies investigating the effects of scaffold architecture on bone formation, many of these scaffolds were fabricated using conventional methods such as salt leaching and phase separation, and were constructed without designed architecture. To study the effects of both designed architecture and material on bone formation, this study designed and fabricated three types of porous scaffold architecture from two biodegradable materials, poly (L-lactic acid) (PLLA) and 50:50 Poly(lactic-co-glycolic acid) (PLGA), using image based design and indirect solid freeform fabrication techniques, seeded them with bone morphogenetic protein-7 transduced human gingival fibroblasts, and implanted them subcutaneously into mice for 4 and 8 weeks. Micro-computed tomography data confirmed that the fabricated porous scaffolds replicated the designed architectures. Histological analysis revealed that the 50:50 PLGA scaffolds degraded but did not maintain their architecture after 4 weeks implantation. However, PLLA scaffolds maintained their architecture at both time points and showed improved bone ingrowth, which followed the internal architecture of the scaffolds. Mechanical properties of both PLLA and 50:50 PLGA scaffolds decreased but PLLA scaffolds maintained greater mechanical properties than 50:50 PLGA after implantation. The increase of mineralized tissue helped support the mechanical properties of bone tissue and scaffold constructs between 4-8 weeks. The results indicate the importance of choice of scaffold materials and computationally designed scaffolds to control tissue formation and mechanical properties for desired bone tissue regeneration. Copyright © 2011 John Wiley & Sons, Ltd.

  3. Effects of bone grafting, performed with corticotomies and buccal tooth movements, on dehiscence formation in dogs.

    Science.gov (United States)

    Bare-Welchel, Britney; Campbell, Phillip M; Gonzalez, Marianela; Buschang, Peter H

    2017-06-01

    A randomized split-mouth experiment was performed in dogs to determine the effects of bone grafting, together with corticotomies and buccal tooth movements, on dehiscence formation. Bilateral full-thickness mucoperiosteal buccal flaps were raised, and corticotomies were performed with a piezosurgery unit adjacent to the maxillary second premolars in 7 dogs. The experimental (graft+) side received a demineralized freeze-dried allograph and a resorbable collagen membrane. The second premolars were expanded with archwires for 9 weeks, followed by 3 weeks of consolidation. Soft tissue measurements included probing depths, attachment loss, and recession. Tooth movements were monitored using intraoral, radiographic, and model measurements. Bone surrounding the second premolars was evaluated with microcomputed tomography. New bone formation was analyzed histologically using calcein and alizarin fluorescent labels, and hematoxylin and eosin stains. Postsurgical healing progressed normally with no signs of infection. The graft+ and control (graft-) second premolars underwent similar amounts of expansion (about 2.5 mm intraorally; about 1.7 mm radiographically) and tipping, with no statistically significant side differences. The soft tissue periodontium was not affected on either side. There were bony dehiscences on both the graft+ and graft- sides, with slightly but significantly (P = 0.038) more bone loss over the mesial root on the graft- side. Bone material density was significantly (P = 0.028) greater on the graft+ side. Buccal bone apposition was evident surrounding graft particles, and mineralized particulate graft material was present at the apical aspect of the roots on the graft+ side. Bone grafting does not prevent dehiscence formation because only a limited amount of new bone is formed, primarily at the more apical aspects of the tooth's roots. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  4. Finite element analysis of steel fiber-reinforced concrete (SFRC): validation of experimental tensile capacity of dog-bone specimens

    Science.gov (United States)

    Islam, Md. Mashfiqul; Chowdhury, Md. Arman; Sayeed, Md. Abu; Hossain, Elsha Al; Ahmed, Sheikh Saleh; Siddique, Ashfia

    2014-09-01

    Finite element analyses are conducted to model the tensile capacity of steel fiber-reinforced concrete (SFRC). For this purpose dog-bone specimens are casted and tested under direct and uniaxial tension. Two types of aggregates (brick and stone) are used to cast the SFRC and plain concrete. The fiber volume ratio is maintained 1.5 %. Total 8 numbers of dog-bone specimens are made and tested in a 1000-kN capacity digital universal testing machine (UTM). The strain data are gathered employing digital image correlation technique from high-definition images and high-speed video clips. Then, the strain data are synthesized with the load data obtained from the load cell of the UTM. The tensile capacity enhancement is found 182-253 % compared to control specimen to brick SFRC and in case of stone SFRC the enhancement is 157-268 %. Fibers are found to enhance the tensile capacity as well as ductile properties of concrete that ensures to prevent sudden brittle failure. The dog-bone specimens are modeled in the ANSYS 10.0 finite element platform and analyzed to model the tensile capacity of brick and stone SFRC. The SOLID65 element is used to model the SFRC as well as plain concretes by optimizing the Poisson's ratio, modulus of elasticity, tensile strength and stress-strain relationships and also failure pattern as well as failure locations. This research provides information of the tensile capacity enhancement of SFRC made of both brick and stone which will be helpful for the construction industry of Bangladesh to introduce this engineering material in earthquake design. Last of all, the finite element outputs are found to hold good agreement with the experimental tensile capacity which validates the FE modeling.

  5. Energy Expenditure and Bone Formation Share a Common Sensitivity to AP-1 Transcription in the Hypothalamus

    Science.gov (United States)

    Rowe, Glenn C.; Vialou, Vincent; Sato, Kazusa; Saito, Hiroaki; Yin, Min; Green, Thomas A.; Lotinun, Sutada; Kveiborg, Marie; Horne, William C.; Nestler, Eric J.; Baron, Roland

    2012-01-01

    The regulation of bone and fat homeostasis and its relationship to energy expenditure has recently been the focus of increased attention due to its potential relevance to osteoporosis, obesity and diabetes. Although central effectors within the hypothalamus have been shown to contribute to the regulation of both energy balance and bone homeostasis, little is known of the underlying mechanisms, including the possible involvement of transcriptional factors within the hypothalamus. Transgenic mice overexpressing ΔFosB, a splice variant of the AP1 transcription factor FosB with mixed agonist-antagonistic properties, have increased energy expenditure and bone mass. Since these mice express ΔFosB in bone, fat and hypothalamus, we sought to determine 1) whether overexpression of ΔFosB within the hypothalamus was sufficient to regulate energy expenditure and whether it would also regulate bone mass, and 2) whether these effects were due to antagonism to AP1. Our results show that stereotactic injection of an adeno-associated virus vector to restrict overexpression of ΔFosB to the ventral hypothalamus of wildtype mice induced a profound increase in both energy expenditure and bone formation and bone mass. This effect was phenocopied, at an even stronger level, by overexpressiong of a dominant-negative DNJunD, a pure AP1 antagonist. Taken together these results suggest that downregulation of AP1 activity in the hypothalamus profoundly increases energy expenditure and bone formation, leading to both a decrease in adipose mass and an increase in bone mass. These findings may have physiological implications since ΔFosB is expressed and regulated in the hypothalamus. PMID:22461201

  6. Nanosized Hydroxyapatite Coating on PEEK Implants Enhances Early Bone Formation: A Histological and Three-Dimensional Investigation in Rabbit Bone

    Directory of Open Access Journals (Sweden)

    Pär Johansson

    2015-06-01

    Full Text Available Polyether ether ketone (PEEK has been frequently used in spinal surgery with good clinical results. The material has a low elastic modulus and is radiolucent. However, in oral implantology PEEK has displayed inferior ability to osseointegrate compared to titanium materials. One idea to reinforce PEEK would be to coat it with hydroxyapatite (HA, a ceramic material of good biocompatibility. In the present study we analyzed HA-coated PEEK tibial implants via histology and radiography when following up at 3 and 12 weeks. Of the 48 implants, 24 were HA-coated PEEK screws (test and another 24 implants served as uncoated PEEK controls. HA-coated PEEK implants were always osseointegrated. The total bone area (BA was higher for test compared to control implants at 3 (p < 0.05 and 12 weeks (p < 0.05. Mean bone implant contact (BIC percentage was significantly higher (p = 0.024 for the test compared to control implants at 3 weeks and higher without statistical significance at 12 weeks. The effect of HA-coating was concluded to be significant with respect to early bone formation, and HA-coated PEEK implants may represent a good material to serve as bone anchored clinical devices.

  7. Is Lipid Profile Associated with Bone Mineral Density and Bone Formation in Subjects with Spinal Cord Injury?

    Directory of Open Access Journals (Sweden)

    Hadis Sabour

    2014-01-01

    Full Text Available Purpose. The association between serum lipids and bone mineral density (BMD has been investigated previously but, up to now, these relationships have not yet been described in spinal cord injury (SCI. We tried to assess the correlation between serum triglyceride (TG, total cholesterol (TC, high-density lipoprotein (HDL, and low-density lipoprotein (LDL and BMD in male subjects with SCI. Methods. Dual-energy X-ray absorptiometry (DXA was used to assess BMD in femoral neck, trochanter, intertrochanteric zone, and lumbar vertebras. Blood samples were taken to measure serums lipids and bone biomarkers including osteocalcin, cross-linked type I collagen (CTX, and bone alkaline phosphatase (BALP. Partial correlation analysis was used to evaluate the relationships between mentioned measurements after adjustment for weight and age. Results. We found a positive correlation between HDL and femoral neck BMD (P: 0.004, r=0.33. HDL was negatively correlated with osteocalcin (P: 0.017, r=-0.31 which was not in consistency with its relationship with BMD. TC and LDL were not related to CTX, BALP and BMD. Conclusion. This study does not support a strong association between serum lipids and BMD in subjects with SCI. Moreover it seems that positive association between HDL and BMD is not mediated through increased bone formation.

  8. The importance of assessing the rate of bone turnover and the balance between bone formation and bone resorption during daily teriparatide administration for osteoporosis: a pilot study.

    Science.gov (United States)

    Nakatoh, Shinichi

    2016-03-01

    This study aimed to examine the importance of simultaneously measuring bone formation and resorption markers during daily teriparatide administration. In 135 women with osteoporosis, bone mineral density (BMD) was measured at 0, 24, and 48 weeks after teriparatide administration. Bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b were measured at 0, 4, 12, 24, 36, and 48 weeks. Subanalyses were performed in groups divided according to the BMD change at 48 weeks (increased and decreased groups), history of fragility fracture (acute and chronic groups), and treatment prior to teriparatide administration (alendronate, raloxifene, and naïve groups). The scatter diagram of multiple of median formation (MoMf) and multiple of median resorption (MoMr) showed that the distribution gradually spread to a high turnover by week 24. A significant correlation was observed between the rate of change in BMD at week 48 and the turnover rate [√(MoMf(2) + MoMr(2))] at week 0. Significant differences were observed in the turnover rate between the acute and chronic groups at weeks 0 and 4 and between the groups divided according to prior treatment from week 0 to 24. Because the assessment of either bone formation markers or bone resorption markers may result in erroneous data, it is necessary to assess them together during teriparatide treatment. The turnover rate at treatment initiation is a useful indicator to predict changes in BMD. When evaluating the turnover rate and balance (MoMf/MoMr), one should consider patient characteristics, including history of fragility fracture and prior treatment.

  9. Osteogenic protein 1 device increases bone formation and bone graft resorption around cementless implants

    DEFF Research Database (Denmark)

    Jensen, Thomas B; Overgaard, Søren; Lind, Martin

    2002-01-01

    In each femoral condyle of 8 Labrador dogs, a non weight-bearing hydroxyapatite-coated implant was inserted surrounded by a 3 mm gap. Each gap was filled with bone allograft or ProOsteon with or without OP-1 delivered in a bovine collagen type I carrier (OP-1 device). 300 microg OP-1 was used...... in the 0.75 cc gap surrounding the implant. After 3 weeks, the OP-1 device enhanced implant fixation by 800% (p...

  10. Effect of gamma irradiation sterilization on the osteoinductive capacity of demineralized bone powder

    International Nuclear Information System (INIS)

    Babak Arjmand; Hamid Reza Aghayan; Mehdi Golestani; Farid Azmoudeh Ardalan

    2008-01-01

    Full text: Gamma irradiation is a well known method for secondary sterilization of bone allograft before clinical use to reduce the risk of infections and complications. The current study evaluated the effect of gamma irradiation on the osteoinductive capability of human demineralized bone powder using a rat model. Twenty rats received two separate implants consisting of 30 mg aseptically-harvested and 30 mg gamma irradiated demineralized bone powder. The implants from each group were placed into two separate muscle pouch in the paravertebral muscles of each rat. All 20 rats were euthanized after 4 weeks and each implantation site was removed with 0.5 cm normal tissue around the implant. Histological examination was done to determine the presence or absence of new bone, cartilage and bone marrow element. All except one of 20 aseptically-harvested demineralized bone powder sites histologically contained new bone elements (95%) and six (30%) of 20 gamma irradiated demineralized bone powder sites showed evidence of new bone elements. There was significant difference between two groups (p<0.05). The results of this study indicate that gamma irradiation reduces osteoinductive properties of demineralized bone powder. But because of its availability and low cost it is widely used for secondary sterilization of bone allografts. (Author)

  11. Orthotopic bone formation in titanium fiber mesh loaded with platelet-rich plasma and placed in segmental defects.

    NARCIS (Netherlands)

    Kroese-Deutman, H.C.; Vehof, J.W.M.; Spauwen, P.H.M.; Stoelinga, P.J.W.; Jansen, J.A.

    2008-01-01

    The effect of platelet-rich plasma (PRP) on bone formation was investigated in a rabbit segmental radial defect model. The purpose of the study was to evaluate the bone inductive properties of PRP with titanium fiber mesh and autologous bone chips in a 15-mm rabbit radial defect model. Eighteen New

  12. Recombinant human bone morphogenetic protein-type 2 (rhBMP-2) enhances local bone formation in the lumbar spine of osteoporotic sheep.

    Science.gov (United States)

    Zarrinkalam, Mohammad Reza; Schultz, Christopher G; Ardern, David W; Vernon-Roberts, Barrie; Moore, Robert J

    2013-09-01

    The failure of orthopedic implants in osteoporotic patients is attributed to the lack of sufficient bone stock and regenerative capacity but most treatments for osteoporosis fail to address this issue. rhBMP-2 is known to promote bone formation under normal conditions but has not been used clinically in the osteoporotic condition. Osteoporosis was induced in 19 ewes using ovariectomy, low calcium diet, and steroid injection. After induction, the steroid was withdrawn and pellets containing inert carrier with rhBMP-2 in either slow or fast-release formulation were implanted into the lumbar vertebrae of each animal. After 2, 3, and 6 months the spines were harvested and assessed for changes in BMD and histomorphometric indices. BMD did not change after cessation of steroid treatment. After 2 months BV/TV increased in the vicinity of the pellets containing the fast-release rhBMP-2 and was sustained for the duration of the study. Focal voids surrounding all implants, particularly the slow-release formulation, were observed initially but resolved with time. Increased BV/TV adjacent to rhBMP-2 pellets suggests it could be used for localized treatment of osteoporosis. Refinement of the delivery system and supplementary treatments may be necessary to overcome the initial catabolic effects of rhBMP-2. Copyright © 2013 Orthopaedic Research Society.

  13. N-terminal region of human ameloblastin synthetic peptide promotes bone formation.

    Science.gov (United States)

    Kitagawa, Masae; Ando, Toshinori; Subarnbhesaj, Ajiravudh; Uchida, Takashi; Miyauchi, Mutsumi; Takata, Takashi

    2017-01-01

    The aim of this study was to examine the effect of 16 amino acids of the N-terminal region of human ameloblastin (16N-AMBN) synthetic peptide, on the proliferation and differentiation of MC3T3-E1 cells and bone regeneration. While 16N-AMBN did not affect the proliferation, it induced mRNA expression of type I collagen, alkaline phosphatase (ALP), bone sialoprotein, and osteocalcin. 16N-AMBN also stimulated ALP activity and promoted mineralized nodule formation. On the other hand, these activities were inhibited by anti-16N-AMBN antibody. Treatment of rat calvarial bone defects with 16N-AMBN resulted in almost complete healing compared to that of the control treatments. These findings suggest that 16N-AMBN may be applicable for regeneration therapy of bone defects.

  14. Effects of static magnetic fields on bone formation in rat osteoblast cultures.

    Science.gov (United States)

    Yamamoto, Y; Ohsaki, Y; Goto, T; Nakasima, A; Iijima, T

    2003-12-01

    Although the promotional effects on osteoblasts of pulsed electromagnetic fields have been well-demonstrated, the effects of static magnetic fields (SMF) remain unclear; nevertheless, magnets have been clinically used as a 'force source' in various orthodontic treatments. We undertook the present investigation to study the effects of SMF on osteoblastic differentiation, proliferation, and bone nodule formation using a rat calvaria cell culture. During a 20-day culture, the values of the total area and the number and average size of bone nodules showed high levels in the presence of SMF. In the matrix development and mineralization stages, the calcium content in the matrix and two markers of osteoblastic phenotype (alkaline phosphatase and osteocalcin) also showed a significant increase. Accordingly, these findings suggest that SMF stimulates bone formation by promoting osteoblastic differentiation and/or activation.

  15. Evaluation of bone formation in calcium phosphate scaffolds with μCT-method validation using SEM.

    Science.gov (United States)

    Lewin, S; Barba, A; Persson, C; Franch, J; Ginebra, M-P; Öhman-Mägi, C

    2017-10-05

    There is a plethora of calcium phosphate (CaP) scaffolds used as synthetic substitutes to bone grafts. The scaffold performance is often evaluated from the quantity of bone formed within or in direct contact with the scaffold. Micro-computed tomography (μCT) allows three-dimensional evaluation of bone formation inside scaffolds. However, the almost identical x-ray attenuation of CaP and bone obtrude the separation of these phases in μCT images. Commonly, segmentation of bone in μCT images is based on gray scale intensity, with manually determined global thresholds. However, image analysis methods, and methods for manual thresholding in particular, lack standardization and may consequently suffer from subjectivity. The aim of the present study was to provide a methodological framework for addressing these issues. Bone formation in two types of CaP scaffold architectures (foamed and robocast), obtained from a larger animal study (a 12 week canine animal model) was evaluated by μCT. In addition, cross-sectional scanning electron microscopy (SEM) images were acquired as references to determine thresholds and to validate the result. μCT datasets were registered to the corresponding SEM reference. Global thresholds were then determined by quantitatively correlating the different area fractions in the μCT image, towards the area fractions in the corresponding SEM image. For comparison, area fractions were also quantified using global thresholds determined manually by two different approaches. In the validation the manually determined thresholds resulted in large average errors in area fraction (up to 17%), whereas for the evaluation using SEM references, the errors were estimated to be less than 3%. Furthermore, it was found that basing the thresholds on one single SEM reference gave lower errors than determining them manually. This study provides an objective, robust and less error prone method to determine global thresholds for the evaluation of bone formation in

  16. Effects of Weight Loss on Lean Mass, Strength, Bone, and Aerobic Capacity

    Science.gov (United States)

    Weiss, Edward P.; Jordan, Richard C.; Frese, Ethel M.; Albert, Stewart G.; Villareal, Dennis T.

    2016-01-01

    Purpose To evaluate the hypothesis that exercise attenuates the reductions in lean mass, muscle strength, BMD, and VO2max that accompany modest weight loss induced by calorie restriction. Methods Overweight, sedentary women and men (n=52, 45–65y) were randomized to 6–8% weight loss by using calorie restriction (CR), endurance exercise (EX), or both (CREX). The CR and CREX groups underwent counseling to reduce energy intake by 20% and 10%, respectively. The EX and CREX groups exercised 7.4±0.5 and 4.4±0.5 hr/wk, respectively. Before and after 16.8±1.1 weeks of weight loss, lean mass and BMD were measured with dual-energy X-ray absorptiometry, strength was measured with dynamometry, and aerobic capacity (VO2max) was measured with indirect calorimetry during maximal-intensity treadmill exercise. Results Weight loss was ~7% in all groups. Decreases in whole body (~2%, p=0.003) and lower extremity (~4%, p<0.0001) lean mass occurred in the CR group (both p<0.05). Despite similar weight loss, these reductions were attenuated in the CREX group (~1%, p=0.44 and ~2%, p=0.05, respectively) and absent in the EX group. Absolute aerobic capacity decreased ~6% in the CR group (p=0.04), was unchanged in the CREX group (p=0.28) and increased ~15% in the EX group (p<0.0001). No changes in muscle strength or bone were observed. Conclusions Modest weight loss (~7%) induced by 20% calorie restriction in overweight women and men decreases lean mass and reduces absolute VO2max. Exercise protects against these effects. While the CR-induced changes might be considered physiologically appropriate for a reduced body weight, exercise preserves and/or improves these parameters during weight loss, which likely improves physical function. These findings support the notion of using exercise as an important component of weight loss programs. PMID:27580151

  17. Estimating the carbon sequestration capacity of shale formations using methane production rates.

    Science.gov (United States)

    Tao, Zhiyuan; Clarens, Andres

    2013-10-01

    Hydraulically fractured shale formations are being developed widely for oil and gas production. They could also represent an attractive repository for permanent geologic carbon sequestration. Shales have a low permeability, but they can adsorb an appreciable amount of CO2 on fracture surfaces. Here, a computational method is proposed for estimating the CO2 sequestration capacity of a fractured shale formation and it is applied to the Marcellus shale in the eastern United States. The model is based on historical and projected CH4 production along with published data and models for CH4/CO2 sorption equilibria and kinetics. The results suggest that the Marcellus shale alone could store between 10.4 and 18.4 Gt of CO2 between now and 2030, which represents more than 50% of total U.S. CO2 emissions from stationary sources over the same period. Other shale formations with comparable pressure-temperature conditions, such as Haynesville and Barnett, could provide significant additional storage capacity. The mass transfer kinetic results indicate that injection of CO2 would proceed several times faster than production of CH4. Additional considerations not included in this model could either reinforce (e.g., leveraging of existing extraction and monitoring infrastructure) or undermine (e.g., leakage or seismicity potential) this approach, but the sequestration capacity estimated here supports continued exploration into this pathway for producing carbon neutral energy.

  18. The effects of prostaglandin E2 in growing rats - Increased metaphyseal hard tissue and cortico-endosteal bone formation

    Science.gov (United States)

    Jee, W. S. S.; Ueno, K.; Deng, Y. P.; Woodbury, D. M.

    1985-01-01

    The role of in vivo prostaglandin E2 (PGE2) in bone formation is investigated. Twenty-five male Sprague-Dawley rats weighing between 223-267 g were injected subcutaneously with 0.3, 1.0, 3.0, and 6.0 mg of PGE2-kg daily for 21 days. The processing of the tibiae for observation is described. Radiographs and histomorphometric analyses are also utilized to study bone formation. Body weight, weights of soft tissues and bones morphometry are evaluated. It is observed that PGE2 depressed longitudinal bone growth, increased growth cartilage thickness, decreased degenerative cartilage cell size and cartilage cell production, and significantly increased proximal tibial metaphyseal hard tissue mass. The data reveal that periosteal bone formation is slowed down at higher doses of PGE2 and endosteal bone formation is slightly depressed less than 10 days post injection; however, here is a late increase (10 days after post injection) in endosteal bone formation and in the formation of trabecular bone in the marrow cavity of the tibial shaft. It is noted that the effects of PGE2 on bone formation are similar to the responses of weaning rats to PGE2.

  19. Influence of fluoride in poly(d,l-lactide)/apatite composites on bone formation.

    Science.gov (United States)

    Luo, X; Barbieri, D; Passanisi, G; Yuan, H; de Bruijn, J D

    2015-05-01

    The influence of fluoride in poly(d,l-lactide)/apatite composites on ectopic bone formation was evaluated in sheep. Nano-apatite powders with different replacement levels of OH groups by fluoride (F) (0% (F0), 50% (F50), 100% (F100), and excessive (F200)) were co-extruded with poly (d,l-lactide) at a weight ratio of 1:1. Fluoride release from the composites (CF0, CF50, CF100, and CF200) was evaluated in vitro and bone formation was assessed after intramuscular implantation in sheep. After 24 weeks in simulated physiological solution, CF0 and CF50 showed negligible fluoride release, whereas it was considerable from the CF100 and CF200 composites. Histology showed that the incidence of de novo bone formation decreased in implants with increasing fluoride content indicating a negative influence of fluoride on ectopic bone formation. Furthermore, a significant decrease in resorption of the high fluoride-content composites and a reduction in the number of multinucleated giant cells were seen. These results show that instead of promoting, the presence of fluoride in poly(d,l-lactide)/apatite composites seemed to suppresses their resorption and osteoinductive potential in non-osseous sites. © 2014 Wiley Periodicals, Inc.

  20. Effects of low‑level laser therapy on osteoblastic bone formation and ...

    African Journals Online (AJOL)

    level laser therapy (LLLT) on osteoblastic bone formation and relapse during expansion of rat palatal sutures. Materials and Methods: Thirty‑two Wistar rats were randomly allocated into two groups of 16 rats each. In the first group, LLLT was ...

  1. Electromagnetic stimulation to optimize the bone regeneration capacity of gelatin-based cryogels.

    Science.gov (United States)

    Fassina, L; Saino, E; Visai, L; Schelfhout, J; Dierick, M; Van Hoorebeke, L; Dubruel, P; Benazzo, F; Magenes, G; Van Vlierberghe, S

    2012-01-01

    One of the key challenges in reconstructive bone surgery is to provide living constructs that possess the ability to integrate in the surrounding host tissue. Bone graft substitutes and biomaterials have already been widely used to heal critical-size bone defects due to trauma, tumor resection and tissue degeneration. In the present study, gelatin-based cryogels have been seeded with human SAOS-2 osteoblasts followed by the in vitro culture of the cells. In order to overcome the drawbacks associated with static culture systems, including limited diffusion and in homogeneous cell-matrix distribution, the present work describes the application of a bioreactor to physically enhance the cell culture in vitro using an electromagnetic stimulus. The results indicate that the physical stimulation of cell-seeded gelatin-based cryogels upregulates the bone matrix production. We anticipate that the scaffolds developed consisting of human bone proteins and cells could be applied for clinical purposes related to bone repair.

  2. Hedgehog signaling mediates woven bone formation and vascularization during stress fracture healing.

    Science.gov (United States)

    Kazmers, Nikolas H; McKenzie, Jennifer A; Shen, Tony S; Long, Fanxin; Silva, Matthew J

    2015-12-01

    Hedgehog (Hh) signaling is critical in developmental osteogenesis, and recent studies suggest it may also play a role in regulating osteogenic gene expression in the post-natal setting. However, there is a void of studies directly assessing the effect of Hh inhibition on post-natal osteogenesis. This study utilized a cyclic loading-induced ulnar stress fracture model to evaluate the hypothesis that Hh signaling contributes to osteogenesis and angiogenesis during stress fracture healing. Immediately prior to loading, adult rats were given GDC-0449 (Vismodegib - a selective Hh pathway inhibitor; 50mg/kg orally twice daily), or vehicle. Hh signaling was upregulated in response to stress fracture at 3 days (Ptch1, Gli1 expression), and was markedly inhibited by GDC-0449 at 1 day and 3 days in the loaded and non-loaded ulnae. GDC-0449 did not affect Hh ligand expression (Shh, Ihh, Dhh) at 1 day, but decreased Shh expression by 37% at 3 days. GDC-0449 decreased woven bone volume (-37%) and mineral density (-17%) at 7 days. Dynamic histomorphometry revealed that the 7 day callus was composed predominantly of woven bone in both groups. The observed reduction in woven bone occurred concomitantly with decreased expression of Alpl and Ibsp, but was not associated with differences in early cellular proliferation (as determined by callus PCNA staining at 3 days), osteoblastic differentiation (Osx expression at 1 day and 3 days), chondrogenic gene expression (Acan, Sox9, and Col2α1 expression at 1 day and 3 days), or bone resorption metrics (callus TRAP staining at 3 days, Rankl and Opg expression at 1 day and 3 days). To evaluate angiogenesis, vWF immunohistochemistry showed that GDC-0449 reduced fracture callus blood vessel density by 55% at 3 days, which was associated with increased Hif1α gene expression (+30%). Dynamic histomorphometric analysis demonstrated that GDC-0449 also inhibited lamellar bone formation. Lamellar bone analysis of the loaded limb (directly adjacent

  3. Differential Gene Expression from Microarray Analysis Distinguishes Woven and Lamellar Bone Formation in the Rat Ulna following Mechanical Loading

    OpenAIRE

    McKenzie, Jennifer A.; Bixby, Elise C.; Silva, Matthew J.

    2011-01-01

    Formation of woven and lamellar bone in the adult skeleton can be induced through mechanical loading. Although much is known about the morphological appearance and structural properties of the newly formed bone, the molecular responses to loading are still not well understood. The objective of our study was to use a microarray to distinguish the molecular responses between woven and lamellar bone formation induced through mechanical loading. Rat forelimb loading was completed in a single bout...

  4. Effect of caffeic acid phenethyl ester on bone formation in the expanded inter-premaxillary suture

    Directory of Open Access Journals (Sweden)

    Kazancioglu HO

    2015-12-01

    Full Text Available Hakki Oguz Kazancioglu,1 Sertac Aksakalli,2 Seref Ezirganli,1 Muhammet Birlik,2 Mukaddes Esrefoglu,3 Ahmet Hüseyin Acar1 1Department of Oral and Maxillofacial Surgery, 2Department of Orthodontics, Faculty of Dentistry, 3Department of Histology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey Background: Narrow maxilla is a common problem in orthodontics and dentofacial orthopedics. To solve this problem, a procedure called rapid maxillary expansion (RME has been used. However, relapse tendency is a major problem of RME. Although relapse tendency is not clearly understood, various treatment procedures and new application has been investigated. The present study aimed to investigate the possible effectiveness of caffeic acid phenethyl ester (CAPE on new bone formation in rat midpalatal suture after RME.Materials and methods: Twenty male Sprague Dawley rats were used in this study. The animals were randomly divided into two groups as control and CAPE group. In CAPE group, CAPE was administered systemically via intraperitoneal injection. RME procedure was performed on all animals. For this purpose, the springs were placed on the maxillary incisors of rats and activated for 5 days. After then, the springs were removed and replaced with short lengths of rectangular retaining wire for consolidation period of 15 days. At the end of the study, histomorphometric analysis was carried out to assess of new bone formation.Results: New bone formation was significantly greater in CAPE group than the control group (P<0.05. CAPE enhances new bone formation in midpalatal suture after RME.Conclusion: These results show that CAPE may decrease the time needed for retention. Keywords: rapid maxillary expansion, bone formation, caffeic acid phenethyl ester, midpalatal suture, histopathology

  5. 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.

  6. The effect of an enamel matrix derivative (Emdogain) combined with bone ceramic on bone formation in mandibular defects: a histomorphometric and immunohistochemical study in the canine.

    Science.gov (United States)

    Birang, Reza; Abouei, Mohammad Shah; Razavi, Sayed Mohammad; Zia, Peyaman; Soolari, Ahmad

    2012-01-01

    The purpose of this study was to evaluate the combination of an enamel matrix derivative (EMD) and an osteoconductive bone ceramic (BC) in improving bone regeneration. Four cylindrical cavities (6 × 6 mm) were prepared bilaterally in the mandible in three dogs. The defects were randomly assigned to four different treatments-filled with EMD/BC and covered with a nonresorbable membrane, filled with EMD/BC without membrane, membrane coverage only, or control (left untreated)-and healed for 2, 4, or 6 weeks. Harvested specimens were prepared for histologic, histomorphometric, and immunohistochemical analyses. Sites treated with EMD/BC with or without membrane showed more total bone formation and lamellar bone formation than membrane-only and control defects. There were no statistically significant differences in total bone formation between EMD/BC with or without membrane. EMD with BC might improve bone formation in osseous defects more than membrane coverage alone; the use of a membrane had no significant additive effect on total bone formation.

  7. The Effect of an Enamel Matrix Derivative (Emdogain Combined with Bone Ceramic on Bone Formation in Mandibular Defects: A Histomorphometric and Immunohistochemical Study in the Canine

    Directory of Open Access Journals (Sweden)

    Reza Birang

    2012-01-01

    Full Text Available Background. The purpose of this study was to evaluate the combination of an enamel matrix derivative (EMD and an osteoconductive bone ceramic (BC in improving bone regeneration. Materials and Methods. Four cylindrical cavities (6×6mm were prepared bilaterally in the mandible in three dogs. The defects were randomly assigned to four different treatments—filled with EMD/BC and covered with a nonresorbable membrane, filled with EMD/BC without membrane, membrane coverage only, or control (left untreated—and healed for 2, 4, or 6 weeks. Harvested specimens were prepared for histologic, histomorphometric, and immunohistochemical analyses. Results. Sites treated with EMD/BC with or without membrane showed more total bone formation and lamellar bone formation than membrane-only and control defects. There were no statistically significant differences in total bone formation between EMD/BC with or without membrane. Conclusion. EMD with BC might improve bone formation in osseous defects more than membrane coverage alone; the use of a membrane had no significant additive effect on total bone formation.

  8. Study of the involvement of allogeneic MSCs in bone formation using the model of transgenic mice.

    Science.gov (United States)

    Kuznetsova, Daria; Prodanets, Natalia; Rodimova, Svetlana; Antonov, Evgeny; Meleshina, Aleksandra; Timashev, Peter; Zagaynova, Elena

    2017-05-04

    Mesenchymal stem cells (MSCs) are thought to be the most attractive type of cells for bone repair. However, much still remains unknown about MSCs and needs to be clarified before this treatment can be widely applied in the clinical practice. The purpose of this study was to establish the involvement of allogeneic MSCs in the bone formation in vivo, using a model of transgenic mice and genetically labeled cells. Polylactide scaffolds with hydroxyapatite obtained by surface selective laser sintering were used. The scaffolds were sterilized and individually seeded with MSCs from the bone marrow of 5-week-old GFP(+) transgenic C57/Bl6 or GFP(-)C57/Bl6 mice. 4-mm-diameter critical-size defects were created on the calvarial bone of mice using a dental bur. Immediately after the generation of the cranial bone defects, the scaffolds with or without seeded cells were implanted into the injury sites. The cranial bones were harvested at either 6 or 12 weeks after the implantation. GFP(+) transgenic mice having scaffolds with unlabeled MSCs were used for the observation of the host cell migration into the scaffold. GFP(-) mice having scaffolds with GFP(+)MSCs were used to assess the functioning of the seeded MSCs. The obtained data demonstrated that allogeneic MSCs were found on the scaffolds 6 and 12 weeks post-implantation. By week 12, a newly formed bone tissue from the seeded cells was observed, without an osteogenic pre-differentiation. The host cells did not appear, and the control scaffolds without seeded cells remained empty. Besides, a possibility of vessel formation from seeded MSCs was shown, without a preliminary cell cultivation under controlled conditions.

  9. The effect of heparan sulfate application on bone formation during distraction osteogenesis.

    Science.gov (United States)

    Gdalevitch, Marie; Kasaai, Bahar; Alam, Norine; Dohin, Bruno; Lauzier, Dominique; Hamdy, Reggie C

    2013-01-01

    Bone morphogenetic proteins (BMPs) are recognized for their ability to induce bone formation in vivo and in vitro. Their osteogenic and osteoinductive properties are tightly regulated by the secretion of specific BMP antagonists, which have been shown to physically bind and sometimes be blocked by the extracellular proteoglycan heparan sulphate side chains (from hereon referred to as HS). The purpose of this study was to investigate if local application of 5 µg of HS proteoglycan to a bone regenerate site in a mouse model of distraction osteogenesis (DO) can accelerate bone healing and affect the expression of key members of the BMP signaling pathway. DO was performed on the right tibia of 115 adult male wild-type mice. At mid-distraction (day 11), half the group was injected locally with 5 µg of HS, while the other half was injected with saline. The mice were sacrificed at 2 time-points: mid-consolidation (34 days) and full consolidation (51 days). The distracted tibial zone was then collected for analysis by μCT, radiology, biomechanical testing, immunohistochemistry, and histology. While μCT data showed no statistically significant difference in bone formation, the results of biomechanical testing in stiffness and ultimate force were significantly lower in the HS-injected bones at 51 days, compared to controls. Immunohistochemistry results also suggested a decrease in expression of several key members of the BMP signaling pathway at 34 days. Furthermore, wound dehiscence and infection rates were significantly elevated in the HS group compared to the controls, which resulted in a higher rate of euthanasia in the treatment group. Our findings demonstrate that exogenous application of 5 µg of HS in the distracted gap of a murine model had a negative impact on bone and wound healing.

  10. The effect of heparan sulfate application on bone formation during distraction osteogenesis.

    Directory of Open Access Journals (Sweden)

    Marie Gdalevitch

    Full Text Available Bone morphogenetic proteins (BMPs are recognized for their ability to induce bone formation in vivo and in vitro. Their osteogenic and osteoinductive properties are tightly regulated by the secretion of specific BMP antagonists, which have been shown to physically bind and sometimes be blocked by the extracellular proteoglycan heparan sulphate side chains (from hereon referred to as HS. The purpose of this study was to investigate if local application of 5 µg of HS proteoglycan to a bone regenerate site in a mouse model of distraction osteogenesis (DO can accelerate bone healing and affect the expression of key members of the BMP signaling pathway. DO was performed on the right tibia of 115 adult male wild-type mice. At mid-distraction (day 11, half the group was injected locally with 5 µg of HS, while the other half was injected with saline. The mice were sacrificed at 2 time-points: mid-consolidation (34 days and full consolidation (51 days. The distracted tibial zone was then collected for analysis by μCT, radiology, biomechanical testing, immunohistochemistry, and histology. While μCT data showed no statistically significant difference in bone formation, the results of biomechanical testing in stiffness and ultimate force were significantly lower in the HS-injected bones at 51 days, compared to controls. Immunohistochemistry results also suggested a decrease in expression of several key members of the BMP signaling pathway at 34 days. Furthermore, wound dehiscence and infection rates were significantly elevated in the HS group compared to the controls, which resulted in a higher rate of euthanasia in the treatment group. Our findings demonstrate that exogenous application of 5 µg of HS in the distracted gap of a murine model had a negative impact on bone and wound healing.

  11. Inhibition of apoptosis signal-regulating kinase 1 enhances endochondral bone formation by increasing chondrocyte survival

    Science.gov (United States)

    Eaton, G J; Zhang, Q-S; Diallo, C; Matsuzawa, A; Ichijo, H; Steinbeck, M J; Freeman, T A

    2014-01-01

    Endochondral ossification is the result of chondrocyte differentiation, hypertrophy, death and replacement by bone. The careful timing and progression of this process is important for normal skeletal bone growth and development, as well as fracture repair. Apoptosis Signal-Regulating Kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK), which is activated by reactive oxygen species and other cellular stress events. Activation of ASK1 initiates a signaling cascade known to regulate diverse cellular events including cytokine and growth factor signaling, cell cycle regulation, cellular differentiation, hypertrophy, survival and apoptosis. ASK1 is highly expressed in hypertrophic chondrocytes, but the role of ASK1 in skeletal tissues has not been investigated. Herein, we report that ASK1 knockout (KO) mice display alterations in normal growth plate morphology, which include a shorter proliferative zone and a lengthened hypertrophic zone. These changes in growth plate dynamics result in accelerated long bone mineralization and an increased formation of trabecular bone, which can be attributed to an increased resistance of terminally differentiated chondrocytes to undergo cell death. Interestingly, under normal cell culture conditions, mouse embryonic fibroblasts (MEFs) derived from ASK1 KO mice show no differences in either MAPK signaling or osteogenic or chondrogenic differentiation when compared with wild-type (WT) MEFs. However, when cultured with stress activators, H2O2 or staurosporine, the KO cells show enhanced survival, an associated decrease in the activation of proteins involved in death signaling pathways and a reduction in markers of terminal differentiation. Furthermore, in both WT mice treated with the ASK1 inhibitor, NQDI-1, and ASK1 KO mice endochondral bone formation was increased in an ectopic ossification model. These findings highlight a previously unrealized role for ASK1 in regulating endochondral bone formation. Inhibition of ASK1 has

  12. The effect of a multicomponent dual-modality exercise program targeting osteoporosis on bone health status and physical function capacity of postmenopausal women.

    Science.gov (United States)

    Tolomio, Silvia; Ermolao, Andrea; Lalli, Alberto; Zaccaria, Marco

    2010-01-01

    Exercise is important for the prevention of osteoporosis and the reduction of fracture risk because it improves muscle mass and strength, besides improving balance. We evaluated the effect of a specific exercise program on bone mass and quality and physical function capacity in postmenopausal women with low bone mineral density. Participants (N = 125) underwent a bone mass (Dual X-ray Absorptiometry), bone quality (osteosonography), and physical functional capacity assessment. Fifty-eight of them took part in an 11-month exercise program (E), that included a multicomponent (strength, aerobic capacity, balance, joint mobility) dual-modality (on ground and in the water; alternating group and home-based exercise periods) exercise regimen. The others represented a control group (C) that did not exercise. After the exercise program all participants were reevaluated. After the training program: femoral neck T-score significantly improved in E; C significantly decreased all bone quality (osteosonography) parameters, whereas E showed no differences; E significantly improved all the physical function capacity parameters, while most of them decreased or did not change in C. A specific exercise program targeting osteoporosis improves physical function capacity, reduces physiological bone loss, and maintains bone quality in low bone mineral density postmenopausal women.

  13. Methyl cellulose gel obstructed bone formation by GBR: an experimental study in rats.

    Science.gov (United States)

    Lioubavina-Hack, Natalia; Karring, Thorkild; Lynch, Samuel E; Lindhe, Jan

    2005-12-01

    To evaluate whether bone formation under Teflon capsules may be enhanced by concomitant implantation of recombinant human platelet-derived growth factor-BB/insulin-like growth factor-I (rhPDGF-BB/IGF-I) incorporated into a methyl cellulose gel. Fifty-five male 6-month-old albino rats of the Wistar strain were used in the study. The lateral aspect of the mandibular ramus was exposed on both sides of the jaw. In 70 sites, the periosteum was removed from the ramus, leaving the bone denuded, while in 35 sites, it was preserved. On 10 non-periosteal (P-) sites and five periosteal (P+) sites, an empty rigid teflon capsule (d=7 mm), serving as control, was placed on the ramus. In the 40 test animals, the capsule placed on the one side of the jaw was filled at random with one of three different concentrations (1,200, 600, 150 microg/ml) of rhPDGF-BB/IGF-I gel. The capsules placed on the contralateral side of the jaw contained a placebo methyl cellulose gel. Each growth factor group, defined according to the gel concentration, and the placebo group contained 10 capsules placed on the P- side and five capsules placed on the P+ side. Two months after surgery, all animals were sacrificed. Histologic analysis revealed that in the non-filled control capsules, the amount of new bone including the bone marrow was 29.9% and 39.7% of the capsule area on the P- and P+ sides, respectively. In the test capsules with the growth factor gel and placed on the P-sides, the amounts of new bone ranged from 5.6% to 6.3%, which were similar (p>0.05) to that formed in the capsules filled with the methyl cellulose gel (5.5%). New bone formation was larger in the capsules on the P+ sides than in those on the P- sides but was similar in the capsules with different growth factor concentrations (range 17.9-19.6%) and in those with placebo gel (21.0%). In all groups, the carrier gel was poorly absorbed and occupied most of the capsules. Local application of a methyl cellulose gel obstructed bone

  14. Ectopic Bone Formation by Mesenchymal Stem Cells Derived from Human Term Placenta and the Decidua.

    Directory of Open Access Journals (Sweden)

    Gina D Kusuma

    Full Text Available Mesenchymal stem cells (MSCs are one of the most attractive cell types for cell-based bone tissue repair applications. Fetal-derived MSCs and maternal-derived MSCs have been isolated from chorionic villi of human term placenta and the decidua basalis attached to the placenta following delivery, respectively. Chorionic-derived MSCs (CMSCs and decidua-derived MSCs (DMSCs generated in this study met the MSCs criteria set by International Society of Cellular Therapy. These criteria include: (i adherence to plastic; (ii >90% expression of CD73, CD105, CD90, CD146, CD44 and CD166 combined with <5% expression of CD45, CD19 and HLA-DR; and (iii ability to differentiate into osteogenic, adipogenic, and chondrogenic lineages. In vivo subcutaneous implantation into SCID mice showed that both bromo-deoxyuridine (BrdU-labelled CMSCs and DMSCs when implanted together with hydroxyapatite/tricalcium phosphate particles were capable of forming ectopic bone at 8-weeks post-transplantation. Histological assessment showed expression of bone markers, osteopontin (OPN, osteocalcin (OCN, biglycan (BGN, bone sialoprotein (BSP, and also a marker of vasculature, alpha-smooth muscle actin (α-SMA. This study provides evidence to support CMSCs and DMSCs as cellular candidates with potent bone forming capacity.

  15. Transgenic Expression of Osteoactivin/gpnmb Enhances Bone Formation In Vivo and Osteoprogenitor Differentiation Ex Vivo.

    Science.gov (United States)

    Frara, Nagat; Abdelmagid, Samir M; Sondag, Gregory R; Moussa, Fouad M; Yingling, Vanessa R; Owen, Thomas A; Popoff, Steven N; Barbe, Mary F; Safadi, Fayez F

    2016-01-01

    Initial identification of osteoactivin (OA)/glycoprotein non-melanoma clone B (gpnmb) was demonstrated in an osteopetrotic rat model, where OA expression was increased threefold in mutant bones, compared to normal. OA mRNA and protein expression increase during active bone regeneration post-fracture, and primary rat osteoblasts show increased OA expression during differentiation in vitro. To further examine OA/gpnmb as an osteoinductive agent, we characterized the skeletal phenotype of transgenic mouse overexpressing OA/gpnmb under the CMV-promoter (OA-Tg). Western blot analysis showed increased OA/gpnmb in OA-Tg osteoblasts, compared to wild-type (WT). In OA-Tg mouse femurs versus WT littermates, micro-CT analysis showed increased trabecular bone volume and thickness, and cortical bone thickness; histomorphometry showed increased osteoblast numbers, bone formation and mineral apposition rates in OA-Tg mice; and biomechanical testing showed higher peak moment and stiffness. Given that OA/gpnmb is also over-expressed in osteoclasts in OA-Tg mice, we evaluated bone resorption by ELISA and histomorphometry, and observed decreased serum CTX-1 and RANK-L, and decreased osteoclast numbers in OA-Tg, compared to WT mice, indicating decreased bone remodeling in OA-Tg mice. The proliferation rate of OA-Tg osteoblasts in vitro was higher, compared to WT, as was alkaline phosphatase staining and activity, the latter indicating enhanced differentiation of OA-Tg osteoprogenitors. Quantitative RT-PCR analysis showed increased TGF-β1 and TGF-β receptors I and II expression in OA-Tg osteoblasts, compared to WT. Together, these data suggest that OA overexpression has an osteoinductive effect on bone mass in vivo and stimulates osteoprogenitor differentiation ex vivo. © 2015 Wiley Periodicals, Inc.

  16. Insulin-like growth factor I has independent effects on bone matrix formation and cell replication

    International Nuclear Information System (INIS)

    Hock, J.M.; Centrella, M.; Canalis, E.

    1988-01-01

    The effects of insulin-like growth factor-I (IGF-I) and insulin on bone matrix synthesis and bone cell replication were studied in cultured 21-day-old fetal rat calvariae. Histomorphometry techniques were developed to measure the incorporation of [2,3- 3 H]proline and [methyl- 3 H]thymidine into bone matrix and bone cell nuclei, respectively, using autoradiographs of sagittal sections of calvariae cultured with IGF-I, insulin, or vehicle for up to 96 h. To confirm an effect on bone formation, IGF-I was also studied for its effects on [ 3 H]proline incorporation into collagenase-digestible protein (CDP) and noncollagen protein and on [ 3 H]thymidine incorporation into acid-precipitable material (DNA). IGF-I at 10(-9)-10(-7) M significantly increased the rate of bone matrix apposition and CDP after 24 h by 45-50% and increased cell labeling by 8-fold in the osteoprogenitor cell zone, by 4-fold in the osteoblast cell zone, and by 2-fold in the periosteal fibroblast zone. Insulin at 10(-9)-10(-6) M also increased matrix apposition rate and CDP by 40-50%, but increased cell labeling by 2-fold only at a concentration of 10(-7) M or higher and then only in the osteoprogenitor cell zone. When hydroxyurea was added to IGF-I-treated bones, the effects of IGF-I on DNA synthesis were abolished, but the increase in bone matrix apposition induced by IGF-I was only partly diminished. In conclusion, IGF-I stimulates matrix synthesis in calvariae, an effect that is partly, although not completely, dependent on its stimulatory effect on DNA synthesis

  17. Addition of Adipose-Derived Stem Cells to Mesenchymal Stem Cell Sheets Improves Bone Formation at an Ectopic Site

    Directory of Open Access Journals (Sweden)

    Zhifa Wang

    2016-02-01

    Full Text Available To determine the effect of adipose-derived stem cells (ADSCs added to bone marrow-derived mesenchymal stem cell (MSC sheets on bone formation at an ectopic site. We isolated MSCs and ADSCs from the same rabbits. We then prepared MSC sheets for implantation with or without ADSCs subcutaneously in the backs of severe combined immunodeficiency (SCID mice. We assessed bone formation at eight weeks after implantation by micro-computed tomography and histological analysis. In osteogenic medium, MSCs grew to form multilayer sheets containing many calcium nodules. MSC sheets without ADSCs formed bone-like tissue; although neo-bone and cartilage-like tissues were sparse and unevenly distributed by eight weeks after implantation. In comparison, MSC sheets with ADSCs promoted better bone regeneration as evidenced by the greater density of bone, increased mineral deposition, obvious formation of blood vessels, large number of interconnected ossified trabeculae and woven bone structures, and greater bone volume/total volume within the composite constructs. Our results indicate that although sheets of only MSCs have the potential to form tissue engineered bone at an ectopic site, the addition of ADSCs can significantly increase the osteogenic potential of MSC sheets. Thus, the combination of MSC sheets with ADSCs may be regarded as a promising therapeutic strategy to stimulate bone regeneration.

  18. Age-related new bone formation following the use of cancellous bone-block allografts for reconstruction of atrophic alveolar ridges.

    Science.gov (United States)

    Nissan, Joseph; Kolerman, Roni; Chaushu, Liat; Vered, Marilena; Naishlos, Sarit; Chaushu, Gavriel

    2018-02-01

    An age-related decrease in the number of osteogenic progenitor cells may compromise bone augmentation. Histomorphometrical assessment of age-related new bone formation, following atrophic alveolar ridge reconstruction, using cancellous bone-block allografts. Ninety-three consecutive patients (58 females and 35 males) were referred for implant-supported restoration of 122 severe atrophic alveolar ridges. Alveolar ridge deficiency locations were classified as anterior maxilla (n = 58), posterior maxilla (n= 32), and posterior mandible (n = 32). A bony deficiency of at least 3 mm horizontally and up to 3 mm vertically according to computerized tomography (CT) in the posterior mandible and anterior maxilla, served as inclusion criteria. In the posterior maxilla, a residual alveolar ridge up to 4 mm vertically according to CT served as inclusion criteria. Augmentation was performed by the use of cancellous bone-block allografts. Bone biopsies (9-month posterior maxilla, 4 months anterior maxilla and posterior mandible) of young (≤40 years) versus older (>40 years) patients were histomorphometrically evaluated. In the posterior maxilla, no statistically significant histomorphometric differences were noted. While at the anterior maxilla and posterior mandible, statistically significant more newly formed bone was found in young versus older individuals, respectively (38.6% vs 19.8%, P = 0.04 and 69% vs 31%, P = .05). New bone formation following residual alveolar ridge bone grafting is age-related. Longer bone consolidation and healing time may be recommended for older individuals. © 2017 Wiley Periodicals, Inc.

  19. Effects of soccer vs swim training on bone formation in sedentary middle-aged women

    DEFF Research Database (Denmark)

    Mohr, Magni; Helge, Eva Wulff; Petersen, Liljan F

    2015-01-01

    PURPOSE: The present study examined the effects of 15 weeks of soccer training and two different swimming training protocols on bone turnover in sedentary middle-aged women. METHODS: Eighty-three premenopausal mildly hypertensive women [age: 45 ± 6 (±SD) years, height: 165 ± 6 cm, weight: 80.0 ± 14.......1 kg, body fat: 42.6 ± 5.7 %, systolic blood pressure/diastolic blood pressure: 138 ± 6/85 ± 3 mmHg] were randomized into soccer training (SOC, n = 21), high-intensity intermittent swimming (HS, n = 21), moderate-intensity swimming (MS, n = 21) intervention groups, and a control group (C, n = 20...... turnover markers, with concomitant increases in leg bone mass. No changes in bone formation and resorption markers were seen after prolonged submaximal or high-intensity intermittent swimming training. Thus, soccer training appears to provide a powerful osteogenic stimulus in middle-aged women....

  20. Growth hormone mitigates loss of periosteal bone formation and muscle mass in disuse osteopenic rats

    DEFF Research Database (Denmark)

    Grubbe, M-C; Thomsen, Jesper Skovhus; Nyengaard, J R

    2014-01-01

    Growth hormone (GH) is a potent anabolic agent capable of increasing both bone and muscle mass. The aim was to investigate whether GH could counteract disuse-induced loss of bone and muscle mass in a rat model. Paralysis was induced by injecting 4 IU Botox (BTX) into the muscles of the right hind...... limb. Sixty female Wistar rats, 14 weeks old, were divided into the following groups: baseline, controls, BTX, BTX+GH, and GH. GH was given at a dosage of 5 mg/kg/d for 4 weeks. Compared with controls, BTX resulted in lower periosteal bone formation rate (BFR/BS,-79%, Pbone mineral density (a......BMD, -13%, Pbone volume (BV/TV, -26%, Pbone strength (-12%, P

  1. Osteogenic capacity of nanocrystalline bone cement in a weight-bearing defect at the ovine tibial metaphysis.

    Science.gov (United States)

    Harms, Christoph; Helms, Kai; Taschner, Tibor; Stratos, Ioannis; Ignatius, Anita; Gerber, Thomas; Lenz, Solvig; Rammelt, Stefan; Vollmar, Brigitte; Mittlmeier, Thomas

    2012-01-01

    The synthetic material Nanobone(®) (hydroxyapatite nanocrystallines embedded in a porous silica gel matrix) was examined in vivo using a standardized bone defect model in the ovine tibial metaphysis. A standardized 6 × 12 × 24-mm bone defect was created below the articular surface of the medial tibia condyles on both hind legs of 18 adult sheep. The defect on the right side was filled with Nanobone(®), while the defect on the contralateral side was left empty. The tibial heads of six sheep were analyzed after 6, 12, and 26 weeks each. The histological and radiological analysis of the defect on the control side did not reveal any bone formation after the total of 26 weeks. In contrast, the microcomputed tomography analysis of the defect filled with Nanobone(®) showed a 55%, 72%, and 74% volume fraction of structures with bone density after 6, 12, and 26 weeks, respectively. Quantitative histomorphological analysis after 6, and 12 weeks revealed an osteoneogenesis of 22%, and 36%, respectively. Hematoxylin and eosin sections demonstrated multinucleated giant cells on the surface of the biomaterial and resorption lacunae, indicating osteoclastic resorptive activity. Nanobone(®) appears to be a highly potent bone substitute material with osteoconductive properties in a loaded large animal defect model, supporting the potential use of Nanobone(®) also in humans.

  2. A reversal phase arrest uncoupling the bone formation and resorption contributes to the bone loss in glucocorticoid treated ovariectomised aged sheep

    DEFF Research Database (Denmark)

    Andreasen, Christina Møller; Ding, Ming; Overgaard, Søren

    2015-01-01

    Large animals as sheep are often used as models for human osteoporosis. Our aim was therefore to determine how glucocorticoid treatment of ovariectomised sheep affects the cancellous bone, determining the cellular events within the bone remodelling process that contributes to their bone loss...... in the mononuclear reversal cells colonising the surfaces. In conclusion, glucocorticoid treatment of ovariectomised sheep induced a significant bone loss, caused by an arrest of the reversal phase, resulting in an uncoupling of the bone formation and resorption during the reversal phase, as recently demonstrated....... Twenty female sheep were assigned for two groups; an untreated control group and an ovariectomised group treated with glucocorticoids (0.6mg/kg/day, 5 times weekly) for 7months. At 7months the glucocorticoid-treated ovariectomised sheep showed a significant change in the bone microstructure revealed...

  3. Hematopoietic stem cell mobilizing agents G-CSF, cyclophosphamide or AMD3100 have distinct mechanisms of action on bone marrow HSC niches and bone formation.

    Science.gov (United States)

    Winkler, I G; Pettit, A R; Raggatt, L J; Jacobsen, R N; Forristal, C E; Barbier, V; Nowlan, B; Cisterne, A; Bendall, L J; Sims, N A; Lévesque, J-P

    2012-07-01

    The CXCR4 antagonist AMD3100 is progressively replacing cyclophosphamide (CYP) as adjuvant to granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) for autologous transplants in patients who failed prior mobilization with G-CSF alone. It has recently emerged that G-CSF mediates HSC mobilization and inhibits bone formation via specific bone marrow (BM) macrophages. We compared the effect of these three mobilizing agents on BM macrophages, bone formation, osteoblasts, HSC niches and HSC reconstitution potential. Both G-CSF and CYP suppressed niche-supportive macrophages and osteoblasts, and inhibited expression of endosteal cytokines resulting in major impairment of HSC reconstitution potential remaining in the mobilized BM. In sharp contrast, although AMD3100 was effective at mobilizing HSC, it did not suppress osteoblasts, endosteal cytokine expression or reconstitution potential of HSC remaining in the mobilized BM. In conclusion, although G-CSF, CYP and AMD3100 efficiently mobilize HSC into the blood, their effects on HSC niches and bone formation are distinct with both G-CSF and CYP targeting HSC niche function and bone formation, whereas AMD3100 directly targets HSC without altering niche function or bone formation.

  4. Twist1- and Twist2-haploinsufficiency results in reduced bone formation.

    Directory of Open Access Journals (Sweden)

    Yanyu Huang

    Full Text Available Twist1 and Twist2 are highly homologous bHLH transcription factors that exhibit extensive highly overlapping expression profiles during development. While both proteins have been shown to inhibit osteogenesis, only Twist1 haploinsufficiency is associated with the premature synostosis of cranial sutures in mice and humans. On the other hand, biallelic Twist2 deficiency causes only a focal facial dermal dysplasia syndrome or additional cachexia and perinatal lethality in certain mouse strains. It is unclear how these proteins cooperate to synergistically regulate bone formation.Twist1 floxed mice (Twist1(f/f were bred with Twist2-Cre knock-in mice (Twist2(Cre/+ to generate Twist1 and Twist2 haploinsufficient mice (Twist1(f/+; Twist2(Cre/+. X-radiography, micro-CT scans, alcian blue/alizarin red staining, trap staining, BrdU labeling, immunohistochemistry, in situ hybridizations, real-time PCR and dual luciferase assay were employed to investigate the overall skeletal defects and the bone-associated molecular and cellular changes of Twist1(f/+;Twist2(Cre/+ mice.Twist1 and Twist2 haploinsufficient mice did not present with premature ossification and craniosynostosis; instead they displayed reduced bone formation, impaired proliferation and differentiation of osteoprogenitors. These mice exhibited decreased expressions of Fgf2 and Fgfr1-4 in bone, resulting in a down-regulation of FGF signaling. Furthermore, in vitro studies indicated that both Twist1 and Twist2 stimulated 4.9 kb Fgfr2 promoter activity in the presence of E12, a Twist binding partner.These data demonstrated that Twist1- and Twist2-haploinsufficiency caused reduced bone formation due to compromised FGF signaling.

  5. Markers of bone destruction and formation and periodontitis in type 1 diabetes mellitus.

    Science.gov (United States)

    Lappin, David F; Eapen, Bob; Robertson, Douglas; Young, Jenny; Hodge, Penny J

    2009-08-01

    To determine plasma concentrations of bone metabolism markers in type 1 diabetes mellitus patients and non-diabetic and to evaluate the influence of periodontitis on biomarkers of bone formation in these patient groups. Plasma concentrations of receptor activator of nuclear factor-kappaB ligand (RANKL), osteoprotegerin (OPG), C-terminal telopeptide of type 1 collagen and osteocalcin were measured in type 1 diabetes mellitus patients (n=63) and non-diabetics (n=38) who were also subdivided on the basis of their periodontal status. Diabetics had significantly lower osteocalcin concentrations, lower RANKL to OPG ratios and higher OPG concentrations (as shown by other researchers) than non-diabetics. The ratio of RANKL to OPG was altered by the periodontal status. Osteocalcin had a negative correlation and OPG a positive correlation with the percentage of glycated haemoglobin in the blood. Because, osteocalcin, a biomarker of bone formation, is lower in patients with periodontitis and in patients with type 1 diabetes mellitus with and without periodontitis than in non-diabetics without periodontitis, this might indicate that diabetics are less able to replace bone lost during active bursts of periodontitis and explain the greater severity of disease seen in studies of patients with diabetes.

  6. Bone formation within alumina tubes: effect of calcium, manganese, and chromium dopants.

    Science.gov (United States)

    Pabbruwe, Moreica B; Standard, Owen C; Sorrell, Charles C; Howlett, C Rolfe

    2004-09-01

    Alumina tubes (1.3mm outer diameter, 0.6mm inner diameter, 15 mm length) doped with Ca, Mn, or Cr at nominal concentrations of 0.5 and 5.0 mol% were implanted into femoral medullary canals of female rats for 16 weeks. Tissue formation within tubes was determined by histology and histomorphometry. Addition of Ca to alumina promoted hypertrophic bone formation at the advancing tissue fronts and tube entrances, and appeared to retard angiogenesis by limiting ongoing cellular migration into the tube. It is speculated that the presence of a secondary phase of calcium hexaluminate, probably having a solubility greater than that of alumina, possibly increased the level of extracellular Ca and, consequently, stimulated osteoclastic activity at the bone-ceramic interface. Addition of Mn significantly enhanced osteogenesis within the tubes. However, it is not possible to determine whether phase composition or microstructure of the ceramic was responsible for this because both were significantly altered by Mn addition. Addition of Cr to the alumina apparently stimulated bone remodelling as indicated by increased cellular activity and bone resorption at the tissue-implant interface. Cr was incorporated into the alumina as a solid solution and the tissue response was speculated to be an effect of surface chemistry rather than microstructure. The work demonstrates that doping a bioinert ceramic with small amounts of specific elements can significantly alter tissue ingrowth, differentiation, and osteogenesis within a porous implant.

  7. Matrix elasticity of void-forming hydrogels controls transplanted-stem-cell-mediated bone formation

    Science.gov (United States)

    Huebsch, Nathaniel; Lippens, Evi; Lee, Kangwon; Mehta, Manav; Koshy, Sandeep T.; Darnell, Max C.; Desai, Rajiv M.; Madl, Christopher M.; Xu, Maria; Zhao, Xuanhe; Chaudhuri, Ovijit; Verbeke, Catia; Kim, Woo Seob; Alim, Karen; Mammoto, Akiko; Ingber, Donald E.; Duda, Georg N.; Mooney, David J.

    2015-12-01

    The effectiveness of stem cell therapies has been hampered by cell death and limited control over fate. These problems can be partially circumvented by using macroporous biomaterials that improve the survival of transplanted stem cells and provide molecular cues to direct cell phenotype. Stem cell behaviour can also be controlled in vitro by manipulating the elasticity of both porous and non-porous materials, yet translation to therapeutic processes in vivo remains elusive. Here, by developing injectable, void-forming hydrogels that decouple pore formation from elasticity, we show that mesenchymal stem cell (MSC) osteogenesis in vitro, and cell deployment in vitro and in vivo, can be controlled by modifying, respectively, the hydrogel’s elastic modulus or its chemistry. When the hydrogels were used to transplant MSCs, the hydrogel’s elasticity regulated bone regeneration, with optimal bone formation at 60 kPa. Our findings show that biophysical cues can be harnessed to direct therapeutic stem cell behaviours in situ.

  8. Runx2 modified dental pulp stem cells (DPSCs) enhance new bone formation during rapid distraction osteogenesis (DO).

    Science.gov (United States)

    Feng, Guijuan; Zhang, Jinlong; Feng, Xingmei; Wu, Senbin; Huang, Dan; Hu, Jing; Zhu, Songsong; Song, Donghui

    Distraction osteogenesis (DO) remains a major challenge in orthopedic and craniofacial surgery. The transplantion of mesenchymal stem cells (MSCs) could reduce the treatment period and the associated complications by increasing new bone formation during long-bone DO. Runt-related transcription factor 2 (Runx2) encodes a nuclear protein that is a pivotal regulator of osteoblast differentiation. It significantly stimulates calcium accumulation and alkaline phosphatase (ALP) activity in dental pulp stem cells (DPSCs). In this study, we investigated the effects of gene therapy using Runx2 on new bone formation during tibia DO of rabbits. The distraction gap of the rabbits was injected with adenovirus (Adv)-Runx2-green fluorescent protein (GFP)-transfected DPSCs (overexpression group, Group OE) or Adv-GFP-transfected DPSCs (negative control group, Group NC). Rabbits in the control group (Groups CON) were injected with physiologic saline. The generation of new bone tissue in the distraction gap was studied by radiographic examination, micro-computed tomography (CT) evaluation, histological analyze, and Mechanical testing at weeks 8 in the consolidation period. Excellent bone formation in the distracted callus was observed in Group OE and Group NC. Moreover, the OE group showed better bone formation and the highest bone mineral density (BMD) and bone mineral content (BMC). Group CON animals showed inadequate bone formation in the distracted callus compared to the other groups. The results suggest that gene therapy using Runx2-modified DPSCs was more effective during bone deposition and new bone formation in tibia DO. Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  9. Interfacial phenomena: an in vitro study of the effect of calcium phosphate (Ca-P) ceramic on bone formation.

    Science.gov (United States)

    Hulshoff, J E; van Dijk, K; de Ruijter, J E; Rietveld, F J; Ginsel, L A; Jansen, J A

    1998-06-05

    In previous studies we developed a RF magnetron sputter technique for the production of thin Ca-P coatings. With this technique coatings can be produced that vary in Ca/P ratio as well as in structural appearance. The aim of this investigation was to obtain more understanding of the biological behavior of these coatings by way of in vitro experiments. The effect of noncoated titanium (Ti) and three different Ca-P-sputtered surfaces on the proliferation and differentiation (morphology and matrix production) of osteoblast-like cells was studied. Proliferation was determined using counting procedures; morphology was studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fluorescent markers and energy-dispersive X-ray microanalysis (EDX) were used to obtain quantitative and compositional information about the resultant calcified extracellular matrix (ECM). Results demonstrated that proliferation of the osteoblast-like cells was significantly (p coated samples. On the other hand, more mineralized ECM was formed on the coated surfaces. In addition, TEM confirmed that the cells on the coated substrates were surrounded by ECM with collagen fibers embedded in crystallized, needle-shaped structures. On the basis of these findings, we concluded that: (1) the investigated Ca-P sputter coatings possess the capacity to activate the differentiation and expression of osteogenic cells, and (2) bone formation proceeds faster on Ca-P surfaces than on Ti substrates. Further, this bone-inductive effect appeared to be dependent on the Ca-P ratio of the deposited coatings.

  10. Capacity of bone marrow colony forming unit-fibroblasts in vitro from mice with combined radiation-burn injury

    International Nuclear Information System (INIS)

    Chen Xinghua; Luo Chengji; Guo Chaohua; Wang Ping

    1999-01-01

    Objective: To investigate the capacity of bone marrow colony forming unit-fibroblasts (CFU-F) from mice with combined radiation-burn injury. Methods: Mice were treated with 5.0 Gy γ-ray radiation alone, 15% total body surface area (TBSA) III degree burn alone or combined radiation-burn. The numbers of CFU-Fs were assayed by Dexter's method. Results: The numbers of CFU-Fs from mice with radiation and combined radiation-burn injury were significantly decreased, compared with those of controls and mice with burn injury alone (P<0.05-0.01). conclusion: The results reveal that the repairing process of bone marrow stromal cells from mice with radiation injury and combined radiation-burn injury is slow, and the combined radiation-burn injury inflicted on the stromal cells possesses the characteristic of radiation injury

  11. Effect of polygonimitin C on bone formation and resorption in human ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of polygonimitin C (PC) on bone formation and resorption in human osteoblast-like MG63 cells. Methods: MG63 cells were treated with PC at doses of 0, 20, 40 or 80 μg/mL for 48 h, with an untreated group as control. The effect of PC on alkaline phosphatase (ALP) activity in MG63 cells ...

  12. New experimental heat capacity and enthalpy of formation of lithium cobalt oxide

    International Nuclear Information System (INIS)

    Gotcu-Freis, Petronela; Cupid, Damian M.; Rohde, Magnus; Seifert, Hans J.

    2015-01-01

    Highlights: • LiCoO 2 heat capacity was measured in the temperature range (160 to 953) K using DSC. • Continuous/discontinuous methods were applied on different types of calorimeters. • Enthalpy increment of LiCoO 2 was determined using drop calorimetry at T = 974 K. • Enthalpies of formation were evaluated from oxide melt drop solution calorimetry. - Abstract: The heat capacity of LiCoO 2 (O3-phase), constituent material in cathodes for lithium-ion batteries, was measured using two differential scanning calorimeters over the temperature range from (160 to 953) K (continuous method). As an alternative, the discontinuous method was employed over the temperature range from (493 to 693) K using a third calorimeter. Based on the results obtained, the enthalpy increment of LiCoO 2 was derived from T = 298.15 K up to 974.15 K. Very good agreement was obtained between the derived enthalpy increment and our independent measurements of enthalpy increment using transposed temperature drop calorimetry at 974.15 K. In addition, values of the enthalpy of formation of LiCoO 2 from the constituent oxides and elements were assessed based on measurements of enthalpy of dissolution using high temperature oxide melt drop solution calorimetry. The high temperature values obtained by these measurements are key input data in safety analysis and optimisation of the battery management systems which accounts for possible thermal runaway events

  13. Oxalate-Degrading Capacities of Gastrointestinal Lactic Acid Bacteria and Urinary Tract Stone Formation

    Directory of Open Access Journals (Sweden)

    Mohammad Kargar

    2013-10-01

    Full Text Available Background: Calcium oxalate is one the most significant causes of human kidney stones. Increasing oxalate uptake results in increased urinary oxalate. Elevated urinary oxalate is one the most important causes of kidney stone formation. This study aims to evaluate oxalate-degrading capacity of lactic acid bacteria and its impact on incidence of kidney stone.Materials and Methods: This case-control study was conducted on serum, urinary, and fecal samples. The research population included a total of 200 subjects divided in two equal groups. They were selected from the patients with urinary tract stones, visiting urologist, and also normal people. The level of calcium, oxalate, and citrate in the urinary samples, parathyroid and calcium in the serum samples, and degrading activity of fecal lactobacillus strains of all the subjects were evaluated. Then, data analysis was carried out using SPSS-11.5, χ2 test, Fisher’s exact test, and analysis of variance. Results: The results revealed that the patients had higher urinary level of oxalate and calcium, as well as higher serum level of parathyroid hormone than normal people. In contrast, urinary level of citrate was higher in normal people. In addition, there was a significant difference between the oxalate-degrading capacities of lactobacillus isolated from the patients and their normal peers.Conclusion: Reduction of digestive lactobacillus-related oxalate-degrading capacity and increased serum level of parathyroid hormone can cause elevated urinary level of oxalate and calcium in people with kidney stone.

  14. Tetraspanin 7 regulates sealing zone formation and the bone-resorbing activity of osteoclasts

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jun-Oh; Lee, Yong Deok; Kim, Haemin; Kim, Min Kyung; Song, Min-Kyoung; Lee, Zang Hee; Kim, Hong-Hee, E-mail: hhbkim@snu.ac.kr

    2016-09-02

    Tetraspanin family proteins regulate morphology, motility, fusion, and signaling in various cell types. We investigated the role of the tetraspanin 7 (Tspan7) isoform in the differentiation and function of osteoclasts. Tspan7 was up-regulated during osteoclastogenesis. When Tspan7 expression was reduced in primary precursor cells by siRNA-mediated gene knock-down, the generation of multinuclear osteoclasts was not affected. However, a striking cytoskeletal abnormality was observed: the formation of the podosome belt structure was inhibited and the microtubular network were disrupted by Tspan7 knock-down. Decreases in acetylated microtubules and levels of phosphorylated Src and Pyk2 in Tspan7 knock-down cells supported the involvement of Tspan7 in cytoskeletal rearrangement signaling in osteoclasts. This cytoskeletal defect interfered with sealing zone formation and subsequently the bone-resorbing activity of mature osteoclasts on dentin surfaces. Our results suggest that Tspan7 plays an important role in cytoskeletal organization required for the bone-resorbing function of osteoclasts by regulating signaling to Src, Pyk2, and microtubules. - Highlights: • Tspan7 expression is up-regulated during osteoclastogenesis. • Tspan7 regulates podosome belt organization in osteoclasts. • Tspan7 is crucial for sealing zone formation and bone-resorption by osteoclasts. • Src and Pyk2 phosphorylation and microtubule acetylation mediate Tspan7 function.

  15. Eldecalcitol improves mechanical strength of cortical bones by stimulating the periosteal bone formation in the senescence-accelerated SAM/P6 mice - a comparison with alfacalcidol.

    Science.gov (United States)

    Shiraishi, Ayako; Sakai, Sadaoki; Saito, Hitoshi; Takahashi, Fumiaki

    2014-10-01

    Eldecalcitol (ELD), a 2β-hydroxypropyloxy derivative of 1α,25(OH)2D3, is a potent inhibitor of bone resorption that has demonstrated a greater effect at reducing the risk of fracture in osteoporotic patients than alfacalcidol (ALF). In the present study, we used the senescence-accelerated mouse strain P6 (SAM/P6), which has low bone mass caused by osteoblast dysfunction, to evaluate the effect of ELD on cortical bone in comparison with ALF. Four-month-old SAM/P6 mice were given either ELD (0.025 or 0.05μg/kg) or ALF (0.2 or 0.4μg/kg) by oral gavage 5 times/week for 6 weeks. Both ELD and ALF increased serum calcium (Ca) in a dose-dependent manner. Serum Ca levels in the ELD 0.05μg/kg group were comparable to those of the ALF 0.2μg/kg group. ELD 0.05μg/kg significantly improved the bone biomechanical properties of the femur compared with the vehicle control group (pBone histomorphometry revealed that in the femoral endocortical surface, the suppression of bone resorption parameters (N.Oc/BS) and bone formation parameters (MS/BS) by ELD (0.05μg/kg) was greater than that by ALF (0.2μg/kg). In contrast, in the femoral periosteal surface, ELD 0.05μg/kg significantly increased bone formation parameters (BFR/BS, MS/BS) compared with the vehicle control group (pbone not only by inhibiting endocortical bone resorption but also by stimulating the periosteal bone formation in SAM/P6 mice. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Sequential Treatment with SDF-1 and BMP-2 Potentiates Bone Formation in Calvarial Defects.

    Science.gov (United States)

    Hwang, Hee-Don; Lee, Jung-Tae; Koh, Jeong-Tae; Jung, Hong-Moon; Lee, Heon-Jin; Kwon, Tae-Geon

    2015-07-01

    Stromal cell-derived factor-1 (SDF-1) protein and its receptor, CXCR-4, play an important role in tissue repair and regeneration in various organs, including the bone. SDF-1 is indispensable for bone morphogenetic protein-2 (BMP-2)-induced osteogenic differentiation. However, SDF-1 is not needed after the osteogenic induction has been activated. Since the precise condition for the additive effects of combined DF-1 and BMP-2 in bone healing had not been fully investigated, we aimed to determine the optimal conditions for SDF-1- and BMP-2-mediated bone regeneration. We examined the in vitro osteoblastic differentiation and cell migration after sequential treatments with SDF-1 and BMP-2. Based on the in vitro additive effects of SDF-1 and BMP-2, the critical size defects of mice calvaria were treated with these cytokines in various sequences. Phosphate buffered saline (PBS)-, SDF-1-, or BMP-2-soaked collagen scaffolds were implanted into the calvarial defects (n=36). Periodic percutaneous injections of PBS or the cytokine SDF-1 and BMP-2 into the implanted scaffolds were performed on days 3 and 6, postoperatively. Six experimental groups were used according to the types and sequences of the cytokine treatments. After 28 days, the mice were euthanized and bone formation was evaluated with microcomputed tomography and histology. The molecular mechanism of the additive effect of SDF-1 and BMP-2 was evaluated by analyzing intracellular signal transduction through Smad and Erk phosphorylation. The in vitro experiments revealed that, among all the treatments, the treatment with BMP-2 after SDF-1 showed the strongest osteoblastic differentiation and enhanced cell migration. Similarly, in the animal model, the treatment with SDF-1 followed by BMP-2 treatment showed the highest degree of new bone regeneration than any other groups, including the one with continuous BMP-2 treatment. This new bone formation can be partially explained by the activation of Smad and Erk pathways

  17. 3D perfusion bioreactor-activated porous granules on implant fixation and early bone formation in sheep

    DEFF Research Database (Denmark)

    Ding, Ming; Snoek Henriksen, Susan; Martinetti, Roberta

    2017-01-01

    Early fixation of total joint arthroplasties is crucial for ensuring implant survival. An alternative bone graft material in revision surgery is needed to replace the current gold standard, allograft, seeing that the latter is associated with several disadvantages. The incubation...... of such a construct in a perfusion bioreactor has been shown to produce viable bone graft materials. This study aimed at producing larger amounts of viable bone graft material (hydroxyapatite 70% and β-tricalcium-phosphate 30%) in a novel perfusion bioreactor. The abilities of the bioreactor-activated graft material...... allograft, granules, granules with bone marrow aspirate or bioreactor-activated graft material. Following an observation time of 6 weeks, early implant fixation and bone formation were assessed by micro-CT scanning, mechanical testing, and histomorphometry. Bone formations were seen in all groups, while...

  18. Building Innovation Capacity: The Role of Human Capital Formation in Enterprises--A Review of the Literature. Occasional Paper

    Science.gov (United States)

    Smith, Andrew; Courvisanos, Jerry; Tuck, Jacqueline; McEachern, Steven

    2011-01-01

    This literature review examines the role of human capital formation in building innovative capacity in firms. The aim of the review is to develop a model of human capital development factors to be used as a basis for a larger research project where the factors that develop innovation capacity in enterprises will be investigated. The review finds…

  19. Osteogenic capacity of nanocrystalline bone cement in a weight-bearing defect at the ovine tibial metaphysis

    Directory of Open Access Journals (Sweden)

    Mittlmeier T

    2012-06-01

    Full Text Available Christoph Harms,1 Kai Helms,1 Tibor Taschner,1 Ioannis Stratos,1 Anita Ignatius,5 Thomas Gerber,2 Solvig Lenz,3 Stefan Rammelt,6 Brigitte Vollmar,4 Thomas Mittlmeier11Department of Trauma and Reconstructive Surgery, 2Department for Materials Research and Nanostructures, Institute for Physics, 3Department of Oral and Maxillofacial Plastic Surgery, 4Institute for Experimental Surgery, University of Rostock, Rostock, 5Institute of Orthopaedic Research and Biomechanics, University of Ulm, Ulm, 6Clinic of Trauma and Reconstructive Surgery, University Hospital "Carl Gustav Carus", Dresden, GermanyAbstract: The synthetic material Nanobone® (hydroxyapatite nanocrystallines embedded in a porous silica gel matrix was examined in vivo using a standardized bone defect model in the ovine tibial metaphysis. A standardized 6 × 12 × 24-mm bone defect was created below the articular surface of the medial tibia condyles on both hind legs of 18 adult sheep. The defect on the right side was filled with Nanobone®, while the defect on the contralateral side was left empty. The tibial heads of six sheep were analyzed after 6, 12, and 26 weeks each. The histological and radiological analysis of the defect on the control side did not reveal any bone formation after the total of 26 weeks. In contrast, the microcomputed tomography analysis of the defect filled with Nanobone® showed a 55%, 72%, and 74% volume fraction of structures with bone density after 6, 12, and 26 weeks, respectively. Quantitative histomorphological analysis after 6, and 12 weeks revealed an osteoneogenesis of 22%, and 36%, respectively. Hematoxylin and eosin sections demonstrated multinucleated giant cells on the surface of the biomaterial and resorption lacunae, indicating osteoclastic resorptive activity. Nanobone® appears to be a highly potent bone substitute material with osteoconductive properties in a loaded large animal defect model, supporting the potential use of Nanobone® also in

  20. Flow cytometric cell sorting and in vitro pre-osteoinduction are not requirements for in vivo bone formation by human adipose-derived stromal cells.

    Science.gov (United States)

    Liu, Yunsong; Zhao, Yan; Zhang, Xiao; Chen, Tong; Zhao, Xianghui; Ma, Gui-e; Zhou, Yongsheng

    2013-01-01

    Human adipose-derived stromal cells (hASCs) are a promising cell source for bone tissue engineering. However, before the clinical application of hASCs for the treatment of bone defects, key questions require answers, including whether pre-osteoinduction (OI) and flow cytometric cell purification are indispensible steps for in vivo bone formation by hASCs. In this study, hASCs were purified by flow cytometric cell sorting (FCCS). The osteogenic capabilities of hASCs and purified hASCs with or without pre-osteoinduction were examined through in vitro and in vivo experiments. We found that pre-OI enhanced the in vitro osteogenic capacity of hASCs. However, 8 weeks after in vivo implantation, there were no significant differences between hASCs and hASCs that had undergone OI (hASCs+OI) or between purified hASCs and purified hASCs+OI (P>0.05). Interestingly, we also found that purified hASCs had an osteogenic potential similar to that of unpurified hASCs in vitro and in vivo. These results suggest that FCCS and in vitro pre-OI are not requirements for in vivo bone formation by hASCs.

  1. Flow cytometric cell sorting and in vitro pre-osteoinduction are not requirements for in vivo bone formation by human adipose-derived stromal cells.

    Directory of Open Access Journals (Sweden)

    Yunsong Liu

    Full Text Available Human adipose-derived stromal cells (hASCs are a promising cell source for bone tissue engineering. However, before the clinical application of hASCs for the treatment of bone defects, key questions require answers, including whether pre-osteoinduction (OI and flow cytometric cell purification are indispensible steps for in vivo bone formation by hASCs. In this study, hASCs were purified by flow cytometric cell sorting (FCCS. The osteogenic capabilities of hASCs and purified hASCs with or without pre-osteoinduction were examined through in vitro and in vivo experiments. We found that pre-OI enhanced the in vitro osteogenic capacity of hASCs. However, 8 weeks after in vivo implantation, there were no significant differences between hASCs and hASCs that had undergone OI (hASCs+OI or between purified hASCs and purified hASCs+OI (P>0.05. Interestingly, we also found that purified hASCs had an osteogenic potential similar to that of unpurified hASCs in vitro and in vivo. These results suggest that FCCS and in vitro pre-OI are not requirements for in vivo bone formation by hASCs.

  2. Increase of homogenous new bone formation using osteoinductive factor rhGDF-5 during sinus floor augmentation in Goettingen Minipigs.

    Science.gov (United States)

    Brockmeyer, Phillipp; Lange, Katharina; Hahn, Wolfram; Schliephake, Henning; Matthias Gruber, Rudolf

    2015-11-01

    The aim of this study was to test the hypothesis that recombinant human growth and differentiation factor-5 (rhGDF-5) induces an increased and homogenous distribution of new bone formation across the entire volume of sinus floor augmentation in 12 Goettingen Minipigs. In a randomized split-mouth design, one maxillary sinus was augmented with the bone substitute β-TCP, whereas a combination of β-TCP and the osteoinductive growth factor rhGDF-5 was used on the contralateral side. To evaluate the influence of dose and time on the effectiveness of the factor, two different concentrations of rhGDF-5 (400 μg and 800 μg) and healing periods (4 and 12 weeks) were each analysed. After 4 weeks, a homogenous gradient of bone formation could be observed for all dosage groups, with decreasing bone density from the local bone towards the sinus membrane. Both test groups, however, achieved a higher total level of bone formation compared with the control group, which was only significant in the low-dose group (P = 0.0184). After 12 weeks, the influence of the growth factor significantly depends on the region (P = 0.023). In the low-dose group, the new bone formation did not differ significantly within the examined regions of the graft (P = 0.1118), suggesting a homogeneous bone formation over the entire augmentation. The gradient of the high-dose group was similar to the control group with a decrease of local bone development. rhGDF-5 delivered on a β-TCP scaffold material leads to an increase in homogeneous new bone formation across the entire volume of the sinus floor augmentation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Glycation of human cortical and cancellous bone captures differences in the formation of Maillard reaction products between glucose and ribose.

    Directory of Open Access Journals (Sweden)

    Grażyna E Sroga

    Full Text Available To better understand some aspects of bone matrix glycation, we used an in vitro glycation approach. Within two weeks, our glycation procedures led to the formation of advanced glycation end products (AGEs at the levels that corresponded to approx. 25-30 years of the natural in vivo glycation. Cortical and cancellous bones from human tibias were glycated in vitro using either glucose (glucosylation or ribose (ribosylation. Both glucosylation and ribosylation led to the formation of higher levels of AGEs and pentosidine (PEN in cancellous than cortical bone dissected from all tested donors (young, middle-age and elderly men and women. More efficient glycation of bone matrix proteins in cancellous bone most likely depended on the higher porosity of this tissue, which facilitated better accessibility of the sugars to the matrix proteins. Notably, glycation of cortical bone from older donors led to much higher AGEs levels as compared to young donors. Such efficient in vitro glycation of older cortical bone could result from aging-related increase in porosity caused by the loss of mineral content. In addition, more pronounced glycation in vivo would be driven by elevated oxidation processes. Interestingly, the levels of PEN formation differed pronouncedly between glucosylation and ribosylation. Ribosylation generated very high levels of PEN (approx. 6- vs. 2.5-fold higher PEN level than in glucosylated samples. Kinetic studies of AGEs and PEN formation in human cortical and cancellous bone matrix confirmed higher accumulation of fluorescent crosslinks for ribosylation. Our results suggest that in vitro glycation of bone using glucose leads to the formation of lower levels of AGEs including PEN, whereas ribosylation appears to support a pathway toward PEN formation. Our studies may help to understand differences in the progression of bone pathologies related to protein glycation by different sugars, and raise awareness for excessive sugar

  4. Effect of a xenograft on early bone formation in extraction sockets: an experimental study in dog.

    Science.gov (United States)

    Araújo, M; Linder, E; Lindhe, J

    2009-01-01

    The aim of this study was to study the effect on early bone formation resulting from the placement of a xenograft in the fresh extraction socket in dogs. Five beagle dogs were used. The distal roots of the third and fourth mandibular premolars were removed. In one quadrant, a graft consisting of Bio-Oss Collagen was placed in the fresh extraction wound, while the corresponding premolar sites in the contra-lateral jaw quadrant were left non-grafted. After 2 weeks of healing, the dogs were perfused with a fixative, the mandibles removed, the experimental sites dissected, demineralized, sectioned in the mesio-distal plane and stained in hematoxyline-eosine. The central portion of the non-grafted sockets was occupied by a provisional matrix comprised of densely packed connective tissue fibers and mesenchymal cells. Apical and lateral to the provisional matrix, newly formed woven bone was found to occupy most of the sockets. In the apical part of the grafted sockets, no particles of the xenograft could be observed but newly formed bone was present in this portion of the experimental site. In addition, limited numbers of woven bone trabeculae occurred along the lateral socket walls. The central and marginal segments of the grafted sockets, however, were occupied by a non-mineralized connective tissue that enclosed Bio-Oss particles that frequently were coated by multinucleated cells. The placement of Bio-Oss Collagen in the fresh extraction wound obviously delayed socket healing. Thus, after 2 weeks of tissue repair, only minute amounts of newly formed bone occurred in the apical and lateral borders of the grafted sockets, while large amounts of woven bone had formed in most parts of the non-grafted sites.

  5. Effects of calcium phosphate/chitosan composite on bone healing in rats: calcium phosphate induces osteon formation.

    Science.gov (United States)

    Fernández, Tulio; Olave, Gilberto; Valencia, Carlos H; Arce, Sandra; Quinn, Julian M W; Thouas, George A; Chen, Qi-Zhi

    2014-07-01

    Vascularization of an artificial graft represents one of the most significant challenges facing the field of bone tissue engineering. Over the past decade, strategies to vascularize artificial scaffolds have been intensively evaluated using osteoinductive calcium phosphate (CaP) biomaterials in animal models. In this work, we observed that CaP-based biomaterials implanted into rat calvarial defects showed remarkably accelerated formation and mineralization of new woven bone in defects in the initial stages, at a rate of ∼60 μm/day (0.8 mg/day), which was considerably higher than normal bone growth rates (several μm/day, 0.1 mg/day) in implant-free controls of the same age. Surprisingly, we also observed histological evidence of primary osteon formation, indicated by blood vessels in early-region fibrous tissue, which was encapsulated by lamellar osteocyte structures. These were later fully replaced by compact bone, indicating complete regeneration of calvarial bone. Thus, the CaP biomaterial used here is not only osteoinductive, but vasculogenic, and it may have contributed to the bone regeneration, despite an absence of osteons in normal rat calvaria. Further investigation will involve how this strategy can regulate formation of vascularized cortical bone such as by control of degradation rate, and use of models of long, dense bones, to more closely approximate repair of human cortical bone.

  6. Differential intensity-dependent effects of pulsed electromagnetic fields on RANKL-induced osteoclast formation, apoptosis, and bone resorbing ability in RAW264.7 cells.

    Science.gov (United States)

    Wang, Pan; Liu, Juan; Yang, Yuefan; Zhai, Mingming; Shao, Xi; Yan, Zedong; Zhang, Xuhui; Wu, Yan; Cao, Lu; Sui, Bingdong; Luo, Erping; Jing, Da

    2017-12-01

    Pulsed electromagnetic fields (PEMF) have been proven to be effective for promoting bone mass and regulating bone turnover both experimentally and clinically. However, the exact mechanisms for the regulation of PEMF on osteoclastogenesis as well as optical exposure parameters of PEMF on inhibiting osteoclastic activities and functions remain unclear, representing significant limitations for extensive scientific application of PEMF in clinics. In this study, RAW264.7 cells incubated with RANKL were exposed to 15 Hz PEMF (2 h/day) at various intensities (0.5, 1, 2, and 3 mT) for 7 days. We demonstrate that bone resorbing capacity was significantly decreased by 0.5 mT PEMF mainly by inhibiting osteoclast formation and maturation, but enhanced at 3 mT by promoting osteoclast apoptosis. Moreover, gene expression of RANK, NFATc1, TRAP, CTSK, BAX, and BAX/BCL-2 was significantly decreased by 0.5 mT PEMF, but increased by 3 mT. Our findings reveal a significant intensity window for low-intensity PEMF in regulating bone resorption with diverse nature for modulating osteoclastogenesis and apoptosis. This study not only enriches our basic knowledge for the regulation of PEMF in osteoclastogenesis, but also may lead to more efficient and scientific clinical application of PEMF in regulating bone turnover and inhibiting osteopenia/osteoporosis. Bioelectromagnetics. 38:602-612, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Formation of Cell-To-Cell Connection between Bone Marrow Cells and Isolated Rat Cardiomyocytes in a Cocultivation Model

    Czech Academy of Sciences Publication Activity Database

    Skopalík, J.; Pásek, Michal; Rychtárik, M.; Koristek, Z.; Gabrielová, E.; Sheer, P.; Matejovič, P.; Modrianský, M.; Klabusay, M.

    2014-01-01

    Roč. 5, č. 5 (2014), s. 1000185 ISSN 2157-7013 Institutional support: RVO:61388998 Keywords : bone marrow * mononuclear cells * isolated cardiomyocytes * cocultivation Subject RIV: BO - Biophysics http://omicsonline.org/ open - access /formation-of-celltocell-connection-between-bone-marrow-cells- and -isolated-rat-cardiomyocytes-2157-7013.1000185.php?aid=33364

  8. Efficacy of a small cell-binding peptide coated hydroxyapatite substitute on bone formation and implant fixation in sheep

    DEFF Research Database (Denmark)

    Ding, Ming; Andreasen, Christina Møller; Dencker, Mads L.

    2015-01-01

    hydroxyapatite (ABM/P-15); hydroxyapatite + βtricalciumphosphate+ Poly-Lactic-Acid (HA/βTCP-PDLLA); or ABM/P-15+HA/βTCP-PDLLA. After nine weeks, bone-implant blocks were harvested and sectioned for micro-CT scanning, push-out test, and histomorphometry. Significant bone formation and implant fixation could...

  9. Evaluation of bone regenerative capacity in rats claverial bone defect using platelet rich fibrin with and without beta tri calcium phosphate bone graft material

    Directory of Open Access Journals (Sweden)

    Walid Ahmed Abdullah

    2016-07-01

    Conclusion: The addition of β-TCP to PRF significantly improved bone regeneration in the first 2 weeks after surgery. Although the differences between results with and without the addition of β-TCP to PRF were statistically insignificant from weeks 3 to 6, it was nevertheless apparent that the group receiving the combination showed better results. We suggest a synergistic mechanism for this effect.

  10. Effects of soccer vs swim training on bone formation in sedentary middle-aged women.

    Science.gov (United States)

    Mohr, Magni; Helge, Eva W; Petersen, Liljan F; Lindenskov, Annika; Weihe, Pál; Mortensen, Jann; Jørgensen, Niklas R; Krustrup, Peter

    2015-12-01

    The present study examined the effects of 15 weeks of soccer training and two different swimming training protocols on bone turnover in sedentary middle-aged women. Eighty-three premenopausal mildly hypertensive women [age: 45 ± 6 (± SD) years, height: 165 ± 6 cm, weight: 80.0 ± 14.1 kg, body fat: 42.6 ± 5.7 %, systolic blood pressure/diastolic blood pressure: 138 ± 6/85 ± 3 mmHg] were randomized into soccer training (SOC, n = 21), high-intensity intermittent swimming (HS, n = 21), moderate-intensity swimming (MS, n = 21) intervention groups, and a control group (C, n = 20). The training groups completed three sessions per week for 15 weeks. DXA scans were performed and resting blood samples were drawn pre- and post-intervention. In SOC, plasma osteocalcin, procollagen type I N propeptide and C-terminal telopeptide increased (P soccer training with sedentary middle-aged women caused marked increases in bone turnover markers, with concomitant increases in leg bone mass. No changes in bone formation and resorption markers were seen after prolonged submaximal or high-intensity intermittent swimming training. Thus, soccer training appears to provide a powerful osteogenic stimulus in middle-aged women.

  11. Anti-osteoporosis activity of a novel Achyranthes bidentata polysaccharide via stimulating bone formation.

    Science.gov (United States)

    Zhang, Shaojie; Zhang, Qian; Zhang, Dawei; Wang, Changsheng; Yan, Chunyan

    2018-03-15

    Achyranthes bidentata is an important Traditional Chinese Medicine for the treatment of osteoporosis. In this study, A. bidentata polysaccharide (ABPB), which was extracted with alkali from the root of A. bidentata at room temperature, significantly increased the bone mineral density, bone mineral content, trabecular thickness, trabecular number and biomechanical properties of ovariectomized (OVX) rats, indicating that ABPB had prominent curative effects on osteoporosis in OVX rats. A novel polysaccharide (ABPB-3) was purified from ABPB, and its structure was characterized as a repeating unit consisting of →4)-α-d-GalpA-(1→, →2,4)-α-l-Rhap-(1→, →5)-α-l-Araf-(1→, →2,3,5)-α-l-Araf-(1→, →3)-β-d-Galp-(1→, →3,4,6)-β-d-Galp-(1→, terminated with α-l-Araf, α-l-Rhap and β-d-Galp. Up to now, there were no literature reports relevant to the structure of ABPB-3. In the zebrafish model of glucocorticoid-induced osteoporosis (GIOP), ABPB-3 significantly increased the relative fluorescence intensity of the skull bone mass in a concentration-dependent manner, indicating that it stimulated bone formation activity. Thus, ABPB and ABPB-3 have the potential to be used for the anti-osteoporosis medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Organization and quantification of the collagen fibers in bone formation during orthodontic tooth movement.

    Science.gov (United States)

    Retamoso, Luciana Borges; da Cunha, Taís De Morais Alves; Knop, Luégya Amorin Henriques; Shintcovsk, Ricardo Lima; Tanaka, Orlando Motohiro

    2009-12-01

    The organic matrix of alveolar bone is composed fundamentally of type I collagen. Polarized light microscopy provides unique information about the structure, composition and polymerization degree of a variety of organic and inorganic tissues that is not available with other techniques. The aim of this research was to compare two methodologies of polarized light analysis for collagen organization in bone formation during orthodontic tooth movement and determined maturity of collagen over the time. Thirty Wistar rats were euthanized 3, 7 and 14 days after the NiTi unilateral closed-coil spring was stretched between the upper right first molar and the incisors. The control consisted by contra-lateral site. The first molar area was fixed, decalcified and histologically processed using picrosirius pigment. The collagen birefringence of bone turnover was analyzed by color percentage and phase retardation. We observed an increase in collagen fiber organization over time with two methodologies. The Pearson coefficient correlation indicated a strong relationship (0.76) among the two polarized light analyses. In summary, there is collagen maturation over 3, 7 and 14 days. We successfully evaluated the molecular organization, arrangement, degree of polymerization and maturation process of collagen fibers in bone turnover through color percentages and phase retardation.

  13. Elevated Expression of Dkk-1 by Glucocorticoid Treatment Impairs Bone Regenerative Capacity of Adipose Tissue-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Kato, Toshiki; Khanh, Vuong Cat; Sato, Kazutoshi; Kimura, Kenichi; Yamashita, Toshiharu; Sugaya, Hisashi; Yoshioka, Tomokazu; Mishima, Hajime; Ohneda, Osamu

    2018-01-15

    Glucocorticoids are steroid hormones used as anti-inflammatory treatments. However, this strong immunomodulation causes undesirable side effects that impair bones, such as osteoporosis. Glucocorticoid therapy is a major risk factor for developing steroid-induced osteonecrosis of the femur head (ONFH). Since ONFH is incurable, therapy with mesenchymal stem cells (MSCs) that can differentiate into osteoblasts are a first-line choice. Bone marrow-derived MSCs (BM-MSCs) are often used as a source of stem cell therapy for ONFH, but their proliferative activity is impaired after steroid treatment. Adipose tissue-derived MSCs (AT-MSCs) may be an attractive alternative source; however, it is unknown whether AT-MSCs from steroid-induced ONFH (sAT-MSCs) have the same differentiation ability as BM-MSCs or normal AT-MSCs (nAT-MSCs). In this study, we demonstrate that nAT-MSCs chronically exposed to glucocorticoids show lower alkaline phosphatase activity leading to reduced osteogenic differentiation ability. This impaired osteogenesis is mediated by high expression of Dickkopf1 (Dkk-1) that inhibits wnt/β-catenin signaling. Increased Dkk-1 also causes impaired osteogenesis along with reductions in bone regenerative capacity in sAT-MSCs. Of note, plasma Dkk-1 levels are elevated in steroid-induced ONFH patients. Collectively, our findings suggest that glucocorticoid-induced expression of Dkk-1 could be a key factor in modulating the differentiation ability of MSCs used for ONFH and other stem cell therapies.

  14. Enhanced bone formation in the vicinity of porous β-TCP scaffolds exhibiting slow release of collagen-derived tripeptides.

    Science.gov (United States)

    Kamikura, Keita; Minatoya, Tsutomu; Terada-Nakaishi, Michiko; Yamamoto, Shoko; Sakai, Yasuo; Furusawa, Toshitake; Matsushima, Yuta; Unuma, Hidero

    2017-09-01

    It has been experimentally proven that orally ingested collagen-derived tripeptides (Ctp) are quickly absorbed in the body and effectively promote the regeneration of connective tissues including bone and skin. Ctp are capable to activate osteoblasts and fibroblasts, which eventually promotes tissue regeneration. Based on these findings, a hypothesis was formulated in this study that direct delivery of Ctp to bone defect would also facilitate tissue regeneration as well as oral administration. To test the hypothesis, we prepared a bone augmentation material with the ability to slowly release Ctp, and investigated its in vivo bone regeneration efficacy. The implant material was porous β-tricalcium phosphate (β-TCP) scaffold which was coated with a co-precipitated layer of bone-like hydroxyapatite and Ctp. The β-TCP was impregnated with approximately 0.8%(w/w) Ctp. Then, the Ctp-modified β-TCP was implanted into bone defects of Wistar rats to evaluate in vivo efficacy of Ctp directly delivered from the material to the bone defects. The control was pristine porous β-TCP. In vitro tests showed that Ctp were steadily released from the co-precipitated layer for approximately two weeks. The Ctp-modified scaffolds significantly promoted new bone formation in vivo in their vicinity as compared with pristine β-TCP scaffolds; 6 weeks after the implantation, Ctp-modified scaffolds promoted twice as much bone formation as the control implants. Consequently, we achieved the slow and steady release of Ctp, and found that direct delivery of Ctp from implant materials was effective for bone regeneration as well as oral administration. A β-TCP scaffold capable of slowly releasing bone-enhancing substances significantly promoted bone formation.

  15. Experimental demonstration of large capacity WSDM optical access network with multicore fibers and advanced modulation formats.

    Science.gov (United States)

    Li, Borui; Feng, Zhenhua; Tang, Ming; Xu, Zhilin; Fu, Songnian; Wu, Qiong; Deng, Lei; Tong, Weijun; Liu, Shuang; Shum, Perry Ping

    2015-05-04

    Towards the next generation optical access network supporting large capacity data transmission to enormous number of users covering a wider area, we proposed a hybrid wavelength-space division multiplexing (WSDM) optical access network architecture utilizing multicore fibers with advanced modulation formats. As a proof of concept, we experimentally demonstrated a WSDM optical access network with duplex transmission using our developed and fabricated multicore (7-core) fibers with 58.7km distance. As a cost-effective modulation scheme for access network, the optical OFDM-QPSK signal has been intensity modulated on the downstream transmission in the optical line terminal (OLT) and it was directly detected in the optical network unit (ONU) after MCF transmission. 10 wavelengths with 25GHz channel spacing from an optical comb generator are employed and each wavelength is loaded with 5Gb/s OFDM-QPSK signal. After amplification, power splitting, and fan-in multiplexer, 10-wavelength downstream signal was injected into six outer layer cores simultaneously and the aggregation downstream capacity reaches 300 Gb/s. -16 dBm sensitivity has been achieved for 3.8 × 10-3 bit error ratio (BER) with 7% Forward Error Correction (FEC) limit for all wavelengths in every core. Upstream signal from ONU side has also been generated and the bidirectional transmission in the same core causes negligible performance degradation to the downstream signal. As a universal platform for wired/wireless data access, our proposed architecture provides additional dimension for high speed mobile signal transmission and we hence demonstrated an upstream delivery of 20Gb/s per wavelength with QPSK modulation formats using the inner core of MCF emulating a mobile backhaul service. The IQ modulated data was coherently detected in the OLT side. -19 dBm sensitivity has been achieved under the FEC limit and more than 18 dB power budget is guaranteed.

  16. Chronic infection and infected non-union of the long bones in paediatric patients: preliminary results of bone versus beta-tricalcium phosphate grafting after induced membrane formation.

    Science.gov (United States)

    Rousset, Marie; Walle, Marjolaine; Cambou, Ludivine; Mansour, Mounira; Samba, Antoine; Pereira, Bruno; Ghanem, Ismat; Canavese, Federico

    2018-02-01

    Chronic infection (CO) and infected non-union of the long bones are relatively rare conditions in paediatric patients. Large bone defects secondary to these conditions can be managed with the induced membrane technique. The technique requires grafting of the bone void, although it is not yet established what bone substitute is the best option. The aim of this work was to evaluate the outcome and efficacy of treatment in children with CO and infected non-union of the long bones using the induced membrane technique and bone (BG) versus beta-tricalcium phosphate (BTP) grafting. Eight skeletally immature patients with CO and infected non-union of the long bones were treated surgically between 2010 and 2017 by a combination of resection of necrotic infected bone, debridement of surrounding soft tissue, osteosynthesis using a stable internal fixation when needed, and application of antibiotic-laden cement (ALC) spacer inducing new membrane before final bone reconstruction with bone substitutes: BTP in five cases, BG (allograft and/or autologous graft) in three cases. A second surgical step, once inflammatory markers had normalized, consisted of ALC spacer removal, application of BG or BTP graft and concomitant stable osteosynthesis, if needed, if this had not been done during the first surgical stage. All the patients underwent clinical, laboratory and imaging evaluation before and after surgery. Antibiotics were adjusted according to culture and sensitivity. Mean patient age at time of diagnosis was 13 ± four years (range, 4-16) and all had at least a 12-month follow-up (range 12-60). Estimated time for induced membrane formation was significantly shorter in patients treated with BTP compared with BG: 3±1 vs. 10±2 (p = 0.02). This result was confirmed by multivariate analysis (p = 0.044) taking into account adjustment for age of patients and time after initial surgery. Time of final union was about 5.5 ± 4.1 months (range 2-66). At the last follow-up visit

  17. Comparative assessment of physico-chemical characteristics and fibril formation capacity of thermostable carp scales collagen.

    Science.gov (United States)

    Pal, Gaurav Kumar; Suresh, P V

    2017-01-01

    Collagen and collagen fibers have been widely documented as a potential and competitive biomaterial for medical applications. However, the searches for safe and realistic new collagen sources are still underway. Currently, fishery by-products (scales), a promising collagen source are usually discarded. In the present study, in vitro fibril-forming ability of the extracted fish scale collagen is reported. The aim of the investigation was to evaluate the concomitant comparison of fibril-forming abilities and characteristics of acid and pepsin soluble collagens from the scales of Indian major carp catla (Catla catla) and rohu (Labeo rohita). The extracted collagens were characterized as type I, with a total yield of 2.80-4.11% (w/w). Denaturation temperature determined for all collagens were between 35.9 and 37.7°C. All collagens exhibited high solubility in acidic pH and low NaCl concentrations. SEM clarified the lyophilized collagens and their fibril-forming capacity. Amino acid content and radical scavenging efficacy were also analyzed for the extracted collagen. The results revealed that extracted scale collagen from a renewable biological source could be used as biomaterials in various sectors. It might be suitable for preparing collagen gel for biomedical devices or as a scaffold for cell culture because of its high stability and fibril formation capacity. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Characterization of the enhanced bone regenerative capacity of human periodontal ligament stem cells engineered to express the gene encoding bone morphogenetic protein 2.

    Science.gov (United States)

    Jung, Im-Hee; Lee, Si-Ho; Jun, Choong-Man; Oh, Namsik; Yun, Jeong-Ho

    2014-08-01

    Human periodontal ligament stem cells (hPDLSCs) are considered an appropriate cell source for therapeutic strategies. The aims of this study were to investigate the sustainability of bone morphogenetic protein 2 (BMP2) secretion and the bone regenerative capacity of hPDLSCs that had been genetically modified to express the gene encoding BMP2 (BMP2). hPDLSCs isolated from healthy third molars were transduced using replication-deficient recombinant adenovirus (rAd) encoding BMP2 (hPDLSCs/rAd-BMP2), and the cellular characteristics and osteogenic potentials of hPDLSCs/rAd-BMP2 were analyzed both in vitro and in vivo. hPDLSCs/rAd-BMP2 successfully secreted BMP2, formed colonies, and expressed immunophenotypes similar to their nontransduced counterparts. As to their osteogenic potential, hPDLSCs/rAd-BMP2 formed greater mineralized nodules and exhibited significantly higher levels of expression of BMP2 and the gene encoding alkaline phosphatase, and formed more and better quality bone than other hPDLSC-containing or recombinant human BMP2-treated groups, being localized at the initial site until 8 weeks. The findings of the present study demonstrate that hPDLSCs/rAd-BMP2 effectively promote osteogenesis not only in vitro but also in vivo. The findings also suggest that hPDLSCs can efficiently carry and deliver BMP2, and that hPDLSCs/rAd-BMP2 could be used in an attractive novel therapeutic approach for the regeneration of deteriorated bony defects.

  19. Efficiently engineered cell sheet using a complex of polyethylenimine–alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation

    Science.gov (United States)

    Jin, Han; Zhang, Kai; Qiao, Chunyan; Yuan, Anliang; Li, Daowei; Zhao, Liang; Shi, Ce; Xu, Xiaowei; Ni, Shilei; Zheng, Changyu; Liu, Xiaohua; Yang, Bai; Sun, Hongchen

    2014-01-01

    Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2) gene-engineered cell sheet using a complex of polyethylenimine–alginate (PEI–al) nanocomposites plus human BMP-2 complementary(c)DNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI–al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI–al nanocomposites efficiently deliver the BMP-2 gene to bone marrow mesenchymal stem cells and that BMP-2 gene-engineered cell sheet is an effective way for promoting bone regeneration. PMID:24855355

  20. 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

    Bone remodeling compartments (BRCs) were recently recognized to be present in patients with primary hyperparathyroidism and critical for bone reconstruction in multiple myeloma and endogenous Cushing's syndrome. The BRCs are outlined by a cellular canopy separating the bone remodeling events on t......, it particularly highlights the role of the BRC canopies to make the reversal phase progressing toward initiation of matrix deposition, thereby preventing bone loss....

  1. The Changes of Bone-Specific Alkaline Phosphatase (BsALP)Associated With Callus Formation and Rate of Bone Healing

    OpenAIRE

    Muljačić, Ante; Poljak-Guberina, Renata; Turčić, Josip; Živković, Ognjen; Guberina, Marko; Klaić, Boris

    2010-01-01

    The aim of this study was to examine whether the volume of bone-specific alkaline phosphatase (BsALP) as a biochemical parameter in the early posttraumatic phase may indicate the speed of fracture healing. The evaluation of the bone healing process has been based on the patient's subjective statement and radiographic findings. The activity of bone-specific alkaline phosphatase has been measured in the sera of 41 patients who have been diagnosed with fractures of long bones. All th...

  2. Bone Formation from Porcine Dental Germ Stem Cells on Surface Modified Polybutylene Succinate Scaffolds

    Directory of Open Access Journals (Sweden)

    Nergis Abay

    2016-01-01

    Full Text Available Designing and providing a scaffold are very important for the cells in tissue engineering. Polybutylene succinate (PBS has high potential as a scaffold for bone regeneration due to its capacity in cell proliferation and differentiation. Also, stem cells from 3rd molar tooth germs were favoured in this study due to their developmentally and replicatively immature nature. In this study, porcine dental germ stem cells (pDGSCs seeded PBS scaffolds were used to investigate the effects of surface modification with fibronectin or laminin on these scaffolds to improve cell attachment, proliferation, and osteogenic differentiation for tissue engineering applications. The osteogenic potentials of pDGSCs on these modified and unmodified foams were examined to heal bone defects and the effects of fibronectin or laminin modified PBS scaffolds on pDGSC differentiation into bone were compared for the first time. For this study, MTS assay was used to assess the cytotoxic effects of modified and unmodified surfaces. For the characterization of pDGSCs, flow cytometry analysis was carried out. Besides, alkaline phosphatase (ALP assay, von Kossa staining, real-time PCR, CM-Dil, and immunostaining were applied to analyze osteogenic potentials of pDGSCs. The results of these studies demonstrated that pDGSCs were differentiated into osteogenic cells on fibronectin modified PBS foams better than those on unmodified and laminin modified PBS foams.

  3. Antiosteoporotic Activity of Dioscorea alata L. cv. Phyto through Driving Mesenchymal Stem Cells Differentiation for Bone Formation

    Directory of Open Access Journals (Sweden)

    Kang-Yung Peng

    2011-01-01

    Full Text Available The aim of this study was to evaluate the effect of an ethanol extract of the rhizomes of Dioscorea alata L. cv. Phyto, Dispo85E, on bone formation and to investigate the mechanisms involved. Our results showed that Dispo85E increased the activity of alkaline phosphatase (ALP and bone nodule formation in primary bone marrow cultures. In addition, Dispo85E stimulated pluripotent C3H10T1/2 stem cells to differentiate into osteoblasts rather than adipocytes. Our in vivo data indicated that Dispo85E promotes osteoblastogenesis by increasing ALP activity and bone nodule formation in both intact and ovariectomized (OVX mice. Microcomputed tomography (μCT analysis also showed that Dispo85E ameliorates the deterioration of trabecular bone mineral density (tBMD, trabecular bone volume/total volume (BV/TV, and trabecular bone number (Tb.N in OVX mice. Our results suggested that Dispo85E is a botanical drug with a novel mechanism that drives the lineage-specific differentiation of bone marrow stromal cells and is a candidate drug for osteoporosis therapy.

  4. Effect of estrogen/gestagen and 24R,25-dihydroxyvitamin D3 therapy on bone formation in postmenopausal women

    Energy Technology Data Exchange (ETDEWEB)

    Thomsen, K.; Riis, B.; Christiansen, C.

    1986-12-01

    The effect of two different estrogen/gestagen regimens and 24R,25-(OH)2-cholecalciferol on bone formation was studied in a randomized trial with 144 healthy postmenopausal women. Urinary excretion (UE) of /sup 99m/technetium-diphosphonate and serum alkaline phosphatase (AP) was determined before and then once a year for 2 years of treatment. Both estimates of bone formation showed highly significant decreases (p less than .001) to normal premenopausal levels in women receiving unopposed 17 beta-estradiol or in a sequential combination with progestagen, whereas unchanged high values were found in the groups receiving 24R,25-(OH)2D3 and placebo. The data show that bone turnover increases in early postmenopausal women concomitantly with the loss of bone mass, and that hormonal substitutional therapy normalizes the total skeletal turnover as well as preventing bone loss.

  5. Effect of estrogen/gestagen and 24R,25-dihydroxyvitamin D3 therapy on bone formation in postmenopausal women

    International Nuclear Information System (INIS)

    Thomsen, K.; Riis, B.; Christiansen, C.

    1986-01-01

    The effect of two different estrogen/gestagen regimens and 24R,25-(OH)2-cholecalciferol on bone formation was studied in a randomized trial with 144 healthy postmenopausal women. Urinary excretion (UE) of /sup 99m/technetium-diphosphonate and serum alkaline phosphatase (AP) was determined before and then once a year for 2 years of treatment. Both estimates of bone formation showed highly significant decreases (p less than .001) to normal premenopausal levels in women receiving unopposed 17 beta-estradiol or in a sequential combination with progestagen, whereas unchanged high values were found in the groups receiving 24R,25-(OH)2D3 and placebo. The data show that bone turnover increases in early postmenopausal women concomitantly with the loss of bone mass, and that hormonal substitutional therapy normalizes the total skeletal turnover as well as preventing bone loss

  6. Bone formation in mono cortical mandibular critical size defects after augmentation with two synthetic nanostructured and one xenogenous hydroxyapatite bone substitute - in vivo animal study.

    Science.gov (United States)

    Dau, Michael; Kämmerer, Peer W; Henkel, Kai-Olaf; Gerber, Thomas; Frerich, Bernhard; Gundlach, Karsten K H

    2016-05-01

    Healing characteristics as well as level of tissue integration and degradation of two different nanostructured hydroxyapatite bone substitute materials (BSM) in comparison with a deproteinized hydroxyapatite bovine BSM were evaluated in an in vivo animal experiment. In the posterior mandible of 18 minipigs, bilateral mono cortical critical size bone defects were created. Randomized augmentation procedures with NanoBone(®) (NHA1), Ostim(®) (NHA2) or Bio-Oss(®) (DBBM) were conducted (each material n = 12). Samples were analyzed after five (each material n = 6) and 8 months (each material n = 6). Defect healing, formation of soft tissue and bone as well as the amount of remaining respective BSM were quantified both macro- and microscopically. For NHA2, the residual bone defect after 5 weeks was significantly less compared to NHA1 or DBBM. There was no difference in residual BSM between NHA1 and DBBM, but the amount in NHA2 was significantly lower. NHA2 also showed the least amount of soft tissue and the highest amount of new bone after 5 weeks. Eight months after implantation, no significant differences in the amount of residual bone defects, in soft tissue or in bone formation were detected between the groups. Again, NHA2 showed significant less residual material than NHA1 and DBBM. We observed non-significant differences in the biological hard tissue response of NHA1 and DBBM. The water-soluble NHA2 initially induced an increased amount of new bone but was highly compressed which may have a negative effect in less stable augmentations of the jaw. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Sodium/myo-inositol cotransporter 1 and myo-inositol are essential for osteogenesis and bone formation.

    Science.gov (United States)

    Dai, Zhijie; Chung, Sookja K; Miao, Dengshun; Lau, Kam S; Chan, Alfred W H; Kung, Annie W C

    2011-03-01

    myo-Inositol (MI) plays an essential role in several important processes of cell physiology, is involved in the neural system, and provides an effective treatment for some psychiatric disorders. Its role in osteogenesis and bone formation nonetheless is unclear. Sodium/MI cotransporter 1 (SMIT1, the major cotransporter of MI) knockout (SMIT1(-/-)) mice with markedly reduced tissue MI levels were used to characterize the essential roles of MI and SMIT1 in osteogenesis. SMIT1(-/-) embryos had a dramatic delay in prenatal mineralization and died soon after birth owing to respiratory failure, but this could be rescued by maternal MI supplementation. The rescued SMIT1(-/-) mice had shorter limbs, decreased bone density, and abnormal bone architecture in adulthood. Deletion of SMIT1 resulted in retarded postnatal osteoblastic differentiation and bone formation in vivo and in vitro. Continuous MI supplementation partially restored the abnormal bone phenotypes in adult SMIT1(-/-) mice and strengthened bone structure in SMIT1(+/+) mice. Although MI content was much lower in SMIT1(-/-) mesenchymal cells (MSCs), the I(1,4,5)P(3) signaling pathway was excluded as the means by which SMIT1 and MI affected osteogenesis. PCR expression array revealed Fgf4, leptin, Sele, Selp, and Nos2 as novel target genes of SMIT1 and MI. SMIT1 was constitutively expressed in multipotential C3H10T1/2 and preosteoblastic MC3T3-E1 cells and could be upregulated during bone morphogenetic protein 2 (BMP-2)-induced osteogenesis. Collectively, this study demonstrated that deficiency in SMIT1 and MI has a detrimental impact on prenatal skeletal development and postnatal bone remodeling and confirmed their essential roles in osteogenesis, bone formation, and bone mineral density (BMD) determination. Copyright © 2011 American Society for Bone and Mineral Research.

  8. The Differential Contributions of Conceptual Representation Format and Language Structure to Levels of Semantic Abstraction Capacity.

    Science.gov (United States)

    Gainotti, Guido

    2017-06-01

    This paper reviews some controversies concerning the original and revised versions of the 'hub-and-spoke' model of conceptual representations and their implication for abstraction capacity levels. The 'hub-and-spoke' model, which is based on data gathered in patients with semantic dementia (SD), is the most authoritative model of conceptual knowledge. Patterson et al.'s (Nature Reviews Neuroscience, 8(12), 976-987, 2007) classical version of this model maintained that conceptual representations are stored in a unitary 'amodal' format in the right and left anterior temporal lobes (ATLs), because in SD the semantic disorder cuts across modalities and categories. Several authors questioned the unitary nature of these representations. They showed that the semantic impairment is 'multi-modal'only in the advanced stages of SD, when atrophy affects the ATLs bilaterally, but that impariments can be modality-specific in lateralised (early) stages of the disease. In these cases, SD mainly affects lexical-semantic knowledge when atrophy predominates on the left side and pictorial representations when atrophy prevails on the right side. Some aspects of the model (i.e. the importance of spokes, the multimodal format of representations and the graded convergence of modalities within the ATLs), which had already been outlined by Rogers et al. (Psychological Review, 111(1), 205-235, 2004) in a computational model of SD, were strengthened by these results. The relevance of these theoretical problems and of empirical data concerning the neural substrate of concrete and abstract words is discussed critically. The conclusion of the review is that the highest levels of abstraction are due more to the structuring influence of language than to the format of representations.

  9. Clinically Relevant Concentrations of Ketamine Inhibit Osteoclast Formation In Vitro in Mouse Bone Marrow Cultures.

    Science.gov (United States)

    Du, Erxia; McAllister, Patrick; Venna, Venugopal Reddy; Xiao, Liping

    2017-04-01

    Ketamine has been used safely in clinics for decades for analgesia and anesthesia. It is increasingly popular in clinical practice due to its new uses and importance for emergency procedures. It is known that ketamine is sequestered in the bone marrow and the major receptors for ketamine, noncompetitive N-methyl-d-aspartate receptors (NMDARs), are expressed in osteoclasts (OCs) and osteoblasts. However, the impact of ketamine on OCs or osteoblasts is unknown. In this study, we investigated the effects of ketamine on osteoclastogenesis and regulation of NMDARs expression in vitro. Bone marrows (BMs) or bone marrow macrophages (BMMs) were cultured in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL) with or without ketamine for up to 6 days. OC formation peaked at day 5. On day 5 of culture, ketamine inhibited OC formation from both BM and BMM cultures at clinically relevant concentrations (3-200 µM). Ketamine inhibited RANKL-induced expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) in BMM cultures. Inhibition of ketamine on RANKL-induced osteoclastogenesis is associated with down-regulation of NMDARs. In addition, ketamine significantly inhibited the M-CSF induced migration of BMMs, inhibited cell fusion and significantly increased mature OC apoptosis. We conclude that clinically relevant concentrations of ketamine inhibit OC formation in both BM and BMM cultures in vitro through inhibiting migration and fusion process and enhancing mature OC apoptosis. It is likely that ketamine regulates osteoclastogenesis, at least in part, via its effects on NMDAR expression. J. Cell. Biochem. 118: 914-923, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. The relationship between inflammation and new bone formation in patients with ankylosing spondylitis.

    Science.gov (United States)

    Baraliakos, Xenofon; Listing, Joachim; Rudwaleit, Martin; Sieper, Joachim; Braun, Juergen

    2008-01-01

    Spinal inflammation as detected by magnetic resonance imaging and new bone formation as identified by conventional radiographs are characteristic of ankylosing spondylitis. Whether and how spondylitis and syndesmophyte formation are linked are unclear. Our objective was to investigate whether and how spinal inflammation are associated with new bone formation in ankylosing spondylitis. Spinal magnetic resonance images and conventional radiographs from 39 ankylosing spondylitis patients treated with anti-tumour necrosis factor (anti-TNF) agents at baseline and after 2 years were analysed for syndesmophyte formation at vertebral edges with or without inflammatory lesions at baseline. Overall, 922 vertebral edges at the cervical and lumbar spine were analysed. At baseline, the proportion of vertebral edges with and without inflammation (magnetic resonance imaging) that showed structural changes (conventional radiographs) was similar (in total, 16.6% of all vertebral edges in 71.4% of patients). From the perspective of syndesmophyte formation (n = 26, 2.9%) after 2 years, there were more vertebral edges without (62%) than with (38%) inflammation at baseline (P = 0.03). From the perspective of spinal inflammation at baseline (n = 153 vertebral edges), more syndesmophytes developed at vertebral edges with (6.5%) than without (2.1%) inflammation (P = 0.002, odds ratio 3.3, 95% confidence interval 1.5 to 7.4). Inflammation persisted in 31% of the initially inflamed vertebral edges (n = 132), and new lesions developed in 8% of the vertebral edges without inflammation at baseline (n = 410). From the perspective of spinal inflammation after 2 years (n = 72 vertebral edges), 5.6% of the vertebral edges showed syndesmophyte development in contrast to 1.9% of the vertebral edges with new syndesmophytes without inflammation (P = 0.06). These findings obtained in patients treated with anti-TNF agents suggest linkage and some dissociation of inflammation and new bone formation in

  11. Bone formation rather than inflammation reflects Ankylosing Spondylitis activity on PET-CT: a pilot study

    OpenAIRE

    Bruijnen, Stefan TG; van der Weijden, Mignon AC; Klein, Joannes P; Hoekstra, Otto S; Boellaard, Ronald; van Denderen, J Christiaan; Dijkmans, Ben AC; Voskuyl, Alexandre E; van der Horst-Bruinsma, Irene E; van der Laken, Conny J

    2012-01-01

    Introduction Positron Emission Tomography - Computer Tomography (PET-CT) is an interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity using specific PET tracers. Previous studies have shown that the PET tracers [18F]FDG and [11C](R)PK11195 can target inflammation (synovitis) in rheumatoid arthritis (RA) and may therefore be useful in AS. Another interesting tracer for AS is [18F]Fluoride, which targets bone formation. In a pilot setting, the potential of PET-CT in ima...

  12. Redundancy and molecular evolution: the rapid Induction of bone formation by the mammalian transforming growth factor-β3 isoform

    Directory of Open Access Journals (Sweden)

    Ugo Ripamonti

    2016-09-01

    Full Text Available The soluble osteogenic molecular signals of the transforming growth factor-β (TGF-β supergene family are the molecular bases of the induction of bone formation and postnatal bone tissue morphogenesis with translation into clinical contexts. The mammalian TGF-β3 isoform, a pleiotropic member of the family, controls a vast array of biological processes including the induction of bone formation. Recombinant hTGF-β3 induces substantial bone formation when implanted with either collagenous bone matrices or coral-derived macroporous bioreactors in the rectus abdominis muscle of the non-human primate Papio ursinus. In marked contrast, the three mammalian TGF-βs do not initiate the induction of bone formation in rodents and lagomorphs. The induction of bone by hTGF-β3/preloaded bioreactors is orchestrated by inducing fibrin-fibronectin rings that structurally organize tissue patterning and morphogenesis within the macroporous spaces. Induced advancing extracellular matrix rings provide the structural anchorage for hyper chromatic cells, interpreted as differentiating osteoblasts re-programmed by hTGF-β3 from invading myoblastic and/or pericytic differentiated cells. Runx2 and Osteocalcin expression are significantly up-regulated correlating to multiple invading cells differentiating into the osteoblastic phenotype. Bioreactors pre-loaded with recombinant human Noggin (hNoggin, a BMPs antagonist, show down-regulation of BMP-2 and other profiled osteogenic proteins’ genes resulting in minimal bone formation. Coral-derived macroporous constructs preloaded with binary applications of hTGF-β3 and hNoggin also show down-regulation of BMP-2 with the induction of limited bone formation. The induction of bone formation by hTGF-β3 is via the BMPs pathway and it is thus blocked by hNoggin. Our systematic studies in Papio ursinus with translational hTGF-β3 in large cranio-mandibulo-facial defects in humans are now requesting the re-evaluation of Bone

  13. 99mTechnetium-methylene diphosphonate bone imaging using low-intensity pulsed ultrasound: promotion of bone formation during mandibular distraction osteogenesis in dogs.

    Science.gov (United States)

    Ding, Yuxiang; Li, Guoquan; Ao, Jianhua; Zhou, Libin; Ma, Qin; Liu, Yanpu

    2010-03-01

    Our objective was to assess the value of (99m)technetium-methylene diphosphonate ((99m)Tc-MDP) bone imaging in the use of low-intensity pulsed ultrasound to promote bony formation during mandibular distraction osteogenesis in dogs. The body of the mandibles in 7 dogs were cut between the first and the second premolar and were lengthened at the rate of 1mm/day, twice a day, for 20 days. During the period of distraction one lateral distraction gap was irradiated with low-intensity pulsed ultrasound (LIPUS) for 10min twice a day, and the other side was used as control. Serial radiographic inspections were made at different periods (0, 1, 2, 4, 6, 8, and 12 weeks) during the consolidation phase, followed by a plain radiograph and histological examination. The (99m)Tc-MDP imaging showed that the ratio of bone formation on the LIPUS-treated side was significantly higher than that on the control side during the early period of consolidation (before the 4th week), but later this was reversed and there were no significant differences between the two sides by the 12th week. Plain radiographs and histological examination showed that the new bone on the experimental side had matured earlier than that on the control side. Radionuclide bone imaging is a good way to assess the formation of bone after distraction osteogenesis.

  14. Thai traditional massage increases biochemical markers of bone formation in postmenopausal women: a randomized crossover trial.

    Science.gov (United States)

    Saetung, Sunee; Chailurkit, La-Or; Ongphiphadhanakul, Boonsong

    2013-03-25

    The effect of massage therapy on bone metabolism in adults has only scarcely been explored. In a randomized crossover trial, we investigated the skeletal effect of Thai traditional massage by examining the changes in biochemical markers of bone turnover. Forty-eight postmenopausal women participated in the study. All volunteers were randomized to a 2-hour session of Thai traditional massage twice a week for 4 weeks and a 4-week control period after a 2-week washout, or vice versa. Twenty-one subjects were allocated to receiving Thai traditional massage first, followed by the control period, while 27 were initially allocated to the control period. Serum P1NP increased significantly after Thai traditional massage (P women whose ages were in the middle and higher tertiles and whose heights were in the lower and middle tertiles (n = 22) had a 14.8 ± 3.3% increase in P1NP after massage (P women (n = 26). Thai traditional massage results in an increase in bone formation as assessed by serum P1NP, particularly in postmenopausal women who are older and have a smaller body build. Future studies with larger samples and additional design features are warranted. ClinicalTrials.gov : NCT01627028.

  15. Local Controlled Release of Polyphenol Conjugated with Gelatin Facilitates Bone Formation

    Directory of Open Access Journals (Sweden)

    Yoshitomo Honda

    2015-06-01

    Full Text Available Catechins are extensively used in health care treatments. Nevertheless, there is scarce information about the feasibility of local administration with polyphenols for bone regeneration therapy, possibly due to lack of effective delivery systems. Here we demonstrated that the epigallocatechin-3-gallate-conjugated gelatin (EGCG/Gel prepared by an aqueous chemical synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl-4-morpholinium chloride (DMT-MM gradually disintegrated with time and facilitated bone formation in a critical size defect of a mouse calvaria. Conjugation of EGCG with the Gel generated cross-linking between the two molecules, thereby leading to a retardation of the degradation of the EGCG/Gel and to a delayed release of EGCG. The prepared EGCG/Gels represented significant osteogenic capability compared with that of the uncross-linked Gel and the cross-linked Gel with uncombined-EGCG. In vitro experiments disclosed that the EGCG/Gel induced osteoblastogenesis of a mouse mesenchymal stem cell line (D1 cells within 14 days. Using fluorescently-labeled EGCG/Gel, we found that the fraction of EGCG/Gel adsorbed onto the cell membrane of the D1 cells possibly via a Gel-cell interaction. The interaction might confer the long-term effects of EGCG on the cells, resulting in a potent osteogenic capability of the EGCG/Gel in vivo. These results should provide insight into local controlled release of polyphenols for bone therapy.

  16. Growth hormone mitigates loss of periosteal bone formation and muscle mass in disuse osteopenic rats.

    Science.gov (United States)

    Grubbe, M-C; Thomsen, J S; Nyengaard, J R; Duruox, M; Brüel, A

    2014-12-01

    Growth hormone (GH) is a potent anabolic agent capable of increasing both bone and muscle mass. The aim was to investigate whether GH could counteract disuse-induced loss of bone and muscle mass in a rat model. Paralysis was induced by injecting 4 IU Botox (BTX) into the muscles of the right hind limb. Sixty female Wistar rats, 14 weeks old, were divided into the following groups: baseline, controls, BTX, BTX+GH, and GH. GH was given at a dosage of 5 mg/kg/d for 4 weeks. Compared with controls, BTX resulted in lower periosteal bone formation rate (BFR/BS,-79%, Pbone mineral density (aBMD, -13%, Pbone volume (BV/TV, -26%, Pbone strength (-12%, Pbone strength was found. In addition, GH partly prevented loss of muscle mass (+29% vs. BTX, P<0.001), and tended to prevent loss of muscle CSA (+11%, P=0.064). In conclusion, GH mitigates disuse-induced loss of periosteal BFR/BS at the mid-femur and rectus femoris muscle mass.

  17. Quantifying the degradation of degradable implants and bone formation in the femoral condyle using micro-CT 3D reconstruction.

    Science.gov (United States)

    Xu, Yichi; Meng, Haoye; Yin, Heyong; Sun, Zhen; Peng, Jiang; Xu, Xiaolong; Guo, Quanyi; Xu, Wenjing; Yu, Xiaoming; Yuan, Zhiguo; Xiao, Bo; Wang, Cheng; Wang, Yu; Liu, Shuyun; Lu, Shibi; Wang, Zhaoxu; Wang, Aiyuan

    2018-01-01

    Degradation limits the application of magnesium alloys, and evaluation methods for non-traumatic in vivo quantification of implant degradation and bone formation are imperfect. In the present study, a micro-arc-oxidized AZ31 magnesium alloy was used to evaluate the degradation of implants and new bone formation in 60 male New Zealand white rabbits. Degradation was monitored by weighing the implants prior to and following implantation, and by performing micro-computed tomography (CT) scans and histological analysis after 1, 4, 12, 24, 36, and 48 weeks of implantation. The results indicated that the implants underwent slow degradation in the first 4 weeks, with negligible degradation in the first week, followed by significantly increased degradation during weeks 12-24 (Posteogenesis. However, from the maximum inner diameter of the new bone loop and diameter of the pin in the same position, the magnesium alloy was not capable of creating sufficient bridges between the bones and biomaterials when there were preexisting gaps. Histological analyses indicated that there were no inflammatory responses around the implants. The results of the present study indicate that a micro-arc-oxidized AZ31 magnesium alloy is safe in vivo and efficiently degraded. Furthermore, the novel bone formation increased as the implant degraded. The findings concluded that micro-CT, which is useful for providing non-traumatic, in vivo , quantitative and precise data, has great value for exploring the degradation of implants and novel bone formation.

  18. Insulin-Like Growth Factor I Does Not Drive New Bone Formation in Experimental Arthritis.

    Directory of Open Access Journals (Sweden)

    Melissa N van Tok

    Full Text Available Insulin like growth factor (IGF-I can act on a variety of cells involved in cartilage and bone repair, yet IGF-I has not been studied extensively in the context of inflammatory arthritis. The objective of this study was to investigate whether IGF-I overexpression in the osteoblast lineage could lead to increased reparative or pathological bone formation in rheumatoid arthritis and/or spondyloarthritis respectively.Mice overexpressing IGF-I in the osteoblast lineage (Ob-IGF-I+/- line 324-7 were studied during collagen induced arthritis and in the DBA/1 aging model for ankylosing enthesitis. Mice were scored clinically and peripheral joints were analysed histologically for the presence of hypertrophic chondrocytes and osteocalcin positive osteoblasts.90-100% of the mice developed CIA with no differences between the Ob-IGF-I+/- and non-transgenic littermates. Histological analysis revealed similar levels of hypertrophic chondrocytes and osteocalcin positive osteoblasts in the ankle joints. In the DBA/1 aging model for ankylosing enthesitis 60% of the mice in both groups had a clinical score 1<. Severity was similar between both groups. Histological analysis revealed the presence of hypertrophic chondrocytes and osteocalcin positive osteoblasts in the toes in equal levels.Overexpression of IGF-I in the osteoblast lineage does not contribute to an increase in repair of erosions or syndesmophyte formation in mouse models for destructive and remodeling arthritis.

  19. Dual Delivery of rhPDGF-BB and Bone Marrow Mesenchymal Stromal Cells Expressing the BMP2 Gene Enhance Bone Formation in a Critical-Sized Defect Model

    Science.gov (United States)

    Park, Shin-Young; Kim, Kyoung-Hwa; Shin, Seung-Yun; Koo, Ki-Tae; Lee, Yong-Moo

    2013-01-01

    Bone tissue healing is a dynamic, orchestrated process that relies on multiple growth factors and cell types. Platelet-derived growth factor-BB (PDGF-BB) is released from platelets at wound sites and induces cellular migration and proliferation necessary for bone regeneration in the early healing process. Bone morphogenetic protein-2 (BMP-2), the most potent osteogenic differentiation inducer, directs new bone formation at the sites of bone defects. This study evaluated a combinatorial treatment protocol of PDGF-BB and BMP-2 on bone healing in a critical-sized defect model. To mimic the bone tissue healing process, a dual delivery approach was designed to deliver the rhPDGF-BB protein transiently during the early healing phase, whereas BMP-2 was supplied by rat bone marrow stromal cells (BMSCs) transfected with an adenoviral vector containing the BMP2 gene (AdBMP2) for prolonged release throughout the healing process. In in vitro experiments, the dual delivery of rhPDGF-BB and BMP2 significantly enhanced cell proliferation. However, the osteogenic differentiation of BMSCs was significantly suppressed even though the amount of BMP-2 secreted by the AdBMP2-transfected BMSCs was not significantly affected by the rhPDGF-BB treatment. In addition, dual delivery inhibited the mRNA expression of BMP receptor type II and Noggin in BMSCs. In in vivo experiments, critical-sized calvarial defects in rats showed enhanced bone regeneration by dual delivery of autologous AdBMP2-transfected BMSCs and rhPDGF-BB in both the amount of new bone formed and the bone mineral density. These enhancements in bone regeneration were greater than those observed in the group treated with AdBMP2-transfected BMSCs alone. In conclusion, the dual delivery of rhPDGF-BB and AdBMP2-transfected BMSCs improved the quality of the regenerated bone, possibly due to the modulation of PDGF-BB on BMP-2-induced osteogenesis. PMID:23901900

  20. Perinatal maternal dietary supplementation of ω3-fatty acids transiently affects bone marrow microenvironment, osteoblast and osteoclast formation, and bone mass in male offspring.

    Science.gov (United States)

    Fong, Laura; Muhlhausler, Beverly S; Gibson, Robert A; Xian, Cory J

    2012-05-01

    It is increasingly evident that micronutrient environment experienced before birth and in infancy is important for achieving optimal bone mass by adolescence and maintaining bone health. This study determined whether maternal supplementation with ω3-polyunsaturated fatty acids (n3FA) improved offspring bone growth and adult bone mass. Female rats were fed a diet containing 0.1% (control, n = 10) or 1% (n3FA, n = 11) docosahexanoic acid (DHA) during pregnancy and lactation. Offspring were weaned onto a control rat chow diet. Tibial growth plate and metaphysis structure, osteoblast/osteoclast density and differentiation, and gene expression were assessed in offspring at 3 wk (weaning), 6 wk (adolescent), and 3 months (adult). Maternal n3FA supplementation elevated offspring plasma n3FA levels at 3 and 6 wk. Although total growth plate heights were unaffected at any age, the resting zone thickness was increased in both male and female offspring at 3 wk. In n3FA males, but not females, bone trabecular number and thickness were increased at 3 wk but not other ages. The wk 3 n3FA males also exhibited an increased bone volume, an increased osteoblast but decreased osteoclast density, and lower expression of osteoclastogenic cytokines receptor activator of nuclear factor-κB ligand, TNF-α, and IL-6. No effects were seen at 6 wk or 3 months in either sex. Thus, perinatal n3FA supplementation is associated with increased bone formation, decreased resorption, and a higher bone mass in males, but not in females, at weaning; these effects do not persist into adolescence and adulthood and are unlikely to produce lasting improvements in bone health.

  1. Inflammation Intensity-dependent Expression of Osteoinductive Wnt Proteins is Critical for Ectopic New Bone Formation in Ankylosing Spondylitis.

    Science.gov (United States)

    Li, Xiang; Wang, Jianru; Zhan, Zhongping; Li, Sibei; Zheng, Zhaomin; Wang, Taiping; Zhang, Kuibo; Pan, Hehai; Li, Zemin; Zhang, Nu; Liu, Hui

    2018-02-26

    To investigate the molecular mechanism underlying the inflammation- related ectopic new bone formation in ankylosing spondylitis (AS). Spinal tissues and sera were collected from patients or normal volunteers to detect the expression of Wnt proteins. An in vitro cell culture system mimicking the local inflammatory microenvironment of bone-forming sites was established to study the relationship between inflammation and Wnt expression, the regulatory mechanism of inflammation-induced Wnt expression and the role of Wnt signaling in new bone formation. A modified collagen-induced arthritis (mCIA) and a proteoglycan -induced spondylitis (PGIS) animal model were used to confirm the key findings in vivo. The levels of osteoinductive Wnt proteins were obviously increased in the sera and spinal ligament tissues of patients with AS. Only constitutive low-intensity TNF-α stimulation, but not short-term or high-intensity TNF-α stimulation, induced persistent expression of osteoinductive Wnt proteins and subsequent bone formation through NF-κB (p65) and JNK/AP-1 (c-Jun) signaling pathways. Furthermore, inhibition of either Wnt/β-catenin or Wnt/PKCδ pathway significantly suppressed new bone formation. The increased expression of Wnt proteins was confirmed in both mCIA and PGIS models. A kyphotic and ankylosing phenotype of the spine was observed during long-term observation in mCIA model. Inhibition of either Wnt/β-catenin or Wnt/PKCδ signaling pathway significantly reduced the incidence and severity of this phenotype. Inflammation intensity-dependent expression of osteoinductive Wnt proteins is a key link between inflammation and ectopic new bone formation in AS. Activation of both canonical Wnt/β-catenin and noncanonical Wnt/PKCδ pathways is required for inflammation-induced new bone formation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Cyst-Like Osteolytic Formations in Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) Augmented Sheep Spinal Fusion.

    Science.gov (United States)

    Pan, Hsin Chuan; Lee, Soonchul; Ting, Kang; Shen, Jia; Wang, Chenchao; Nguyen, Alan; Berthiaume, Emily A; Zara, Janette N; Turner, A Simon; Seim, Howard B; Kwak, Jin Hee; Zhang, Xinli; Soo, Chia

    2017-07-01

    Multiple case reports using recombinant human bone morphogenetic protein-2 (rhBMP-2) have reported complications. However, the local adverse effects of rhBMP-2 application are not well documented. In this report we show that, in addition to promoting lumbar spinal fusion through potent osteogenic effects, rhBMP-2 augmentation promotes local cyst-like osteolytic formations in sheep trabecular bones that have undergone anterior lumbar interbody fusion. Three months after operation, conventional computed tomography showed that the trabecular bones of the rhBMP-2 application groups could fuse, whereas no fusion was observed in the control group. Micro-computed tomography analysis revealed that the core implant area's bone volume fraction and bone mineral density increased proportionately with rhBMP-2 dose. Multiple cyst-like bone voids were observed in peri-implant areas when using rhBMP-2 applications, and these sites showed significant bone mineral density decreases in relation to the unaffected regions. Biomechanically, these areas decreased in strength by 32% in comparison with noncystic areas. Histologically, rhBMP-2-affected void sites had an increased amount of fatty marrow, thinner trabecular bones, and significantly more adiponectin- and cathepsin K-positive cells. Despite promoting successful fusion, rhBMP-2 use in clinical applications may result in local adverse structural alterations and compromised biomechanical changes to the bone. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Effect of recombinant PDGF-BB on bone formation in the presence of β-tricalcium phosphate and bovine bone mineral matrix: a pilot study in rat calvarial defects.

    Science.gov (United States)

    Luvizuto, Eloá R; Tangl, Stefan; Dobsak, Toni; Reich, Karoline; Gruber, Reinhard; Sonoda, Celso K; Okamoto, Roberta

    2016-05-04

    Supplementation of bone substitutes with recombinant platelet-derived growth factor-BB (PDGF-BB) can enhance bone regeneration. The aim of the study was to evaluate the effect of PDGF-BB on bone formation in the presence of β-tricalcium phosphate and bovine bone mineral matrix in a rat calvaria defect model. The authors examined 5 mm rat calvarial defects treated with β-tricalcium phosphate (TCP) or demineralized bovine bone mineral (DBBM) with and without 0.3 mg/ml recombinant PDGF-BB. Calvaria defects were randomly divided into the following treatment groups (n = 5); TCP; TCP plus PDGF-BB; DBBM; DBBM plus PDGF-BB; and untreated empty control. After 45 days, bone formation was evaluated by histomorphometry and fluorescence microscopy. The authors report that the area of newly formed bone was similar between the empty controls and the two bone substitutes, TCP and DBBM. Supplementation of TCP and DBBM with PDGF-BB had no significant impact on bone formation. Fluorochrome staining revealed no visible changes in the pattern of bone formation in defects filled with TCP and DBBM, irrespective of PDGF-BB. Furthermore, supplementation with PDGF-BB did not influence biomaterial degradation. The authors concluded that PDGF-BB had no impact on bone formation and degradation of bone substitutes in the respective rodent models. Thus, possible beneficial effects of PDGF-BB may require other model situations.

  4. Postoperative radiation therapy after hip replacement in high-risk patients for development of heterotopic bone formation

    International Nuclear Information System (INIS)

    Hashem, R.; Rene, N.; Souhami, L.; Tanzer, M.; Evans, M.

    2011-01-01

    Purpose. - To report the results of postoperative radiation therapy in preventing the development of heterotopic bone formation after hip replacement surgery in high-risk patients. Patients and methods. - Between 1991 and 2007, 44 patients were preventively treated with postoperative RT after total hip replacement. In total, 47 hips were treated. All patients were considered at high risk for developing heterotopic bone formation. Most patients (63.5%) were treated because of a history of severe osteoarthritis or ankylosing spondylitis. All patients were treated with shaped parallel-opposed fields with a single fraction of 7 Gy using 6 or 18 MV photons. Most patients (94%) received radiation therapy within 72 hours postoperative and in only three patients radiation therapy was delivered after 72 hours post-surgery (5-8 days). Results. - Minimum follow-up was 1 year. There were 18 females and 26 males. Median age was 63 years (range: 18-80). Treatments were well tolerated and no acute toxicity was seen post-radiation therapy. Only one of the 47 hips (2%) developed heterotopic bone formation. This patient received postoperative radiation therapy to both hips but only developed heterotopic bone formation in one of them. None of the three patients treated beyond 72 hours failed. To date no late toxicity has been observed. Conclusion. - The use of postoperative radiation therapy was an effective and safe treatment in the prevention of heterotopic bone formation in a high-risk group of patients undergoing total hip replacement. (authors)

  5. Quantifying Capacity Loss due to Solid-Electrolyte-Interphase Layer Formation on Silicon Negative Electrodes in Lithium-ion Batteries

    OpenAIRE

    Nadimpalli, Siva P. V.; Sethuraman, Vijay A.; Dalavi, Swapnil; Lucht, Brett; Chon, Michael J.; Shenoy, Vivek B.; Guduru, Pradeep R.

    2012-01-01

    Charge lost per unit surface area of a silicon electrode due to the formation of solid-electrolyte-interphase (SEI) layer during initial lithiation was quantified, and the species that constitute this layer were identified. Coin cells made with Si thin-film electrodes were subjected to a combination of galvanostatic and potentiostatic lithiation and delithiation cycles to accurately measure the capacity lost to SEI-layer formation. While the planar geometry of amorphous thin films allows accu...

  6. The carboxy-terminal propeptide of type I procollagen in serum as a marker of bone formation

    DEFF Research Database (Denmark)

    Hassager, C; Jensen, L T; Johansen, J S

    1991-01-01

    injection every 3 weeks for 1 year; and (2) 40 women received either 2 mg 17 beta-estradiol plus 1 mg norethisterone acetate or placebo tablets daily for 1 year. Sixty-seven (85%) completed the 1 year of treatment. Serum concentration of type I procollagen carboxy-terminal propeptide (PICP) was measured...... before and at 3, 6, 9, and 12 months of therapy. In addition, 32 of the women had an iliac bone biopsy taken after double tetracycline labeling. Initial serum PICP correlated significantly with histomorphometrically measured rate of bone formation (r = .4; P less than .05) and plasma bone Gla protein (r...... = .6; P less than .001), but not with histomorphometrically measured bone resorption or biochemical estimates of bone resorption (fasting urinary hydroxyproline and calcium). Estrogen-progestogen therapy significantly decreased (P less than .001) serum PICP by about 30%, whereas anabolic steroid...

  7. A primary phosphorus-deficient skeletal phenotype in juvenile Atlantic salmon Salmo salar: the uncoupling of bone formation and mineralization.

    Science.gov (United States)

    Witten, P E; Owen, M A G; Fontanillas, R; Soenens, M; McGurk, C; Obach, A

    2016-02-01

    To understand the effect of low dietary phosphorus (P) intake on the vertebral column of Atlantic salmon Salmo salar, a primary P deficiency was induced in post-smolts. The dietary P provision was reduced by 50% for a period of 10 weeks under controlled conditions. The animal's skeleton was subsequently analysed by radiology, histological examination, histochemical detection of minerals in bones and scales and chemical mineral analysis. This is the first account of how a primary P deficiency affects the skeleton in S. salar at the cellular and at the micro-anatomical level. Animals that received the P-deficient diet displayed known signs of P deficiency including reduced growth and soft, pliable opercula. Bone and scale mineral content decreased by c. 50%. On radiographs, vertebral bodies appear small, undersized and with enlarged intervertebral spaces. Contrary to the X-ray-based diagnosis, the histological examination revealed that vertebral bodies had a regular size and regular internal bone structures; intervertebral spaces were not enlarged. Bone matrix formation was continuous and uninterrupted, albeit without traces of mineralization. Likewise, scale growth continues with regular annuli formation, but new scale matrix remains without minerals. The 10 week long experiment generated a homogeneous osteomalacia of vertebral bodies without apparent induction of skeletal malformations. The experiment shows that bone formation and bone mineralization are, to a large degree, independent processes in the fish examined. Therefore, a deficit in mineralization must not be the only cause of the alterations of the vertebral bone structure observed in farmed S. salar. It is discussed how the observed uncoupling of bone formation and mineralization helps to better diagnose, understand and prevent P deficiency-related malformations in farmed S. salar. © 2015 The Authors.Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of The Fisheries Society of the

  8. Effects of AISI 316L corrosion products in in vitro bone formation.

    Science.gov (United States)

    Morais, S; Sousa, J P; Fernandes, M H; Carvalho, G S; de Bruijn, J D; van Blitterswijk, C A

    1998-06-01

    Rat bone marrow cells were cultured in experimental conditions that favour the proliferation and differentiation of osteoblastic cells (i.e., 2.52 x 10(-4) mol l(-1) ascorbic acid, 10(-2) mol l(-1) beta-glycerophosphate and 10(-8) mol l(-1) dexamethasone) in the absence and in the presence of stainless-steel corrosion products, for a period of 18 days. An AISI 316L stainless-steel slurry (SS) was obtained by electrochemical means and the concentrations of the major metal ions, determined by atomic absorption spectrometry, were 8.78 x 10(-3) mol l(-1) of Fe, 4.31 x 10(-3) mol l(-1) of Cr and 2.56 x 10(-3) mol l(-1) of Ni. Bone marrow cells were exposed to 0.01, 0.1 and 1% of the SS and at the end of the incubation period, control and treated cultures were evaluated by histochemical assays for the identification of the presence of alkaline phosphatase and also calcium and phosphate deposition. Cultures were further observed by scanning electron microscopy. Levels of total and ionised calcium and phosphorus in the culture media collected from control and metal exposed cell cultures were also quantified. Histochemical staining showed that control cultures presented a strong reaction for the presence of alkaline phosphatase and exhibited formation of calcium and phosphates deposits. The presence of 0.01% SS caused no detectable biological effects in these cultures, 0.1% SS impaired osteoblastic behaviour and, 1% SS resulted in cell death. In the absence of bone cells, levels of total and ionised calcium and phosphorus in the control and metal added culture medium were similar throughout the incubation period. A significant decrease in the levels of ionised calcium and phosphorus were observed in the culture medium of control cultures and also in cultures exposed to 0.01% SS after two weeks of incubation, an event related with the formation of mineral calcium phosphate deposits in these cultures. In cultures grown in the presence of 0.1 and 1% SS corrosion products

  9. Bone formation rather than inflammation reflects ankylosing spondylitis activity on PET-CT: a pilot study.

    Science.gov (United States)

    Bruijnen, Stefan T G; van der Weijden, Mignon A C; Klein, Joannes P; Hoekstra, Otto S; Boellaard, Ronald; van Denderen, J Christiaan; Dijkmans, Ben A C; Voskuyl, Alexandre E; van der Horst-Bruinsma, Irene E; van der Laken, Conny J

    2012-04-02

    Positron Emission Tomography - Computer Tomography (PET-CT) is an interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity using specific PET tracers. Previous studies have shown that the PET tracers [18F]FDG and [11C](R)PK11195 can target inflammation (synovitis) in rheumatoid arthritis (RA) and may therefore be useful in AS. Another interesting tracer for AS is [18F]Fluoride, which targets bone formation. In a pilot setting, the potential of PET-CT in imaging AS activity was tested using different tracers, with Magnetic Resonance Imaging (MRI) and conventional radiographs as reference. In a stepwise approach different PET tracers were investigated. First, whole body [18F]FDG and [11C](R)PK11195 PET-CT scans were obtained of ten AS patients fulfilling the modified New York criteria. According to the BASDAI five of these patients had low and five had high disease activity. Secondly, an extra PET-CT scan using [18F]Fluoride was made of two additional AS patients with high disease activity. MRI scans of the total spine and sacroiliac joints were performed, and conventional radiographs of the total spine and sacroiliac joints were available for all patients. Scans and radiographs were visually scored by two observers blinded for clinical data. No increased [18F]FDG and [11C](R)PK11195 uptake was noticed on PET-CT scans of the first 10 patients. In contrast, MRI demonstrated a total of five bone edema lesions in three out of 10 patients. In the two additional AS patients scanned with [18F]Fluoride PET-CT, [18F]Fluoride depicted 17 regions with increased uptake in both vertebral column and sacroiliac joints. In contrast, [18F]FDG depicted only three lesions, with an uptake of five times lower compared to [18F]Fluoride, and again no [11C](R)PK11195 positive lesions were found. In these two patients, MRI detected nine lesions and six out of nine matched with the anatomical position of [18F]Fluoride uptake. Conventional radiographs showed structural

  10. Exercise enhance the ectopic bone formation of calcium phosphate biomaterials in muscles of mice.

    Science.gov (United States)

    Cheng, Lijia; Yan, Shuo; Zhu, Jiang; Cai, Peiling; Wang, Ting; Shi, Zheng

    2017-08-01

    To investigate whether exercise can enhance ectopic bone formation of calcium phosphate (Ca-P) biomaterials in muscles of mice. Firstly, ten transient receptor potential vanilloid subfamily member 1 (TRPV1) knockout mice (group KO) and ten C57BL/6 mice (group WT) were randomly chosen, 10μg Ca-P biomaterials were implanted into the thigh muscle pouch of each mouse which was far away from femur; after that, all animals were kept in open field for free exploration 5min, and the movement time and distance were automatically analyzed. Ten weeks later, the Ca-P samples were harvested for histological staining and immunochemistry. Secondly, the Ca-P biomaterials were implanted into the thigh muscle pouch of C57BL/6 mice the same as previous operation, and then randomly divided into two groups: running group and non-running group (n=10); in running group, all mice run 1h as a speed of 6m/h in a treadmill for 10weeks. Ten weeks later, the blood was collected to detect the interleukin-4 (IL-4) and IL-12 levels by enzyme linked immunosorbent assay (ELISA), and the samples were harvested for histological staining. In groups KO and WT, both the movement time and distance were significant higher in group KO than that in group WT (Pbone and bone marrow tissues were observed in group KO, but only bone matrix-like substances were observed in group WT. In running group and non-running group, the ELISA results indicated that the immunological genes, both IL-4 and IL-12 levels were significant higher in running group than that in non-running group (Pbone tissues were observed in running group than that in non-running group. Knockout of TRPV1 in mice could reduce algesia and induce the stronger athletic ability of mice, causing better osteoinductivity of Ca-P biomaterials both in TRPV1 -/- mice and running mice; according to this, we want to offer a proposal to patients who suffer from bone defects and artificial bone transplantation: do moderate exercise, don't convalesce all the

  11. Optimizing combination of vascular endothelial growth factor and mesenchymal stem cells on ectopic bone formation in SCID mice

    DEFF Research Database (Denmark)

    Dreyer, Chris H; Kjaergaard, Kristian; Ditzel, Nicholas

    2017-01-01

    combined immunodeficient (SCID) mice were used in this study to evaluate optimal time points for VEGF stimulation to increase bone formation. METHODS: Twenty-eight SCID (NOD.CB17-Prkdcscid/J) mice had hydroxyapatite granules seeded with 5 × 105MSCs inserted subcutaneous. Pellets released VEGF on days 1......INTRODUCTION: Insufficient blood supply may limit bone regeneration in bone defects. Vascular endothelial growth factor (VEGF) promotes angiogenesis by increasing endothelial migration. This outcome, however, could depend on time of application. Sheep mesenchymal stem cells (MSCs) in severe...

  12. Quantifying capacity loss due to solid-electrolyte-interphase layer formation on silicon negative electrodes in lithium-ion batteries

    Science.gov (United States)

    Nadimpalli, Siva P. V.; Sethuraman, Vijay A.; Dalavi, Swapnil; Lucht, Brett; Chon, Michael J.; Shenoy, Vivek B.; Guduru, Pradeep R.

    2012-10-01

    Charge lost per unit surface area of a silicon electrode due to the formation of solid-electrolyte-interphase (SEI) layer during initial lithiation was quantified, and the species that constitute this layer were identified. Coin cells made with Si thin-film electrodes were subjected to a combination of galvanostatic and potentiostatic lithiation and delithiation cycles to accurately measure the capacity lost to SEI layer formation. While the planar geometry of amorphous thin films allows accurate calculation of surface area, creation of additional surface by cracking was prevented by minimizing the thickness of the Si film. The cycled electrodes were analyzed with X-ray photoelectron spectroscopy to characterize the composition of the SEI layer. The charge lost due to SEI formation measured from coin cell experiments was found to be in good agreement with the first-cycle capacity loss during the initial lithiation of a Si(100) crystal with planar geometry. The methodology presented in this work is expected to provide a useful practical tool for battery-material developers in estimating the expected capacity loss due to first cycle SEI layer formation and in choosing an appropriate particle size distribution that balances mechanical integrity and the first cycle capacity loss in large volume expansion electrodes for lithium-ion batteries.

  13. Transforming growth factor-betas and CD105 expression in calcification and bone formation in human atherosclerotic lesions.

    Science.gov (United States)

    Jeziorska, M

    2001-01-01

    To investigate the expression and localisation of transforming growth factor betas (TGF beta s) and their receptor CD105 (endoglin) in relation to calcification and bone formation in atherosclerotic lesions of human carotid arteries. The TGF beta family regulates cellular growth, differentiation and angiogenesis and plays a key role in enchondral bone formation. CD105 is part of the TGF beta receptor complex preferentially expressed on endothelial cells (EC). Immunohistochemical methods were used to determine the localisation of TGF beta isoforms 1, 2 and 3 and their spatial expression patterns in relation to calcification and bone formation in atherosclerotic lesions. Cellular sources of TGF beta s and CD105 were assessed using cell-type specific antibodies. There was marked variability in TGF beta expression in different cell types associated with calcification. Smooth muscle cells (SMC) in the atheroma cap showed higher levels of TGF beta 3 and 2 than 1, but in the deep musculoelastic intima there were higher levels of TGF beta 1 and alpha-actin. All three TGF beta isoforms were expressed in monocyte-macro-phages. Giant cells associated with calcifications showed intense staining for TGF beta 2. TGF beta 1 was most strongly expressed on matrix and cells associated with bone formation. CD105 expression on SMCs and monocyte-macrophages was lower on cells in close association with calcification. SMCs associated with bone formation expressed high levels of CD105. The different TGF beta isoforms exhibit distinct but overlapping patterns of expression, and support the hypothesis that they are involved in the process of calcification and bone formation in human atherosclerotic lesions. Lower expression of CD105 on cells associated with calcification may represent their state of lower responsiveness to TGF beta s.

  14. Evaluation of circulating levels of inflammatory and bone formation markers in axial spondyloarthritis.

    Science.gov (United States)

    de Andrade, Kenia Rodrigues; de Castro, Gláucio Ricardo Werner; Vicente, Geison; da Rosa, Julia Salvan; Nader, Marina; Pereira, Ivanio Alves; Fröde, Tânia Silvia

    2014-08-01

    Studies have demonstrated the important role of bone remodelling and osteoimmunology in the progression of inflammatory lesions in axial spondyloarthritis (SpA) disease. This study was conducted to evaluate the inflammatory response by analysis of the serum levels of pro-inflammatory and new bone formation markers in patients with axial SpA who were treated or not treated with anti-tumour necrosis factor-α (anti-TNF-α) or non-steroidal drugs (NSAIDs) and to identify whether these drugs modify the activity and severity of the disease. The serum levels of myeloperoxidase (MPO), adenosine deaminase (ADA), nitric oxide metabolites (NOx), bone alkaline phosphatase (BAP), Dickkopf-1 (DKK-1), and osteoprotegerin (OP) were measured in 52 SpA patients who were treated or not with anti-TNF-α or NSAIDs and in 26 healthy controls using colourimetric and enzyme immunoassay tests. The activity and the severity of illness in patients with SpA were assessed using questionnaires (Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)). A significant difference between the controls and the patients without medication was observed in relation to NOx, BAP, and OP (p0.05). In conclusion, The NOx, BAP, and OP are emerging as important inflammatory pathways in axial SpA. Also the anti-TNF-α or non-steroidal drugs reduce the inflammation and destructions, however these treatments do not modify the serum levels of these biomarkers. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. THE RAILROAD CAPACITY CRISIS: After Cutting to the Bone and More, Trains Are Back

    Directory of Open Access Journals (Sweden)

    Richard D. Stone

    2008-01-01

    Full Text Available During the Era of Railroad building (primarily the last half of the 19th century, it was far more profitable to lay track than to operate railroads due to the subsidiesfrom various levels ofgovernment and the competition between cities to be located on as many lines as possible, and the overcharging of the railroads by the construction companies. Railroads compensated for this glut by cross-subsidizing the unprofitable branch lines with revenues from the main lines. But as competition from other modes took hold, this was increasingly difficult to do. Therefore, by the early 20th century, railroads began to slowly shed some of the lightly trafficked lines. Regulatory changes in the 1980s made abandonment easier, and wholesale discarding of lines, including former mainlines, became common. But by the turn of the century,foreign imports put a greater demand on rail transportation, and lack of capacity caused many of the remaining lines to become very congested, in turn, causing extensive delays.

  16. Efficiently engineered cell sheet using a complex of polyethylenimine–alginate nanocomposites plus bone morphogenetic protein 2 gene to promote new bone formation

    Directory of Open Access Journals (Sweden)

    Jin H

    2014-05-01

    Full Text Available Han Jin,1 Kai Zhang,2 Chunyan Qiao,1 Anliang Yuan,1 Daowei Li,1 Liang Zhao,1 Ce Shi,1 Xiaowei Xu,1 Shilei Ni,1 Changyu Zheng,3 Xiaohua Liu,4 Bai Yang,2 Hongchen Sun11Department of Pathology, School of Stomatology, Jilin University, Changchun, People’s Republic of China; 2State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, People’s Republic of China; 3Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA; 4Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, TX, USAAbstract: Regeneration of large bone defects is a common clinical problem. Recently, stem cell sheet has been an emerging strategy in bone tissue engineering. To enhance the osteogenic potential of stem cell sheet, we fabricated bone morphogenetic protein 2 (BMP-2 gene-engineered cell sheet using a complex of polyethylenimine–alginate (PEI–al nanocomposites plus human BMP-2 complementary(cDNA plasmid, and studied its osteogenesis in vitro and in vivo. PEI–al nanocomposites carrying BMP-2 gene could efficiently transfect bone marrow mesenchymal stem cells. The cell sheet was made by culturing the cells in medium containing vitamin C for 10 days. Assays on the cell culture showed that the genetically engineered cells released the BMP-2 for at least 14 days. The expression of osteogenesis-related gene was increased, which demonstrated that released BMP-2 could effectively induce the cell sheet osteogenic differentiation in vitro. To further test the osteogenic potential of the cell sheet in vivo, enhanced green fluorescent protein or BMP-2-producing cell sheets were treated on the cranial bone defects. The results indicated that the BMP-2-producing cell sheet group was more efficient than other groups in promoting bone formation in the defect area. Our results suggested that PEI

  17. A dynamic capacity degradation model and its applications considering varying load for a large format Li-ion battery

    International Nuclear Information System (INIS)

    Ouyang, Minggao; Feng, Xuning; Han, Xuebing; Lu, Languang; Li, Zhe; He, Xiangming

    2016-01-01

    Highlights: • A dynamic capacity degradation model for large format Li-ion battery is proposed. • The change of the model parameters directly link with the degradation mechanisms. • The model can simulate the fading behavior of Li-ion battery under varying loads. • The model can help evaluate the longevity of a battery system under specific load. • The model can help predict the evolution of cell variations within a battery pack. - Abstract: The capacity degradation of the lithium ion battery should be well predicted during battery system design. Therefore, high-fidelity capacity degradation models that are suitable for the task of capacity prediction are required. This paper proposes a novel capacity degradation model that can simulate the degradation dynamics under varying working conditions for large-format lithium ion batteries. The degradation model is built based on a mechanistic and prognostic model (MPM) whose parameters are closely linked with the degradation mechanisms of lithium ion batteries. Chemical kinetics was set to drive the parameters of the MPM to change as capacity degradation continues. With the dynamic parameters of the MPM, the capacity predicted by the degradation model decreases as the cycle continues. Accelerated aging tests were conducted on three types of commercial lithium ion batteries to calibrate the capacity degradation model. The good fit with the experimental data indicates that the model can capture the degradation mechanisms well for different types of commercial lithium ion batteries. Furthermore, the calibrated model can be used to (1) evaluate the longevity of a battery system under a specific working load and (2) predict the evolution of cell variations within a battery pack when different cell works at different conditions. Correlated applications are discussed using the calibrated degradation model.

  18. Inhibition of bone formation in rats by aluminum exposure via Wnt/β-catenin pathway.

    Science.gov (United States)

    Sun, Xudong; Wang, Haoran; Huang, Wanyue; Yu, Hongyan; Shen, Tongtong; Song, Miao; Han, Yanfei; Li, Yanfei; Zhu, Yanzhu

    2017-06-01

    The previous research found that aluminum trichloride (AlCl 3 ) inhibited rat osteoblastic differentiation through inactivation of Wnt/β-catenin signaling pathway in vitro. On that basis, the experiment in vivo was conducted in this study. Rats were orally exposed to 0 (control group) and 0.4 g/L AlCl 3 (AlCl 3 -treated group) for 30, 60, 90 or 120 days, respectively. We found that mRNA expressions of type I collagen and insulin-like growth factor-1, mRNA and protein expressions of Runx2 and survivin, ratio of p-GSK3β/GSK3β and protein expression of β-catenin were all decreased, whereas the mRNA and protein expressions Dkk1 and sFRP1 and the mRNA expressions and activity of Caspase-3 were increased in the AlCl 3 -treated group compared with the control group with time prolonged. These results suggest that AlCl 3 inhibits bone formation and induces bone impairment by inhibiting the Wnt/β-catenin signaling pathway in young growing rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Effects of strontium ranelate on sutural bone formation: a histological and immunohistochemical study.

    Science.gov (United States)

    Karatas, Orhan H; Toy, Ebubekir; Demir, Abdullah; Toy, Hatice; Kozacioglu, Sumeyye

    2016-11-01

    Rapid maxillary expansion is performed to correct a skeletal transverse deficiency of the maxilla, which is a frequently- encountered orthodontic anomaly. Strontium ranelate (SrR) is a novel agent that has a dual action, involving anti-resorptive and bone-forming effects. The aim of this study was to evaluate the effects of systemically applied SrR on osteoblastic bone formation after maxillary expansion on the mid-palatal suture of rats using histological and immunohistochemical tests. A total of 24 Wistar rats were randomly divided into two equal groups. In all animals, five-day inter-premaxillary expansion was applied and maintained for a seven-day retention period, during which 625mg/kg/day SrR diluted with saline solution was administered orally to the experimental group. The rats were sacrificed and the tissues prepared for histological and immunohistochemical examinations after the retention period. Osteoblastic activity and the width of the blood vessels in the suture area were significantly increased in the SrR group compared with the control group (p osteocalcin, TGF-P and VEGF antibodies revealed significant immunoreactivity in the experimental group (p < 0.05). It may be concluded that SrR contributed to stimulatory osteogenesis in the expansion region. Therefore, a retention period may be shortened and relapse possibly reduced, following the application of SrR after the expansion.

  20. Bone tissue formation in extraction sockets from sites with advanced periodontal disease: a histomorphometric study in humans.

    Science.gov (United States)

    Ahn, Jae-Jin; Shin, Hong-In

    2008-01-01

    To investigate postextraction bone formation over time in both diseased and healthy sockets. Core specimens of healing tissues following tooth extraction were obtained at the time of implant placement in patients treated between October 2005 and December 2007. A disease group and a control group were classified according to socket examination at the time of extraction. The biopsy specimens were analyzed histomorphometrically to measure the dimensional changes among 3 tissue types: epithelial layer, connective tissue area, and new bone tissue area. Fifty-five specimens from sites of previously advanced periodontal disease from 45 patients were included in the disease group. Another 12 specimens of previously healthy extraction sockets were collected from 12 different patients as a control. The postextraction period of the disease group varied from 2 to 42 weeks. In the disease group, connective tissue occupied most of the socket during the first 4 weeks. New bone area progressively replaced the connective tissue area after the first 4 weeks. The area proportion of new bone tissue exceeded that of connective tissue by 14 weeks. After 20 weeks, most extraction sockets in the disease group demonstrated continuous new bone formation. The control group exhibited almost complete socket healing after 10 weeks, with no more new bone formation after 20 weeks. Osseous regeneration in the diseased sockets developed more slowly than in the disease-free sockets. After 16 weeks, new bone area exceeded 50% of the total newly regenerated tissue in the sockets with severe periodontal destruction. In the control group, after 8 weeks, new bone area exceeded 50% of the total tissue.

  1. New bone formation in a true bone ceramic scaffold loaded with desferrioxamine in the treatment of segmental bone defect: a preliminary study.

    Science.gov (United States)

    Zhang, Weibin; Li, Guosong; Deng, Ruoxian; Deng, Lianfu; Qiu, Shijing

    2012-05-01

    Desferrioxamine (DFO), an iron chelator, can stimulate osteogenesis and angiogenesis by stabilizing hypoxia-inducible factor 1α. We postulate that a bone graft substitute combined with DFO is beneficial to the reconstruction of bone defects. We implanted pure true bone ceramic (TBC) and DFO-loaded TBC (DFO/TBC) scaffolds into 15-mm rabbit radial defects for 8 weeks. The bone segments were examined with X-ray, micro-CT and histology. Radiographs showed that the DFO/TBC scaffold became radiopaque, and the gaps between the scaffold and radial cut ends were often invisible. Variables from micro-CT, including the bone volume fraction (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N), were significantly increased in pure TBC and DFO/TBC scaffolds that had been implanted for 8 weeks compared to unimplanted TBC scaffolds (p values <0.05-0.001). Between the former two groups, BV/TV and Tb.Th were significantly increased in DFO/TBC scaffolds (p < 0.001), but Tb.N did not show significant differences. Histological examinations showed considerably increased new bone and decreased TBC trabecular remnants in DFO/TBC scaffolds compared to pure TBC scaffolds. Many cavities in the new bone area in DFO/TBC scaffolds were occupied by bone marrow elements and blood vessels. Percent of new bone with tetracycline labeling was significantly greater in DFO/TBC scaffolds than in pure TBC scaffolds (p < 0.001). This preliminary study reveals that DFO can effectively induce new bone growing into TBC scaffolds, suggesting that the DFO/TBC composite is a promising bone graft substitute for the treatment of bone defects.

  2. Early bone formation adjacent to rough and turned endosseous implant surfaces. An experimental study in the dog.

    Science.gov (United States)

    Abrahamsson, Ingemar; Berglundh, Tord; Linder, Elena; Lang, Niklaus P; Lindhe, Jan

    2004-08-01

    To validate a proposed model (Berglundh et al. 2003) and to evaluate the rate and degree of osseointegration at turned (T) and sand blasted and acid etched (SLA) implant surfaces during early phases of healing. The devices used for the study of early healing had a geometry that corresponded to that of a solid screw implant with either a SLA or a T surface configuration. A circumferential trough had been prepared within the thread region (intra-osseous portion) that established a geometrically well-defined wound chamber. Twenty Labrador dogs received totally 160 experimental devices to allow the evaluation of healing between 2 h and 12 weeks. Both ground and decalcified sections were prepared from mesial/distal and buccal/lingual device sites. Histometric and morphometric analyses of the ground sections and morphometric analysis of the tissue components in decalcified sections were performed. The ground sections provided an overview of the various phases of tissue formation, while the decalcified, thin sections enabled a more detailed study of events involved in bone tissue modeling and remodeling for both SLA and T surfaces. The initially empty wound chamber became occupied with a coagulum and a granulation tissue that was replaced by a provisional matrix. The process of bone formation started already during the first week. The newly formed bone present at the lateral border of the cut bony bed appeared to be continuous with the parent bone, but on the SLA surface woven bone was also found at a distance from the parent bone. Parallel-fibered and/or lamellar bone as well as bone marrow replaced this primary bone after 4 weeks. In the SLA chambers, more bone-to-device contact, more initial woven bone and earlier lamellar bone formation was found than in the T chambers. Osseointegration represents a dynamic process both during its establishment and its maintenance. While healing showed similar characteristics with resorptive and appositional events for both SLA and T

  3. Osteopontin functionalization of hydroxyapatite nanoparticles in a PDLLA matrix promotes bone formation.

    Science.gov (United States)

    Jensen, T; Baas, J; Dolathshahi-Pirouz, A; Jacobsen, T; Singh, G; Nygaard, J V; Foss, M; Bechtold, J; Bünger, C; Besenbacher, F; Søballe, K

    2011-10-01

    We studied the osteoconductive tissue response of hydroxyapatite (HA) nanoparticles functionalized with osteopontin (OPN) in a matrix of poly-D,L-lactic-acid (PDLLA). In a canine endosseus 0.75-mm gap implant model, we tested the osteointegrative impact of the OPN functionalized composite as an implant coating, and a non-functionalized composite was used as reference control. During the four weeks of observation, the OPN functionalized composite coating significantly increased the formation of new bone in the porosities of the implant, but no differences were observed in the gap. The study provides evidence of its potential use either alone or in combination with other osteoconductive compounds. Copyright © 2011 Wiley Periodicals, Inc.

  4. Inhibiting actin depolymerization enhances osteoblast differentiation and bone formation in human stromal stem cells

    DEFF Research Database (Denmark)

    Chen, Li; Shi, Kaikai; Frary, Charles

    2015-01-01

    Remodeling of the actin cytoskeleton through actin dynamics is involved in a number of biological processes, but its role in human stromal (skeletal) stem cells (hMSCs) differentiation is poorly understood. In the present study, we demonstrated that stabilizing actin filaments by inhibiting gene...... expression of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) in hMSCs, enhanced cell viability and differentiation into osteoblastic cells (OB) in vitro, as well as heterotopic bone formation in vivo. Similarly, treating hMSC with Phalloidin, which is known to stabilize...... polymerized actin filaments, increased hMSCs viability and OB differentiation. Conversely, Cytocholasin D, an inhibitor of actin polymerization, reduced cell viability and inhibited OB differentiation of hMSC. At a molecular level, preventing Cofilin phosphorylation through inhibition of LIM domain kinase 1...

  5. Inflammation-driven bone formation in a mouse model of ankylosing spondylitis: sequential not parallel processes.

    Science.gov (United States)

    Tseng, Hsu-Wen; Pitt, Miranda E; Glant, Tibor T; McRae, Allan F; Kenna, Tony J; Brown, Matthew A; Pettit, Allison R; Thomas, Gethin P

    2016-01-29

    Ankylosing spondylitis (AS) is an immune-mediated arthritis particularly targeting the spine and pelvis and is characterised by inflammation, osteoproliferation and frequently ankylosis. Current treatments that predominately target inflammatory pathways have disappointing efficacy in slowing disease progression. Thus, a better understanding of the causal association and pathological progression from inflammation to bone formation, particularly whether inflammation directly initiates osteoproliferation, is required. The proteoglycan-induced spondylitis (PGISp) mouse model of AS was used to histopathologically map the progressive axial disease events, assess molecular changes during disease progression and define disease progression using unbiased clustering of semi-quantitative histology. PGISp mice were followed over a 24-week time course. Spinal disease was assessed using a novel semi-quantitative histological scoring system that independently evaluated the breadth of pathological features associated with PGISp axial disease, including inflammation, joint destruction and excessive tissue formation (osteoproliferation). Matrix components were identified using immunohistochemistry. Disease initiated with inflammation at the periphery of the intervertebral disc (IVD) adjacent to the longitudinal ligament, reminiscent of enthesitis, and was associated with upregulated tumor necrosis factor and metalloproteinases. After a lag phase, established inflammation was temporospatially associated with destruction of IVDs, cartilage and bone. At later time points, advanced disease was characterised by substantially reduced inflammation, excessive tissue formation and ectopic chondrocyte expansion. These distinct features differentiated affected mice into early, intermediate and advanced disease stages. Excessive tissue formation was observed in vertebral joints only if the IVD was destroyed as a consequence of the early inflammation. Ectopic excessive tissue was predominantly

  6. Implantation of silicon dioxide-based nanocrystalline hydroxyapatite and pure phase beta-tricalciumphosphate bone substitute granules in caprine muscle tissue does not induce new bone formation

    Directory of Open Access Journals (Sweden)

    Ghanaati Shahram

    2013-01-01

    Full Text Available Abstract Background Osteoinductive bone substitutes are defined by their ability to induce new bone formation even at heterotopic implantation sites. The present study was designed to analyze the potential osteoinductivity of two different bone substitute materials in caprine muscle tissue. Materials and methods One gram each of either a porous beta-tricalcium phosphate (β-TCP or an hydroxyapatite/silicon dioxide (HA/SiO2-based nanocrystalline bone substitute material was implanted in several muscle pouches of goats. The biomaterials were explanted at 29, 91 and 181 days after implantation. Conventional histology and special histochemical stains were performed to detect osteoblast precursor cells as well as mineralized and unmineralized bone matrix. Results Both materials underwent cellular degradation in which tartrate-resistant acid phosphatase (TRAP-positive osteoclast-like cells and TRAP-negative multinucleated giant cells were involved. The ß-TCP was completely resorbed within the observation period, whereas some granules of the HA-groups were still detectable after 180 days. Neither osteoblasts, osteoblast precursor cells nor extracellular bone matrix were found within the implantation bed of any of the analyzed biomaterials at any of the observed time points. Conclusions This study showed that ß-TCP underwent a faster degradation than the HA-based material. The lack of osteoinductivity for both materials might be due to their granular shape, as osteoinductivity in goat muscle has been mainly attributed to cylindrical or disc-shaped bone substitute materials. This hypothesis however requires further investigation to systematically analyze various materials with comparable characteristics in the same experimental setting.

  7. De-novo Collateral Formation Following Acute Myocardial Infarction: Dependence on CCR2+ Bone Marrow Cells

    Science.gov (United States)

    Zhang, Hua; Faber, James E

    2015-01-01

    Wide variation exists in the extent (number and diameter) of native pre-existing collaterals in tissues of different strains of mice, with supportive indirect evidence recently appearing for humans. This variation is a major determinant of the wide variation in severity of tissue injury in occlusive vascular disease. Whether such genetic-dependent variation also exists in the heart is unknown because no model exists for study of mouse coronary collaterals. Also owing to methodological limitations, it is not known if ischemia can induce new coronary collaterals to form (“neo-collaterals”) versus remodeling of pre-existing ones. The present study sought to develop a model to study coronary collaterals in mice, determine whether neo-collateral formation occurs, and investigate the responsible mechanisms. Four strains with known rank-ordered differences in collateral extent in brain and skeletal muscle were studied: C57BLKS>C57BL/6>A/J>BALB/c. Unexpectedly, these and 5 additional strains lacked native coronary collaterals. However after ligation, neo-collaterals formed rapidly within 1-to-2 days, reaching their maximum extent in ≤ 7 days. Rank-order for neo-collateral formation differed from the above: C57BL/6>BALB/c>C57BLKS>A/J. Collateral network conductance, infarct volume−1, and contractile function followed this same rank-order. Neo-collateral formation and collateral conductance were reduced and infarct volume increased in MCP1−/− and CCR2−/− mice. Bone-marrow transplant rescued collateral formation in CCR2−/− mice. Involvement of fractalkine→CX3CR1 signaling and endothelial cell proliferation were also identified. This study introduces a model for investigating the coronary collateral circulation in mice, demonstrates that neocollaterals form rapidly after coronary occlusion, and finds that MCP→CCR2-mediated recruitment of myeloid cells is required for this process. PMID:26254180

  8. Bio-activated titanium surface utilizable for mimetic bone implantation in dentistry—Part III: Surface characteristics and bone implant contact formation

    Science.gov (United States)

    Strnad, Jakub; Strnad, Zdeněk; Šesták, Jaroslav; Urban, Karel; Povýšil, Ctibor

    2007-05-01

    This study was carried out to quantify the effect of an alkali-modified surface on the bone implant interface formation during healing using an animal model. A total of 24 screw-shaped, self-tapping, (c.p.) titanium dental implants, divided into test group B—implants with alkali-modified surface (Bio surface) and control group M—implants with turned, machined surface, were inserted without pre-tapping in the tibiae of three beagle dogs. The animals were sacrificed after 2, 5 and 12 weeks and the bone implant contact (BIC%) was evaluated histometrically. The surface characteristics that differed between the implant surfaces, i.e. specific surface area, contact angle, may represent factors that influence the rate of osseointegration and the secondary implant stability. The alkali-treated surface enhances the BIC formation during the first 2 5 weeks of healing compared to the turned, machined surface.

  9. Generation of an rhBMP-2-loaded beta-tricalcium phosphate/hydrogel composite and evaluation of its efficacy on peri-implant bone formation

    International Nuclear Information System (INIS)

    Lee, Jae Hyup; Baek, Hae-Ri; Lee, Ji-Ho; Ryu, Mi Young; Seo, Jun-Hyuk; Lee, Kyung-Mee

    2014-01-01

    Dental implant insertion on a site with low bone quality or bone defect should be preceded by a bone graft or artificial bone graft insertion to heal the defect. We generated a beta-tricalcium phosphate (β-TCP) and poloxamer 407-based hydrogel composite and penetration of the β-TCP/hydrogel composite into the peri-implant area of bone was evaluated by porous bone block experiments. The maximum penetration depth for porous bone blocks and dense bone blocks were 524 μm and 464 μm, respectively. We report the in-vivo performance of a composite of β-TCP/hydrogel composite as a carrier of recombinant human bone morphogenetic protein (rhBMP-2), implanted into a rabbit tibial defect model. Three holes drilled into each tibia of eight male rabbits were (1) grafted with dental implant fixtures; (2) filled with β-TCP/hydrogel composite (containing 5 μg of rhBMP-2), followed by grafting of the dental implant fixtures. Four weeks later, bone-implant contact ratio and peri-implant bone formation were analyzed by radiography, micro-CT and histology of undecalcified specimens. The micro-CT results showed a significantly higher level of trabecular thickness and new bone and peri-implant new bone formation in the experimental treatment compared to the control treatment. Histomorphometry revealed a significantly higher bone-implant contact ratio and peri-implant bone formation with the experimental treatment. The use of β-TCP/poloxamer 407 hydrogel composite as a carrier of rhBMP-2 significantly promoted new bone formation around the dental implant fixture and it also improved the quality of the new bone formed in the tibial marrow space. (paper)

  10. Mesenchymal stem cells from cortical bone demonstrate increased clonal incidence, potency, and developmental capacity compared to their bone marrow–derived counterparts

    Directory of Open Access Journals (Sweden)

    Daniel Blashki

    2016-08-01

    Full Text Available In this study, we show that matrix dense cortical bone is the more potent compartment of bone than bone marrow as a stromal source for mesenchymal stem cells as isolated from adult rats. Lineage-depleted cortical bone-mesenchymal stem cells demonstrated >150-fold enrichment of colony forming unit–fibroblasts per cell incidence. compared to lineage-depleted bone marrow-mesenchymal stem cells, corresponding to a 70-fold increase in absolute recovered colony forming unit–fibroblasts. The composite phenotype Lin−/CD45−/CD31−/VLA-1+/Thy-1+ enriched for clonogenic mesenchymal stem cells solely from cortical bone–derived cells from which 70% of clones spontaneously differentiated into all lineages of bone, cartilage, and adipose. Both populations generated vascularized bone tissue within subcutaneous implanted collagen scaffolds; however, cortical bone–derived cells formed significantly more osteoid than bone marrow counterparts, quantified by histology. The data demonstrate that our isolation protocol identifies and validates mesenchymal stem cells with superior clonal, proliferative, and developmental potential from cortical bone compared to the bone marrow niche although marrow persists as the typical source for mesenchymal stem cells both in the literature and current pre-clinical therapies.

  11. NSAIDS inhibit in vitro MSC chondrogenesis but not osteogenesis: implications for mechanism of bone formation inhibition in man.

    Science.gov (United States)

    Pountos, Ippokratis; Giannoudis, Peter V; Jones, Elena; English, Anne; Churchman, Sarah; Field, Sarah; Ponchel, Frederique; Bird, Howard; Emery, Paul; McGonagle, Dennis

    2011-03-01

    The non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for analgesia but may inhibit bone formation. We investigated whether the reported NSAID effect on bone is related to inhibition of bone marrow mesenchymal stem cell (MSC) proliferation and osteogenic and chondrogenic differentiation and evaluated both cyclooxygenase (COX)-1 and COX-2 specific drugs. The effects of seven COX-1 and COX-2 inhibitors on MSC proliferation and osteogenic and chondrogenic differentiation were tested using Vybrant, sodium 3'-[1-(phenylaminocarbonyl)- 3,4-tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate (XTT), functional and quantitative assays of MSC differentiation. The MSC expression of COX-1 and COX-2 and prostaglandin E2 (PGE-2) levels were evaluated serially during lineage differentiation by quantitative PCR and ELISA. None of the NSAIDs at broad range of concentration (range 10(-3) to 100 μg/ml) significantly affected MSC proliferation. Surprisingly, MSC osteogenic differentiation inhibition was not evident. However, NSAIDs affected chondrogenic potential with a reduction in sulphated glycosaminoglycans (sGAG) content by 45% and 55% with diclofenac and ketorolac, respectively (P NSAIDs may inhibit bone formation via blockage of MSC chondrogenic differentiation which is an important intermediate phase in normal endochondral bone formation. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

  12. 1. modification of the proliferative capacity of transplanted bone marrow colony forming units by changes in the host environment

    International Nuclear Information System (INIS)

    Beran, M.; Tribukait, B.

    1974-01-01

    Regulation of the proliferation of transplanted colony forming units (CFUs) was investigated in lethally irradiated mice, pretreated by methods known to accelerate hemopoietic recovery after sublethal irradiation. Prospective recipients were exposed to either hypoxia, vinblastine or priming irradiation and at different intervals thereafter lethally irradiated and transplanted with bone marrow. Repopulation of CFUs was determined by counting the number of splenic colonies in primary recipients or by retransplantation. Regeneration of grafted CFUs was greatly accelerated and their self-renewal capacity increased in mice grafted within 2 days after hypoxia. Also the number of splenic colonies formed by grafted syngeneic CFUs as well as by C57B1 parent CFUs growing in BC3F1 hosts was significantly increased. The effect was not dependent on the seeding efficiency of CFUs and apparently resulted from hypoxia induced changes in the hosts' physiological environment. Proliferative capacity of grafted CFUs increased remarkably in hosts receiving vinblastine 2 or 4 days prior to irradiation. Priming irradiation given 6 days before main irradiation accelerated, given 2 days before impaired regeneration of CFUs. The increased rate of regeneration was not related to the cellularity of hemopoietic organs at the time of transplantation. The growth of CFUs in diffusion chambers implanted into posthypoxic mice was only slightly improved which does indicate that the accelerated regeneration of CFUs in posthypoxic mice is mainly due to the changes in the hemopoietic microenvironment. A short conditioning of transplanted CFUs by host factor(s) was sufficient to improve regeneration. The results might suggest that the speed of hemopoietic regeneration depends on the number of CFUs being induced to proliferate shortly after irradiation, rather than on the absolute numbers of CFUs available to the organism. (author)

  13. Trivalent chromium incorporated in a crystalline calcium phosphate matrix accelerates materials degradation and bone formation in vivo.

    Science.gov (United States)

    Rentsch, Barbe; Bernhardt, Anne; Henß, Anja; Ray, Seemun; Rentsch, Claudia; Schamel, Martha; Gbureck, Uwe; Gelinsky, Michael; Rammelt, Stefan; Lode, Anja

    2018-03-15

    Remodeling of calcium phosphate bone cements is a crucial prerequisite for their application in the treatment of large bone defects. In the present study trivalent chromium ions were incorporated into a brushite forming calcium phosphate cement in two concentrations (10 and 50 mmol/mol β-tricalcium phosphate) and implanted into a femoral defect in rats for 3 and 6 month, non-modified brushite was used as reference. Based on our previous in vitro findings indicating both an enhanced osteoclastic activity and cytocompatibility towards osteoprogenitor cells we hypothesized a higher in vivo remodeling rate of the Cr 3+ doped cements compared to the reference. A significantly enhanced degradation of the modified cements was evidenced by micro computed tomography, X-ray and histological examinations. Furthermore the formation of new bone tissue after 6 month of implantation was significantly increased from 29% to 46% during remodeling of cements, doped with the higher Cr 3+ amount. Time of flight secondary ion mass spectrometry (ToF-SIMS) of histological sections was applied to investigate the release of Cr 3+ ions from the cement after implantation and to image their distribution in the implant region and the surrounding bone tissue. The relatively weak incorporation of chromium into the newly formed bone tissue is in agreement to the low chromium concentrations which were released from the cements in vitro. The faster degradation of the Cr 3+ doped cements was also verified by ToF-SIMS. The positive effect of Cr 3+ doping on both degradation and new bone formation is discussed as a synergistic effect of Cr 3+ bioactivity on osteoclastic resorption on one hand and improvement of cytocompatibility and solubility by structural changes in the calcium phosphate matrix on the other hand. While biologically active metal ions like strontium, magnesium and zinc are increasingly applied for the modification of ceramic bone graft materials, the present study is the first

  14. The transcription factor early B-cell factor 1 regulates bone formation in an osteoblast-nonautonomous manner.

    Science.gov (United States)

    Zee, Tiffany; Boller, Sören; Györy, Ildiko; Makinistoglu, Munevver P; Tuckermann, Jan P; Grosschedl, Rudolf; Karsenty, Gerard

    2013-03-18

    Early B-cell factor 1 (Ebf1) is a transcription factor whose inactivation in all cells results in high bone mass because of an increase in bone formation. This observation suggests Ebf1 may be an inhibitor of osteoblast differentiation. To test this contention, we analyzed Ebf1 pattern of expression and function in osteoblasts ex vivo and in vivo through osteoblast-specific inactivation in the mouse. We show here that in vivo deletion of Ebf1 in osteoblast progenitors does not affect osteoblast differentiation or bone formation accrual post-natally. These observations indicate that the phenotype described in Ebf1(-/)(-) mice is not osteoblast-autonomous. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  15. 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.

  16. A comparison inhibitory effects of cisplatin and MNPs-PEG-cisplatin on the adhesion capacity of bone metastatic breast cancer.

    Science.gov (United States)

    Mokhtari, Mohammad Javad; Koohpeima, Fatemeh; Mohammadi, Hadi

    2017-10-01

    To date, high mortality in women due to malignancy breast cancer related to the metastasis to the bone is a significant challenge. As, magnetic nanoparticles (MNPs) conjugated with the biocompatible polymers was employed for the delivery of some hydrophobic anticancer agents, the main aim of the current research was to assess whether cisplatin-loaded MNPs enhanced the anticancer effect of free cisplatin in breast cancer cells. MNPs decorated with PEG were synthesized by an improved coprecipitation technique, and then cisplatin was loaded onto the MNPs via a simple mixing method. Afterward, its morphology, size, chemical structure, magnetic property, hydrodynamic diameter, zeta potential, and crystal structure were characterized by scanning and transmittance electron microscopy, Fourier transforms infrared spectroscopy, vibrating sample magnetometer, dynamic light scattering, and X-ray powder diffraction and flame atomic absorption spectroscopy respectively. Additionally, the effects of cisplatin and MNPs-PEG-cisplatin on viability, migration and adhesion capacity of T47D cells were investigated by evaluating α2-integrin and β1-integrin; mRNAs were assessed by real-time RT-PCR. Consequently, the in vitro assay results showed a considerable dose-dependent inhibitory effect of cisplatin and MNPs-PEG-cisplatin on proliferation, migration, and adhesion of T47D cells. Finally, current research was shown that MNPs-PEG-cisplatin strongly increased anticancer effects compared with free cisplatin in the T47D cell line. © 2017 John Wiley & Sons A/S.

  17. Histomorphometric analysis of bone formation in bony defects around implants in adult dogs: a comparison of grafts of low and high heat-treated autogenous tooth ash.

    Science.gov (United States)

    Kim, Jin-Ha; Kim, Su-Gwan; Lim, Sung-Chul; Oh, Ji-Su; You, Jae-Seek; Jeong, Mi-Ae

    2013-12-01

    The purpose of this study was to compare the bone formation of autogenous tooth ash treated with different temperatures. Heat treatment was rendered by powder after extraction of teeth from dogs. The bony defects were made at iliac and resorbable blast medium surfaced implant placement and bone graft was performed; no bone graft group (control group), low heat-treated tooth ash group (group 1), high heat-treated tooth ash group (group 2). Right side had healing periods of 12 weeks, and the left side had 6 weeks. Histomorphometrical analysis was performed at 12 weeks. The control group had poor bone formation and showed large loose connective tissue. Group 1 displayed good healing and bone formation. Group 2 showed higher rate of bone formation than group 1 and the control group. The high heat-treated tooth ash group showed a statistically significant increase in the rate of bone formation in the early stage. The heat-treated autogenous tooth ash powder showed excellent new bone formation. The temperature of heat treatment is an important factor in new bone formation. The high heat treatment was the optimal treatment method for making tooth ash than the low heat treatment.

  18. Postlaminectomy Bone and Scar Formations in Presence of Ankaferd Blood Stopper and Bitter Melon (Momordica Charantia): An Experimental Study.

    Science.gov (United States)

    Kuruoglu, Enis; Onger, Mehmet Emin; Marangoz, Abdullah Hilmi; Kocacan, Suleyman Emre; Cokluk, Cengiz; Kaplan, Suleyman

    2017-01-01

    A quantitative model of postlaminectomy was designed in rats. The effects of Momordica Charantia (MC) and Ankaferd blood stopper (ABS) on the bone and scar formation after laminectomy were concurrently evaluated. Eighteen adult Wistar albino rats underwent lumbar laminectomy at L2-L3 vertebral levels, and were randomly assigned to one of three groups of six rats each. The Treatment group received MC and ABS treatment and the Control group was left untreated. Rats were sacrificed 4 weeks after treatment. Then; the lumbar spine was excised en-block, fixed and decalcified. Sections were stained with hematoxylin and eosin (H&E) and Masson"s trichrome, and evaluated for peridural fibrosis (PF), new bone formation, and vascular proliferation. Total volume of new bone in the MC group was significantly increased in comparison to the Control group (p < 0.05). Also; there was highly significant increase in terms of the total volume of fibrous tissue in the MC and ABS groups when compared with the Control group (p < 0.01). Besides; there was a highly significant difference between the MC and the Control groups (p < 0.01) in point of total volume of vessel. Both MC and ABS are not convenient to prevent the PF formation and MC may promote new bone formation and angiogenesis after lumbar laminectomy in rats.

  19. A relationship between spinal new bone formation in ankylosing spondylitis and the sonographically determined Achilles tendon enthesophytes.

    Science.gov (United States)

    Aydin, Sibel Zehra; Can, Meryem; Alibaz-Oner, Fatma; Keser, Gokhan; Kurum, Esra; Inal, Vedat; Yazisiz, Veli; Birlik, Merih; Emmungil, Hakan; Atagunduz, Pamir; Direskeneli, Haner; McGonagle, Dennis; Pay, Salih

    2016-03-01

    Spinal new bone formation is a major but incompletely understood manifestation of ankylosing spondylitis (AS). We explored the relationship between spinal new bone formation and ultrasound (US)-determined Achilles enthesophytes to test the hypothesis that spinal new bone formation is part of a generalized enthesis bone-forming phenotype. A multicenter, case control study of 225 consecutive AS patients and 95 age/body mass index (BMI) matched healthy controls (HC) was performed. US scans of Achilles tendons and cervical and lumbar spine radiographs were obtained. All images were centrally scored by one investigator for US and one for radiographs, blinded to medical data. The relation between syndesmophytes (by modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) and the number of syndesmophytes) and enthesophytes (with a semi-quantitative scoring of the US findings) was investigated. AS patients had significantly higher US enthesophyte scores than HCs (2.1(1.6) vs. 1.6(1.6); p = 0.004). The difference was significant in males (p = 0.001) but not in females (p = 0.5). The enthesophyte scores significantly correlated with mSASSS scores (ρ = 0.274, p formation.

  20. Induction of bone formation by smart biphasic hydroxyapatite tricalcium phosphate biomimetic matrices in the non-human primate Papio ursinus

    CSIR Research Space (South Africa)

    Ripamonti, U

    2008-01-01

    Full Text Available Long-term studies in the non-human primate Chacma baboon Papio ursinus were set to investigate the induction of bone formation by biphasic hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) biomimetic matrices. HA/β-TCP biomimetic matrices in a pre...

  1. Ectopic bone formation cannot occur by hydroxyapatite/{beta}-tricalcium phosphate bioceramics in green fluorescent protein chimeric mice

    Energy Technology Data Exchange (ETDEWEB)

    Cheng Lijia [Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu (China); Duan Xin [Department of Orthopaedics, Chengdu Second People' s Hospital, Chengdu (China); Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu (China); Xiang Zhou [Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu (China); Shi Yujun; Lu Xiaofeng; Ye Feng [Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu (China); Bu Hong, E-mail: hongbu@scu.edu.cn [Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu (China); Department of Pathology, West China Hospital, Sichuan University, Chengdu (China)

    2012-12-01

    Highlights: Black-Right-Pointing-Pointer Firstly, chimeric mouse model could be established successfully by bone marrow transplantation after irradiation. Black-Right-Pointing-Pointer Secondly, bone induction can occur in wild-type mice 90 days after implantation, but not occur in chimeric mice. Black-Right-Pointing-Pointer Thirdly, destruction of immune function will block osteoinduction by calcium phosphate ceramics. - Abstract: Many studies have shown that calcium phosphate ceramics (CP) have osteoconductive and osteoinductive properties; however, the exact mechanism of bone induction has not yet been reported. This study was performed to investigate if destroying immunological function will influence osteogenesis, to explain the mechanism which is unclear. In this study, twenty C57BL/6 mice were divided into two groups (n = 10), in group 1, a hydroxyapatite/{beta}-tricalcium phosphate (HA/{beta}-TCP) ceramic was implanted into both the left and right leg muscles of each mouse; in group 2, ten mice experienced lethal irradiation, then were injected bone marrow (BM) cells from green fluorescent protein (GFP) transgenic mice by tail veil, after bone marrow transplantation (BMT), heart, liver, spleen, lung, kidney, and muscle were harvested for biological analysis, after the GFP chimera model was established successfully, the same HA/{beta}-TCP ceramic was implanted into both leg muscles of each mouse immediately after irradiation. 45 and 90 days after implantation, the ceramics of the two groups were harvested to perform with hematoxylin and eosin (HE) and immunohistochemistry (IHC) staining; the results showed that there was no bone formation in group 2, while new bone tissues were detected in group 1. Our findings suggest that the BM cell from GFP transgenic mice is a good biomarker and it could set a good platform for chimera model; it also shows that BM cell is one of cell resources of bone induction, and destruction of immune function will impede

  2. Ectopic bone formation cannot occur by hydroxyapatite/β-tricalcium phosphate bioceramics in green fluorescent protein chimeric mice

    International Nuclear Information System (INIS)

    Cheng Lijia; Duan Xin; Xiang Zhou; Shi Yujun; Lu Xiaofeng; Ye Feng; Bu Hong

    2012-01-01

    Highlights: ► Firstly, chimeric mouse model could be established successfully by bone marrow transplantation after irradiation. ► Secondly, bone induction can occur in wild-type mice 90 days after implantation, but not occur in chimeric mice. ► Thirdly, destruction of immune function will block osteoinduction by calcium phosphate ceramics. - Abstract: Many studies have shown that calcium phosphate ceramics (CP) have osteoconductive and osteoinductive properties; however, the exact mechanism of bone induction has not yet been reported. This study was performed to investigate if destroying immunological function will influence osteogenesis, to explain the mechanism which is unclear. In this study, twenty C57BL/6 mice were divided into two groups (n = 10), in group 1, a hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) ceramic was implanted into both the left and right leg muscles of each mouse; in group 2, ten mice experienced lethal irradiation, then were injected bone marrow (BM) cells from green fluorescent protein (GFP) transgenic mice by tail veil, after bone marrow transplantation (BMT), heart, liver, spleen, lung, kidney, and muscle were harvested for biological analysis, after the GFP chimera model was established successfully, the same HA/β-TCP ceramic was implanted into both leg muscles of each mouse immediately after irradiation. 45 and 90 days after implantation, the ceramics of the two groups were harvested to perform with hematoxylin and eosin (HE) and immunohistochemistry (IHC) staining; the results showed that there was no bone formation in group 2, while new bone tissues were detected in group 1. Our findings suggest that the BM cell from GFP transgenic mice is a good biomarker and it could set a good platform for chimera model; it also shows that BM cell is one of cell resources of bone induction, and destruction of immune function will impede osteoinduction by CP. Overall, our results may shed light on clear mechanism study of bone

  3. Collagen immobilization of multi-layered BCP-ZrO{sub 2} bone substitutes to enhance bone formation

    Energy Technology Data Exchange (ETDEWEB)

    Linh, Nguyen Thuy Ba [Department of Regenerative Medicine, College of Medicine, Soonchunhyang University, Cheonan, 330-090 (Korea, Republic of); Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University, Cheonan, 330-090 (Korea, Republic of); Jang, Dong-Woo [Department of Regenerative Medicine, College of Medicine, Soonchunhyang University, Cheonan, 330-090 (Korea, Republic of); Lee, Byong-Taek, E-mail: lbt@sch.ac.kr [Department of Regenerative Medicine, College of Medicine, Soonchunhyang University, Cheonan, 330-090 (Korea, Republic of); Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University, Cheonan, 330-090 (Korea, Republic of)

    2015-08-01

    Graphical abstract: - Highlights: • Col-BCP-ZrO. • Collagen fibers were formed and attached firmly on the surface of BCP-ZrO. • Highly interconnected but uniform porosity were obtained. • High biocompatible, strength scaffolds and new bone were evident in Col-BCP-ZrO{sub 2}. - Abstract: A porous microstructure of multi-layered BCP-ZrO{sub 2} bone substitutes was fabricated using the sponge replica method in which the highly interconnected structure was immobilized with collagen via ethyl(dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide crosslinking. Their struts are combined with a three-layered BCP/BCP-ZrO{sub 2}/ZrO{sub 2} microstructure. Collagen fibers were firmly attached to the strut surface of the BCP-ZrO{sub 2} scaffolds. With control of the three-layered microstructure and collagen immobilization, the compressive strength of the scaffolds increased significantly to 6.8 MPa compared to that of the monolithic BCP scaffolds (1.3 MPa). An in vitro study using MTT, confocal observation, and real-time polymer chain reaction analysis demonstrated that the proliferation and differentiation of the pre-osteoblast-like MC3T3-E1 cells was improved due to the collagen incorporation. Remarkable enhancement of bone regeneration was observed without any immunological reaction in the femurs of rabbits during 1 and 5 months of implantation. Furthermore, the interfaces between new bone and the scaffold struts bonded directly without any gaps.

  4. Bone formation by three-dimensional stromal osteoblast culture in biodegradable polymer scaffolds

    Science.gov (United States)

    Ishaug, S. L.; Crane, G. M.; Miller, M. J.; Yasko, A. W.; Yaszemski, M. J.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

    1997-01-01

    Bone formation was investigated in vitro by culturing stromal osteoblasts in three-dimensional (3-D), biodegradable poly(DL-lactic-co-glycolic acid) foams. Three polymer foam pore sizes, ranging from 150-300, 300-500, and 500-710 microns, and two different cell seeding densities, 6.83 x 10(5) cells/cm2 and 22.1 x 10(5) cells/cm2, were examined over a 56-day culture period. The polymer foams supported the proliferation of seeded osteoblasts as well as their differentiated function, as demonstrated by high alkaline phosphatase activity and deposition of a mineralized matrix by the cells. Cell number, alkaline phosphatase activity, and mineral deposition increased significantly over time for all the polymer foams. Osteoblast foam constructs created by seeding 6.83 x 10(5) cells/cm2 on foams with 300-500 microns pores resulted in a cell density of 4.63 x 10(5) cells/cm2 after 1 day in culture; they had alkaline phosphatase activities of 4.28 x 10(-7) and 2.91 x 10(-6) mumol/cell/min on Days 7 and 28, respectively; and they had a cell density that increased to 18.7 x 10(5) cells/cm2 by Day 56. For the same constructs, the mineralized matrix reached a maximum penetration depth of 240 microns from the top surface of the foam and a value of 0.083 mm for mineralized tissue volume per unit of cross sectional area. Seeding density was an important parameter for the constructs, but pore size over the range tested did not affect cell proliferation or function. This study suggests the feasibility of using poly(alpha-hydroxy ester) foams as scaffolding materials for the transplantation of autogenous osteoblasts to regenerate bone tissue.

  5. Preservation and promotion of bone formation in the mandible as a response to a novel calcium-phosphate based biomaterial in mineral deficiency induced low bone mass male versus female rats.

    Science.gov (United States)

    Srinivasan, Kritika; Naula, Diana P; Mijares, Dindo Q; Janal, Malvin N; LeGeros, Racquel Z; Zhang, Yu

    2016-07-01

    Calcium and other trace mineral supplements have previously demonstrated to safely improve bone quality. We hypothesize that our novel calcium-phosphate based biomaterial (SBM) preserves and promotes mandibular bone formation in male and female rats on mineral deficient diet (MD). Sixty Sprague-Dawley rats were randomly assigned to receive one of three diets (n = 10): basic diet (BD), MD or mineral deficient diet with 2% SBM. Rats were sacrificed after 6 months. Micro-computed tomography (µCT) was used to evaluate bone volume and 3D-microarchitecture while microradiography (Faxitron) was used to measure bone mineral density from different sections of the mandible. Results showed that bone quality varied with region, gender and diet. MD reduced bone mineral density (BMD) and volume and increased porosity. SBM preserved BMD and bone mineral content (BMC) in the alveolar bone and condyle in both genders. In the alveolar crest and mandibular body, while preserving more bone in males, SBM also significantly supplemented female bone. Results indicate that mineral deficiency leads to low bone mass in skeletally immature rats, comparatively more in males. Furthermore, SBM administered as a dietary supplement was effective in preventing mandibular bone loss in all subjects. This study suggests that the SBM preparation has potential use in minimizing low peak bone mass induced by mineral deficiency and related bone loss irrespective of gender. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1622-1632, 2016. © 2016 Wiley Periodicals, Inc.

  6. Differential bone-forming capacity of osteogenic cells from either embryonic stem cells or bone marrow-derived mesenchymal stem cells

    NARCIS (Netherlands)

    Both, Sanne Karijn; van Apeldoorn, Aart A.; Jukes, J.M.; Englund, Mikael C.O.; Hyllner, Johan; van Blitterswijk, Clemens; de Boer, Jan

    2011-01-01

    For more than a decade, human mesenchymal stem cells (hMSCs) have been used in bone tissue-engineering research. More recently some of the focus in this field has shifted towards the use of embryonic stem cells. While it is well known that hMSCs are able to form bone when implanted subcutaneously in

  7. Muramyl Dipeptide Enhances Lipopolysaccharide-Induced Osteoclast Formation and Bone Resorption through Increased RANKL Expression in Stromal Cells

    Directory of Open Access Journals (Sweden)

    Masahiko Ishida

    2015-01-01

    Full Text Available Lipopolysaccharide (LPS is bacterial cell wall component capable of inducing osteoclast formation and pathological bone resorption. Muramyl dipeptide (MDP, the minimal essential structural unit responsible for the immunological activity of peptidoglycans, is ubiquitously expressed by bacterium. In this study, we investigated the effect of MDP in LPS-induced osteoclast formation and bone resorption. LPS was administered with or without MDP into the supracalvariae of mice. The number of osteoclasts, the level of mRNA for cathepsin K and tartrate-resistant acid phosphatase (TRAP, the ratio of the bone destruction area, the level of tartrate-resistant acid phosphatase form 5b (TRACP 5b, and C-terminal telopeptides fragments of type I collagen as a marker of bone resorption in mice administrated both LPS and MDP were higher than those in mice administrated LPS or MDP alone. On the other hand, MDP had no effect on osteoclastogenesis in parathyroid hormone administrated mice. MDP enhanced LPS-induced receptor activator of NF-κB ligand (RANKL expression and Toll-like receptor 4 (TLR4 expression in vivo and in stromal cells in vitro. MDP also enhanced LPS-induced mitogen-activated protein kinase (MAPK signaling, including ERK, p38, and JNK, in stromal cells. These results suggest that MDP might play an important role in pathological bone resorption in bacterial infection diseases.

  8. An orally active calcium-sensing receptor antagonist that transiently increases plasma concentrations of PTH and stimulates bone formation.

    Science.gov (United States)

    Kumar, Sanjay; Matheny, Christopher J; Hoffman, Sandra J; Marquis, Robert W; Schultz, Maggie; Liang, Xiaoguang; Vasko, Janice A; Stroup, George B; Vaden, Vernal R; Haley, Hyking; Fox, John; DelMar, Eric G; Nemeth, Edward F; Lago, Amparo M; Callahan, James F; Bhatnagar, Pradip; Huffman, William F; Gowen, Maxine; Yi, Bingming; Danoff, Theodore M; Fitzpatrick, Lorraine A

    2010-02-01

    Daily subcutaneous administration of exogenous parathyroid hormone (PTH) promotes bone formation in patients with osteoporosis. Here we describe two novel, short-acting calcium-sensing receptor antagonists (SB-423562 and its orally bioavailable precursor, SB-423557) that elicit transient PTH release from the parathyroid gland in several preclinical species and in humans. In an ovariectomized rat model of bone loss, daily oral administration of SB-423557 promoted bone formation and improved parameters of bone strength at lumbar spine, proximal tibia and midshaft femur. Chronic administration of SB-423557 did not increase parathyroid cell proliferation in rats. In healthy human volunteers, single doses of intravenous SB-423562 and oral SB-423557 elicited transient elevations of endogenous PTH concentrations in a profile similar to that observed with subcutaneously administered PTH. Both agents were well tolerated in humans. Transient increases in serum calcium, an expected effect of increased parathyroid hormone concentrations, were observed post-dose at the higher doses of SB-423557 studied. These data constitute an early proof of principle in humans and provide the basis for further development of this class of compound as a novel, orally administered bone-forming treatment for osteoporosis. (c) 2009 Elsevier Inc. All rights reserved.

  9. Mesenchymal Stem Cells in Perichondrium Express Activated Leukocyte Cell Adhesion Molecule and Participate in Bone Marrow Formation

    Science.gov (United States)

    Arai, Fumio; Ohneda, Osamu; Miyamoto, Takeshi; Zhang, Xiu Qin; Suda, Toshio

    2002-01-01

    Perichondrium in fetal limb is composed of undifferentiated mesenchymal cells. However, the multipotency of cells in this region and the role of perichondrium in bone marrow formation are not well understood. In this report, we purified and characterized perichondrial cells using a monoclonal antibody against activated leukocyte cell adhesion molecule (ALCAM) and investigated the role of perichondrial cells in hematopoietic bone marrow formation. ALCAM is expressed on hematopoietic cells, endothelial cells, bone marrow stromal cells, and mesenchymal stem cells and mediates homophilic (ALCAM–ALCAM)/heterophilic (ALCAM-CD6) cell adhesion. Here we show by immunohistochemical staining that ALCAM is expressed in perichondrium. ALCAM+ perichondrial cells isolated by FACS® exhibit the characteristics of mesenchymal stem cells. ALCAM+ cells can differentiate into osteoblasts, adipocytes, chondrocytes, and stromal cells, which can support osteoclastogenesis, hematopoiesis, and angiogenesis. Furthermore, the addition of ALCAM-Fc or CD6-Fc to the metatarsal culture, the invasion of the blood vessels to a cartilage was inhibited. Our findings indicate that ALCAM+ perichondrial cells participate in vascular invasion by recruiting osteoclasts and vessels. These findings suggest that perichondrium might serve as a stem cell reservoir and play an important role in the early development of a bone and bone marrow. PMID:12070283

  10. Effect of platelet-derived growth factor-BB on bone formation in calvarial defects: an experimental study in rabbits

    DEFF Research Database (Denmark)

    Vikjaer, D; Blom, S; Hjørting-Hansen, E

    1997-01-01

    The effect of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) on bone healing was examined in calvarial defects in rabbits. Bicortical circular (critical size) defects were prepared in the calvarial bone of 16 rabbits. The defects were closed on the dural side and covered externally......, and the bone formation was evaluated after 8 weeks. Healing of defects in both groups was characterized by the presence of newly formed bone along the edges of the original defect and by a central area of fibrous connective tissue. The newly formed bone in the rhPDGF-BB treated defects had a trabecular...... structure; in contrast, a more compact structure was found in the control defects. In the rhPDGF-BB-treated defects, the bone ingrowth was 51.8 +/- 7.1% compared to 30.5 +/- 3.3% in the control defects. Furthermore, the amount of mineralized tissue was increased 112% in the rhPDGF-BB group. The amount...

  11. The p27 Pathway Modulates the Regulation of Skeletal Growth and Osteoblastic Bone Formation by Parathyroid Hormone-Related Peptide.

    Science.gov (United States)

    Zhu, Min; Zhang, Jing; Dong, Zhan; Zhang, Ying; Wang, Rong; Karaplis, Andrew; Goltzman, David; Miao, Dengshun

    2015-11-01

    Parathyroid hormone-related peptide (PTHrP) 1-84 knock-in mice (Pthrp KI) develop skeletal growth retardation and defective osteoblastic bone formation. To further examine the mechanisms underlying this phenotype, microarray analyses of differential gene expression profiles were performed in long bone extracts from Pthrp KI mice and their wild-type (WT) littermates. We found that the expression levels of p27, p16, and p53 were significantly upregulated in Pthrp KI mice relative to WT littermates. To determine whether p27 was involved in the regulation by PTHrP of skeletal growth and development in vivo, we generated compound mutant mice, which were homozygous for both p27 deletion and the Pthrp KI mutation (p27(-/-) Pthrp KI). We then compared p27(-/-) Pthrp KI mice with p27(-/-), Pthrp KI, and WT littermates. Deletion of p27 in Pthrp KI mice resulted in a longer lifespan, increased body weight, and improvement in skeletal growth. At 2 weeks of age, skeletal parameters, including length of long bones, size of epiphyses, numbers of proliferating cell nuclear antigen (PCNA)-positive chondrocytes, bone mineral density, trabecular bone volume, osteoblast numbers, and alkaline phosphatase (ALP)-, type I collagen-, and osteocalcin-positive bone areas were increased in p27(-/-) mice and reduced in both Pthrp KI and p27(-/-) Pthrp KI mice compared with WT mice; however, these parameters were increased in p27(-/-) Pthrp KI mice compared with Pthrp KI mice. As well, protein expression levels of PTHR, IGF-1, and Bmi-1, and the numbers of total colony-forming unit fibroblastic (CFU-f) and ALP-positive CFU-f were similarly increased in p27(-/-) Pthrp KI mice compared with Pthrp KI mice. Our results demonstrate that deletion of p27 in Pthrp KI mice can partially rescue defects in skeletal growth and osteoblastic bone formation by enhancing endochondral bone formation and osteogenesis. These studies, therefore, indicate that the p27 pathway may function downstream in the action

  12. The transcription factor early B-cell factor 1 regulates bone formation in an osteoblast-nonautonomous manner

    OpenAIRE

    Zee, Tiffany; Boller, Sören; Györy, Ildiko; Makinistoglu, Munevver P.; Tuckermann, Jan P.; Grosschedl, Rudolf; Karsenty, Gerard

    2013-01-01

    Early B-cell factor 1 (Ebf1) is a transcription factor whose inactivation in all cells results in high bone mass because of an increase in bone formation. This observation suggests Ebf1 may be an inhibitor of osteoblast differentiation. To test this contention, we analyzed Ebf1 pattern of expression and function in osteoblasts ex vivo and in vivo through osteoblast-specific inactivation in the mouse. We show here that in vivo deletion of Ebf1 in osteoblast progenitors does not affect osteobla...

  13. Tiludronate: bone pharmacology and safety.

    Science.gov (United States)

    Bonjour, J P; Ammann, P; Barbier, A; Caverzasio, J; Rizzoli, R

    1995-11-01

    The pharmacological properties of tiludronate (4-chlorophenyl)thiomethylene bisphosphonate), a sulfured bisphosphonate, have been characterized in a series of preclinical in vivo and in vitro studies. In vivo, tiludronate exerts a dose-dependent inhibitory activity on bone resorption. This property was demonstrated in several animal models, including rats, ewes, and dogs, when bone resorption was induced by administration of retinoid acid or parathyroid hormone, or by immobilization, ovariectomy or orchidectomy. By uncoupling bone resorption from bone formation, tiludronate can induce a positive calcium and phosphate balance. When administered either continuously or intermittently to ovariectomized osteoporotic rats, tiludronate promotes a significant increase in bone mass. This positive effect is associated with an increase in mechanical resistance. Bone tolerance studies indicate that tiludronate is a safe compound with an appreciable therapeutic margin since it can effectively inhibit bone resorption without reducing bone mineralization and strength. In vitro, tiludronate added to bone tissue culture inhibits calcium release, lysosomal enzyme secretion and collagen matrix degradation when induced by various stimulators of bone resorption. At the cellular level, tiludronate does not appear to exert its inhibitory effect on bone resorption by impairing either the recruitment, the migration or the fusion of osteoclast precursors. Tiludronate could act on mature osteoclasts by reducing their capacity to secrete proton into the resorption space and also by favoring their detachment from the bone matrix. The available preclinical data indicate that tiludronate should be an efficacious bisphosphonate in the management of clinical conditions characterized by excessive bone resorption.

  14. Collagen immobilization of multi-layered BCP-ZrO2 bone substitutes to enhance bone formation

    Science.gov (United States)

    Linh, Nguyen Thuy Ba; Jang, Dong-Woo; Lee, Byong-Taek

    2015-08-01

    A porous microstructure of multi-layered BCP-ZrO2 bone substitutes was fabricated using the sponge replica method in which the highly interconnected structure was immobilized with collagen via ethyl(dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide crosslinking. Their struts are combined with a three-layered BCP/BCP-ZrO2/ZrO2 microstructure. Collagen fibers were firmly attached to the strut surface of the BCP-ZrO2 scaffolds. With control of the three-layered microstructure and collagen immobilization, the compressive strength of the scaffolds increased significantly to 6.8 MPa compared to that of the monolithic BCP scaffolds (1.3 MPa). An in vitro study using MTT, confocal observation, and real-time polymer chain reaction analysis demonstrated that the proliferation and differentiation of the pre-osteoblast-like MC3T3-E1 cells was improved due to the collagen incorporation. Remarkable enhancement of bone regeneration was observed without any immunological reaction in the femurs of rabbits during 1 and 5 months of implantation. Furthermore, the interfaces between new bone and the scaffold struts bonded directly without any gaps.

  15. Mixed colony formation in vitro by the heterogeneous compartment of multipotential progenitors in human bone marrow.

    Science.gov (United States)

    Holyoake, T L; Freshney, M G; Konwalinka, G; Haun, M; Petzer, A; Fitzsimons, E; Lucie, N P; Wright, E G; Pragnell, I B

    1993-02-01

    The physiology of the human haemopoietic primitive progenitor populations can be studied in normal and disease states by clonal in vitro cultures in which the primitive progenitor cells proliferate and differentiate to form mixed colonies. For many applications it is essential that such assays detect a high proportion of primitive progenitor cells. We describe an in vitro assay which detects a high incidence of human CD34+ multipotential progenitor cells. Bone marrow mononuclear cells (MNC) or selected CD34+ cells were plated at low cell concentrations in semisolid agar cultures with synergizing growth factor combinations. The optimum growth factor combination of conditioned medium from Mia PaCa-2 cells (Mia-CM), recombinant granulocyte-macrophage colony-stimulating factor and recombinant stem cell factor (SCF) supported the formation of macroscopic (> or = mm) colonies (97% of which were multilineage), at an average incidence of 250/10(5) MNC. The colony-forming cells (human colony-forming unit, type A) detected, showed a low cycling status (7.3%) and the macroscopic colonies had a high replating efficiency (46%), reflecting their probable primitive nature. This assay should prove invaluable, for studies on the regulation of proliferation of the multipotential compartment and in studies involving the assessment of these cells in transplantation and neoplastic disease.

  16. Regulation of extracellular matrix vesicles via rapid responses to steroid hormones during endochondral bone formation.

    Science.gov (United States)

    Asmussen, Niels; Lin, Zhao; McClure, Michael J; Schwartz, Zvi; Boyan, Barbara D

    2017-12-09

    Endochondral bone formation is a precise and highly ordered process whose exact regulatory framework is still being elucidated. Multiple regulatory pathways are known to be involved. In some cases, regulation impacts gene expression, resulting in changes in chondrocyte phenotypic expression and extracellular matrix synthesis. Rapid regulatory mechanisms are also involved, resulting in release of enzymes, factors and micro RNAs stored in extracellular matrisomes called matrix vesicles. Vitamin D metabolites modulate endochondral development via both genomic and rapid membrane-associated signaling pathways. 1α,25-dihydroxyvitamin D3 [1α,25(OH) 2 D 3 ] acts through the vitamin D receptor (VDR) and a membrane associated receptor, protein disulfide isomerase A3 (PDIA3). 24R,25-dihydroxyvitamin D3 [24R,25(OH) 2 D 3 ] affects primarily chondrocytes in the resting zone (RC) of the growth plate, whereas 1α,25(OH) 2 D 3 affects cells in the prehypertrophic and upper hypertrophic cell zones (GC). This includes genomically directing the cells to produce matrix vesicles with zone specific characteristics. In addition, vitamin D metabolites produced by the cells interact directly with the matrix vesicle membrane via rapid signal transduction pathways, modulating their activity in the matrix. The matrix vesicle payload is able to rapidly impact the extracellular matrix via matrix processing enzymes as well as providing a feedback mechanism to the cells themselves via the contained micro RNAs. Copyright © 2017. Published by Elsevier Inc.

  17. Biphasic β-TCP mixed with silicon increases bone formation in critical site defects in rabbit calvaria.

    Science.gov (United States)

    Calvo-Guirado, José Luis; Garces, Miguel; Delgado-Ruiz, Rafael Arcesio; Ramirez Fernandez, Maria P; Ferres-Amat, Eduard; Romanos, Georgios E

    2015-08-01

    The aim of this study was to assess the bone regeneration of critical size defects in rabbit calvarias filled with β-TCP doped with silicon. Twenty-one New Zealand rabbits were used in this study. Two critical size defects were created in the parietal bones. Three experimental groups were evaluated: Test A (HA/β-TCP granules alone), Test B (HA/β-TCP granules plus 3% silicon), Control (empty defect). The animals were sacrificed at 8 and 12 weeks. Evaluation was performed by μCT analysis and histomorphometry. μCT evaluation showed higher volume reduction in Test A group compared with Test B (P TCP plus 3% silicon increases bone formation in critical size defects in rabbit calvarias, and the incorporation of 3% silicon reduces the resorption rate of the HA/β-TCP granules. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Effects of strontium ranelate on bone formation in the mid-palatal suture after rapid maxillary expansion

    Directory of Open Access Journals (Sweden)

    Zhao SY

    2015-05-01

    Full Text Available Shuya Zhao,1,* Xuxia Wang,2,* Na Li,3 Yun Chen,1 Yuran Su,1 Jun Zhang1 1Department of Orthodontics, 2Department of Oral and Maxillofacial Surgery, Faculty of Stomatology, Shandong University; 3Department of Orthodontics, Shandong Provincial Qianfoshan Hospital, Jinan, People’s Republic of China *These authors contributed equally to this work Background: The aim of this experimental study was to investigate the effects of strontium ranelate on bone regeneration in the mid-palatal suture in response to rapid maxillary expansion (RME.Methods: Thirty-six male 6-week-old Wistar rats were randomly divided into three groups, ie, an expansion only (EO group, an expansion plus strontium ranelate (SE group, and a control group. An orthodontic appliance was set between the right and left upper molars of rats with an initial expansive force of 0.98 N. Rats in the SE group were administered strontium ranelate (600 mg/kg body weight and then euthanized in batches on days 4, 7, and 10. Morphological changes in the mid-palatal suture were investigated using micro-computed tomography and hematoxylin and eosin staining after RME. Bone morphogenetic protein-2 expression in the suture was also examined to evaluate bone formation in the mid-palatal suture. Image-Pro Plus software was then used to determine the mean optical density of the immunohistochemical images. Analysis of variance was used for statistical evaluation at the P<0.05 level.Results: With expansive force, the mid-palatal suture was expanded, but there was no statistically significant difference (P>0.05 between the SE and EO groups. The bone volume of the suture decreased after RME, but was higher in the SE group than in the EO group on days 7 and 10. Further, expression of bone morphogenetic protein-2 in the SE group was higher than in the other two groups (P<0.05.Conclusion: Strontium ranelate may hasten new bone formation in the expanded mid-palatal suture, which may be therapeutically

  19. Selective effect of hydroxyapatite nanoparticles on osteoporotic and healthy bone formation correlates with intracellular calcium homeostasis regulation.

    Science.gov (United States)

    Zhao, Rui; Xie, Pengfei; Zhang, Kun; Tang, Zhurong; Chen, Xuening; Zhu, Xiangdong; Fan, Yujiang; Yang, Xiao; Zhang, Xingdong

    2017-09-01

    Adequate bone substitutes osseointegration has been difficult to achieve in osteoporosis. Hydroxyapatite of the osteoporotic bone, secreted by pathologic osteoblasts, had a smaller crystal size and lower crystallinity than that of the normal. To date, little is known regarding the interaction of synthetic hydroxyapatite nanoparticles (HANPs) with osteoblasts born in bone rarefaction. The present study investigated the biological effects of HANPs on osteoblastic cells derived from osteoporotic rat bone (OVX-OB), in comparison with the healthy ones (SHM-OB). A selective effect of different concentrations of HANPs on the two cell lines was observed that the osteoporotic osteoblasts had a higher tolerance. Reductions in cell proliferation, ALP activity, collagen secretion and osteoblastic gene expressions were found in the SHM-OB when administered with HANPs concentration higher than 25µg/ml. In contrast, those of the OVX-OB suffered no depression but benefited from 25 to 250µg/ml HANPs in a dose-dependent manner. We demonstrated that the different effects of HANPs on osteoblasts were associated with the intracellular calcium influx into the endoplasmic reticulum. The in vivo bone defect model further confirmed that, with a critical HANPs concentration administration, the osteoporotic rats had more and mechanically matured new bone formation than the non-treated ones, whilst the sham rats healed no better than the natural healing control. Collectively, the observed epigenetic regulation of osteoblastic cell function by HANPs has significant implication on defining design parameters for a potential therapeutic use of nanomaterials. In this study, we investigated the biological effects of hydroxyapatite nanoparticles (HANPs) on osteoporotic rat bone and the derived osteoblast. Our findings revealed a previously unrecognized phenomenon that the osteoporotic individuals could benefit from higher concentrations of HANPs, as compared with the healthy individuals. The in

  20. Endurance exercise and growth hormone improve bone formation in young and growth-retarded chronic kidney disease rats.

    Science.gov (United States)

    Troib, Ariel; Guterman, Mayan; Rabkin, Ralph; Landau, Daniel; Segev, Yael

    2016-08-01

    Childhood chronic kidney disease (CKD) is associated with both short stature and abnormal bone mineralization. Normal longitudinal growth depends on proper maturation of epiphyseal growth plate (EGP) chondrocytes, leading to the formation of trabecular bone in the primary ossification centre. We have recently shown that linear growth impairment in CKD is associated with impaired EGP growth hormone (GH) receptor signalling and that exercise improved insulin-like growth factor I (IGF-I) signalling in CKD-related muscle atrophy. In this study, 20-day-old rats underwent 5/6 nephrectomy (CKD) or sham surgery (C) and were exercised with treadmill, with or without GH supplementation. CKD-related growth retardation was associated with a widened EGP hypertrophic zone. This was not fully corrected by exercise (except for tibial length). Exercise in CKD improved the expression of EGP key factors of endochondral ossification such as IGF-I, vascular endothelial growth factor (VEGF), receptor activator of nuclear factor kappa-B ligand (RANKL) and osteocalcin. Combining GH treatment with treadmill exercise for 2 weeks improved the decreased trabecular bone volume in CKD, as well as the expression of growth plate runt-related transcription factor 2, RANKL, metalloproteinase 13 and VEGF, while GH treatment alone could not do that. Treadmill exercise improves tibial bone linear growth, as well as growth plate local IGF-I. When combined with GH treatment, running exercise shows beneficial effects on trabecular bone formation, suggesting the potential benefit of this combination for CKD-related short stature and bone disease. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  1. Synergistic effects of high dietary calcium and exogenous parathyroid hormone in promoting osteoblastic bone formation in mice.

    Science.gov (United States)

    Feng, Yuxu; Zhou, Min; Zhang, Qunhu; Liu, Huan; Xu, Yong; Shu, Lei; Zhang, Jue; Miao, Dengshun; Ren, Yongxin

    2015-03-28

    In the present study, we investigated whether high dietary Ca and exogenous parathyroid hormone 1-34 fragments (PTH 1-34) have synergistic effects on bone formation in adult mice, and explored the related mechanisms. Adult male mice were fed a normal diet, a high-Ca diet, a PTH-treated diet, or a high-Ca diet combined with subcutaneously injected PTH 1-34 (80 μg/kg per d) for 4 weeks. Bone mineral density, trabecular bone volume, osteoblast number, alkaline phosphatase (ALP)- and type I collagen-positive areas, and the expression levels of osteoblastic bone formation-related genes and proteins were increased significantly in mice fed the high-Ca diet, the PTH-treated diet, and, even more dramatically, the high-Ca diet combined with PTH. Osteoclast number and surface and the ratio of receptor activator for nuclear factor-κB ligand (RANKL):osteoprotegerin (OPG) were decreased in the high-Ca diet treatment group, increased in the PTH treatment group, but not in the combined treatment group. Furthermore, third-passage osteoblasts were treated with high Ca (5 mM), PTH 1-34 (10⁻⁸ M) or high Ca combined with PTH 1-34. Osteoblast viability and ALP activity were increased in either the high Ca-treated or PTH-treated cultures and, even more dramatically, in the cultures treated with high Ca plus PTH, with consistent up-regulation of the expression levels of osteoblast proliferation and differentiation-related genes and proteins. These results indicate that dietary Ca and PTH play synergistic roles in promoting osteoblastic bone formation by stimulating osteoblast proliferation and differentiation.

  2. Effects of pulsed electromagnetic field (PEMF) stimulation on bone tissue like formation are dependent on the maturation stages of the osteoblasts.

    Science.gov (United States)

    Diniz, Pericles; Shomura, Kenji; Soejima, Kazuhisa; Ito, Gakuji

    2002-07-01

    The effects of pulsed electromagnetic field (PEMF, 15 Hz pulse burst, 7 mT peak) stimulation on bone tissue-like formation on osteoblasts (MC3T3-E1 cell line) in different stages of maturation were assessed to determine whether the PEMF stimulatory effect on bone tissue-like formation was associated with the increase in the number of cells and/or with the enhancement of the cellular differentiation. The cellular proliferation (DNA content), differentiation (alkaline phosphatase activity), and bone tissue-like formation (area of mineralized matrix) were determined at different time points. PEMF treatment of osteoblasts in the active proliferation stage accelerated cellular proliferation, enhanced cellular differentiation, and increased bone tissue-like formation. PEMF treatment of osteoblasts in the differentiation stage enhanced cellular differentiation and increased bone tissue-like formation. PEMF treatment of osteoblasts in the mineralization stage decreased bone tissue-like formation. In conclusion, PEMF had a stimulatory effect on the osteoblasts in the early stages of culture, which increased bone tissue-like formation. This stimulatory effect was most likely associated with enhancement of the cellular differentiation, but not with the increase in the number of cells. Copyright 2002 Wiley-Liss, Inc.

  3. Impact of equol-producing capacity and soy-isoflavone profiles of supplements on bone calcium retention in postmenopausal women: a randomized crossover trial12

    Science.gov (United States)

    Pawlowski, Jessica W; Martin, Berdine R; McCabe, George P; McCabe, Linda; Jackson, George S; Peacock, Munro; Barnes, Stephen; Weaver, Connie M

    2015-01-01

    Background: Postmenopausal estrogen depletion is a major contributing factor to bone loss. Soy isoflavones have variable effects on the prevention of postmenopausal bone loss, which is possibly related to the specific isoflavone content or the variable equol-producing capacity of individuals. Objective: We aimed to determine the effects of the content of isoflavones in a soy supplement and the equol-producing ability of the individual on postmenopausal bone calcium retention. Design: The study was a blinded, randomized, crossover intervention trial in 24 postmenopausal women who were prescreened for their ability to convert daidzein to equol. Women were equilibrated with 41Ca before the intervention. Interventions were 5 soy isoflavone oral supplements (2 doses of a genistein-rich soy supplement and 3 doses of mixed isoflavones in various proportions) and a bisphosphonate (risedronate). Each intervention was given sequentially for 50 d followed by a 50-d washout period. The percentage of bone calcium retention was determined from the change in urinary 41Ca:calcium. Results: Interventions that ranged from 52 to 220 mg total isoflavones/d increased bone calcium retention between 3.4% and 7.6% (P soy intervention delivered 105.23 mg total isoflavones/d as genistein, daidzein, and glycitein in their natural ratios and increased bone calcium retention by 7.6% (95% CI: 4.9%, 10.2%; P Soy isoflavones, although not as potent as risedronate, are effective bone-preserving agents in postmenopausal women regardless of their equol-producing status, and mixed isoflavones in their natural ratios are more effective than enriched genistein. This trial was registered at clinicaltrials.gov as NCT00244907. PMID:26245807

  4. The fluoride coated AZ31B magnesium alloy improves corrosion resistance and stimulates bone formation in rabbit model.

    Science.gov (United States)

    Sun, Wei; Zhang, Guangdao; Tan, Lili; Yang, Ke; Ai, Hongjun

    2016-06-01

    This study aimed to evaluate the effect of fluorine coated Mg alloy and clarify its mechanism in bone formation. We implanted the fluorine coated AZ31B Mg alloy screw (group F) in rabbit mandibular and femur in vivo. Untreated AZ31B Mg alloy screw (group A) and titanium screw (group T) were used as control. Then, scanning electron microscopy, the spectral energy distribution analysis, hard and decalcified bone tissues staining were performed. Immunohistochemistry was employed to examine the protein expressions of bone morphogenetic protein 2 (BMP-2) and collagen type I in the vicinity of the implant. Compared with the group A, the degradation of the alloy was reduced, the rates of Mg corrosion and Mg ion release were slowed down, and the depositions of calcium and phosphate increased in the group F in the early stage of implantation. Histological results showed that fluorine coated Mg alloy had well osteogenic activity and biocompatibility. Moreover, fluoride coating obviously up-regulated the expressions of collagen type I and BMP-2. This study confirmed that the fluorine coating might improve the corrosion resistance of AZ31B Mg alloy and promote bone formation by up-regulated the expressions of collagen type I and BMP-2. Copyright © 2016. Published by Elsevier B.V.

  5. Influence of Implant Neck Design on Bone Formation Under Mechanical Repetitive Loading: Histomorphometric and Microcomputed Tomographic Studies in Rabbit Tibiae.

    Science.gov (United States)

    Yasutake, Munenori; Kuroshima, Shinichiro; Ishimoto, Takuya; Nakano, Takayoshi; Sawase, Takashi

    2016-04-01

    The aim of this study was to investigate effects of implant neck design on the original concept of osseointegration and bone formation when applying mechanical repetitive loading by bone-integrated implants. Twenty-eight anodized Ti-6Al-4V alloy implants with +60° or -60° grooves in the implant neck were placed in the proximal tibial metaphysis of 14 rabbits. Fourteen implants received mechanical repetitive loading along the long axis of the implant for 8 weeks at 12 weeks after implant placement. The remaining 14 implants received no loading. Histomorphometric and microcomputed tomographic analyses were then performed. No effect of neck design was observed without mechanical loading, whereas osseointegration around the +60° grooves was upregulated with mechanical loading. Calculated load effects on bone structure around the implant neck with +60° grooves were larger when compared with the -60° grooves under mechanical loading. These findings indicate that the establishment of osseointegration and bone formation around the implant neck with +60° grooves is superior to those with -60° grooves under loaded conditions.

  6. Ectopic bone formation cannot occur by hydroxyapatite/β-tricalcium phosphate bioceramics in green fluorescent protein chimeric mice

    Science.gov (United States)

    Cheng, Lijia; Duan, Xin; Xiang, Zhou; Shi, Yujun; Lu, Xiaofeng; Ye, Feng; Bu, Hong

    2012-12-01

    Many studies have shown that calcium phosphate ceramics (CP) have osteoconductive and osteoinductive properties; however, the exact mechanism of bone induction has not yet been reported. This study was performed to investigate if destroying immunological function will influence osteogenesis, to explain the mechanism which is unclear. In this study, twenty C57BL/6 mice were divided into two groups (n = 10), in group 1, a hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) ceramic was implanted into both the left and right leg muscles of each mouse; in group 2, ten mice experienced lethal irradiation, then were injected bone marrow (BM) cells from green fluorescent protein (GFP) transgenic mice by tail veil, after bone marrow transplantation (BMT), heart, liver, spleen, lung, kidney, and muscle were harvested for biological analysis, after the GFP chimera model was established successfully, the same HA/β-TCP ceramic was implanted into both leg muscles of each mouse immediately after irradiation. 45 and 90 days after implantation, the ceramics of the two groups were harvested to perform with hematoxylin and eosin (HE) and immunohistochemistry (IHC) staining; the results showed that there was no bone formation in group 2, while new bone tissues were detected in group 1. Our findings suggest that the BM cell from GFP transgenic mice is a good biomarker and it could set a good platform for chimera model; it also shows that BM cell is one of cell resources of bone induction, and destruction of immune function will impede osteoinduction by CP. Overall, our results may shed light on clear mechanism study of bone induction in the future.

  7. Impact of occupational health hazards on serum markers of bone formation in spray painters of Chennai region in Tamil Nadu.

    Science.gov (United States)

    Muthaiah, Vijaya Prakash Krishnan; Nathan, Abel Arul; Balakrishnan, Anandan; Rose, Rajiv; Gopalsamy, Jayaraman

    2012-05-01

    The association between spray paint exposure and bone remodeling received little attention despite the high usage of spray paints in automobile industries, steel furniture workshops etc. The present study was aimed at investigating the level of serum markers of bone formation in spray painters. The spray painting subjects were selected from automobile body repair workshops in Chennai region of TamilNadu which constitutes 30% of India's automobile industry. All the study subjects, exposed to spray paint were working in a workshop without standard spraying room and did not wore any aerosol removing respirator. The controls were selected from random population irrespective of occupation. Data relevant to the socioeconomic features and personal history was collected using a questionnaire. The current study included 50 spray painters and 25 control subjects of same age group. We examined the level of serum calcium, serum phosphorus, serum differentiation markers of bone such as alkaline phosphatase (bone specific) and serum osteocalcin in which these levels were found to be high in serum of spray painters. The current study concludes dysregulation in bone remodeling of spray painters exposed to chronic solvents and paint pigments.

  8. A Novel HA/β-TCP-Collagen Composite Enhanced New Bone Formation for Dental Extraction Socket Preservation in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Ko-Ning Ho

    2016-03-01

    Full Text Available Past studies in humans have demonstrated horizontal and vertical bone loss after six months following tooth extraction. Many biomaterials have been developed to preserve bone volume after tooth extraction. Type I collagen serves as an excellent delivery system for growth factors and promotes angiogenesis. Calcium phosphate ceramics have also been investigated because their mineral chemistry resembles human bone. The aim of this study was to compare the performance of a novel bioresorbable purified fibrillar collagen and hydroxyapatite/β-tricalcium phosphate (HA/β-TCP ceramic composite versus collagen alone and a bovine xenograft-collagen composite in beagles. Collagen plugs, bovine graft-collagen composite and HA/β-TCP-collagen composite were implanted into the left and right first, second and third mandibular premolars, and the fourth molar was left empty for natural healing. In total, 20 male beagle dogs were used, and quantitative and histological analyses of the extraction ridge was done. The smallest width reduction was 19.09% ± 8.81% with the HA/β-TCP-collagen composite at Week 8, accompanied by new bone formation at Weeks 4 and 8. The HA/β-TCP-collagen composite performed well, as a new osteoconductive and biomimetic composite biomaterial, for socket bone preservation after tooth extraction.

  9. Effects of different consolidation periods on bone formation and implant success in alveolar distraction osteogenesis: a clinical study.

    Science.gov (United States)

    Faysal, Ugurlu; Cem, Sener B; Atilla, Sertgöz

    2013-04-01

    The aims of this study were to compare the consolidation periods in alveolar distraction osteogenesis and evaluate the effects of this condition on bone formation, bone relapse and implant success in reconstruction of resorbed edentulous mandibles. Eighteen patients were underwent vertical alveolar distraction osteogenesis under the same distraction protocol, except for variations in consolidation time. After a consolidation period of 5 weeks for Group 1 and 14 weeks for Group 2, 36 implants were placed to support their dentures. Bone height and relapse were evaluated using digital orthopantomographic radiographs. The radiological findings showed that the mean distraction was 6.968 mm in Group 1 and 7.031 mm in Group 2. At the end of the consolidation period, the mean bone relapse was 0.832 ± 0.135 mm in Group 1 and 0.738 ± 0.135 mm in Group 2. At the end of 6 months, the mean bone relapse was 1.380 ± 0.144 mm in Group 1 and 1.112 ± 0.144 mm in Group 2. No significant difference existed between the two groups at any time. Consolidation periods may be reduced in alveolar distraction osteogenesis to enable more patient comfort by providing dentures early. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  10. Does stinging nettle (Urtica dioica) have an effect on bone formation in the expanded inter-premaxillary suture?

    Science.gov (United States)

    Irgin, Celal; Çörekçi, Bayram; Ozan, Fatih; Halicioğlu, Koray; Toptaş, Orçun; Birinci Yildirim, Arzu; Türker, Arzu; Yilmaz, Fahri

    2016-09-01

    To determine whether systemically given stinging nettle (SN) has an effect on bone formation in response to expansion of the rat inter-premaxillary suture. A total of 28 male Wistar albino rats were randomly divided into 4 equal groups: control (C), only expansion (OE), SN extract given only during the expansion and retention periods (SN group; a total of 17days), and SN extract given during the nursery phase before expansion (a period of 40days) and during the expansion and retention periods (N+SN group; a total of 57days). After the 5-day expansion period was completed, the rats in the OE, SN, and N+SN groups underwent 12days of mechanical retention, after which they were sacrificed, and their premaxilla were dissected and fixed. A histologic evaluation was done to determine the number of osteoblasts, osteoclasts, and capillaries, as well as the number and intensity of inflammatory cells and new bone formation. Statistically significant differences were found between the groups in all histologic parameters except the ratio of intensities of inflammatory cells. New bone formation and the number of capillaries were significantly higher in the SN groups than in the other groups. The statistical analysis also showed that the numbers of osteoblasts, osteoclasts, and capillaries were highest in the N+SN group. Systemic administration of SN may be effective in accelerating new bone formation and reducing inflammation in the maxillary expansion procedure. It may also be beneficial in preventing relapse after the expansion procedure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Induced hemocompatibility and bone formation as biological scaffold for cell therapy implant

    Directory of Open Access Journals (Sweden)

    Keng-Liang Ou

    2016-06-01

    Full Text Available Although stem cells can become almost any type of specialized cell in the human body and may have the potential to generate replacement cells for tissues and organs, the transplantation of these cells are hindered by immune rejection and teratoma formation. However, scientists have found a promising solution for these problems-they have discovered the ability to isolate stem cells from a patient’s umbilical cord blood or bone marrow. Even more recently, small stem cells, such as spore-like stem cells, Blastomere-Like Stem Cells (BLSCs, and Very-Small Embryonic-Like stem cells (VSELs isolated directly from the peripheral blood have beeninvestigated as a novel approach to stem cell therapy as they can be isolated directly from the peripheral blood. A newly-discovered population of multipotent stem cells in this class has been dubbed StemBios (SB cells. The potential therapeutic uses of such stem cells have been explored in many ways, one of which includes dental remodeling and construction. Using adult stem cells, scientists have engineered and cultivated teeth in mice that may one day be used for human implantation.It follows that such regeneration may be possible, to a certain degree, in human patients as well. This idea leads to the present study on the effect of SB cell therapy on early osseointegrationof dental implants. Titanium (Ti dental implants have been proven to be a reliable and predictable treatment for restoration of edentulous regions. The osseointegration process can be described in two stages: primary stability (mechanical stability and secondary stability (biological stability. The mechanical stabilization of the implant reflects the interaction between the bone density and the features of the implant designs and can be determined after implant insertion. Alternatively,the biological stabilization of the implant is a physiologic healing process. It is couple to the biological interaction between the external surface of the

  12. P38 MAPK / beta-catenin canonical wnt signaling mediated bone formation effects of blueberries

    Science.gov (United States)

    Appropriate nutrition is one of the critical factors that influences bone development. We studied the effects of dietary blueberry supplementation on bone growth in weanling rats. Weanling male and female rats were fed AIN-93G semi-purified diets supplemented with 10% whole blueberry powder for 14 a...

  13. Ectopic bone formation in rats: the importance of vascularity of the acceptor site.

    NARCIS (Netherlands)

    Hartman, E.H.M.; Vehof, J.W.M.; Ruijter, J.E. de; Spauwen, P.H.M.; Jansen, J.A.

    2004-01-01

    Bone graft substitutes (BGS) can be fabricated by the combination of three key ingredients: (1) competent bone-forming cells, (2) a suitable framework or scaffold, and (3) the presence of biological stimulants. Although much research has been done to develop the ideal BGS, still the results are not

  14. Castor oil polymer induces bone formation with high matrix metalloproteinase-2 expression.

    Science.gov (United States)

    Saran, Wallace Rocha; Chierice, Gilberto Orivaldo; da Silva, Raquel Assed Bezerra; de Queiroz, Alexandra Mussolino; Paula-Silva, Francisco Wanderley Garcia; da Silva, Léa Assed Bezerra

    2014-02-01

    The aim of this study was to evaluate the modulation of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) expression in newly formed bone tissue at the interface between implants derived from castor oil (Ricinus communis) polymer and the tibia medullary canal. Forty-four rabbits were assigned to either Group 1 (n = 12; control) or Group 2 (n = 30), which had the tibial medullary canals reamed bilaterally and filled with polymer. CT scans showed no space between the material surface and the bone at the implant/bone marrow interface, and the density of the tissues at this interface was similar to the density measured of other regions of the bone. At 90 days postimplantation, the interface with the polymer presented a thick layer of newly formed bone tissue rich in osteocytes. This tissue exhibited ongoing maturation at 120 and 150 days postimplantation. Overall, bone remodeling process was accompanied by positive modulation of MMP-2 and low MMP-9 expression. Differently, in control group, the internal surface close to the medullary canal was lined by osteoblasts, followed by a bone tissue zone with few lacunae filled with osteocytes. Maturation of the tissue of the medullary internal surface occurred in the inner region, with the bone being nonlamellar. © 2013 Wiley Periodicals, Inc.

  15. A histomorphometric study of the effect of doxycycline and erythromycin on bone formation in dental alveolar socket of rat

    Directory of Open Access Journals (Sweden)

    Mohammad Shahabooei

    2015-01-01

    Full Text Available Background: The aim of the present study was to evaluate whether subantimicrobial doses of doxycycline (DOX and erythromycin (EM used for the treatment of peri-implant osteolysis due to their anti-osteoclastogenesis can interfere with the osseous wound healing process in rat alveolar socket. Materials and Methods: Forty-five male Wistar rats had their first maxillary right molar extracted and were divided into three groups. DOX and EM at the doses of 5 mg/kg/day orally (p.o. and 2 mg/kg/day intraperitoneally (i.p. were administered respectively to two separate groups for 7 days after operation. In the control group the animals received normal saline (5 ml/kg. Five rats were sacrificed at 7, 14 and 21 days post-extraction in each study group. A histomorphometric analysis was used to evaluate new bone formation inside the alveolar socket. Significant level was set at 0.05. Results: The findings showed that the percentage of new bone formation (NBF enhanced significantly on days 7 and 14. There was no significant difference in the NBF between DOX and EM groups. Conclusion: Short-term treatment with both DOX and EM enhanced new bone formation without any advances in favor of each drug.

  16. Influence of immediate/delayed implant placement and implant platform on the peri-implant bone formation.

    Science.gov (United States)

    Passoni, Bernardo B; Marques de Castro, Daniel S; de Araújo, Maria Angelica R; de Araújo, Carlos D R P; Piatelli, Adriano; Benfatti, César A M

    2016-11-01

    To determinate the influence of the timing and position of the implant placement, as well as the presence and absence of a buccal gap, associated with different implant platforms on bone formation around implants. In a first surgical stage, two premolars in one side of the mandibular arch of 07 mongrel dogs were extracted. After a 120-day healing period, a second-stage surgery was performed, in which a full flap was raised and two implants were installed. At this same stage, two contralateral premolars were extracted and two immediate implants were placed into the fresh sockets, through the "palatal approach technique" without flap elevation, totaling four implants per animal. The 28 installed implants constituted groups according to the timing (Immediate or delayed) of placement and the type of surface treatment. After 4 months, samples were collected and histomorphometric analysis was performed to determinate buccal surface BIC, lingual surface BIC, total BIC, buccal area, and lingual area of all implants. Kruskal-Wallis and pared Wilcoxon (P immediate implants presented better BIC scores, mainly on the buccal surface. Data also suggest better bone area formation around the implants of these same groups. Concerning the type of implant platform, better results were found using Morse taper. The flapless technique with "palatal approach," Morse taper implants, and immediate implant placement all have favorable influence on the bone formation around the implants. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. A New Piezoelectric Actuator Induces Bone Formation In Vivo: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Joana Reis

    2012-01-01

    Full Text Available This in vivo study presents the preliminary results of the use of a novel piezoelectric actuator for orthopedic application. The innovative use of the converse piezoelectric effect to mechanically stimulate bone was achieved with polyvinylidene fluoride actuators implanted in osteotomy cuts in sheep femur and tibia. The biological response around the osteotomies was assessed through histology and histomorphometry in nondecalcified sections and histochemistry and immunohistochemistry in decalcified sections, namely, through Masson's trichrome, and labeling of osteopontin, proliferating cell nuclear antigen, and tartrate-resistant acid phosphatase. After one-month implantation, total bone area and new bone area were significantly higher around actuators when compared to static controls. Bone deposition rate was also significantly higher in the mechanically stimulated areas. In these areas, osteopontin increased expression was observed. The present in vivo study suggests that piezoelectric materials and the converse piezoelectric effect may be used to effectively stimulate bone growth.

  18. Effects of a self-assembling peptide as a scaffold on bone formation in a defect.

    Science.gov (United States)

    Ando, Kei; Imagama, Shiro; Kobayashi, Kazuyoshi; Ito, Kenyu; Tsushima, Mikito; Morozumi, Masayoshi; Tanaka, Satoshi; Machino, Masaaki; Ota, Kyotaro; Nishida, Koji; Nishida, Yoshihiro; Ishiguro, Naoki

    2018-01-01

    Spinal fusion and bone defect after injuries, removal of bone tumors, and infections need to be repaired by implantation. In an aging society, recovery from these procedures is often difficult. In this study, we found that injection of SPG-178 leads to expression of several bone marker genes and mineralization in vitro, and revealed a significantly higher degree of newly formed bone matrix with use of SPG-178 in vivo. MC3T3-E1 cells were used to evaluate osteoblast differentiation promoted by SPG-178. To analyze gene expression, total RNA was isolated from MC3T3-E1 cells cultured for 7 and 14 days with control medium or SPG-178 medium. Among the several bone marker genes examined, SPG-178 significantly increased the mRNA levels for ALP, BMP-2 and Osteocalcin, OPN, BSP and for the Osterix. Ten-week-old female Wistar rats were used for all transplantation procedures. A PEEK cage was implanted into a bony defect (5 mm) within the left femoral mid-shaft, and stability was maintained by an external fixator. The PEEK cages were filled with either a SPG-178 hydrogel plus allogeneic bone chips (n = 4) or only allogeneic bone chips (n = 4). The rats were then kept for 56 days. Newly formed bone matrix was revealed inside the PEEK cage and there was an increased bone volume per total volume with the cage filled with SPG-178, compared to the control group. SPG-178 has potential in clinical applications because it has several benefits. These include its favorable bone conduction properties its ability to act as a support for various different cells and growth factors, its lack of infection risk compared with materials of animal origin such as ECM, and the ease with which it can be used to fill defects with complex shapes and combined with a wide range of other materials.

  19. Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity arthritis (DTHA) model

    DEFF Research Database (Denmark)

    Atkinson, Sara Marie; Bleil, Janine; Maier, Rene

    2016-01-01

    . Periarticular bone formation was observed from day 10. Induction of new bone formation indicated by enhanced Runx2, collagen X, osteocalcin, MMP2, MMP9, and MMP13 mRNA expression was observed only between days 8 and 11. Anti-RANKL treatment resulted in a modest reduction in paw and ankle swelling...... and bone formation were analyzed by mRNA deep sequencing. Serum concentrations of tartrate-resistant acid phosphatase 5b, carboxy-terminal telopeptide I (CTX-I), matrix metalloproteinase 3 (MMP3), and serum amyloid P component (SAP) were determined by enzyme-linked immunosorbent assay. Anti......-RANKL monoclonal antibody treatment was initiated at the time of immunization. Results: Bone destruction (MMP3 serum levels, cathepsin B activity, and RANKL mRNA) peaked at day 3 after arthritis induction, followed by a peak in cartilage destruction and bone erosion on day 5 after arthritis induction...

  20. Solcoseryl, a tissue respiration stimulating agent, significantly enhances the effect of capacitively coupled electric field on the promotion of bone formation around dental implants.

    Science.gov (United States)

    Ochi, Morio; Wang, Pao-Li; Ohura, Kiyoshi; Takashima, Shigenori; Kagami, Hiroyuki; Hirose, Yukito; Kaku, Tohru; Sakaguchi, Kunihiko

    2003-06-01

    In the present study we examined the combined effect of application of a capacitively coupled electric field (CCEF) and the tissue respiration stimulating agent, Solcoseryl, on the promotion of bone formation around dental implants histologically and mechanically. After a dental implant was inserted into each femur of Japanese white rabbits, Solcoseryl (2 ml/kg) was administered intravenously in the ear vein and a CCEF was applied for 4 h per day for 14 days. The degree of bone formation on microscopic observation, bone contact ratio, bone surface area ratio, and the level of removal torque of the implant in the Solcoseryl- and CCEF-treated group were significantly higher than the respective value in the control group, which had not been treated with Solcoseryl nor CCEF. Thus, the combination of CCEF stimulation and Solcoseryl effectively promoted the formation of new bone. It is suggested that the clinical use of a combination of CCEF stimulation and Solcoseryl for dental implants promotes osseointegration.

  1. Prevention of Bone Bridge Formation Using Transplantation of the Autogenous Mesenchymal Stem Cells to Physeal Defects: An Experimental Study in Rabbits

    Directory of Open Access Journals (Sweden)

    L. Plánka

    2007-01-01

    Full Text Available Physeal cartilage is known to have poor self-repair capacity after injury. Evaluation of the ability of cultured mesenchymal stem cells to repair damaged physis is the topic of current research. In 10 immature New Zealand white rabbits autogenous mesenchymal stem cells were transplanted into a iatrogenic physeal defect in a lateral portion of the distal growth plate of the right femur. The same defect without stem cells transplantation in the left femoral distal physis served as a control. In our study, we used our own technique of implantation of MSCs with a newly modified gel scaffold (New Composite Hyaluronate/Collagen Type I/Fibrin Scaffold. The rabbits were euthanized 4 months after transplantation. Bone length discrepancy and valgus deformity were measured from femoral radiographs. Healing of the defect was investigated histologically. The ability of mesenchymal stem cells to survive and promote cartilage healing in the physeal defect was assessed by immunofluorescence. Average difference in femur length measured from surgery to euthanasia (4 months was 0.61 ± 0.19 cm after preventive transplantation of MSCs in the right femur, but only 0.11 ± 0.07 cm in the left femur. Average angular (valgus deformity of the right femur with MSCs preventively transplanted to iatrogenically damaged distal femoral physis was 1.2 ± 0.72 °. Valgus deformity in the left femur was 5.4 ± 2.5 °. Prophylactic transplantation of autogenous mesenchymal stem cells to iatrogenically damaged distal growth plate of the rabbit femur prevented a bone bridge formation and resulted in healing of the physeal defect with hyaline cartilage. Immunofluorescence examination showed that the chondrocytes newly formed in growth zone are the result of implanted MSCs differentiation. Femur growth in traumatized physis was maintained even after transplantation of autogenous MSCs. As compared with the opposite femur (with physeal defect but without transplanted MSCs, the bone

  2. Chemical modification of extracellular matrix by cold atmospheric plasma-generated reactive species affects chondrogenesis and bone formation.

    Science.gov (United States)

    Eisenhauer, Peter; Chernets, Natalie; Song, You; Dobrynin, Danil; Pleshko, Nancy; Steinbeck, Marla J; Freeman, Theresa A

    2016-09-01

    The goal of this study was to investigate whether cold plasma generated by dielectric barrier discharge (DBD) modifies extracellular matrices (ECM) to influence chondrogenesis and endochondral ossification. Replacement of cartilage by bone during endochondral ossification is essential in fetal skeletal development, bone growth and fracture healing. Regulation of this process by the ECM occurs through matrix remodelling, involving a variety of cell attachment molecules and growth factors, which influence cell morphology and protein expression. The commercially available ECM, Matrigel, was treated with microsecond or nanosecond pulsed (μsp or nsp, respectively) DBD frequencies conditions at the equivalent frequencies (1 kHz) or power (~1 W). Recombinant human bone morphogenetic protein-2 was added and the mixture subcutaneously injected into mice to simulate ectopic endochondral ossification. Two weeks later, the masses were extracted and analysed by microcomputed tomography. A significant increase in bone formation was observed in Matrigel treated with μsp DBD compared with control, while a significant decrease in bone formation was observed for both nsp treatments. Histological and immunohistochemical analysis showed Matrigel treated with μsp plasma increased the number of invading cells, the amount of vascular endothelial growth factor and chondrogenesis while the opposite was true for Matrigel treated with nsp plasma. In support of the in vivo Matrigel study, 10 T1/2 cells cultured in vitro on μsp DBD-treated type I collagen showed increased expression of adhesion proteins and activation of survival pathways, which decreased with nsp plasma treatments. These results indicate DBD modification of ECM can influence cellular behaviours to accelerate or inhibit chondrogenesis and endochondral ossification. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Information capacity and pattern formation in a tent map network featuring statistical periodicity

    Science.gov (United States)

    Hauptmann, C.; Touchette, H.; Mackey, M. C.

    2003-02-01

    We provide quantitative support to the observation that lattices of coupled maps are “efficient” information coding devices. It has been suggested recently that lattices of coupled maps may provide a model of information coding in the nervous system because of their ability to create structured and stimulus-dependent activity patterns which have the potential to be used for storing information. In this paper, we give an upper bound to the effective number of patterns that can be used to store information in the lattice by evaluating numerically its information capacity or information rate as a function of the coupling strength between the maps. We also estimate the time taken by the lattice to establish a limiting activity pattern.

  4. Influence of the cutting edge angle of a titanium instrument on chip formation in the machining of trabecular and cortical bone.

    Science.gov (United States)

    von See, Constantin; Stoetzer, Marcus; Ruecker, Martin; Wagner, Max; Schumann, Paul; Gellrich, Nils-Claudius

    2014-01-01

    The placement of self-tapping implants is associated with microfractures and the formation of bone chips along the cutting flutes. This study was conducted to investigate the effect of different cutting edge angles on chip formation during the machining of trabecular and cortical bone using instruments with a rough titanium surface. Mandibular cortical and trabecular bone specimens were obtained from freshly slaughtered domestic pigs. A predefined thrust force was applied to the specimens. Four specially designed cutting instruments that simulated dental implants and had a rough titanium surface were allowed to complete one full revolution at cutting edge angles of 55, 65, 75, and 85 degrees, respectively. Torque and thrust were measured during the cutting process. Bone chips were measured and weighed under a microscope. Different cutting edge angles did not lead to significant differences in torque. The lowest torque values were measured when the cutting edges were positioned at 65 degrees in trabecular bone and at 85 degrees in cortical bone. Bone chips were significantly larger and heavier at angles of 55 and 65 degrees than at angles of 75 and 85 degrees in trabecular bone. Instruments with a rough titanium surface show considerable angle-dependent differences in chip formation. In addition to bone density, the angle of the cutting edges should be taken into consideration during the placement of dental implants. Good results were obtained when the cutting edges were positioned at an angle of 65 degrees. This angle can have positive effects on osseointegration.

  5. A data driven model for the impact of IFT and density variations on CO2 storage capacity in geologic formations

    Science.gov (United States)

    Nomeli, Mohammad A.; Riaz, Amir

    2017-09-01

    Carbon dioxide (CO2) storage in depleted hydrocarbon reservoirs and deep saline aquifers is one of the most promising solutions for decreasing CO2 concentration in the atmosphere. One of the important issues for CO2 storage in subsurface environments is the sealing efficiency of low-permeable cap-rocks overlying potential CO2 storage reservoirs. Though we focus on the effect of IFT in this study as a factor influencing sealing efficiency or storage capacity, other factors such as interfacial interactions, wettability, pore radius and interfacial mass transfer also affect the mobility and storage capacity of CO2 phase in the pore space. The study of the variation of IFT is however important because the pressure needed to penetrate a pore depends on both the pore size and the interfacial tension. Hence small variations in IFT can affect flow across a large population of pores. A novel model is proposed to find the IFT of the ternary systems (CO2/brine-salt) in a range of temperatures (300-373 K), pressures (50-250 bar), and up to 6 molal salinity applicable to CO2 storage in geological formations through a multi-variant non-linear regression of experimental data. The method uses a general empirical model for the quaternary system CO2/brine-salts that can be made to coincide with experimental data for a variety of solutions. We introduce correction parameters into the model, which compensates for uncertainties, and enforce agreement with experimental data. The results for IFT show a strong dependence on temperature, pressure, and salinity. The model has been found to describe the experimental data in the appropriate parameter space with reasonable precision. Finally, we use the new model to evaluate the effects of formation depth on the actual efficiency of CO2 storage. The results indicate that, in the case of CO2 storage in deep subsurface environments as a global-warming mitigation strategy, CO2 storage capacity increases with reservoir depth.

  6. The effect of enamel matrix derivative (Emdogain) on bone formation: a systematic review.

    NARCIS (Netherlands)

    Rathe, F.; Junker, R.; Chesnutt, B.C.; Jansen, J.A.

    2009-01-01

    This systematic review focused on the question, if and to what extent enamel matrix derivative (Emdogain) [EMD]) promotes the regeneration of bone. The influence of combinations with other biomaterials was additionally evaluated. Twenty histomorphometric studies were included in this systematic

  7. Study of in Vitro and in Vivo Bone Formation in Composite Cryogels and the Influence of Electrical Stimulation.

    Science.gov (United States)

    Mishra, Ruchi; Raina, Deepak Bushan; Pelkonen, Mea; Lidgren, Lars; Tägil, Magnus; Kumar, Ashok

    2015-01-01

    This work studies osteoinduction and bone conduction in polyvinyl alcohol-tetraethylorthosilicate-alginate-calcium oxide (PTAC) biocomposite cryogels along with the synergistic effect of electrical stimulation. In vitro osteoinduction of C2C12 myoblast towards osteogenic lineage is demonstrated through alkaline phosphatase assay, scanning electron microscopy and energy dispersive X-ray spectroscopy. These results were followed by in vivo implantation studies of PTAC biocomposite cryogel scaffolds in the bone conduction chamber model depicting bone formation after 24 days based on immunohistological staining for osteogenic markers, i.e., collagen type I (Col I), osteocalcin (OCN), osteopontin (OPN) and bone sialoprotein (BSP). Further, osteogenic differentiation of murine mesenchymal stem cells was studied with and without electrical stimulation. The q-PCR analysis shows that the electrically stimulated cryogels exhibit ~ 6 folds higher collagen type I and ~ 10 folds higher osteopontin mRNA level, in comparison to the unstimulated cryogels. Thus, PTAC biocomposite cryogels present osteoinductive and osteoconductive properties during in vitro and in vivo studies and support osteogenic differentiation of mesenchymal stem cells under the influence of electrical stimulation.

  8. The role of estrogen in bone growth and formation: changes at puberty

    Directory of Open Access Journals (Sweden)

    Divya Singh

    2010-12-01

    Full Text Available Divya Singh1, Sabyasachi Sanyal2, Naibedya Chattopadhyay11Division of Endocrinology, 2Division of Drug Target Discovery and Development, Central Drug Research Institute (Council of Scientific and Industrial Research, Lucknow, Uttar Pradesh, IndiaAbstract: A high peak bone mass (PBM at skeletal maturity is a good predictor for lower rate of fracture risks in later life. Growth during puberty contributes significantly to PBM achievement in women and men. The growth hormone (GH/insulin-like growth factor 1 (IGF-1 axis has a critical role in pubertal bone growth. There is an increase in GH and IGF-1 levels during puberty; thus, it is assumed that sex steroids contribute to higher GH/IGF-1 action during growth. Recent studies indicate that estrogen increases GH secretion in boys and girls, and the major effect of testosterone on GH secretion is via aromatization to estrogen. Estrogen is pivotal for epiphyseal fusion in young men and women. From studies of individuals with a mutated aromatase gene and a case study of male patient with defective estrogen receptor-alpha (ER-α, it is clear that estrogen is indispensable for normal pubertal growth and growth plate fusion. ER-α and estrogen receptor-beta (ER-β have been localized in growth plate and bone. ER knockout studies have shown that ER-α-/- female mice have reduced linear appendicular growth, while ER-β-/- mice have increased appendicular growth. No such effect is seen in ER-β-/- males; however, repressed growth is seen in ER-α-/- males, resulting in shorter long bones. Thus, ER-β represses longitudinal bone growth in female mice, while it has no function in the regulation of longitudinal bone growth in male mice. These findings indicate that estrogen plays a critical role in skeletal physiology of males as well as females.Keywords: peak bone mass, puberty, estrogen, growth plate

  9. Monostotic fibrous dysplasia of a lumbar vertebral body with secondary aneurysmal bone cyst formation: a case report

    Directory of Open Access Journals (Sweden)

    Snieders Marieke N

    2009-06-01

    Full Text Available Abstract We report the case of a 25-year-old Caucasian woman with symptomatic monostotic fibrous dysplasia of the fourth lumbar vertebral body. The patient suffered from a five-week history of progressive low back pain, radiating continuously to the left leg. Her medical history and physical and neurological examination did not demonstrate any significant abnormalities. Radiographs, computed tomography and magnetic resonance imaging revealed an osteolytic expansive lesion with a cystic component of the fourth lumbar vertebral body. Percutaneous transpedicular biopsy showed histological characteristics of fibrous dysplasia superimposed by the formation of aneurysmal bone cyst components. The patient was treated by subtotal vertebrectomy of the L4 vertebral body with anterior reconstruction and her postoperative course was uncomplicated. To our knowledge, this is the first reported case of a monostotic fibrous dysplasia with superimposed secondary aneurysmal bone cysts of a lumbar vertebral body.

  10. Effects of 1-week head-down tilt bed rest on bone formation and the calcium endocrine system

    Science.gov (United States)

    Arnaud, Sara B.; Whalen, Robert T.; Fung, Paul; Sherrard, Donald J.; Maloney, Norma

    1992-01-01

    The -6-deg head-down tilt (HDT) is employed in the study of 8 subjects to determine early responses in human bone and calcium endocrines during spaceflight. The average rates of bone formation in the iliac crest are determined by means of a single-dose labeling schedule and are found to decrease in 6 of the subjects. The decrease varies directly with walking miles, and increased excretion of urinary Ca and Na are observed preceding increased levels of ionized serum calcium on a bed-rest day late in the week. Reduced phosphorous excretions are also followed by increased serum phosphorous on day six, and reductions are noted in parathyroid hormone and vitamin D by the end of the experiment. The data demonstrate the responsiveness of the skeletal system to biomechanical stimuli such as the HDT.

  11. Commercial Honeybush (Cyclopia spp. Tea Extract Inhibits Osteoclast Formation and Bone Resorption in RAW264.7 Murine Macrophages—An in vitro Study

    Directory of Open Access Journals (Sweden)

    Amcois Visagie

    2015-10-01

    Full Text Available Honeybush tea, a sweet tasting caffeine-free tea that is indigenous to South Africa, is rich in bioactive compounds that may have beneficial health effects. Bone remodeling is a physiological process that involves the synthesis of bone matrix by osteoblasts and resorption of bone by osteoclasts. When resorption exceeds formation, bone remodeling can be disrupted resulting in bone diseases such as osteoporosis. Osteoclasts are multinucleated cells derived from hematopoietic precursors of monocytic lineage. These precursors fuse and differentiate into mature osteoclasts in the presence of receptor activator of NF-kB ligand (RANKL, produced by osteoblasts. In this study, the in vitro effects of an aqueous extract of fermented honeybush tea were examined on osteoclast formation and bone resorption in RAW264.7 murine macrophages. We found that commercial honeybush tea extract inhibited osteoclast formation and TRAP activity which was accompanied by reduced bone resorption and disruption of characteristic cytoskeletal elements of mature osteoclasts without cytotoxicity. Furthermore, honeybush tea extract decreased expression of key osteoclast specific genes, matrix metalloproteinase-9 (MMP-9, tartrate resistant acid phosphatase (TRAP and cathepsin K. This study demonstrates for the first time that honeybush tea may have potential anti-osteoclastogenic effects and therefore should be further explored for its beneficial effects on bone.

  12. The fluoride coated AZ31B magnesium alloy improves corrosion resistance and stimulates bone formation in rabbit model

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Wei; Zhang, Guangdao [Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang 110001 (China); Tan, Lili; Yang, Ke [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Ai, Hongjun, E-mail: aihongjuna@sina.com [Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang 110001 (China)

    2016-06-01

    This study aimed to evaluate the effect of fluorine coated Mg alloy and clarify its mechanism in bone formation. We implanted the fluorine coated AZ31B Mg alloy screw (group F) in rabbit mandibular and femur in vivo. Untreated AZ31B Mg alloy screw (group A) and titanium screw (group T) were used as control. Then, scanning electron microscopy, the spectral energy distribution analysis, hard and decalcified bone tissues staining were performed. Immunohistochemistry was employed to examine the protein expressions of bone morphogenetic protein 2 (BMP-2) and collagen type I in the vicinity of the implant. Compared with the group A, the degradation of the alloy was reduced, the rates of Mg corrosion and Mg ion release were slowed down, and the depositions of calcium and phosphate increased in the group F in the early stage of implantation. Histological results showed that fluorine coated Mg alloy had well osteogenic activity and biocompatibility. Moreover, fluoride coating obviously up-regulated the expressions of collagen type I and BMP-2. This study confirmed that the fluorine coating might improve the corrosion resistance of AZ31B Mg alloy and promote bone formation by up-regulated the expressions of collagen type I and BMP-2. - Highlights: • Fluoride coating inhibited the degradation of the alloy in the early implantation. • Fluorine coating could slow down the rate of Mg corrosion and Mg ion release. • Fluorine coating could promote the deposition of Ca and P in vivo. • Fluorine coated Mg alloy had well osteogenic activity and biocompatibility. • Fluorine coating up-regulated the expression of BMP-2 and collagen type I protein.

  13. Osteoblast maturation and new bone formation in response to titanium implant surface features are reduced with age.

    Science.gov (United States)

    Olivares-Navarrete, Rene; Raines, Andrew L; Hyzy, Sharon L; Park, Jung Hwa; Hutton, Daphne L; Cochran, David L; Boyan, Barbara D; Schwartz, Zvi

    2012-08-01

    The surface properties of materials contribute to host cellular response and play a significant role in determining the overall success or failure of an implanted biomaterial. Rough titanium (Ti) surface microtopography and high surface free energy have been shown to enhance osteoblast maturation in vitro and increase bone formation in vivo. Whereas the surface properties of Ti are known to affect osteoblast response, host bone quality also plays a significant role in determining successful osseointegration. One factor affecting host bone quality is patient age. We examined both in vitro and in vivo whether response to Ti surface features was affected by animal age. Calvarial osteoblasts isolated from 1-, 3-, and 11-month-old rats all displayed a reduction in cell number and increases in alkaline phosphatase-specific activity and osteocalcin in response to increasing Ti surface microtopography and surface energy. Further, osteoblasts from the three ages examined displayed increased production of osteocalcin and local factors osteoprotegerin, vascular endothelial growth factor (VEGF)-A, and active transforming growth factor (TGF)-β1 in response to increasing Ti surface roughness and surface energy. Latent TGF-β1 only increased in cultures of osteoblasts from 1- and 3-month-old rats. Treatment with the systemic osteotropic hormone 1α,25(OH)(2)D(3) further enhanced the response of osteoblasts to Ti surface features for all three age groups. However, osteoblasts derived from 11-month-old animals had a reduced response to 1α,25(OH)(2)D(3) compared to osteoblasts derived from 1- or 3-month-old animals. These results were confirmed in vivo. Ti implants placed in the femoral intramedullary canal of old (9-month-old) mice yielded lower bone-to-implant contact and neovascularization in response to Ti surface roughness and energy compared to younger (2-month-old) mice. These results show that rodent osteoblast maturation in vitro as well as new bone formation in vivo is

  14. The Role of Ultrasound Imaging of Callus Formation in the Treatment of Long Bone Fractures in Children.

    Science.gov (United States)

    Wawrzyk, Magdalena; Sokal, Jan; Andrzejewska, Ewa; Przewratil, Przemysław

    2015-01-01

    In the process of diagnosis and treatment of fractures, an X-ray study is typically performed. In modern medicine very important is the development of new diagnostic methods without adverse effects on the body. One of such techniques is ultrasound imaging. It has a high value in imaging most areas of the body, including the musculoskeletal system. Reports on the use of ultrasound in the evaluation of the callus are rare and this could be a method equivalent to or even better than standard radiographs. The aim of the study was to analyze the correlation of ultrasound with radiographs in imaging of callus formation after fractures of long bones in children and to analyze the correlation of vascular resistance index (RI) and the degree of vascularization of the callus with a subjective radiological assessment of the bone union quality. The prospective study was planned to qualify 50 children treated for long bones fractures of the arm, forearm, thigh and lower leg. Ultrasound diagnosis was carried out using a Philips iU22 camera equipped with a linear probe with 17-5-MHz resolution and MSK Superficial program. During ultrasound examination measurements of the callus were performed. Using the Power Doppler callus vascularity was visualized and vascular resistance index (RI) was measured. The same measurements were made within the corresponding area of the healthy limb. The results obtained by ultrasound were compared with radiograph measurements and with the subjective assessment of the callus quality. Preliminary results were developed on a group of 24 patients, where 28 fractured bones and 28 corresponding healthy bones were examined. Fifteen boys and 9 girls participated in the study. The average age at injury was, respectively, 11 and 9 years. In both groups fractures without displacement were the most frequent. A similar frequency was observed in fractures requiring reposition and subperiosteal fractures. In contrast, fractures with a slight displacement of the

  15. The Role of Ultrasound Imaging of Callus Formation in the Treatment of Long Bone Fractures in Children

    International Nuclear Information System (INIS)

    Wawrzyk, Magdalena; Sokal, Jan; Andrzejewska, Ewa; Przewratil, Przemysław

    2015-01-01

    In the process of diagnosis and treatment of fractures, an X-ray study is typically performed. In modern medicine very important is the development of new diagnostic methods without adverse effects on the body. One of such techniques is ultrasound imaging. It has a high value in imaging most areas of the body, including the musculoskeletal system. Reports on the use of ultrasound in the evaluation of the callus are rare and this could be a method equivalent to or even better than standard radiographs. The aim of the study was to analyze the correlation of ultrasound with radiographs in imaging of callus formation after fractures of long bones in children and to analyze the correlation of vascular resistance index (RI) and the degree of vascularization of the callus with a subjective radiological assessment of the bone union quality. The prospective study was planned to qualify 50 children treated for long bones fractures of the arm, forearm, thigh and lower leg. Ultrasound diagnosis was carried out using a Philips iU22 camera equipped with a linear probe with 17-5-MHz resolution and MSK Superficial program. During ultrasound examination measurements of the callus were performed. Using the Power Doppler callus vascularity was visualized and vascular resistance index (RI) was measured. The same measurements were made within the corresponding area of the healthy limb. The results obtained by ultrasound were compared with radiograph measurements and with the subjective assessment of the callus quality. Preliminary results were developed on a group of 24 patients, where 28 fractured bones and 28 corresponding healthy bones were examined. Fifteen boys and 9 girls participated in the study. The average age at injury was, respectively, 11 and 9 years. In both groups fractures without displacement were the most frequent. A similar frequency was observed in fractures requiring reposition and subperiosteal fractures. In contrast, fractures with a slight displacement of the

  16. Oriented bone regenerative capacity of octacalcium phosphate/gelatin composites obtained through two-step crystal preparation method.

    Science.gov (United States)

    Ishiko-Uzuka, Risa; Anada, Takahisa; Kobayashi, Kazuhito; Kawai, Tadashi; Tanuma, Yuji; Sasaki, Keiichi; Suzuki, Osamu

    2017-07-01

    The present study was designed to investigate whether composite of coprecipitating octacalcium phosphate and gelatin (C-OCP/Gel) has an effect in repairing critical-sized defect of rat calvaria with oriented regenerative bone if implanted. The materials were prepared through two steps to disperse homogenous and well-elongated OCP toward long axis of the crystals in gelatin (Gel) matrix with the distinct concentration 17-44 wt %: OCP precipitates recovered from the coprecipitated with Gel molecules in aqueous solution (referred to as C-OCP hereafter) were mixed again in fresh aqueous Gel solution with various mixing ratio to form C-OCP/Gel for implantation. C-OCP/Gel disks with 9 mm diameter and 1 mm thickness after the dehydrothermal treatment was implanted in 9 mm diameter rat calvaria critical-sized defect. The histology, the histomorphometry in the regenerated bone and the quantitative analysis of the orientation of collagen with picrosirius red staining were carried out. It was found that C-OCP/Gel is capable of not only inducing sufficiently regenerative bone over 80% of the defect coupled with practically complete material biodegradation but also forming oriented bone significantly in relation to the amount of C-OCP in Gel matrix until 12 weeks after the implantation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1029-1039, 2017. © 2016 Wiley Periodicals, Inc.

  17. Antibody formation in mouse bone marrow. II. Evidence for a memory-dependent phenomenon

    International Nuclear Information System (INIS)

    Benner, R.; Meima, F.; Meulen, G.M. van der

    1974-01-01

    Mouse bone marrow is barely capable of plaque-forming cell (PFC) activity in a primary response to sheep red blood cells (SRBC), while PFC activity in the secondary response to SRBC can be clearly demonstrated. This phenomenon was studied by means of cell transfer experiments. T cells, which are involved in an anti-SRBC PFC response, were shown to be very scarce in normal mouse bone marrow. This is considered to be the cause of the low PFC activity in the marrow during the primary response to SRBC. In normal mouse bone marrow precursors of IgM-PFC but not of IgG- and IgA-PFC could be found. Priming with SRBC induced the appearance of IgM-, IgG-, IgA- and T-memory cells in the marrow. These B- and T-memory cells were shown to be specific for the antigen which induced their appearance. It is thought that after a second injection of SRBC the IgM-, IgG- and IgA-memory cells can differentiate with the help of the T-memory cells within the bone marrow into IgM-, IgG- and IgA-PFC respectively. The sequence of appearance of the B-memory cells in the bone marrow was shown to be IgM--IgG--IgA. Six months after the intravenous injection of SRBC, the presence of B-memory cells could be demonstrated not only in spleen and bone marrow, but also in peripheral lymph nodes, mesenteric lymph node, Peyer's patches, thymus and blood. The increase in amount of B-memory cells was most prominent in the spleen

  18. Comparison of the capacity of enamel matrix derivative gel and enamel matrix derivative in liquid formulation to adsorb to bone grafting materials.

    Science.gov (United States)

    Miron, Richard J; Bosshardt, Dieter D; Buser, Daniel; Zhang, Yufeng; Tugulu, Stefano; Gemperli, Anja; Dard, Michel; Caluseru, Oana M; Chandad, Fatiha; Sculean, Anton

    2015-04-01

    The use of an enamel matrix derivative (EMD) has been shown to enhance periodontal regeneration (e.g., formation of root cementum, periodontal ligament, and alveolar bone). However, in certain clinical situations, the use of EMD alone may not be sufficient to prevent flap collapse or provide sufficient stability of the blood clot. Data from clinical and preclinical studies have demonstrated controversial results after application of EMD combined with different types of bone grafting materials in periodontal regenerative procedures. The aim of the present study is to investigate the adsorption properties of enamel matrix proteins to bone grafts after surface coating with either EMD (as a liquid formulation) or EMD (as a gel formulation). Three different types of grafting materials, including a natural bone mineral (NBM), demineralized freeze-dried bone allograft (DFDBA), or a calcium phosphate (CaP), were coated with either EMD liquid or EMD gel. Samples were analyzed by scanning electron microscopy or transmission electron microscopy (TEM) using an immunostaining assay with gold-conjugated anti-EMD antibody. Total protein adsorption to bone grafting material was quantified using an enzyme-linked immunosorbent assay (ELISA) kit for amelogenin. The adsorption of amelogenin to the surface of grafting material varied substantially based on the carrier system used. EMD gel adsorbed less protein to the surface of grafting particles, which easily dissociated from the graft surface after phosphate-buffered saline rinsing. Analyses by TEM revealed that adsorption of amelogenin proteins were significantly farther from the grafting material surface, likely a result of the thick polyglycolic acid gel carrier. ELISA protein quantification assay demonstrated that the combination of EMD liquid + NBM and EMD liquid + DFDBA adsorbed higher amounts of amelogenin than all other treatment modalities. Furthermore, amelogenin proteins delivered by EMD liquid were able to penetrate the

  19. Enhanced Bone Formation in Segmental Defects with BMP2 in a Biologically Relevant Molecular Context

    Science.gov (United States)

    2016-10-16

    gun shots. These do not heal on their own once a ‘critical size’ segment of bone is missing. One strategy to induce healing is to use bone-inducing...1772.aspx#characteristics) that are cultured in base-osteogenic media. The C2C12 cell line is a mouse myoblast precursor cell that spontaneously...mineralized matrix within 14-21 days. These properties make the C2C12 cell culture an excellent experimental system to test for the osteogenic potency of

  20. Low-temperature heat capacity and standard molar enthalpy of formation of 9-fluorenemethanol (C14H12O)

    International Nuclear Information System (INIS)

    Di, You-Ying; Tan, Zhi-Cheng.; Sun, Xiao-Hong; Wang, Mei-Han; Xu, Fen; Liu, Yuan-Fa; Sun, Li-Xian; Zhang, Hong-Tao

    2004-01-01

    Low-temperature heat capacities of the 9-fluorenemethanol (C 14 H 12 O) have been precisely measured with a small sample automatic adiabatic calorimeter over the temperature range between T=78 K and T=390 K. The solid-liquid phase transition of the compound has been observed to be T fus =(376.567±0.012) K from the heat-capacity measurements. The molar enthalpy and entropy of the melting of the substance were determined to be Δ fus H m =(26.273±0.013) kJ · mol -1 and Δ fus S m =(69.770±0.035) J · K -1 · mol -1 . The experimental values of molar heat capacities in solid and liquid regions have been fitted to two polynomial equations by the least squares method. The constant-volume energy and standard molar enthalpy of combustion of the compound have been determined, Δ c U(C 14 H 12 O, s)=-(7125.56 ± 4.62) kJ · mol -1 and Δ c H m compfn (C 14 H 12 O, s)=-(7131.76 ± 4.62) kJ · mol -1 , by means of a homemade precision oxygen-bomb combustion calorimeter at T=(298.15±0.001) K. The standard molar enthalpy of formation of the compound has been derived, Δ f H m compfn (C 14 H 12 O,s)=-(92.36 ± 0.97) kJ · mol -1 , from the standard molar enthalpy of combustion of the compound in combination with other auxiliary thermodynamic quantities through a Hess thermochemical cycle

  1. MicroRNA-34a inhibits osteoblast differentiation and in vivo bone formation of human stromal stem cells

    DEFF Research Database (Denmark)

    Chen, Li; Holmstrøm, Kim; Qiu, Weimin

    2014-01-01

    of miR-34a. siRNA-mediated reduction of JAG1 expression inhibited OB differentiation. Moreover, a number of known cell cycle regulator and cell proliferation proteins, such as cyclin D1, cyclin-dependent kinase 4 and 6 (CDK4 and CDK6), E2F transcription factor three, and cell division cycle 25 homolog......Osteoblast differentiation and bone formation (osteogenesis) are regulated by transcriptional and post-transcriptional mechanisms. Recently, microRNAs (miRNAs) were identified as novel key regulators of human stromal (skeletal, mesenchymal) stem cells (hMSC) differentiation. Here, we identified mi...

  2. Bone formation induced in an infant by systemic prostaglandin-E2 administration

    DEFF Research Database (Denmark)

    Jørgensen, H R; Svanholm, H; Høst, A

    1988-01-01

    We report a case of long-term systemic administration of prostaglandin E2 (PGE2) to a newborn infant with ductus-dependent congenital heart disease. After 46 days of treatment, radiography showed cortical hyperostosis of the long bones. The child died 62 days after discontinuation of prostaglandin...

  3. 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

    follows resorption during these respective treatments. Furthermore, canopy cells exhibit uPARAP/Endo180, a receptor able to bind the collagen made available by osteoclasts, and reported to mediate osteoblast recruitment. Overall these observations support a mechanism where the recruitment of bone forming...

  4. Effect of polygonimitin C on bone formation and resorption in human ...

    African Journals Online (AJOL)

    Western blot assay was used to evaluate the effect of PC on the expressions of osterix (OSX), bone morphogenetic protein-2 (BMP-2), runt-related transcription factor 2 (RUNX-2), osteocalcin (OC), fibronectin (FN), type I collagen (COL I), osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) proteins in ...

  5. Trpv5/6 is vital for epithelial calcium uptake and bone formation

    NARCIS (Netherlands)

    Vanoevelen, J.; Janssens, A.C.; Huitema, L.F.; Hammond, C.J.; Metz, J.R.; Flik, G.; Voets, T.; Schulte-Merker, S.

    2011-01-01

    Calcium is an essential ion serving a multitude of physiological roles. Aside from its role as a second messenger, it is an essential component of the vertebrate bone matrix. Efficient uptake and storage of calcium are therefore indispensable for all vertebrates. Transient receptor potential family,

  6. Contribution of Implanted, Genetically Modified Muscle Progenitor Cells Expressing BMP-2 to New Bone Formation in a Rat Osseous Defect.

    Science.gov (United States)

    De La Vega, Rodolfo E; De Padilla, Consuelo Lopez; Trujillo, Miguel; Quirk, Nicholas; Porter, Ryan M; Evans, Christopher H; Ferreira, Elisabeth

    2018-01-03

    Because muscle contains osteoprogenitor cells and has a propensity to form bone, we have explored its utility in healing large osseous defects. Healing is achieved by the insertion of muscle fragments transduced with adenovirus encoding BMP-2 (Ad.BMP-2). However, it is not known whether the genetically modified muscle contributes osteoprogenitor cells to healing defects or merely serves as a local source of BMP-2. This question is part of the larger debate on the fate of progenitor cells introduced into sites of tissue damage to promote regeneration. To address this issue, we harvested fragments of muscle from rats constitutively expressing GFP, transduced them with Ad.BMP-2, and implanted them into femoral defects in wild-type rats under various conditions. GFP + cells persisted within defects for the entire 8 weeks of the experiments. In the absence of bone formation, these cells presented as fibroblasts. When bone was formed, GFP + cells were present as osteoblasts and osteocytes and also among the lining cells of new blood vessels. The genetically modified muscle thus contributed progenitor cells as well as BMP-2 to the healing defect, a property of great significance in light of the extensive damage to soft tissue and consequent loss of endogenous progenitors in problematic fractures. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  7. Protein-free formation of bone-like apatite: New insights into the key role of carbonation.

    Science.gov (United States)

    Deymier, Alix C; Nair, Arun K; Depalle, Baptiste; Qin, Zhao; Arcot, Kashyap; Drouet, Christophe; Yoder, Claude H; Buehler, Markus J; Thomopoulos, Stavros; Genin, Guy M; Pasteris, Jill D

    2017-05-01

    The nanometer-sized plate-like morphology of bone mineral is necessary for proper bone mechanics and physiology. However, mechanisms regulating the morphology of these mineral nanocrystals remain unclear. The dominant hypothesis attributes the size and shape regulation to organic-mineral interactions. Here, we present data supporting the hypothesis that physicochemical effects of carbonate integration within the apatite lattice control the morphology, size, and mechanics of bioapatite mineral crystals. Carbonated apatites synthesized in the absence of organic molecules presented plate-like morphologies and nanoscale crystallite dimensions. Experimentally-determined crystallite size, lattice spacing, solubility and atomic order were modified by carbonate concentration. Molecular dynamics (MD) simulations and density functional theory (DFT) calculations predicted changes in surface energy and elastic moduli with carbonate concentration. Combining these results with a scaling law predicted the experimentally observed scaling of size and energetics with carbonate concentration. The experiments and models describe a clear mechanism by which crystal dimensions are controlled by carbonate substitution. Furthermore, the results demonstrate that carbonate substitution is sufficient to drive the formation of bone-like crystallites. This new understanding points to pathways for biomimetic synthesis of novel, nanostructured biomaterials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Biosilica-glass formation using enzymes from sponges [silicatein]: Basic aspects and application in biomedicine [bone reconstitution material and osteoporosis

    Science.gov (United States)

    Wang, Shun-Feng; Wang, Xiao-Hong; Gan, Lu; Wiens, Matthias; Schröder, Heinz C.; Müller, Werner E. G.

    2011-09-01

    In the last 15 years biomineralization, in particular biosilicification (i.e., the formation of biogenic silica, SiO2), has become an exciting source of inspiration for the development of novel bionic approaches, following "Nature as model". Among the silica forming organisms there are the sponges that have the unique property to catalyze their silica skeletons by a specific enzyme termed silicatein. In the present review we summarize the present state of knowledge on silicatein-mediated "biosilica" formation in marine sponges, the involvement of further molecules in silica metabolism and their potential application in biomedicine. Recent advancements in the production of bone replacement material and in the potential use as a component in the treatment of osteoporosis are highlighted.

  9. Poly(Vinylidene Fluoride-Trifluorethylene)/barium titanate membrane promotes de novo bone formation and may modulate gene expression in osteoporotic rat model.

    Science.gov (United States)

    Scalize, Priscilla Hakime; Bombonato-Prado, Karina F; de Sousa, Luiz Gustavo; Rosa, Adalberto Luiz; Beloti, Marcio Mateus; Semprini, Marisa; Gimenes, Rossano; de Almeida, Adriana L G; de Oliveira, Fabíola Singaretti; Hallak Regalo, Simone Cecilio; Siessere, Selma

    2016-12-01

    Osteoporosis is a chronic disease that impairs proper bone remodeling. Guided bone regeneration is a surgical technique that improves bone defect in a particular region through new bone formation, using barrier materials (e.g. membranes) to protect the space adjacent to the bone defect. The polytetrafluorethylene membrane is widely used in guided bone regeneration, however, new membranes are being investigated. The purpose of this study was to evaluate the effect of P(VDFTrFE)/BT [poly(vinylidene fluoride-trifluoroethylene)/barium titanate] membrane on in vivo bone formation. Twenty-three Wistar rats were submitted to bilateral ovariectomy. Five animals were subjected to sham surgery. After 150 days, bone defects were created and filled with P(VDF-TrFE)/BT membrane or PTFE membrane (except for the sham and OVX groups). After 4 weeks, the animals were euthanized and calvaria samples were subjected to histomorphometric and computed microtomography analysis (microCT), besides real time polymerase chain reaction (real time PCR) to evaluate gene expression. The histomorphometric analysis showed that the animals that received the P(VDF-TrFE)/BT membrane presented morphometric parameters similar or even better compared to the animals that received the PTFE membrane. The comparison between groups showed that gene expression of RUNX2, BSP, OPN, OSX and RANKL were lower on P(VDF-TrFE)/BT membrane; the gene expression of ALP, OC, RANK and CTSK were similar and the gene expression of OPG, CALCR and MMP9 were higher when compared to PTFE. The results showed that the P(VDF-TrFE)/BT membrane favors bone formation, and therefore, may be considered a promising biomaterial to support bone repair in a situation of osteoporosis.

  10. [Frontier in bone biology].

    Science.gov (United States)

    Takeda, Shu

    2015-10-01

    Bone is an active organ in which bone mass is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption, i.e., coupling of bone formation and bone resorption. Recent advances in molecular bone biology uncovered the molecular mechanism of the coupling. A fundamental role of osteocyte in the maintenance of bone mass and whole body metabolism has also been revealed recently. Moreover, neurons and neuropeptides have been shown to be intimately involved in bone homeostasis though inter-organ network, in addition to "traditional" regulators of bone metabolism such as soluble factors and cytokines

  11. [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.

  12. Influence of Interleukin-1 Beta on Platelet-Poor Plasma Clot Formation: A Potential Impact on Early Bone Healing.

    Directory of Open Access Journals (Sweden)

    Xin Wang

    Full Text Available Hematoma quality (especially the fibrin matrix plays an important role in the bone healing process. Here, we investigated the effect of interleukin-1 beta (IL-1β on fibrin clot formation from platelet-poor plasma (PPP.Five-milliliter of rat whole-blood samples were collected from the hepatic portal vein. All blood samples were firstly standardized via a thrombelastograph (TEG, blood cell count, and the measurement of fibrinogen concentration. PPP was prepared by collecting the top two-fifths of the plasma after centrifugation under 400 × g for 10 min at 20°C. The effects of IL-1β cytokines on artificial fibrin clot formation from PPP solutions were determined by scanning electronic microscopy (SEM, confocal microscopy (CM, turbidity, and clot lysis assays.The lag time for protofibril formation was markedly shortened in the IL-1β treatment groups (243.8 ± 76.85 in the 50 pg/mL of IL-1β and 97.5 ± 19.36 in the 500 pg/mL of IL-1β compared to the control group without IL-1β (543.8 ± 205.8. Maximal turbidity was observed in the control group. IL-1β (500 pg/mL treatment significantly decreased fiber diameters resulting in smaller pore sizes and increased density of the fibrin clot structure formed from PPP (P < 0.05. The clot lysis assay revealed that 500 pg/mL IL-1β induced a lower susceptibility to dissolution due to the formation of thinner and denser fibers.IL-1β can significantly influence PPP fibrin clot structure, which may affect the early bone healing process.

  13. Improved Characterization and Modeling of Tight Oil Formations for CO2 Enhanced Oil Recovery Potential and Storage Capacity Estimation

    Energy Technology Data Exchange (ETDEWEB)

    Sorensen, James; Smith, Steven; Kurz, Bethany; Hawthorne, Steven; Jin, Lu; Bosshart, Nicholas; Torres, Jose; Nyberg, Carolyn; Heebink, Loreal; Hurley, John

    2018-03-09

    Tight oil formations such as those in the Bakken petroleum system are known to hold hundreds of billions of barrels of oil in place; however, the primary recovery factor for these plays is typically less than 10%. Tight oil formations, including the Bakken Formation, therefore, may be attractive candidates for enhanced oil recovery (EOR) using CO2. Multiphase fluid behavior and flow in fluid-rich shales can vary substantially depending on the size of pore throats, and properties such as fluid viscosity and density are much different in nanoscale pores than in macroscale pores. Thus it is critical to understand the nature and distribution of nano-, micro-, and macroscale pores and fracture networks. To address these issues, the Energy & Environmental Research Center (EERC) has been conducting a research program entitled “Improved Characterization and Modeling of Tight Oil Formations for CO2 Enhanced Oil Recovery Potential and Storage Capacity Estimation.” The objectives of the project are 1) the use of advanced characterization methods to better understand and quantify the petrophysical and geomechanical factors that control CO2 and oil mobility within tight oil formation samples, 2) the determination of CO2 permeation and oil extraction rates in tight reservoir rocks and organic-rich shales of the Bakken, and 3) the integration of the laboratory-based CO2 permeation and oil extraction data and the characterization data into geologic models and dynamic simulations to develop predictions of CO2 storage resource and EOR in the Bakken tight oil formation. A combination of standard and advanced petrophysical characterization techniques were applied to characterize samples of Bakken Formation tight reservoir rock and shales from multiple wells. Techniques included advanced computer tomography (CT) imaging, scanning electron microscopy (SEM) techniques, whole-core and micro x-ray CT imaging, field emission (FE) SEM, and focused ion beam (FIB) SEM. Selected samples

  14. Insight into the transgenerational effect of benzo[a]pyrene on bone formation in a teleost fish (Oryzias latipes).

    Science.gov (United States)

    Seemann, Frauke; Peterson, Drew R; Witten, P Eckhard; Guo, Bao-Sheng; Shanthanagouda, Adamane H; Ye, Rui R; Zhang, Ge; Au, Doris W T

    2015-12-01

    Recent cross-generational studies in teleost fish have raised the awareness that high levels of benzo[a]pyrene (BaP) could affect skeletal integrity in the directly exposed F0 and their F1-F2. However, no further details were provided about the causes for abnormalities on the molecular and cellular level and the persistence of such sub-organismal impairments at the transgenerational scale (beyond F2). Adult Oryzias latipes were exposed to 1μg/L BaP for 21days. The F1-F3 were examined for skeletal deformities, histopathological alterations of vertebral bodies and differential expression of key genes of bone metabolism. Significant increase of dorsal-ventral vertebral compression was evident in ancestrally exposed larvae. Histopathological analysis revealed abnormal loss of notochord sheath, a lack of notochord epithelial integrity, reduced bone tissue and decreased osteoblast abundance. A significant downregulation of ATF4 and/or osterix and a high biological variability of COL10, coupled with a significant deregulation of SOX9a/b in the F1-F3 suggest that ancestral BaP exposure most likely perturbed chordoblasts, chondroblast and osteoblast differentiation, resulting in defective notochord sheath repair and rendering the vertebral column more vulnerable to compression. The present findings provide novel molecular and cellular insights into BaP-induced transgenerational bone impairment in the unexposed F3. From the ecological risk assessment perspective, BaP needs to be regarded as a transgenerational skeletal toxicant, which exerts a far-reaching impact on fish survival and fitness. Given that basic mechanisms of cartilage/bone formation are conserved between medaka and mammals, the results may also shed light on the potential transgenerational effect of BaP on the genesis of skeletal diseases in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Concave pit-containing scaffold surfaces improve stem cell-derived osteoblast performance and lead to significant bone tissue formation.

    Directory of Open Access Journals (Sweden)

    Antonio Graziano

    2007-06-01

    Full Text Available Scaffold surface features are thought to be important regulators of stem cell performance and endurance in tissue engineering applications, but details about these fundamental aspects of stem cell biology remain largely unclear.In the present study, smooth clinical-grade lactide-coglyolic acid 85:15 (PLGA scaffolds were carved as membranes and treated with NMP (N-metil-pyrrolidone to create controlled subtractive pits or microcavities. Scanning electron and confocal microscopy revealed that the NMP-treated membranes contained: (i large microcavities of 80-120 microm in diameter and 40-100 microm in depth, which we termed primary; and (ii smaller microcavities of 10-20 microm in diameter and 3-10 microm in depth located within the primary cavities, which we termed secondary. We asked whether a microcavity-rich scaffold had distinct bone-forming capabilities compared to a smooth one. To do so, mesenchymal stem cells derived from human dental pulp were seeded onto the two types of scaffold and monitored over time for cytoarchitectural characteristics, differentiation status and production of important factors, including bone morphogenetic protein-2 (BMP-2 and vascular endothelial growth factor (VEGF. We found that the microcavity-rich scaffold enhanced cell adhesion: the cells created intimate contact with secondary microcavities and were polarized. These cytological responses were not seen with the smooth-surface scaffold. Moreover, cells on the microcavity-rich scaffold released larger amounts of BMP-2 and VEGF into the culture medium and expressed higher alkaline phosphatase activity. When this type of scaffold was transplanted into rats, superior bone formation was elicited compared to cells seeded on the smooth scaffold.In conclusion, surface microcavities appear to support a more vigorous osteogenic response of stem cells and should be used in the design of therapeutic substrates to improve bone repair and bioengineering applications in the

  16. Effects of a Combination Therapy of Sclerostin Antibody III and Raloxifene on Bone Formation Markers in Ovariectomized Rats

    International Nuclear Information System (INIS)

    Allam, H. I. G.

    2016-01-01

    Objective: To determine the systemic effect of sclerostin monoclonal antibody (Scl-AbIII) administration on markers of bone formation and compare it with a combination of sclerostin antibody and raloxifene. Study Design: Experimental study. Place and Duration of Study: Medical College Animal House at King Khaled University Hospital, Riyadh, Saudi Arabia, from January to November 2014. Methodology: Forty-five female rats were divided into 5 groups equally; 1 control group and 4 groups of ovariectomized (OVX) rats: control OVX rats and OVX rats treated by Scl-AbIII, raloxifene or Scl-AbIII+raloxifene one month after ovariectomy, continued for 4 weeks. At the end of treatment, serum levels of Bone Specific Alkaline Phosphatase (BSAP), alkaline phosphatase, osteocalcin, Insulin-like Growth Factor-1 (IGF-1), Parathyroid Hormone (PTH), Ca/sup 2+/ and phosphorus were measured. Uterus was weighed and body weight change was calculated. Results: Scl-AbIII or raloxifene treatment produced significant increase of serum BSAP, osteocalcin, IGF-1, PTH and Ca/sup 2+/ levels. Raloxifene, either alone or combined with Scl-AbIII attenuated the decrease in uterus wet weight, and the increase in body weight seen in OVX rats. Combination therapy of Scl-AbIII, and raloxifene produced significant increase of serum alkaline phosphatase, osteocalcin and IGF-1 levels than treatment with either Scl-AbIII or raloxifene alone. Conclusion: Combination therapy of Scl-AbIII and raloxifene is an attractive strategy to enhance bone formation and can offer better gain over treatment with either one of them alone. Confirmation of these preliminary observations must await careful long-term studies. (author)

  17. Hydrothermal Synthesis of Hydroxyapatite Nanorods for Rapid Formation of Bone-Like Mineralization

    Science.gov (United States)

    Hoai, Tran Thanh; Nga, Nguyen Kim; Giang, Luu Truong; Huy, Tran Quang; Tuan, Phan Nguyen Minh; Binh, Bui Thi Thanh

    2017-08-01

    Hydroxyapatite (HAp) is an excellent biomaterial for bone repair and regeneration. The biological functions of HAp particles, such as biomineralization, cell adhesion, and cell proliferation, can be enhanced when their size is reduced to the nanoscale. In this work, HAp nanoparticles were synthesized by the hydrothermal technique with addition of cetyltrimethylammonium bromide (CTAB). These particles were also characterized, and their size controlled by modifying the CTAB concentration and hydrothermal duration. The results show that most HAp nanoparticles were rod-like in shape, exhibiting the most uniform and smallest size (mean diameter and length of 39 nm and 125 nm, respectively) at optimal conditions of 0.64 g CTAB and hydrothermal duration of 12 h. Moreover, good biomineralization capability of the HAp nanorods was confirmed through in vitro tests in simulated body fluid. A bone-like mineral layer of synthesized HAp nanorods formed rapidly after 7 days. This study shows that highly bioactive HAp nanorods can be easily prepared by the hydrothermal method, being a potential nanomaterial for bone regeneration.

  18. Simultaneous gene transfer of bone morphogenetic protein (BMP -2 and BMP-7 by in vivo electroporation induces rapid bone formation and BMP-4 expression

    Directory of Open Access Journals (Sweden)

    Miyazaki Jun-ichi

    2006-08-01

    Full Text Available Abstract Background Transcutaneous in vivo electroporation is expected to be an effective gene-transfer method for promoting bone regeneration using the BMP-2 plasmid vector. To promote enhanced osteoinduction using this method, we simultaneously transferred cDNAs for BMP-2 and BMP-7, as inserts in the non-viral vector pCAGGS. Methods First, an in vitro study was carried out to confirm the expression of BMP-2 and BMP-7 following the double-gene transfer. Next, the individual BMP-2 and BMP-7 plasmids or both together were injected into rat calf muscles, and transcutaneous electroporation was applied 8 times at 100 V, 50 msec. Results In the culture system, the simultaneous transfer of the BMP-2 and BMP-7 genes led to a much higher ALP activity in C2C12 cells than did the transfer of either gene alone. In vivo, ten days after the treatment, soft X-ray analysis showed that muscles that received both pCAGGS-BMP-2 and pCAGGS-BMP-7 had better-defined opacities than those receiving a single gene. Histological examination showed advanced ossification in calf muscles that received the double-gene transfer. BMP-4 mRNA was also expressed, and RT-PCR showed that its level increased for 3 days in a time-dependent manner in the double-gene transfer group. Immunohistochemistry confirmed that BMP-4-expressing cells resided in the matrix between muscle fibers. Conclusion The simultaneous transfer of BMP-2 and BMP-7 genes using in vivo electroporation induces more rapid bone formation than the transfer of either gene alone, and the increased expression of endogenous BMP-4 suggests that the rapid ossification is related to the induction of BMP-4.

  19. A rate-limiting role for Dickkopf-1 in bone formation and the remediation of bone loss in mouse and primate models of postmenopausal osteoporosis by an experimental therapeutic antibody.

    Science.gov (United States)

    Glantschnig, Helmut; Scott, Kevin; Hampton, Richard; Wei, Nan; McCracken, Paul; Nantermet, Pascale; Zhao, Jing Z; Vitelli, Salvatore; Huang, Lingyi; Haytko, Peter; Lu, Ping; Fisher, John E; Sandhu, Punam; Cook, Jacquelynn; Williams, Donald; Strohl, William; Flores, Osvaldo; Kimmel, Donald; Wang, Fubao; An, Zhiqiang

    2011-08-01

    Genetic studies have linked both osteoporotic and high bone mass phenotypes to low-density lipoprotein receptor-related proteins (LRP4, LRP5, and LRP6). LRPs are receptors for inhibitory Dickkopf-1 (DKK1) protein, and treatment modalities that modulate LRP/DKK1 binding therefore may act as stimulators of bone mass accrual. Here, we report that RH2-18, a fully human monoclonal anti-DKK1 antibody elicits systemic pharmacologic bone efficacy and new bone formation at endosteal bone surfaces in vivo in a mouse model of estrogen-deficiency-induced osteopenia. This was paralleled by partial-to-complete resolution of osteopenia (bone mineral density) at all of the skeletal sites investigated in femur and lumbar-vertebral bodies and the restoration of trabecular bone microarchitecture. More importantly, testing of RH2-18 in adult, osteopenic rhesus macaques demonstrated a rate-limiting role of DKK1 at multiple skeletal sites and responsiveness to treatment. In conclusion, this study provides pharmacologic evidence for the modulation of DKK1 bioactivity in the adult osteopenic skeleton as a viable approach to resolve osteopenia in animal models. Thus, data described here suggest that targeting DKK1 through means such as a fully human anti-DKK1-antibody provides a potential bone-anabolic treatment for postmenopausal osteoporosis.

  20. Novel Radiomitigator for Radiation-Induced Bone Loss

    Science.gov (United States)

    Schreurs, A-S; Shirazi-fard, Y.; Terada, M.; Alwood, J. S.; Steczina, S.; Medina, C.; Tahimic, C. G. T.; Globus, R. K.

    2016-01-01

    Radiation-induced bone loss can occur with radiotherapy patients, accidental radiation exposure and during long-term spaceflight. Bone loss due to radiation is due to an early increase in oxidative stress, inflammation and bone resorption, resulting in an imbalance in bone remodeling. Furthermore, exposure to high-Linear Energy Transfer (LET) radiation will impair the bone forming progenitors and reduce bone formation. Radiation can be classified as high-LET or low-LET based on the amount of energy released. Dried Plum (DP) diet prevents bone loss in mice exposed to total body irradiation with both low-LET and high-LET radiation. DP prevents the early radiation-induced bone resorption, but furthermore, we show that DP protects the bone forming osteoblast progenitors from high-LET radiation. These results provide insight that DP re-balances the bone remodeling by preventing resorption and protecting the bone formation capacity. This data is important considering that most of the current osteoporosis treatments only block the bone resorption but do not protect bone formation. In addition, DP seems to act on both the oxidative stress and inflammation pathways. Finally, we have preliminary data showing the potential of DP to be radio-protective at a systemic effect and could possible protect other tissues at risk of total body-irradiation such as skin, brain and heart.

  1. Convergence of bone morphogenetic protein and laminin-1 signaling pathways promotes proliferation and colony formation by fetal mouse pancreatic cells

    International Nuclear Information System (INIS)

    Jiang Fangxu; Harrison, Leonard C.

    2005-01-01

    We previously reported that bone morphogenetic proteins (BMPs), members of the transforming growth factor superfamily, together with the basement membrane glycoprotein laminin-1 (Ln-1), promote proliferation of fetal pancreatic cells and formation of colonies containing peripheral insulin-positive cells. Here, we further investigate the cross-talk between BMP and Ln-1 signals. By RT-PCR, receptors for BMP (BMPR) (excepting BMPR-1B) and Ln-1 were expressed in the fetal pancreas between E13.5 and E17.5. Specific blocking antibodies to BMP-4 and -6 and selective BMP antagonists partially inhibited colony formation by fetal pancreas cells. Colony formation induced by BMP-6 and Ln-1 was completely abolished in a dose-dependent manner by blocking Ln-1 binding to its α 6 integrin and α-dystroglycan receptors or by blocking the Ln-1 signaling molecules, phosphatidyl-inositol-3-kinase (P13K) and MAP kinase kinase-1. These results demonstrate a convergence of BMP and Ln-1 signaling through P13K and MAP kinase pathways to induce proliferation and colony formation in E15.5 fetal mouse pancreatic cells

  2. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation.

    Science.gov (United States)

    Xue, Feng; Wu, Er-Jun; Zhang, Pei-Xun; Li-Ya, A; Kou, Yu-Hui; Yin, Xiao-Feng; Han, Na

    2015-01-01

    We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker) and glial fibrillary acidic protein (glial cell marker) at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.

  3. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

    Directory of Open Access Journals (Sweden)

    Feng Xue

    2015-01-01

    Full Text Available We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker and glial fibrillary acidic protein (glial cell marker at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.

  4. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

    Science.gov (United States)

    Xue, Feng; Wu, Er-jun; Zhang, Pei-xun; Li-ya, A; Kou, Yu-hui; Yin, Xiao-feng; Han, Na

    2015-01-01

    We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker) and glial fibrillary acidic protein (glial cell marker) at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury. PMID:25788929

  5. Multifunctional surfaces with biomimetic nanofibres and drug-eluting micro-patterns for infection control and bone tissue formation

    Directory of Open Access Journals (Sweden)

    XN Chen

    2012-09-01

    Full Text Available For long-term orthopaedic implants, the creation of a surface that is repulsive to bacteria while adhesive to tissue cells represents a promising strategy to control infection. To obtain such multifunctional surfaces, two possible approaches were explored to incorporate a model antibiotic, rifampicin (Rf, into the osteogenic polycaprolactone (PCL/chitosan (CHS biomimetic nanofibre meshes by (1 blending Rf into the electrospinning solutions and then electrospinning into nanofibres (i.e., Rf-incorporating fibres, or (2 depositing Rf-containing poly(D,L-lactic-co-glycolic acid (PLGA micro-patterns onto the PCL/chitosan nanofibre meshes via ink-jet printing (i.e., Rf-eluting micro-pattern/fibre. Rapid release of Rf from both meshes was measured even though a relatively slower release rate was obtained from the Rf-eluting micro-pattern ones. Antibacterial assay with Staphylococcus epidermidis showed that both mesh surfaces could effectively kill bacteria and prevent biofilm formation. However, only Rf-eluting micro-pattern meshes favoured the attachment, spreading and metabolic activity of preosteoblasts in the cell culture study. Furthermore, the Rf-eluting micro-pattern meshes could better support the osteogenic differentiation of preosteoblasts by up-regulating the gene expression of bone markers (type I collagen and alkaline phosphatase. Clearly, compared to Rf-incorporating nanofibre meshes, Rf-eluting micro-patterns could effectively prevent biofilm formation without sacrificing the osteogenic properties of PCL/chitosan nanofibre surfaces. This finding provides an innovative avenue to design multifunctional surfaces for enhancing bone tissue formation while controlling infection.

  6. Engineering biomimetic periosteum with β-TCP scaffolds to promote bone formation in calvarial defects of rats.

    Science.gov (United States)

    Zhang, Dan; Gao, Peng; Li, Qin; Li, Jinda; Li, Xiaojuan; Liu, Xiaoning; Kang, Yunqing; Ren, Liling

    2017-06-05

    There is a critical need for the management of large bone defects. The purpose of this study was to engineer a biomimetic periosteum and to combine this with a macroporous β-tricalcium phosphate (β-TCP) scaffold for bone tissue regeneration. Rat bone marrow-derived mesenchymal stem cells (rBMSCs) were harvested and cultured in different culture media to form undifferentiated rBMSC sheets (undifferentiated medium (UM)) and osteogenic cell sheets (osteogenic medium (OM)). Simultaneously, rBMSCs were differentiated to induced endothelial-like cells (iECs), and the iECs were further cultured on a UM to form a vascularized cell sheet. At the same time, flow cytometry was used to detect the conversion rates of rBMSCs to iECs. The pre-vascularized cell sheet (iECs/UM) and the osteogenic cell sheet (OM) were stacked together to form a biomimetic periosteum with two distinct layers, which mimicked the fibrous layer and cambium layer of native periosteum. The biomimetic periostea were wrapped onto porous β-TCP scaffolds (BP/β-TCP) and implanted in the calvarial bone defects of rats. As controls, autologous periostea with β-TCP (AP/β-TCP) and β-TCP alone were implanted in the calvarial defects of rats, with a no implantation group as another control. At 2, 4, and 8 weeks post-surgery, implants were retrieved and X-ray, microcomputed tomography (micro-CT), histology, and immunohistochemistry staining analyses were performed. Flow cytometry results showed that rBMSCs were partially differentiated into iECs with a 35.1% conversion rate in terms of CD31. There were still 20.97% rBMSCs expressing CD90. Scanning electron microscopy (SEM) results indicated that cells from the wrapped cell sheet on the β-TCP scaffold apparently migrated into the pores of the β-TCP scaffold. The histology and immunohistochemistry staining results from in vivo implantation indicated that the BP/β-TCP and AP/β-TCP groups promoted the formation of blood vessels and new bone tissues in the bone

  7. Melatonin therapy reduces the risk of osteoporosis and normalizes bone formation in multiple sclerosis.

    Science.gov (United States)

    Ghareghani, Majid; Scavo, Linda; Arnoult, Damien; Zibara, Kazem; Farhadi, Naser

    2018-04-01

    Multiple sclerosis (MS) is a common autoimmune and neurodegenerative disease of the central nervous system. Serum levels of melatonin decrease in MS patients who are also at risk of osteoporosis. Procalcitonin (proCT) has been reported as a biomarker of systemic inflammation and autoimmune disease; however, its changes in MS patients have not been well explored. This study investigated, using ELISA, the clinical correlation between serum melatonin and proCT in MS patients. We then assessed the effect of melatonin (10 mg/kg) therapy on bone metabolism and osteoporosis in experimental autoimmune encephalomyelitis (EAE) model of MS and in MS patients. Data showed a significant increase (*P < 0.05) in serum levels of proCT in MS patients, inversely correlated (r  =  -0.945; P  =  0.0001) with melatonin levels, compared to healthy participants. On the other hand, melatonin therapy ameliorated EAE severity by significantly decreasing (*P < 0.05) mean clinical scores, compared to control EAE mice. In addition, serum levels of proCT significantly (**P < 0.01) increased in EAE mice, compared to controls, which was significantly (*P < 0.05) reduced by melatonin. Moreover, EAE-induced decrease in 25-hydroxyvitamin D, calcium, and osteocalcin (OCN) in EAE mice, compared to controls, was significantly (*P < 0.05) increased by melatonin. Finally, OCN serum levels were found to be significantly decreased (*P < 0.05) in MS patients, in comparison with controls. Taken together, we suggest that proCT could be used as a diagnostic biomarker in MS patients and that melatonin normalizes bone metabolites in MS. Further clinical and experimental investigations are needed to understand bone metabolism in MS. © 2017 Société Française de Pharmacologie et de Thérapeutique.

  8. Regulation of bone formation by baicalein via the mTORC1 pathway

    Directory of Open Access Journals (Sweden)

    Li SF

    2015-09-01

    Full Text Available Sheng-fa Li,1,2,* Jia-jun Tang,1,2,* Jian Chen,1–3,* Pei Zhang,4,* Ting Wang,5 Tian-yu Chen,1,2 Bo Yan,1,2 Bin Huang,1,2 Liang Wang,1,2 Min-jun Huang,1,2 Zhong-min Zhang,1,2 Da-di Jin1,21Academy of Orthopedics of Guangdong Province, Guangzhou, People’s Republic of China; 2Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Three Gorges Central Hospital of Chongqing, Chongqing, People’s Republic of China; 4School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 5Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workAbstract: Osteoporosis is a systemic skeletal disease that is characterized by low bone density and microarchitectural deterioration of bone tissue. The increasing prevalence of osteoporosis has attracted much attention. In this study, MC3T3-E1 pre-osteoblasts were treated with the natural compound, baicalein (0.1 µmol/L, 1 µmol/L, 10 µmol/L, to stimulate differentiation over a 14-day period. In addition, a canonical ovariectomized (OVX mouse model was used to investigate the effect of 3-month baicalein treatment (10 mg/kg per day in preventing postmenopausal osteoporosis. In vitro, we found that baicalein induced activation of alkaline phosphatase, stimulated the mammalian target of rapamycin complex 1 (mTORC1 signaling pathway, and induced expression of osteoblast differentiation markers, ie, osteocalcin, osterix, collagen Iα1, and runt-related transcription factor 2 (RUNX2, in osteoblasts. In vivo, several bone parameters, including trabecular thickness, trabecular bone mineral density, and trabecular number, in the distal femoral metaphysis were significantly increased in OVX mice treated intragastrically with baicalein for 3 months

  9. 3D printed scaffolds of calcium silicate-doped β-TCP synergize with co-cultured endothelial and stromal cells to promote vascularization and bone formation.

    Science.gov (United States)

    Deng, Yuan; Jiang, Chuan; Li, Cuidi; Li, Tao; Peng, Mingzheng; Wang, Jinwu; Dai, Kerong

    2017-07-17

    Synthetic bone scaffolds have potential application in repairing large bone defects, however, inefficient vascularization after implantation remains the major issue of graft failure. Herein, porous β-tricalcium phosphate (β-TCP) scaffolds with calcium silicate (CS) were 3D printed, and pre-seeded with co-cultured human umbilical cord vein endothelial cells (HUVECs) and human bone marrow stromal cells (hBMSCs) to construct tissue engineering scaffolds with accelerated vascularization and better bone formation. Results showed that in vitro β-TCP scaffolds doped with 5% CS (5%CS/β-TCP) were biocompatible, and stimulated angiogenesis and osteogenesis. The results also showed that 5%CS/β-TCP scaffolds not only stimulated co-cultured cells angiogenesis on Matrigel, but also stimulated co-cultured cells to form microcapillary-like structures on scaffolds, and promoted migration of BMSCs by stimulating co-cultured cells to secrete PDGF-BB and CXCL12 into the surrounding environment. Moreover, 5%CS/β-TCP scaffolds enhanced vascularization and osteoinduction in comparison with β-TCP, and synergized with co-cultured cells to further increase early vessel formation, which was accompanied by earlier and better ectopic bone formation when implanted subcutaneously in nude mice. Thus, our findings suggest that porous 5%CS/β-TCP scaffolds seeded with co-cultured cells provide new strategy for accelerating tissue engineering scaffolds vascularization and osteogenesis, and show potential as treatment for large bone defects.

  10. Thermochemistry of Oxabicyclo-Heptanes, Oxabicyclo-Heptene: Enthalpy of Formation, Entropy, Heat Capacity, and Group Additivity

    Science.gov (United States)

    Bozzelli, Joseph W.; Rajasekaran, Indumathi

    2007-06-01

    Thermochemical properties, ΔfH°(298), S °(298) and [Cp°(T)] (10K⩽T⩽5000) of the seven target bicyclic epoxides are calculated using the density functional methods. Molecular structures and vibration frequencies for 6-oxabicyclo[3.1.0]hexane, 7-oxabicyclo[4.1.0]heptane, 8-oxabicyclo[5.1.0]octane, 7-oxabicyclo[2.2.1]heptane, endo-2-methyl-7-oxabicyclo[2.2.1]heptane, exo-2-methyl-7-oxabicyclo[2.2.1]heptane and 7-oxabicyclo[4.1.0]hept-2,4-ene are calculated at the B3LYP /6-31G(d,p) level of theory. Enthalpies of formation are determined at B3LYP /6-31G(d,p) calculation level using isodesmic and homodesmic working reactions with the ΔrxnH ° and known enthalpies of reference species in each of three different work reactions. Entropy (298) and heat capacity [Cp°(T)] values along with Benson Group additivity parameters are reported for each ring system. Data previously reported on oxybicyclo-epoxides are summarized.

  11. Polarized light microscopic analysis of bone formation after inhibition of cyclooxygenase 1 and 2.

    Science.gov (United States)

    Retamoso, Luciana Borges; Montagner, Francisco; Camargo, Elisa Souza; Vitral, Roberto Willer Farinazzo; Tanaka, Orlando Motohiro

    2010-02-01

    Potassium diclofenac is a potent nonsteroidal anti-inflammatory drug (NSAID) and COX isoforms (COX-1 and COX-2) inhibitor. Quantitative analysis of birefringence with polarized light microscopy is a useful method to investigate the macromolecular orientation and organization of collagen fibers in connective tissues. The aim of this research was to analyze the collagen structure and maturation in bone formed after potassium diclofenac administration, during first molar orthodontic movement. Sixty Wistar rats were divided in two equal groups (N = 30): control (C) and potassium diclofenac (PD). The animals in Group C received 0.9% saline solution and the PD group received potassium diclofenac Cataflam (5 mg/kg). Animals were sacrificed 3, 7, or 14 days after a NiTi unilateral closed-coil spring was stretched between the upper right first molar and the incisors. The first molar area was fixed, decalcified, and histologically processed using picrosirius pigment. The collagen birefringence of bone turnover was analyzed by phase retardation. Two-way ANOVA and Tukey's test showed that optical retardation was influenced by time and treatment. There was increase in the collagen organization over time. On the third day, the C group showed better collagen organization than the PD group. Potassium diclofenac interfered in collagen maturation, reducing fibril organization in the initial phase of orthodontic movement. 2009 Wiley-Liss, Inc.

  12. Snail/Slug-YAP/TAZ complexes cooperatively regulate mesenchymal stem cell function and bone formation.

    Science.gov (United States)

    Tang, Yi; Weiss, Stephen J

    2017-03-04

    Snail and Slug are zinc-finger transcription factors that play key roles in directing the epithelial-mesenchymal transition (EMT) programs associated with normal development as well as disease progression. More recent work suggests that these EMT-associated transcription factors also modulate the function of both embryonic and adult stem cells. Interestingly, YAP and TAZ, the co-transcriptional effectors of the Hippo pathway, likewise play an important role in stem cell self-renewal and lineage commitment. While direct intersections between the Snail/Slug and Hippo pathways have not been described previously, we recently described an unexpected cooperative interaction between Snail/Slug and YAP/TAZ that controls the self-renewal and differentiation properties of bone marrow-derived mesenchymal stem cells (MSCs), a cell population critical to bone development. Additional studies revealed that both Snail and Slug are able to form binary complexes with either YAP or TAZ that, together, control YAP/TAZ transcriptional activity and function throughout mouse development. Given the more recent observations that MSC-like cell populations are found in association throughout the vasculature where they participate in tissue regeneration, fibrosis and cancer, the Snail/Slug-YAP/TAZ axis is well-positioned to regulate global stem cell function in health and disease.

  13. Fluoride’s Effects on the Formation of Teeth and Bones, and the Influence of Genetics

    Science.gov (United States)

    Everett, E.T.

    2011-01-01

    Fluorides are present in the environment. Excessive systemic exposure to fluorides can lead to disturbances of bone homeostasis (skeletal fluorosis) and enamel development (dental/enamel fluorosis). The severity of dental fluorosis is also dependent upon fluoride dose and the timing and duration of fluoride exposure. Fluoride’s actions on bone cells predominate as anabolic effects both in vitro and in vivo. More recently, fluoride has been shown to induce osteoclastogenesis in mice. Fluorides appear to mediate their actions through the MAPK signaling pathway and can lead to changes in gene expression, cell stress, and cell death. Different strains of inbred mice demonstrate differential physiological responses to ingested fluoride. Genetic studies in mice are capable of identifying and characterizing fluoride-responsive genetic variations. Ultimately, this can lead to the identification of at-risk human populations who are susceptible to the unwanted or potentially adverse effects of fluoride action and to the elucidation of fundamental mechanisms by which fluoride affects biomineralization. PMID:20929720

  14. Cartilage Protective and Chondrogenic Capacity of WIN-34B, a New Herbal Agent, in the Collagenase-Induced Osteoarthritis Rabbit Model and in Progenitor Cells from Subchondral Bone

    Directory of Open Access Journals (Sweden)

    Jeong-Eun Huh

    2013-01-01

    Full Text Available We sought to determine the cartilage repair capacity of WIN-34B in the collagenase-induced osteoarthritis rabbit model and in progenitor cells from subchondral bone. The cartilage protective effect of WIN-34B was measured by clinical and histological scores, cartilage area, and proteoglycan and collagen contents in the collagenase-induced osteoarthritis rabbit model. The efficacy of chondrogenic differentiation of WIN-34B was assessed by expression of CD105, CD73, type II collagen, and aggrecan in vivo and was analyzed by the surface markers of progenitor cells, the mRNA levels of chondrogenic marker genes, and the level of proteoglycan, GAG, and type II collagen in vitro. Oral administration of WIN-34B significantly increased cartilage area, and this was associated with the recovery of proteoglycan and collagen content. Moreover, WIN-34B at 200 mg/kg significantly increased the expression of CD105, CD73, type II collagen, and aggrecan compared to the vehicle group. WIN-34B markedly enhanced the chondrogenic differentiation of CD105 and type II collagen in the progenitor cells from subchondral bone. Also, we confirmed that treatment with WIN-34B strongly increased the number of SH-2(CD105 cells and expression type II collagen in subchondral progenitor cells. Moreover, WIN-34B significantly increased proteoglycan, as measured by alcian blue staining; the mRNA level of type II α1 collagen, cartilage link protein, and aggrecan; and the inhibition of cartilage matrix molecules, such as GAG and type II collagen, in IL-1β-treated progenitor cells. These findings suggest that WIN-34B could be a potential candidate for effective anti-osteoarthritic therapy with cartilage repair as well as cartilage protection via enhancement of chondrogenic differentiation in the collagenase-induced osteoarthritis rabbit model and progenitor cells from subchondral bone.

  15. Human Umbilical Cord Perivascular Cells Exhibited Enhanced Migration Capacity towards Hepatocellular Carcinoma in Comparison with Bone Marrow Mesenchymal Stromal Cells: A Role for Autocrine Motility Factor Receptor

    Directory of Open Access Journals (Sweden)

    Juan Bayo

    2014-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the third cause of cancer-related death worldwide. Unfortunately, the incidence and mortality associated with HCC are increasing. Therefore, new therapeutic strategies are urgently needed and the use of mesenchymal stromal cells (MSCs as carrier of therapeutic genes is emerging as a promising option. Different sources of MSCs are being studied for cell therapy and bone marrow-derived cells are the most extensively explored; however, birth associated-tissues represent a very promising source. The aim of this work was to compare the in vitro and in vivo migration capacity between bone marrow MSCs (BM-MSCs and human umbilical cord perivascular cells (HUCPVCs towards HCC. We observed that HUCPVCs presented higher in vitro and in vivo migration towards factors released by HCC. The expression of autocrine motility factor (AMF receptor, genes related with the availability of the receptor on the cell surface (caveolin-1 and -2 and metalloproteinase 3, induced by the receptor activation and important for cell migration, was increased in HUCPVCs. The chemotactic response towards recombinant AMF was increased in HUCPVCs compared to BM-MSCs, and its inhibition in the conditioned medium from HCC induced higher decrease in HUCPVC migration than in BM-MSC. Our results indicate that HUCPVCs could be a useful cellular source to deliver therapeutic genes to HCC.

  16. Effects of Palm Vitamin E on Bone-Formation-Related Gene Expression in Nicotine-Treated Rats

    Directory of Open Access Journals (Sweden)

    Seham Salem Ahmed Abukhadir

    2012-01-01

    Full Text Available The study determines the effects of palm vitamin E on the gene expression of bone-formation-related genes in nicotine-treated rats. Male rats were divided into three groups: normal saline olive oil (NSO, nicotine olive oil (NO, and nicotine palm vitamin E (NE. The treatment was carried out in 2 phases. During the first 2 months, the NSO group received normal saline while the NO and NE groups received nicotine 7 mg/kg, 6 days a week, intraperitoneally. The following 2 months, normal saline and nicotine administration was stopped and was replaced with oral supplementation of olive oil for the NSO and NO groups and oral supplementation of palm vitamin E (60 mg/kg for the NE group. Both femurs were harvested to determine the gene expression of bone morphogenetic protein-2 (BMP-2, Osterix (OSX, and Runt-related transcription factor 2 (RUNX2. Nicotine significantly downregulated the gene expression. This effect was reversed by palm vitamin E treatment. In conclusion, palm vitamin E may play a role in osteoblast differentiation and can be considered as an anabolic agent to treat nicotine-induced osteoporosis.

  17. Effects of cell-attachment and extracellular matrix on bone formation in vivo in collagen-hydroxyapatite scaffolds.

    Directory of Open Access Journals (Sweden)

    Max M Villa

    Full Text Available Cell-based tissue engineering can be used to replace missing or damaged bone, but the optimal methods for delivering therapeutic cells to a bony defect have not yet been established. Using transgenic reporter cells as a donor source, two different collagen-hydroxyapatite (HA scaffolds, and a critical-size calvarial defect model, we investigated the effect of a cell-attachment period prior to implantation, with or without an extracellular matrix-based seeding suspension, on cell engraftment and osteogenesis. When quantitatively compared, the in-house scaffold implanted immediately had a higher mean radiopacity than in-house scaffolds incubated overnight. Both scaffold types implanted immediately had significantly higher area fractions of donor cells, while the in-house collagen-HA scaffolds implanted immediately had higher area fractions of the mineralization label compared with groups incubated overnight. When the cell loading was compared in vitro for each delivery method using the in-house scaffold, immediate loading led to higher numbers of delivered cells. Immediate loading may be preferable in order to ensure robust bone formation in vivo. The use of a secondary ECM carrier improved the distribution of donor cells only when a pre-attachment period was applied. These results have improved our understanding of cell delivery to bony defects in the context of in vivo outcomes.

  18. Low-level laser therapy enhances the stability of orthodontic mini-implants via bone formation related to BMP-2 expression in a rat model.

    Science.gov (United States)

    Omasa, Saori; Motoyoshi, Mitsuru; Arai, Yoshinori; Ejima, Ken-Ichiro; Shimizu, Noriyoshi

    2012-05-01

    The aim of this study was to investigate the stimulatory effects of low-level laser therapy (LLLT) on the stability of mini-implants in rat tibiae. In adolescent patients, loosening is a notable complication of mini-implants used to provide anchorage in orthodontic treatments. Previously, the stimulatory effects of LLLT on bone formation were reported; here, it was examined whether LLLT enhanced the stability of mini-implants via peri-implant bone formation. Seventy-eight titanium mini-implants were placed into both tibiae of 6-week-old male rats. The mini-implants in the right tibia were subjected to LLLT of gallium-aluminium-arsenide laser (830 nm) once a day during 7 days, and the mini-implants in the left tibia served as nonirradiated controls. At 7 and 35 days after implantation, the stability of the mini-implants was investigated using the diagnostic tool (Periotest). New bone volume around the mini-implants was measured on days 3, 5, and 7 by in vivo microfocus CT. The gene expression of bone morphogenetic protein (BMP)-2 in bone around the mini-implants was also analyzed using real-time reverse-transcription polymerase chain reaction assays. The data were statistically analyzed using Student's t test. Periotest values were significantly lower (0.79- to 0.65-fold) and the volume of newly formed bone was significantly higher (1.53-fold) in the LLLT group. LLLT also stimulated significant BMP-2 gene expression in peri-implant bone (1.92-fold). LLLT enhanced the stability of mini-implants placed in rat tibiae and accelerated peri-implant bone formation by increasing the gene expression of BMP-2 in surrounding cells.

  19. Effect of the HDAC inhibitor vorinostat on the osteogenic differentiation of mesenchymal stem cells in vitro and bone formation in vivo.

    Science.gov (United States)

    Xu, Song; De Veirman, Kim; Evans, Holly; Santini, Gaia Cecilia; Vande Broek, Isabelle; Leleu, Xavier; De Becker, Ann; Van Camp, Ben; Croucher, Peter; Vanderkerken, Karin; Van Riet, Ivan

    2013-05-01

    Vorinostat, a histone deacetylase (HDAC) inhibitor currently in a clinical phase III trial for multiple myeloma (MM) patients, has been reported to cause bone loss. The purpose of this study was to test whether, and to what extent, vorinostat influences the osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro and bone formation in vivo. Bone marrow-derived MSCs were prepared from both normal donors and MM patients. The MSCs were cultured in an osteogenic differentiation induction medium to induce osteogenic differentiation, which was evaluated by alkaline phosphatase (ALP) staining, Alizarin Red S staining and the mRNA expression of osteogenic markers. Naïve mice were administered vorinostat (100 mg/kg, ip) every other day for 3 weeks. After the mice were sacrificed, bone formation was assessed based on serum osteocalcin level and histomorphometric analysis. Vorinostat inhibited the viability of hMSCs in a concentration-dependent manner (the IC50 value was 15.57 μmol/L). The low concentration of vorinostat (1 μmol/L) did not significantly increase apoptosis in hMSCs, whereas pronounced apoptosis was observed following exposure to higher concentrations of vorinostat (10 and 50 μmol/L). In bone marrow-derived hMSCs from both normal donors and MM patients, vorinostat (1 μmol/L) significantly increased ALP activity, mRNA expression of osteogenic markers, and matrix mineralization. These effects were associated with upregulation of the bone-specifying transcription factor Runx2 and with the epigenetic alterations during normal hMSCs osteogenic differentiation. Importantly, the mice treated with vorinostat did not show any bone loss in response to the optimized treatment regimen. Vorinostat, known as a potent anti-myeloma drug, stimulates MSC osteogenesis in vitro. With the optimized treatment regimen, any decrease in bone formation was not observed in vivo.

  20. Effect of surface alkali-based treatment of titanium implants on ability to promote in vitro mineralization and in vivo bone formation.

    Science.gov (United States)

    Camargo, Winston A; Takemoto, Shinji; Hoekstra, Jan Willem; Leeuwenburgh, Sander C G; Jansen, John A; van den Beucken, Jeroen J J P; Alghamdi, Hamdan S

    2017-07-15

    This study investigated whether a novel alkali-based surface modification enhances in vitro mineralization as well as in vivo bone formation around titanium (Ti) implants in a femoral condyle model of 36 male Wister rats. All implant surfaces were grit-blasted and then received either acid-etching treatment, alkali-based treatment, or were left untreated (controls). Histological and histomorphometrical analyses were performed on retrieved specimens after 4 and 8weeks of healing to assess peri-implant bone formation. Results of implants surface characterisation showed notable differences in the topography and composition of alkali-treated surfaces, reflecting the formation of submicron-structured alkali-titanate layer. In the in vitro test, alkali-treated Ti surfaces showed the ability to stimulate mineralization upon soaking in simulated body fluid (SBF). In vivo histomorphometrical analyses showed similar values for bone area (BA%) and bone-to-implant contact (BIC%) for all experimental groups after both 4- and 8-week implantation periods. In conclusion, the surface topography and composition of the grit-blasted Ti implants was significantly modified using alkali-based treatment. With respect to the present in vivo model, the biological performance of alkali-treated Ti implants is comparable to the commercially available, grit-blasted, acid-etched Ti implants. Since success rate of dental implants might be challenged in bone of low density, an optimum implant surface characteristic is demanding. In this work, alkali treatment of Ti implants showed significant advantage of surface mineralization upon soaking in simulated body fluid. Using an in vivo rat model, Ti surfaces with either acid-etching treatment or alkali-based treatment evoked robust bone formation around Ti implants. Such information may be utilized for the advancement of biomaterials research for bone implants in future. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights

  1. Bone grafts in dentistry

    Directory of Open Access Journals (Sweden)

    Prasanna Kumar

    2013-01-01

    Full Text Available Bone grafts are used as a filler and scaffold to facilitate bone formation and promote wound healing. These grafts are bioresorbable and have no antigen-antibody reaction. These bone grafts act as a mineral reservoir which induces new bone formation.

  2. Mechanical stimulation enhanced estrogen receptor expression and callus formation in diaphyseal long bone fracture healing in ovariectomy-induced osteoporotic rats.

    Science.gov (United States)

    Chow, S K H; Leung, K S; Qin, J; Guo, A; Sun, M; Qin, L; Cheung, W H

    2016-10-01

    Estrogen receptor (ER) in ovariectomy-induced osteoporotic fracture was reported to exhibit delayed expression. Mechanical stimulation enhanced ER-α expression in osteoporotic fracture callus at the tissue level. ER was also found to be required for the effectiveness of vibrational mechanical stimulation treatment in osteoporotic fracture healing. Estrogen receptor(ER) is involved in mechanical signal transduction in bone metabolism. Its expression was reported to be delayed in osteoporotic fracture healing. The purpose of this study was to investigate the roles played by ER during osteoporotic fracture healing enhanced with mechanical stimulation. Ovariectomy-induced osteoporotic SD rats that received closed femoral fractures were divided into five groups, (i) SHAM, (ii) SHAM-VT, (iii) OVX, (iv) OVX-VT, and (v) OVX-VT-ICI, where VT stands for whole-body vibration treatment and ICI for ER antagonization by ICI 182,780. Callus formation and gene expression were assessed at 2, 4, and 8 weeks postfracture. In vitro osteoblastic differentiation, mineralization, and ER-α expression were assessed. The delayed ER expression was found to be enhanced by vibration treatment. Callus formation enhancement was shown by callus morphometry and micro-CT analysis. Enhancement effects by vibration were partially abolished when ER was modulated by ICI 182,780, in terms of callus formation capacity at 2-4 weeks and ER gene and protein expression at all time points. In vitro, ER expression in osteoblasts was not enhanced by VT treatment, but osteoblastic differentiation and mineralization were enhanced under estrogen-deprived condition. When osteoblastic cells were modulated by ICI 182,780, enhancement effects of VT were eliminated. Vibration was able to enhance ER expression in ovariectomy-induced osteoporotic fracture healing. ER was essential in mechanical signal transduction and enhancement in callus formation effects during osteoporotic fracture healing enhanced by vibration

  3. Conservative treatment of bone tissue metabolic disorders among patients with vitamin D-dependent rickets type II with genetic abnormality of type I collagen formation

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    S.M. Martsyniak

    2017-08-01

    Full Text Available Background. The purpose of the article is to determine the effect of conservative therapy on genetically caused disorders of bone tissue metabolism in patients with vitamin D-dependent rickets type II and genetic abnormality of type I collagen formation (VDDR(COL1. Materials and methods. At the premises of consulting and outpatient department of SI “Institute of Traumatology and Orthopaedics of the NAMS of Ukraine”, 13 patients having VDDR type II and genetic damage of type I collagen formation were examined and treated. The medical treatment was conducted in four stages. The first stage included full examination of patients (calcium and phosphorus levels in the blood serum and their urinary excretion, as well as determination of calcidiol and calcitriol serum levels, indicators of parathyroid hormone and osteocalcin, and a marker of bone formation P1NP and osteoresorption b-CTx. At this stage, children were obligated to undergo a genetic test to detect changes (polymorphism in alleles of receptors to vitamin D and type I collagen. Besides genetic tests, examinations at the other stages were conducted in full. Results. The study has shown the following. The genetically caused abnormality of reception to vitamin D results into substantial accumulation of vitamin D active metabolite in the blood serum. When combined with gene­tic abnormality of type I collagen formation, it significantly affected bone formation and destruction processes that causes development of osteomalacia (parathormone — vitamin D — osteocalcin system. The comprehensive study of vitamin D metabolism and biochemical vitals of bone tissue in patients having VDDR (COL1 brought us to understanding of some issues related to pathogenesis and nature of osteomalacia and, in future, osteoporotic changes on different levels, ensured us to express these changes by corresponding indices in the biochemical research and, finally, to develop appropriate schemes for the treatment of

  4. Bordetella pertussis Isolates from Argentinean Whooping Cough Patients Display Enhanced Biofilm Formation Capacity Compared to Tohama I Reference Strain.

    Science.gov (United States)

    Arnal, Laura; Grunert, Tom; Cattelan, Natalia; de Gouw, Daan; Villalba, María I; Serra, Diego O; Mooi, Frits R; Ehling-Schulz, Monika; Yantorno, Osvaldo M

    2015-01-01

    Pertussis is a highly contagious disease mainly caused by Bordetella pertussis. Despite the massive use of vaccines, since the 1950s the disease has become re-emergent in 2000 with a shift in incidence from infants to adolescents and adults. Clearly, the efficacy of current cellular or acellular vaccines, formulated from bacteria grown in stirred bioreactors is limited, presenting a challenge for future vaccine development. For gaining insights into the role of B. pertussis biofilm development for host colonization and persistence within the host, we examined the biofilm forming capacity of eight argentinean clinical isolates recovered from 2001 to 2007. All clinical isolates showed an enhanced potential for biofilm formation compared to the reference strain Tohama I. We further selected the clinical isolate B. pertussis 2723, exhibiting the highest biofilm biomass production, for quantitative proteomic profiling by means of two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry, which was accompanied by targeted transcriptional analysis. Results revealed an elevated expression of several virulence factors, including adhesins involved in biofilm development. In addition, we observed a higher expression of energy metabolism enzymes in the clinical isolate compared to the Tohama I strain. Furthermore, all clinical isolates carried a polymorphism in the bvgS gene. This mutation was associated to an increased sensitivity to modulation and a faster rate of adhesion to abiotic surfaces. Thus, the phenotypic biofilm characteristics shown by the clinical isolates might represent an important, hitherto underestimated, adaptive strategy for host colonization and long time persistence within the host.

  5. Bordetella pertussis isolates from Argentinean whooping cough patients display enhanced biofilm formation capacity compared to Tohama I reference strain

    Directory of Open Access Journals (Sweden)

    Laura eArnal

    2015-12-01

    Full Text Available Pertussis is a highly contagious disease mainly caused by Bordetella pertussis. Despite the massive use of vaccines since the 1950´s the disease has become re-emergent in 2000 with a shift in incidence from infants to adolescents and adults. Clearly, the efficacy of current cellular or acellular vaccines, formulated from bacteria grown in stirred bioreactors is limited, presenting a challenge for future vaccine development. For gaining insights into the role of B. pertussis biofilm development for host colonization and persistence within the host, we examined the biofilm forming capacity of eight argentinean clinical isolates recovered from 2001 to 2007. All clinical isolates showed an enhanced potential for biofilm formation compared to the reference strain Tohama I. We further selected the clinical isolate B. pertussis 2723, exhibiting the highest biofilm biomass production, for quantitative proteomic profiling by means of two-dimensional fluorescence difference gel electrophoresis (2D-DIGE coupled with mass spectrometry (MS, which was accompanied by targeted transcriptional analysis. Results revealed an elevated expression of several virulence factors, including adhesins involved in biofilm development. In addition, we observed a higher expression of energy metabolism enzymes in the clinical isolate compared to the Tohama I strain. Furthermore, all clinical isolates carried a polymorphism in the bvgS gene. This mutation was associated to an increased sensitivity to modulation and a faster rate of adhesion to abiotic surfaces. Thus, the phenotypic biofilm characteristics shown by the clinical isolates might represent an important, hitherto underestimated, adaptive strategy for host colonization and long time persistence within the host.

  6. De-novo collateral formation following acute myocardial infarction: Dependence on CCR2⁺ bone marrow cells.

    Science.gov (United States)

    Zhang, Hua; Faber, James E

    2015-10-01

    Wide variation exists in the extent (number and diameter) of native pre-existing collaterals in tissues of different strains of mice, with supportive indirect evidence recently appearing for humans. This variation is a major determinant of the wide variation in severity of tissue injury in occlusive vascular disease. Whether such genetic-dependent variation also exists in the heart is unknown because no model exists for study of mouse coronary collaterals. Also owing to methodological limitations, it is not known if ischemia can induce new coronary collaterals to form ("neo-collaterals") versus remodeling of pre-existing ones. The present study sought to develop a model to study coronary collaterals in mice, determine whether neo-collateral formation occurs, and investigate the responsible mechanisms. Four strains with known rank-ordered differences in collateral extent in brain and skeletal muscle were studied: C57BLKS>C57BL/6>A/J>BALB/c. Unexpectedly, these and 5 additional strains lacked native coronary collaterals. However after ligation, neo-collaterals formed rapidly within 1-to-2 days, reaching their maximum extent in ≤7 days. Rank-order for neo-collateral formation differed from the above: C57BL/6>BALB/c>C57BLKS>A/J. Collateral network conductance, infarct volume(-1), and contractile function followed this same rank-order. Neo-collateral formation and collateral conductance were reduced and infarct volume increased in MCP1(-/-) and CCR2(-/-) mice. Bone-marrow transplant rescued collateral formation in CCR2(-/-) mice. Involvement of fractalkine➔CX3CR1 signaling and endothelial cell proliferation were also identified. This study introduces a model for investigating the coronary collateral circulation in mice, demonstrates that neo-collaterals form rapidly after coronary occlusion, and finds that MCP➔CCR2-mediated recruitment of myeloid cells is required for this process. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Zebrafish sp7:EGFP: a transgenic for studying otic vesicle formation, skeletogenesis, and bone regeneration

    Science.gov (United States)

    DeLaurier, April; Eames, B. Frank; Blanco-Sánchez, Bernardo; Peng, Gang; He, Xinjun; Swartz, Mary E.; Ullmann, Bonnie; Westerfield, Monte; Kimmel, Charles B.

    2010-01-01

    Summary We report the expression pattern and construction of a transgenic zebrafish line for a transcription factor involved in otic vesicle formation and skeletogenesis. The zinc finger transcription factor sp7 (formerly called osterix) is reported as a marker of osteoblasts. Using bacterial artificial chromosome (BAC)-mediated transgenesis, we generated a zebrafish transgenic line for studying skeletal development, Tg(sp7:EGFP)b1212. Using a zebrafish BAC, EGFP was introduced downstream of the regulatory regions of sp7 and injected into 1 cell-stage embryos. In this transgenic line, GFP expression reproduces endogenous sp7 gene expression in the otic placode and vesicle, and in forming skeletal structures. GFP-positive cells were also detected in adult fish, and were found associated with regenerating fin rays post-amputation. This line provides an essential tool for the further study of zebrafish otic vesicle formation and the development and regeneration of the skeleton. PMID:20506187

  8. Evaluation of the biofilm formation capacity of Pasteurella multocida strains isolated from cases of fowl cholera and swine lungs and its relationship with pathogenicity

    Directory of Open Access Journals (Sweden)

    Brunna D. de Emery

    Full Text Available ABSTRACT: Pasteurella multocida is a Gram-negative bacillus that causes economic losses due to the development of respiratory diseases in several animal species. Among the mechanisms of virulence, the formation of biofilms is an important factor for bacterial survival in hostile environments. Studies of biofilm formation by P. multocida are needed because P. multocida is an important pathogen involved in respiratory infections. However, in contrast to other microorganisms, few studies of biofilm formation have examined P. multocida. Studies comparing the pathogenicity of microbial strains as a function of their biofilm production capacity are also rare. Consequently, the aim of this study was to evaluate the biofilm formation capacity of 94 P. multocida strains isolated from cases of fowl cholera and from swine lungs on polystyrene plates. The associations of the biofilm formation capacity with the pathogenicity index (PI in vivo and with the presence of four genes (screened by PCR of the tad locus (tadB, tadD, tadE and tadG, described as adhesion markers, were also determined. Strains from both animal origins were able to form biofilms. However, most of the specimens (52.13% were classified as weak producers, and more than 40% of the strains of P. multocida (40.42% did not produce biofilms. There was no significant difference (p>0.05 in the degree of biofilm production between the two sources of isolation. Of the analyzed strains, 56.52% contained all four genes (tadB, tadD, tadE and tadG. The PI arithmetic mean of the strains classified as non-biofilm producers was significantly different (p0.05 with the production of biofilms and with the origin of a given strain. Finally, low virulence strains may suggest a higher biofilm formation capacity on polystyrene plates.

  9. Mechanical Loading Improves Tendon-Bone Healing in a Rabbit Anterior Cruciate Ligament Reconstruction Model by Promoting Proliferation and Matrix Formation of Mesenchymal Stem Cells and Tendon Cells

    Directory of Open Access Journals (Sweden)

    Fanglong Song

    2017-02-01

    Full Text Available Background/Aims: This study investigated the effect of mechanical stress on tendon-bone healing in a rabbit anterior cruciate ligament (ACL reconstruction model as well as cell proliferation and matrix formation in co-culture of bone-marrow mesenchymal stem cells (BMSCs and tendon cells (TCs. Methods: The effect of continuous passive motion (CPM therapy on tendon-bone healing in a rabbit ACL reconstruction model was evaluated by histological analysis, biomechanical testing and gene expressions at the tendon-bone interface. Furthermore, the effect of mechanical stretch on cell proliferation and matrix synthesis in BMSC/TC co-culture was also examined. Results: Postoperative CPM therapy significantly enhanced tendon-bone healing, as evidenced by increased amount of fibrocartilage, elevated ultimate load to failure levels, and up-regulated gene expressions of Collagen I, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin at the tendon-bone junction. In addition, BMSC/TC co-culture treated with mechanical stretch showed a higher rate of cell proliferation and enhanced expressions of Collagen I, Collagen III, alkaline phosphatase, osteopontin, Tenascin C and tenomodulin than that of controls. Conclusion: These results demonstrated that proliferation and differentiation of local precursor cells could be enhanced by mechanical stimulation, which results in enhanced regenerative potential of BMSCs and TCs in tendon-bone healing.

  10. Influence of Particle Size of Deproteinized Bovine Bone Mineral on New Bone Formation and Implant Stability after Simultaneous Sinus Floor Elevation

    DEFF Research Database (Denmark)

    Jensen, Simon S; Aaboe, Merete; Janner, Simone F M

    2013-01-01

    BACKGROUND: Deproteinized bovine bone mineral (DBBM) is one of the best-documented bone substitute materials for sinus floor elevation (SFE). PURPOSE: DBBM is available in two particle sizes. Large particles are believed to facilitate improved neoangiogenesis compared with small ones. However, th...

  11. Silicon-Doped Titanium Dioxide Nanotubes Promoted Bone Formation on Titanium Implants.

    Science.gov (United States)

    Zhao, Xijiang; Wang, Tao; Qian, Shi; Liu, Xuanyong; Sun, Junying; Li, Bin

    2016-02-26

    While titanium (Ti) implants have been extensively used in orthopaedic and dental applications, the intrinsic bioinertness of untreated Ti surface usually results in insufficient osseointegration irrespective of the excellent biocompatibility and mechanical properties of it. In this study, we prepared surface modified Ti substrates in which silicon (Si) was doped into the titanium dioxide (TiO₂) nanotubes on Ti surface using plasma immersion ion implantation (PIII) technology. Compared to TiO₂ nanotubes and Ti alone, Si-doped TiO₂ nanotubes significantly enhanced the expression of genes related to osteogenic differentiation, including Col-I, ALP, Runx2, OCN, and OPN, in mouse pre-osteoblastic MC3T3-E1 cells and deposition of mineral matrix. In vivo, the pull-out mechanical tests after two weeks of implantation in rat femur showed that Si-doped TiO₂ nanotubes improved implant fixation strength by 18% and 54% compared to TiO₂-NT and Ti implants, respectively. Together, findings from this study indicate that Si-doped TiO₂ nanotubes promoted the osteogenic differentiation of osteoblastic cells and improved bone-Ti integration. Therefore, they may have considerable potential for the bioactive surface modification of Ti implants.

  12. Effect of hyaluronic acid in bone formation and its applications in dentistry.

    Science.gov (United States)

    Zhao, Ningbo; Wang, Xin; Qin, Lei; Zhai, Min; Yuan, Jing; Chen, Ji; Li, Dehua

    2016-06-01

    Hyaluronic acid (HA), the simplest glycosaminoglycan, participates in several important biological procedures, including mediation of cellular signaling, regulation of cell adhesion and proliferation, and manipulation of cell differentiation. The effect of HA on cell proliferation and differentiation depends on its molecular weight (MW) and concentration. Moreover, the properties of high viscosity, elasticity, highly negative charge, biocompatibility, biodegradability, and nonimmunogenicity make HA attractive in tissue engineering and disease treatment. This review comprises an overview of the effect of HA on cell proliferation and differentiation in vitro, the role of HA in bone regeneration in vivo, and the clinical applications of HA in dentistry, focusing on the mechanism underlining the effect of MW and concentration of HA on cell proliferation and osteogenic differentiation. It is expected that practical progress of HA both in laboratory-based experiments and clinical applications will be achieved in the next few years. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1560-1569, 2016. © 2016 Wiley Periodicals, Inc.

  13. Effect of Extracellular Matrix Membrane on Bone Formation in a Rabbit Tibial Defect Model

    Directory of Open Access Journals (Sweden)

    Jin Wook Hwang

    2016-01-01

    Full Text Available Absorbable extracellular matrix (ECM membrane has recently been used as a barrier membrane (BM in guided tissue regeneration (GTR and guided bone regeneration (GBR. Absorbable BMs are mostly based on collagen, which is more biocompatible than synthetic materials. However, implanted absorbable BMs can be rapidly degraded by enzymes in vivo. In a previous study, to delay degradation time, collagen fibers were treated with cross-linking agents. These compounds prevented the enzymatic degradation of BMs. However, cross-linked BMs can exhibit delayed tissue integration. In addition, the remaining cross-linker could induce inflammation. Here, we attempted to overcome these problems using a natural ECM membrane. The membrane consisted of freshly harvested porcine pericardium that was stripped from cells and immunoreagents by a cleaning process. Acellular porcine pericardium (APP showed a bilayer structure with a smooth upper surface and a significantly coarser bottom layer. APP is an ECM with a thin layer (0.18–0.35 mm but with excellent mechanical properties. Tensile strength of APP was 14.15±2.24 MPa. In in vivo experiments, APP was transplanted into rabbit tibia. The biocompatible material was retained for up to 3 months without the need for cross-linking. Therefore, we conclude that APP could support osteogenesis as a BM for up to 3 months.

  14. Flavonoid intake and bone health.

    Science.gov (United States)

    Weaver, Connie M; Alekel, D Lee; Ward, Wendy E; Ronis, Martin J

    2012-01-01

    Flavonoids, found in a wide diversity of plant foods from fruits and vegetables, herbs and spices, essential oils, and beverages, have the most potential of dietary components for promotion of bone health beyond calcium and vitamin D. Recent epidemiological studies show flavonoid consumption to have a stronger association with bone than general fruit and vegetable consumption. Bioactive flavonoids are being assessed for properties beyond their chemical antioxidant capacity, including anti-inflammatory actions. Some have been reported to enhance bone formation and to inhibit bone resorption through their action on cell signaling pathways that influence osteoblast and osteoclast differentiation. Future research is needed to determine which of the flavonoids and their metabolites are most effective and at what dose, as well as the mechanism of modulating cellular events, in order to set priorities for clinical trials.

  15. Biological width formation to immediate implants placed at different level in relation to the crestal bone: an experimental study in dogs.

    Science.gov (United States)

    Negri, Bruno; López Marí, Marta; Maté Sánchez de Val, José Eduardo; Iezzi, Giovanna; Bravo González, Luis Alberto; Calvo Guirado, José Luis

    2015-07-01

    Evaluate differences in bone remodeling, soft tissue reactions and biological width formation around immediate implants placed at different level in relation to the crestal bone in beagle dogs. The mandibular second, third and fourth premolars of six beagle dogs were extracted, and three implants were placed in the right side of each dog. Healing abutments were adjusted (n = 18). After 4 weeks, the procedure was repeated on the left side of the mandible (n = 18). Randomly, three implants were placed at crestal level (control group), and three implants were placed 2 mm subcrestally (test group) in relation to the crestal bone in each animal. The dogs were sacrificed after 8 weeks from the first surgical procedure, and biopsies were obtained. Samples were processed for ground sectioning. Histometric analysis was carried out to compare buccal and lingual bone resorption, soft tissue behavior and biological width formation in both groups. Crestal bone resorption was higher in the test group when considering the difference of 2 mms (IS-B = 2.05 ± 0.36 mm, control; 1.75 (+2) ± 0.38 mm, test). However, the dimensions of the biological width were similar for both groups (PM-C = 3.34 ± 0.53 mm, control; 3.13 ± 0.55 mm, test). The alterations that occurred in the peri-implant soft tissues may be related to the hard tissue remodeling, showing similar quantitative findings in the biological width formation in both groups. Even though the subcrestal placement might reduce the distance from the implant shoulder to the first bone-to-implant contact and reestablish the biological width dimension in a most coronal position, it might not have any effect on minimizing the marginal bone loss. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Influence of interimplant distance on papilla formation and bone resorption: a clinical-radiographic study in dogs.

    Science.gov (United States)

    de Oliveira, Rafael R; Novaes, Arthur B; Papalexiou, Vula; Muglia, Valdir A; Taba, Mário

    2006-01-01

    Implant esthetics has been the focus of attention for the past decade, and one vital issue is the effect of interimplant distance on interimplant papilla formation and crestal bone loss. The aim of this study was to evaluate the effect of 1, 2, and 3 mm of interimplant distance on papilla formation and crestal resorption in submerged and nonsubmerged Ankylos implants after prosthetic restoration. Bilateral mandibular premolars of 7 dogs were extracted, and after 12 weeks each dog received 8 implants. Implants were placed so that 3 interimplant distances were created at 1 mm (group 1), 2 mm (group 2), and 3 mm (group 3). The sides and the position of the groups were randomly selected. Twelve weeks after placement, the implants received metallic prostheses that allowed 5 mm of space between the prosthetic contact point (CP) and the crestal bone (CB). After 8 weeks, the distance between the CP and the papilla (CP-P) and the gingival height at the distal proximal aspect of the prosthesis (CP-DE) was clinically measured. Radiographic images were obtained to measure the distance of the CP to the CB within the interimplant surfaces (CP-IP) an